KR101855962B1 - Composition for increase of exercise capacity comprising extract of Sigesbeckia spp. - Google Patents
Composition for increase of exercise capacity comprising extract of Sigesbeckia spp. Download PDFInfo
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- KR101855962B1 KR101855962B1 KR1020170096847A KR20170096847A KR101855962B1 KR 101855962 B1 KR101855962 B1 KR 101855962B1 KR 1020170096847 A KR1020170096847 A KR 1020170096847A KR 20170096847 A KR20170096847 A KR 20170096847A KR 101855962 B1 KR101855962 B1 KR 101855962B1
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- KR
- South Korea
- Prior art keywords
- extract
- sigesveccia
- sigesbeckia
- exercise performance
- orientalis
- Prior art date
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Abstract
본 발명은 키레놀(kirenol) 또는 이를 함유하는 희첨(Hui Chum, Siegesbeckia spp.) 추출물을 유효성분으로 포함하는 운동수행능력 증강용, 특히 지구력 향상용 조성물에 관한 것이다. 본 발명에 따른 키레놀(kirenol), 또는 이를 함유하는 희첨 추출물 또는 이의 분획물은 운동수행능력, 특히 지구력 항샹에 관여하는 주요 유전자의 단백질 발현을 증가시킴에 따라, 운동수행능력을 탁월하게 증강하는 효과가 있다. 또한, 본 발명은 천연물이므로 부작용 없이 안전하게 사용될 수 있어, 의약품 또는 식품으로 사용될 수 있다.The present invention relates to a glow Kastrup (kirenol) or huicheom composition (Hui Chum, Siegesbeckia spp.) For performing motion including the extract as an active ingredient, enhancing the ability, in particular, improved endurance containing the same. The kirenol according to the present invention, or the squalane extract containing the same or a fraction thereof, increases protein expression of a major gene involved in exercise performance, in particular, endurance power, and thus exerts an excellent effect . In addition, since the present invention is a natural product, it can be safely used without side effects and can be used as a medicine or food.
Description
본 발명은 희첨(Sigesbeckia spp.) 추출물을 유효성분으로 함유하는 운동수행능력 증강용 조성물에 관한 것이다. The present invention relates to a composition for enhancing exercise performance, containing an extract of Heecheom (Sigesbeckia spp.) as an active ingredient.
지난 50∼100년간, 인간 신체활동의 감소현상은 제 2형 당뇨, 비만, 심혈관 질환 등과 같은 대사성 질환의 발병률 증가와 연관되어 있음이 알려졌다. 신체활동 부족은 세계보건기구에서 발표한 사망 원인 중 4위를 차지한다. 이러한 현상들로 인해 세계보건기구, 미국심장협회, 영국심장재단 등의 단체에서는 일주일에 5일 이상, 최소 30분의 유산소 운동을 권장하고 있다. 실제로 운동은 당뇨, 비만, 유방암과 대장암의 발병률을 줄이고, 우울증에도 좋은 치료효과를 나타낸다(Br. J. Pharmacol. 170:1153-1166, 2013, Am. J. Cardiol. 110: 58B-68B, 2012).Over the past 50-100 years, it has been known that the decrease in human physical activity is associated with an increased incidence of metabolic diseases such as type 2 diabetes, obesity, and cardiovascular disease. Lack of physical activity ranks fourth among the causes of death published by the World Health Organization. Due to these phenomena, organizations such as the World Health Organization, the American Heart Association, and the British Heart Foundation recommend at least 30 minutes of aerobic exercise for at least 5 days a week. In fact, exercise reduces the incidence of diabetes, obesity, breast and colon cancer, and has a good therapeutic effect on depression (Br. J. Pharmacol. 170:1153-1166, 2013, Am. J. Cardiol. 110: 58B-68B, 2012).
에너지 소비를 촉진하여 운동수행능력을 향상하기 위한 대표적인 방법 중의 하나로는 미토콘드리아에 의한 지방산 산화(fatty acid oxidation)를 증가시켜 ATP 에너지를 생성시키는 방법이 있다. 이를 관장하는 미토콘드리아의 개수와 능력은 PGC-1α(peroxisome proliferator-activated receptor-gamma coactivator 1 alpha) 이라는 보조활성자에 의해 조절되고, PGC-1α의 활성은 SIRT1(sirtulin)에 의해 조절되는 것으로 밝혀졌다(EMBO. J. 26: 1913-1923, 2007, Cell Metab. 1: 361-370, 2005).One of the representative methods for promoting energy consumption and improving exercise performance is a method of generating ATP energy by increasing fatty acid oxidation by mitochondria. It was found that the number and ability of mitochondria in charge of this is regulated by a coactivator called PGC-1α (peroxisome proliferator-activated receptor-
Scarpulla와 그의 공동연구자들은 NRF(nuclear respiratory factor)라는 단백질을 동정하였다(J. Cell. Biochem. 97: 673-683, 2006). NRF 군의 단백질들은 핵에서 미토콘드리아의 다양한 유전자들의 프로모터에 결합을 하여 미토콘드리아의 복제와 전사를 활성화시킨다. 미토콘드리아의 복제 및 전사의 활성화에 의하여 미토콘드리아의 생성이 유도되는 것으로 밝혀졌다. 또한, NRF 군의 단백질은 PGC-1α 보조활성자와 물리적으로 상호작용하여 발현이 증진되는 것으로 밝혀졌다(Cell 98: 115-24, 1999).Scarpulla and his collaborators have identified a protein called nuclear respiratory factor (NRF) (J. Cell. Biochem. 97: 673-683, 2006). Proteins of the NRF group bind to promoters of various mitochondrial genes in the nucleus, thereby activating mitochondrial replication and transcription. It has been found that mitochondrial production is induced by mitochondrial replication and activation of transcription. In addition, it was found that proteins of the NRF group physically interact with PGC-1α co-activators to enhance their expression (Cell 98: 115-24, 1999).
그 외에, AMPK, pAMPK, PPARδ, ERRα 및 Tfam 등이 운동수행능력 향상과 관련이 있는 인자로 알려져 있다.In addition, AMPK, pAMPK, PPARδ, ERRα, and Tfam are known as factors associated with improving exercise performance.
희첨(일명 희렴)은 국화과의 시게스벡키아속 식물(Siegesbeckia spp.)인 시게스벡키아 글라브레센스(Siegesbeckia glabrescens Mak.), 시게스벡키아 푸베센스(Siegesbeckia pubescens Mak.) 또는 시게스벡키아 오리엔탈리스(Siegesbeckia orientalis L.)의 지상부를 건조한 것이다. 진득찰이라고 불리우는 시게스벡키아 글라브레센스는 항균(Int. J. Food Microbiol. 160: 260-266, 2013), 항암(Oncol. Rep. 30: 221-226, 2013), 항당뇨(J. Enzyme Inhib. Med. Chem. 21: 379-383, 2006), 항염(Food Agric. Immunol. 22: 145-160, 2011) 등의 활성이 보고되어 있다. 털진득찰이라고 불리우는 시게스벡키아 푸베센스는 항염 및 진통(Pak. J. Pharm. Sci. 21: 89-91, 2008), 항산화 및 항비만(Kor. J. Microbiol. Biotechnol. 41: 341-349, 2013), 상처치유(J. Ethnopharmacol. 134: 1033-1038, 2011), 관절염 효과(Phytomedicine 19: 882-889, 2012) 등의 활성이 보고되어 있다. 제주진득찰이라고 불리우는 시게스벡키아 오리엔탈리스는 항암(Natural Product Radiance 6: 34-39, 2007), 항염(Chem. Biodivers. 3: 754-761, 2006), 항산화(Korean J. Pharmacogn. 36: 150-163, 2005) 등의 활성이 보고되어 있다. Huicheom (aka huiryeom) is Shige's Becky Ashok plant of the Asteraceae (Siegesbeckia spp.), Siegesbeckia Glabrecens (Siegesbeckia glabrescens Mak.), Siegesbeckia pubescens Mak., or Siegesbeckia orientalis L. Sigesveccia Glabrecens, which is called jindeukchal, is antibacterial (Int. J. Food Microbiol. 160: 260-266, 2013), anti-cancer (Oncol. Rep. 30: 221-226, 2013), and anti-diabetes (J. Enzyme). Inhib. Med. Chem. 21: 379-383, 2006), anti-inflammatory (Food Agric. Immunol. 22: 145-160, 2011) and the like have been reported. Sigesveccia fuvesense, also known as hairy skin, is anti-inflammatory and analgesic (Pak. J. Pharm. Sci. 21: 89-91, 2008), antioxidant and anti-obesity (Kor. J. Microbiol. Biotechnol. 41: 341-349) , 2013), wound healing (J. Ethnopharmacol. 134: 1033-1038, 2011), and arthritis effect (Phytomedicine 19: 882-889, 2012). Sigesveccia Orientalis, also called Jeju Jindeukchal, is anti-cancer (Natural Product Radiance 6: 34-39, 2007), anti-inflammatory (Chem. Biodivers. 3: 754-761, 2006), and antioxidant (Korean J. Pharmacogn. 36: 150). -163, 2005) has been reported.
키레놀(Kirenol)은 주로 희첨에서 발견되는 다이터페노이드(diterpenoid)로서 항염효과 및 진통효과(J. Ethnopharmacol. 137: 1089-1094, 2011), 항균효과(Pharmacogn. Mag. 8: 149-155, 2012), 관절염효과(Phytomedicine 19: 882-889, 2012), 항비만 효과(BBRC 445, 433-438, 2014) 등을 갖는 것으로 보고되어 있다.Kirenol is a diterpenoid mainly found in olivine and has anti-inflammatory and analgesic effects (J. Ethnopharmacol. 137: 1089-1094, 2011), and antibacterial effects (Pharmacogn. Mag. 8: 149-155) , 2012), arthritis effect (Phytomedicine 19: 882-889, 2012), and anti-obesity effect (BBRC 445, 433-438, 2014).
그러나, 본 발명의 이전에는 희첨 또는 키레놀의 운동수행능력 증강효과에 관해서는 알려진 바 없었다.However, prior to the present invention, the effect of enhancing exercise performance of huicheom or kylenol was not known.
이에 본 발명자들은 우수한 운동수행능력 활성을 가지며 안전하게 적용될 수 있는 천연물질을 탐색한 결과, 키레놀(kirenol) 또는 이를 함유하는 희첨(Hui Chum, Siegesbeckia spp.) 추출물 또는 이의 분획물이 운동수행능력 증강활성이 있음을 확인하여 본 발명을 완성하였다.The present inventors have found that excellent physical performance result of browsing the natural substances that can have an active safely applied, Kastrup play (kirenol) or huicheom (Hui Chum, Siegesbeckia spp.) Containing the same extract or a fraction of the physical performance enhancing activity It was confirmed that the present invention was completed.
따라서, 본 발명의 목적은 희첨 추출물을 유효성분으로 포함하는 운동수행능력 증강용 조성물을 제공하는데 있다.Therefore, it is an object of the present invention to provide a composition for enhancing exercise performance, comprising the extract as an active ingredient.
본 발명의 다른 목적은 하기 화학식 1의 화합물을 유효성분으로 포함하는 운동수행능력 증강용 조성물을 제공하는데 있다:Another object of the present invention is to provide a composition for enhancing athletic performance comprising the compound of Formula 1 as an active ingredient:
[화학식 1][Formula 1]
상기 과제를 해결하기 위한 수단으로서, 본 발명은 As a means for solving the above problems, the present invention
희첨 추출물 또는 이의 분획물을 유효성분으로 포함하는 운동수행능력 증강용 약학 조성물 및 식품 조성물을 제공한다.It provides a pharmaceutical composition and a food composition for enhancing exercise performance, comprising the extract or a fraction thereof as an active ingredient.
상기 과제를 해결하기 위한 또 다른 수단으로서, 본 발명은As another means for solving the above problem, the present invention
하기 화학식 1로 표시되는 화합물을 유효성분으로 포함하는 운동수행능력 증강용 약학 조성물 및 식품 조성물을 제공한다:It provides a pharmaceutical composition and a food composition for enhancing exercise performance, comprising a compound represented by the following
[화학식 1][Formula 1]
상기 운동수행능력 증강은 지구력 향상일 수 있다. The exercise performance enhancement may be endurance improvement.
본 발명에 따른 키레놀(kirenol), 또는 이를 함유하는 희첨 추출물 또는 이의 분획물은 운동수행능력에 관여하는 주요 유전자인 PGC-1α의 단백질 발현을 증가시킴에 따라, 운동수행능력을 탁월하게 증강하는 효과가 있다. 또한, 본 발명은 천연물이므로 부작용 없이 안전하게 사용될 수 있어, 의약품 또는 식품으로 사용될 수 있다.Kirenol according to the present invention, or extract or a fraction thereof containing the same increases the protein expression of PGC-1α, a major gene involved in exercise performance, and thus excellently enhances exercise performance. There is. In addition, since the present invention is a natural product, it can be safely used without side effects, and thus can be used as a medicine or food.
도 1은 L6 근육 세포에서, 키레놀 또는 이를 함유하는 시게스벡키아 글라브레센스 에탄올 추출물, 시게스벡키아 푸베센스 에탄올 추출물, 시게스벡키아 오리엔탈리스 에탄올 추출물의 처리에 따른 PGC-1α의 단백질 발현량을 측정한 결과를 보여준다.
도 2는 L6 근육 세포에서, 키레놀을 함유하는 시게스벡키아 오리엔탈리스 초고압 추출물의 처리에 따른 PGC-1α의 단백질 발현량을 측정한 결과를 보여준다.
도 3은 정상식이 동물 모델에서 키레놀을 함유하는 시게스벡키아 오리엔탈리스 에탄올 추출물 투여에 의한 운동수행능력의 변화를 측정한 결과를 보여준다(a:운동 거리, b:운동 시간).
도 4는 고지방식이로 유도된 비만 동물 모델에서 키레놀을 함유하는 시게스벡키아 오리엔탈리스 에탄올 추출물 투여에 의한 운동수행능력의 변화를 측정한 결과를 보여준다(a:운동 거리, b:운동 시간).
도 5는 동물 모델의 종아리 근육에서 키레놀을 함유하는 시게스벡키아 오리엔탈리스 에탄올 추출물 투여에 의한 운동능력향상과 관련된 유전자인 p-AMPK, SIRT1, PGC-1α, PPARδ의 단백질 발현량을 측정한 결과를 보여준다.
도 6은 동물 모델의 종아리 근육에서 키레놀을 함유하는 시게스벡키아 오리엔탈리스 에탄올 추출물 투여에 의한 미토콘드리아 생합성과 관련된 유전자인 PGC-1α, NRF-1, ERRα, Tfam의 mRNA발현량을 측정한 결과를 보여준다.1 is a protein of PGC-1α in L6 muscle cells according to the treatment of kyrenol or a Sigesveccia glavresense ethanol extract, a Sigesveccia fuvesense ethanol extract, and a Sigesveccia orientalis ethanol extract containing the same. It shows the result of measuring the expression level.
FIG. 2 shows the results of measuring the protein expression level of PGC-1α in L6 muscle cells according to the treatment of Sigesbeckia orientalis ultra-high pressure extract containing kylenol.
FIG. 3 shows the results of measuring changes in exercise performance by administration of an ethanol extract of Sigesbeckia Orientalis containing kylenol in a normal diet animal model (a: exercise distance, b: exercise time).
Figure 4 shows the results of measuring the change in exercise performance by administration of an ethanol extract of Sigesbeckia Orientalis containing kylenol in an obese animal model induced by a high fat diet (a: exercise distance, b: exercise time ).
5 is a measurement of the protein expression levels of p-AMPK, SIRT1, PGC-1α, and PPARδ, genes related to the improvement of exercise capacity by administration of an ethanol extract of Sigesbeckia orientalis containing kylenol in the calf muscle of an animal model. Show the results.
6 is a result of measuring the mRNA expression levels of PGC-1α, NRF-1, ERRα, and Tfam, genes related to mitochondrial biosynthesis by administration of an ethanol extract of Sigesbeckia Orientalis containing kylenol in the calf muscle of an animal model. Show.
이하, 본 발명의 구성을 구체적으로 설명한다.Hereinafter, the configuration of the present invention will be described in detail.
본 발명은 희첨 추출물 또는 이의 분획물, 또는 하기 화학식 1로 표시되는 화합물의 운동수행능력 증강 용도; 희첨 추출물 또는 이의 분획물, 또는 하기 화학식 1로 표시되는 화합물을 포함하는 운동수행능력 증강용 조성물; 또는 희첨 추출물 또는 이의 분획물, 또는 하기 화학식 1로 표시되는 화합물을 개체에 투여하는 것을 포함하는 운동수행능력 증강 방법을 제공한다.The present invention is used to enhance the exercise performance of the extract or a fraction thereof, or a compound represented by the following formula (1); A composition for enhancing exercise performance, including a whitish extract or a fraction thereof, or a compound represented by the following formula (1); Or it provides a method for enhancing exercise performance, comprising administering to an individual a compound represented by the following formula (1), or a fraction thereof, or the extract or a fraction thereof.
[화학식 1][Formula 1]
본 명세서에서 '희첨' 또는 '희렴'은 국화과의 시게스벡키아속 식물(Siegesbeckia spp.)인 시게스벡키아 글라브레센스(Siegesbeckia glabrescens Mak.), 시게스벡키아 푸베센스(Siegesbeckia pubescens Mak.) 또는 시게스벡키아 오리엔탈리스(Siegesbeckia orientalis L.)의 지상부를 건조한 것을 의미한다. 시게스벡키아 글라브레센스는 진득찰, 시게스벡키아 푸베센스는 털진득찰, 시게스벡키아 오리엔탈리스는 제주진득찰 이라고도 한다.In this specification, huicheom 'or' huiryeom 'is Shige's Becky Ashok plant of the Asteraceae (Siegesbeckia spp.) In Shige's Becky Oh Mugla Brenna sense (Siegesbeckia glabrescens Mak.), Siegesbeckia pubescens Mak.) or Siegesbeckia orientalis L. It is also said that Siges Veckia Glabrecens is called Jindeukchal, Siges Veckia Fuvesense is hairy Jindeukchal, and Siges Veckia Orientalis is called Jeju Jindeukchal.
본 명세서에서 '희첨 추출물' 또는 '희렴 추출물'은 상호 교환적으로 사용되며, 희첨(희렴)을 추출하여 수득한 추출물을 의미한다. 희첨 추출물의 제조방법은 당업계에 공지된 통상의 추출방법을 제한 없이 이용할 수 있고, 예를 들어, 희첨 식물 또는 식물의 일부 (잎 또는 뿌리)로부터 물, 탄소수 1 내지 6의 유기용매 및 아임계 또는 초임계 유체로 이루어진 군에서 선택된 하나 이상의 용매로 추출하여 수득할 수 있다. In the present specification, the term "Huichom extract" or "Himreum extract" is used interchangeably, and refers to an extract obtained by extracting Heechoom (Himyeom). The preparation method of the rarity extract can use a conventional extraction method known in the art without limitation, for example, water, an organic solvent having 1 to 6 carbon atoms, and a subcritical system from a rarity plant or part of a plant (leaves or roots). Alternatively, it may be obtained by extraction with one or more solvents selected from the group consisting of supercritical fluids.
본 명세서에서 '분획물'은 다양한 구성성분을 포함하는 혼합물로부터 특정 성분 또는 특정 그룹을 분리하는 분획방법에 의하여 얻어진 결과물을 의미한다. 분획물을 제조하는 방법은 당업계에 잘 알려져 있으며, 공지의 방법을 제한 없이 이용 가능하다. 예를 들어, 용매 분획, 실리카 겔 크로마토그라피(silica gel chromatography), prep-HPLC 등의 기술을 이용하여 활성물질이 농축된 특정 분획물을 제조할 수 있다.In the present specification, "fraction" means a result obtained by a fractionation method for separating a specific component or a specific group from a mixture containing various constituents. Methods for preparing fractions are well known in the art, and known methods can be used without limitation. For example, a specific fraction in which the active material is concentrated may be prepared using techniques such as solvent fractionation, silica gel chromatography, and prep-HPLC.
한 구체예에서 희첨 추출물의 분획물은 희첨 추출물을 에틸아세테이트, 메탄올 또는 이들의 혼합용매로 분획하여 수득할 수 있다.In one embodiment, the fraction of the daisy extract can be obtained by fractionating the daisy extract with ethyl acetate, methanol, or a mixed solvent thereof.
본 명세서에서, '운동수행능력'은 일상생활이나 스포츠에서 볼 수 있는 신체동작을 외형적으로 달리기, 뛰기, 던지기, 헤엄치기 등으로 구분할 때, 상기 동작을 빠르게, 강하게, 정확하게, 오래, 능숙하게 할 수 있는 정도를 나타내는 것으로, 운동수행능력은 근력, 민첩성 및 지구력 등의 인자로 규정된다. 용어 '운동수행능력 증강'은 운동수행능력을 개선하거나 향상시키는 것을 말한다.In the present specification,'exercise performance ability' refers to physical movements found in daily life or sports externally, such as running, running, throwing, swimming, etc., when the movement is quickly, strongly, accurately, long, skillfully It indicates the degree to which it can be done, and exercise performance is defined by factors such as muscle strength, agility, and endurance. The term'enhancing exercise performance ability' refers to improving or improving exercise performance ability.
본 명세서에서, '운동수행능력 증강용 조성물'이란 운동수행능력 증강 효과가 있는 물질을 유효성분으로 포함하는 조성물로, 약학 조성물 또는 식품 조성물을 포함한다.In the present specification, the term "composition for enhancing exercise performance" refers to a composition comprising a substance having an effect of enhancing exercise performance as an active ingredient, and includes a pharmaceutical composition or a food composition.
본 발명의 운동수행능력 증강용 조성물은, 희첨 추출물 또는 이의 분획물 이외에, 추가로 동일 또는 유사한 기능을 나타내는 유효성분을 1종 이상 함유할 수 있다. 예컨대, 공지의 운동수행능력 증강 성분을 포함할 수 있다. 추가적인 성분을 포함하게 되면 본 발명의 조성물의 운동수행능력 증강 효과가 더욱 증진될 수 있을 것이다. 상기 성분 추가 시에는 복합 사용에 따른 피부 안전성, 제형화의 용이성, 유효성분들의 안정성을 고려할 수 있다. 본 발명의 한 구체예에서, 상기 조성물은 당업계에 공지된 운동수행능력 증강 성분으로서, 파이퍼 레트로프락텀(Piperretrofractum Vahl.) 열매의 추출물, 미리세틴, 쿠커비테인 추출물, 판두라타 추출물, 포도근 추출물, 노근 추출물 및 홍삼 추출물로 이루어진 군으로부터 선택되는 1종 이상의 성분을 추가로 포함할 수 있다. 추가의 성분은 전체 조성물 중량에 대하여 0.0001 중량% 이상 내지 10 중량% 이하로 포함될 수 있다. 예를 들어, 0.0001 중량% 이상 내지 1 중량% 이하, 0.0001중량% 이상 내지 0.1중량% 이하, 0.0001 중량% 이상 내지 0.001 중량% 이하, 0.001중량% 이상 내지 10중량% 이하, 0.001중량% 이상 내지 1중량% 이하, 0.001 중량% 이상 내지 0.1중량% 이하, 0.01 중량% 이상 내지 10중량% 이하, 0.01중량% 이상 내지 1 중량% 이하일 수 있다. 상기 함량 범위는 피부 안전성, 상기 화학식 1의 화합물의 제형화 시의 용이성 등의 요건에 따라 조절될 수 있을 것이다.The composition for enhancing exercise performance of the present invention may further contain one or more active ingredients exhibiting the same or similar functions in addition to the extract or fractions thereof. For example, it may contain a known component for enhancing exercise performance. If additional ingredients are included, the effect of enhancing exercise performance of the composition of the present invention may be further enhanced. When the above ingredients are added, skin safety, ease of formulation, and stability of active ingredients can be considered in combination with use. In one embodiment of the present invention, the composition is an exercise performance enhancing component known in the art, as an extract of Piperretrofractum Vahl. fruit, paroxetine, cucurbitein extract, pandurata extract, grape It may further include one or more components selected from the group consisting of root extract, nogeun extract, and red ginseng extract. Additional ingredients may be included in an amount of 0.0001% by weight or more and 10% by weight or less based on the total weight of the composition. For example, 0.0001% by weight or more and 1% by weight or more, 0.0001% by weight or more and 0.1% by weight or less, 0.0001% by weight or more and 0.001% by weight or less, 0.001% by weight or more and 10% by weight or less, 0.001% by weight or more and 1 It may be less than or equal to 0.001% by weight and less than or equal to 0.1% by weight, less than or equal to 0.01% by weight and less than or equal to 10% by weight, and less than or equal to 0.01% by weight and less than 1% by weight. The content range may be adjusted according to requirements such as skin safety and ease of formulation of the compound of
본 발명의 희첨 추출물 또는 이의 분획물을 유효성분으로 포함하는 운동수행능력 증강용 조성물은 약학 조성물 또는 식품 조성물일 수 있다.The composition for enhancing exercise performance comprising the extract of the present invention or a fraction thereof as an active ingredient may be a pharmaceutical composition or a food composition.
본 발명의 화학식 1로 표시되는 화합물을 유효성분으로 포함하는 운동수행능력 증강용 조성물은 약학 조성물 또는 식품 조성물일 수 있다:The composition for enhancing exercise performance comprising the compound represented by
[화학식 1][Formula 1]
상기 화학식 1의 화합물은 가능한 모든 이성질체를 포함할 수 있으며, 예를 들어, 하기 화학식 2의 화합물을 포함할 수 있다.The compound of
[화학식 2][Formula 2]
상기 화학식 2의 화합물은 일명 키레놀(kirenol)이라 한다.The compound of Formula 2 is referred to as kirenol.
상기 화학식 1의 화합물 또는 상기 화학식 2의 화합물은 식물 추출물로부터 분리 또는 합성하여 이용하거나, 시판되고 있는 화합물을 이용할 수 있다.The compound of
한 구체예에서, 상기 화학식 1로 표시되는 화합물 또는 화학식 2로 표시되는 화합물은 희첨 추출물로부터 분리된 것일 수 있다.In one embodiment, the compound represented by
한 구체예에서, 희첨 추출물은 시게스벡키아 글라브레센스, 시게스벡키아 푸베센스 및 시게스벡키아 오리엔탈리스로 이루어진 군으로부터 선택되는 하나 이상의 식물의 추출물일 수 있다. 예를 들어, 시게스벡키아 글라브레센스, 시게스벡키아 푸베센스 또는 시게스벡키아 오리엔탈리스의 건조된 잎과 줄기를 이용한 에탄올 추출물, 열수 추출물, 헥산 추출물, 에틸아세테이트 추출물, 초고압 추출물일 수 있다.In one embodiment, the olivine extract may be an extract of one or more plants selected from the group consisting of Sigesveccia glavresense, Sigesveccia fuvesense, and Sigesveccia orientalis. For example, ethanol extract, hot water extract, hexane extract, ethyl acetate extract, ultra-high pressure extract using dried leaves and stems of Sigesveccia glavresense, Sigesveccia fuvesense, or Sigesveccia orientalis. have.
한 구체예에서, 희첨 추출물은 물, 탄소수 1 내지 6의 유기용매, 아임계 유체 및 초임계 유체로 이루어진 군으로부터 선택되는 하나 이상의 용매로 희첨을 추출하여 수득할 수 있다. 예를 들어, 희첨 식물을 100 MPa 이상의 초고압 조건 하에서 추출하여 수득할 수도 있다. 필요한 경우에는 당업계에 공지된 방법에 따라 여과 및 농축 단계를 추가적으로 포함하여 제조할 수 있다.In one embodiment, the dilute extract may be obtained by extracting the dilute extract with one or more solvents selected from the group consisting of water, an organic solvent having 1 to 6 carbon atoms, a subcritical fluid, and a supercritical fluid. For example, rare plants can also be obtained by extraction under ultra-high pressure conditions of 100 MPa or more. If necessary, it can be prepared by additionally including filtration and concentration steps according to methods known in the art.
한 구체예에서, 탄소수 1 내지 6의 유기용매는 탄소수 1 내지 6개의 알코올(alcohol), 아세톤(acetone), 에테르(ether), 벤젠(benzene), 클로로포름(chloroform), 에틸아세테이트(ethyl acetate), 메틸렌 클로라이드(methylene chloride), 헥산(hexane), 시클로헥산(cyclohexane) 및 석유에테르(petroleum ether)로 이루어진 군 중에서 선택되는 하나 이상일 수 있다.In one embodiment, the organic solvent having 1 to 6 carbon atoms is an alcohol having 1 to 6 carbon atoms, acetone, ether, benzene, chloroform, ethyl acetate, It may be at least one selected from the group consisting of methylene chloride, hexane, cyclohexane, and petroleum ether.
또한, 본 발명의 희첨 추출물은 건조시킨 희첨을 식품가공에 적합한 정제수, 에탄올 및 아임계수 또는 초임계 이산화탄소를 이용하여 추출, 정제하여 얻을 수 있거나, 초고압 추출 장치를 이용하여 추출, 정제하여 얻을 수 있으며, 또는 희첨 식물을 직접 압착하여 얻은 오일로부터 분리 정제하여 얻을 수 있다. 예를 들어, 100 MPa 이상의 초고압 조건 하에서 희첨을 추출하여 추출물을 수득할 수 있다.In addition, the luteum extract of the present invention can be obtained by extracting and purifying the dried whitish using purified water suitable for food processing, ethanol, subcritical water, or supercritical carbon dioxide, or extracted and purified using an ultra-high pressure extraction device. Or, it can be obtained by separating and purifying from oil obtained by directly compressing rare plants. For example, it is possible to obtain an extract by extracting lychee under ultra-high pressure conditions of 100 MPa or more.
한 구체예에서, 희첨 추출물의 분획물은 에틸아세테이트, 메탄올 또는 이들의 혼합용매로 희첨 추출물을 분획하여 수득할 수 있다.In one embodiment, the fraction of the lean extract may be obtained by fractionating the whitish extract with ethyl acetate, methanol, or a mixed solvent thereof.
본 발명의 운동수행능력 증강용 조성물이 약학 조성물인 경우, 상기 약학 조성물은 키레놀 또는, 이를 함유하는 희첨 추출물 또는 이의 분획물의 약제학적으로 허용 가능한 염을 포함할 수 있다. 본 명세서에서 용어 '약제학적으로 허용 가능한'이란 생리학적으로 허용되고 인간에게 투여될 때, 통상적으로 알레르기 반응 또는 이와 유사한 반응을 일으키지 않는 것을 말하며, 상기 염으로는 약제학적으로 허용 가능한 유리산(free acid)에 의하여 형성된 산 부가염이 바람직하다. When the composition for enhancing exercise performance of the present invention is a pharmaceutical composition, the pharmaceutical composition may contain kylenol or a pharmaceutically acceptable salt of a lychee extract containing the same or a fraction thereof. In the present specification, the term'pharmaceutically acceptable' refers to physiologically acceptable and when administered to humans, usually does not cause an allergic reaction or a similar reaction, and as the salt, a pharmaceutically acceptable free acid (free Acid addition salts formed by acid) are preferred.
상기 키레놀 또는, 이를 함유하는 희첨 추출물 또는 이의 분획물의 약제학적으로 허용 가능한 염은 유기산 또는 무기산을 이용하여 형성된 산 부가염일 수 있으며, 상기 유기산은 예를 들면 포름산, 아세트산, 프로피온산, 락트산, 부티르산, 이소부티르산, 트리플루오로아세트산, 말산, 말레산, 말론산, 푸마르산, 숙신산, 숙신산 모노아미드, 글루탐산, 타르타르산, 옥살산, 시트르산, 글리콜산, 글루쿠론산, 아스코르브산, 벤조산, 프탈산, 살리실산, 안트라닐산, 디클로로아세트산, 아미노옥시 아세트산, 벤젠술폰산, p-톨루엔술폰산 또는 메탄술폰산을 포함한다. 무기산은 예를 들면 염산, 브롬산, 황산, 인산, 질산, 탄산 또는 붕산을 포함한다. 산 부가염은 바람직하게는 염산염 또는 아세트산염 형태일 수 있으며, 보다 바람직하게는 염산염 형태일 수 있다.The chilenol or a pharmaceutically acceptable salt of the dilution extract or fraction thereof may be an acid addition salt formed using an organic acid or an inorganic acid, and the organic acid may be, for example, formic acid, acetic acid, propionic acid, lactic acid, butyric acid, Isobutyric acid, trifluoroacetic acid, malic acid, maleic acid, malonic acid, fumaric acid, succinic acid, succinic acid monoamide, glutamic acid, tartaric acid, oxalic acid, citric acid, glycolic acid, glucuronic acid, ascorbic acid, benzoic acid, phthalic acid, salicylic acid, anthranilic acid , Dichloroacetic acid, aminooxy acetic acid, benzenesulfonic acid, p-toluenesulfonic acid or methanesulfonic acid. Inorganic acids include, for example, hydrochloric acid, bromic acid, sulfuric acid, phosphoric acid, nitric acid, carbonic acid or boric acid. The acid addition salt may be preferably in the form of hydrochloride or acetate, and more preferably in the form of hydrochloride.
상기 언급된 산 부가염은 a) 키레놀 또는, 이를 함유하는 희첨 추출물 또는 이의 분획물 및 산을 직접 혼합하거나, b) 이들 중 한 가지를 용매 또는 함수 용매 중에 용해시키고 혼합시키거나, 또는 c) 키레놀 또는, 이를 함유하는 희첨 추출물 또는 이의 분획물을 용매 또는 수하 용매 중의 산에 위치시키고 이들을 혼합하는 일반적인 염 제조방법으로 제조된다.The acid addition salts mentioned above may be a) directly mixing Kylenol or a rare extract containing it or a fraction thereof and an acid, b) dissolving and mixing one of them in a solvent or a water-containing solvent, or c) Kyre It is prepared by a general salt preparation method of placing the knol or a rare extract containing the same or a fraction thereof in an acid in a solvent or a submerged solvent and mixing them.
위와는 별도로 추가적으로 염이 가능한 형태는 가바염, 가바펜틴염, 프레가발린염, 니코틴산염, 아디페이트염, 헤미말론산염, 시스테인염, 아세틸시스테인염, 메티오닌염, 아르기닌염, 라이신염, 오르니틴염 또는 아스파르트산염 등이 있다. In addition to the above, additional salts are possible: gaba salt, gabapentin salt, pregabalin salt, nicotinic acid salt, adipate salt, hemimalonic acid salt, cysteine salt, acetylcysteine salt, methionine salt, arginine salt, lysine salt, ornithine salt or And aspartate.
또한, 본 발명의 운동수행능력 증강용 약학 조성물은 약학적으로 허용 가능한 담체를 더 포함할 수 있다.In addition, the pharmaceutical composition for enhancing exercise performance of the present invention may further include a pharmaceutically acceptable carrier.
약학적으로 허용되는 담체로는 예컨대, 경구 투여용 담체 또는 비경구 투여용 담체를 추가로 포함할 수 있다. 경구 투여용 담체는 락토스, 전분, 셀룰로스 유도체, 마그네슘 스테아레이트, 스테아르산 등을 포함할 수 있다. 또한 비경구 투여용 담체는 물, 적합한 오일, 식염수, 수성 글루코스 및 글리콜 등을 포함할 수 있다. 또한, 안정화제 및 보존제를 추가로 포함할 수 있다. 적합한 안정화제로는 아황산수소나트륨, 아황산나트륨 또는 아스코르브산과 같은 항산화제가 있다. 적합한 보존제로는 벤즈알코늄 클로라이드, 메틸- 또는 프로필-파라벤 및 클로로부탄올이 있다. 그 밖의 약학적으로 허용되는 담체로는 다음의 문헌에 기재되어 있는 것을 참고로 할 수 있다(Remington's Pharmaceutical Sciences, 19th ed., Mack Publishing Company, Easton, PA, 1995).The pharmaceutically acceptable carrier may further include, for example, a carrier for oral administration or a carrier for parenteral administration. Carriers for oral administration may include lactose, starch, cellulose derivatives, magnesium stearate, stearic acid, and the like. In addition, the carrier for parenteral administration may include water, suitable oil, saline, aqueous glucose and glycol. In addition, it may further include a stabilizer and a preservative. Suitable stabilizers are antioxidants such as sodium hydrogen sulfite, sodium sulfite or ascorbic acid. Suitable preservatives are benzalkonium chloride, methyl- or propyl-paraben and chlorobutanol. Other pharmaceutically acceptable carriers may be referred to as those described in the following literature (Remington's Pharmaceutical Sciences, 19th ed., Mack Publishing Company, Easton, PA, 1995).
본 발명의 약학 조성물은 인간을 비롯한 포유동물에 어떠한 방법으로도 투여할 수 있다. 예를 들어, 경구 또는 비경구로 투여할 수 있으며, 비경구적인 투여방법으로는 이에 제한되는 것은 아니나, 정맥내, 근육내, 동맥내, 골수내, 경막내, 심장내, 경피, 피하, 복강내, 비강내, 장관, 국소, 설하 또는 직장내 투여일 수 있다.The pharmaceutical composition of the present invention can be administered to mammals including humans by any method. For example, it can be administered orally or parenterally, and parenteral administration methods are not limited thereto, but intravenous, intramuscular, intraarterial, intramedullary, intrathecal, intracardiac, transdermal, subcutaneous, intraperitoneal , Intranasal, intestinal, topical, sublingual or rectal administration.
본 발명의 약학 조성물은 상술한 바와 같은 투여 경로에 따라 경구 투여용 또는 비경구 투여용 제제로 제형화 할 수 있다. 제형화할 경우에는 하나 이상의 완충제(예를 들어, 식염수 또는 PBS), 항산화제, 정균제, 킬레이트화제(예를 들어, EDTA 또는 글루타치온), 충진제, 증량제, 결합제, 아쥬반트(예를 들어, 알루미늄 하이드록사이드), 현탁제, 농후제 습윤제, 붕해제 또는 계면활성제, 희석제 또는 부형제를 사용하여 조제될 수 있다.The pharmaceutical composition of the present invention can be formulated as a formulation for oral administration or parenteral administration according to the route of administration as described above. When formulated, one or more buffers (e.g., saline or PBS), antioxidants, bacteriostatic agents, chelating agents (e.g., EDTA or glutathione), fillers, bulking agents, binders, adjuvants (e.g., aluminum hydroxide). Side), suspending agents, thickening agents, wetting agents, disintegrants or surfactants, diluents or excipients.
경구투여를 위한 제제에는 정제, 환제, 산제, 과립제, 액제, 겔제, 시럽제, 슬러리제, 현탁액 또는 캡슐제 등이 포함되며, 이러한 고형제제는 본 발명의 약학 조성물에 적어도 하나 이상의 부형제 예를 들면, 전분(옥수수 전분, 밀 전분, 쌀 전분, 감자 전분 등 포함), 칼슘카보네이트(Calcium carbonate), 수크로스(Sucrose), 락토오스(Lactose), 덱스트로오스, 솔비톨, 만니톨, 자일리톨, 에리스리톨 말티톨, 셀룰로즈, 메틸 셀룰로즈, 나트륨 카르복시메틸셀룰로오즈 및 하이드록시프로필메틸-셀룰로즈 또는 젤라틴 등을 섞어 조제될 수 있다. 예컨대, 활성성분을 고체 부형제와 배합한 다음 이를 분쇄하고 적합한 보조제를 첨가한 후 과립 혼합물로 가공함으로써 정제 또는 당의정제를 수득할 수 있다. Formulations for oral administration include tablets, pills, powders, granules, liquids, gels, syrups, slurries, suspensions or capsules, and the like, and such solid formulations are at least one excipient in the pharmaceutical composition of the present invention, for example, Starch (including corn starch, wheat starch, rice starch, potato starch, etc.), calcium carbonate, sucrose, lactose, dextrose, sorbitol, mannitol, xylitol, erythritol maltitol, cellulose, It may be prepared by mixing methyl cellulose, sodium carboxymethylcellulose, and hydroxypropylmethyl-cellulose or gelatin. For example, tablets or dragees can be obtained by blending the active ingredient with a solid excipient, pulverizing it, adding a suitable auxiliary, and processing it into a granule mixture.
단순한 부형제 이외에 마그네슘 스티레이트 탈크 같은 윤활제들도 사용된다. 경구를 위한 액상 제제로는 현탁제, 내용액제, 유제 또는 시럽제 등이 해당되는데 흔히 사용되는 단순 희석제인 물 또는 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제 또는 보존제 등이 포함될 수 있다.In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral use include suspensions, liquid solutions, emulsions, or syrups, but may include various excipients, such as wetting agents, sweetening agents, fragrances, or preservatives, in addition to water or liquid paraffin, which are commonly used simple diluents. .
또한, 경우에 따라 가교결합 폴리비닐피롤리돈, 한천, 알긴산 또는 나트륨 알기네이트 등을 붕해제로 첨가할 수 있으며, 항응집제, 윤활제, 습윤제, 향료, 유화제 및 방부제 등을 추가로 포함할 수 있다.In addition, in some cases, cross-linked polyvinylpyrrolidone, agar, alginic acid, or sodium alginate may be added as a disintegrant, and an anti-aggregating agent, a lubricant, a wetting agent, a fragrance, an emulsifying agent and a preservative, etc. may be additionally included. .
비경구적으로 투여하는 경우 본 발명의 약학 조성물은 적합한 비경구용 담체와 함께 주사제, 경피 투여제 및 비강 흡입제의 형태로 당 업계에 공지된 방법에 따라 제형화될 수 있다. 상기 주사제의 경우에는 반드시 멸균되어야 하며 박테리아 및 진균과 같은 미생물의 오염으로부터 보호되어야 한다. 주사제의 경우 적합한 담체의 예로는 이에 한정되지는 않으나, 물, 에탄올, 폴리올(예를 들어, 글리세롤, 프로필렌 글리콜 및 액체 폴리에틸렌 글리콜 등), 이들의 혼합물 및/또는 식물유를 포함하는 용매 또는 분산매질일 수 있다. 보다 바람직하게는, 적합한 담체로는 행크스 용액, 링거 용액, 트리에탄올 아민이 함유된 PBS(phosphate buffered saline) 또는 주사용 멸균수, 10% 에탄올, 40% 프로필렌 글리콜 및 5% 덱스트로즈와 같은 등장 용액 등을 사용할 수 있다. 상기 주사제를 미생물 오염으로부터 보호하기 위해서는 파라벤, 클로로부탄올, 페놀, 소르빈산, 티메로살 등과 같은 다양한 항균제 및 항진균제를 추가로 포함할 수 있다. 또한, 상기 주사제는 대부분의 경우 당 또는 나트륨 클로라이드와 같은 등장화제를 추가로 포함할 수 있다.When administered parenterally, the pharmaceutical composition of the present invention may be formulated according to a method known in the art in the form of an injection, a transdermal administration, and a nasal inhalation agent together with a suitable parenteral carrier. In the case of the injection, it must be sterilized and protected from contamination by microorganisms such as bacteria and fungi. Examples of suitable carriers for injections include, but are not limited to, water, ethanol, polyols (e.g., glycerol, propylene glycol and liquid polyethylene glycol, etc.), mixtures thereof, and/or solvents or dispersion media containing vegetable oils. I can. More preferably, suitable carriers include isotonic solutions such as Hanks' solution, Ringer's solution, phosphate buffered saline (PBS) containing triethanol amine or sterile water for injection, 10% ethanol, 40% propylene glycol and 5% dextrose. Etc. can be used. In order to protect the injection from microbial contamination, various antibacterial and antifungal agents such as paraben, chlorobutanol, phenol, sorbic acid, thimerosal, and the like may be additionally included. In addition, the injection may further contain an isotonic agent such as sugar or sodium chloride in most cases.
경피 투여제의 경우 연고제, 크림제, 로션제, 겔제, 외용액제, 파스타제, 리니멘트제, 에어롤제 등의 형태가 포함된다. 상기에서 '경피 투여'는 약학적 조성물을 국소적으로 피부에 투여하여 약학적 조성물에 함유된 유효한 양의 활성성분이 피부 내로 전달되는 것을 의미한다. In the case of transdermal administration, ointments, creams, lotions, gels, external solutions, pasta, liniment, and air rolls are included. In the above, "transdermal administration" means that the active ingredient in an effective amount contained in the pharmaceutical composition is delivered into the skin by topically administering the pharmaceutical composition to the skin.
흡입 투여제의 경우, 본 발명에 따라 사용되는 화합물은 적합한 추진제, 예를 들면, 디클로로플루오로메탄, 트리클로로플루오로메탄, 디클로로테트라플루오로에탄, 이산화탄소 또는 다른 적합한 기체를 사용하여, 가압 팩 또는 연무기로부터 에어로졸 스프레이 형태로 편리하게 전달할 수 있다. 가압 에어로졸의 경우, 투약 단위는 계량된 양을 전달하는 밸브를 제공하여 결정할 수 있다. 예를 들면, 흡입기 또는 취입기에 사용되는 젤라틴 캡슐 및 카트리지는 화합물, 및 락토즈 또는 전분과 같은 적합한 분말 기제의 분말 혼합물을 함유하도록 제형화할 수 있다. 비경구 투여용 제형은 모든 제약 화학에 일반적으로 공지된 처방서인 문헌(Remington's Pharmaceutical Science, 15th Edition, 1975. Mack Publishing Company, Easton, Pennsylvania 18042, Chapter 87: Blaug, Seymour)에 기재되어 있다.In the case of inhalation dosages, the compounds used according to the invention can be used in a pressurized pack or with a suitable propellant, for example dichlorofluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas. It can be conveniently delivered from a nebulizer in the form of an aerosol spray. In the case of a pressurized aerosol, the dosage unit can be determined by providing a valve that delivers a metered amount. For example, gelatin capsules and cartridges for use in an inhaler or insufflator can be formulated to contain a powder mixture of the compound and a suitable powder base such as lactose or starch. Formulations for parenteral administration are described in Remington's Pharmaceutical Science, 15th Edition, 1975. Mack Publishing Company, Easton, Pennsylvania 18042, Chapter 87: Blaug, Seymour, a formula generally known for all pharmaceutical chemistry.
본 발명의 약학 조성물은 키레놀 또는, 희첨 추출물 또는 이의 분획물을 유효량으로 포함할 때 바람직한 운동수행능력 증강 효과를 제공할 수 있다. 본 명세서에서, '유효량'이라 함은 음성 대조군에 비해 그 이상의 반응을 나타내는 양을 말하며 바람직하게는 운동수행 능력 향상하기에 충분한 양을 말한다. 본 발명의 약학적 조성물에 키레놀 또는 이를 함유하는 희첨 추출물이 0.01 내지 99.99% 포함될 수 있으며, 잔량은 약학적으로 허용 가능한 담체가 차지할 수 있다. 본 발명의 약학 조성물에 포함되는 키레놀 또는 희첨 추출물 또는 이의 분획물의 유효량은 조성물이 제품화되는 형태 등에 따라 달라질 것이다.The pharmaceutical composition of the present invention may provide a desirable effect of enhancing exercise performance when it contains an effective amount of kylenol, or extract or a fraction thereof. In the present specification, the term "effective amount" refers to an amount that exhibits a higher response compared to the negative control group, and preferably refers to an amount sufficient to improve exercise performance. The pharmaceutical composition of the present invention may contain 0.01 to 99.99% of kylenol or a rare extract containing the same, and the remaining amount may be occupied by a pharmaceutically acceptable carrier. The effective amount of the kylenol or olivine extract or fractions thereof contained in the pharmaceutical composition of the present invention will vary depending on the form in which the composition is commercialized.
본 발명의 약학적 조성물의 총 유효량은 단일 투여량(single dose)으로 환자에게 투여될 수 있으며, 다중 투여량(multiple dose)으로 장기간 투여되는 분할 치료 방법(fractionated treatment protocol)에 의해 투여될 수 있다. 본 발명의 약학 조성물은 질환의 정도에 따라 유효성분의 함량을 달리할 수 있다. 비경구 투여시는 상기 키레놀 또는 이를 함유하는 희첨 추출물을 기준으로 하루에 체중 1 kg당 바람직하게 0.01 내지 50 mg, 더 바람직하게는 0.1 내지 30 mg의 양으로 투여되도록, 그리고 경구 투여시는 키레놀 또는 이를 함유하는 희첨 추출물을 기준으로 하루에 체중 1 kg당 바람직하게 0.01 내지 100 mg, 더 바람직하게는 0.1 내지 50 mg의 양으로 투여되도록 1 내지 수회에 나누어 투여할 수 있다. 그러나 상기 키레놀 또는 이를 함유하는 희첨 추출물의 용량은 약학적 조성물의 투여 경로 및 치료 횟수뿐만 아니라 환자의 연령, 체중, 건강 상태, 성별, 질환의 중증도, 식이 및 배설율 등 다양한 요인들을 고려하여 환자에 대한 유효 투여량이 결정되는 것이므로, 이러한 점을 고려할 때 당 분야의 통상적인 지식을 가진 자라면 상기 키레놀 또는 이를 함유하는 희첨 추출물을 운동수행능력 증강을 위한 특정한 용도에 따른 적절한 유효 투여량을 결정할 수 있을 것이다. 본 발명에 따른 약학 조성물은 본 발명의 효과를 보이는 한 그 제형, 투여 경로 및 투여 방법에 특별히 제한되지 아니한다.The total effective amount of the pharmaceutical composition of the present invention may be administered to a patient in a single dose, and may be administered by a fractionated treatment protocol that is administered for a long time in multiple doses. . The pharmaceutical composition of the present invention may vary the content of the active ingredient according to the severity of the disease. When parenterally administered, it is preferably administered in an amount of 0.01 to 50 mg, more preferably 0.1 to 30 mg per 1 kg of body weight per day based on the chilenol or the lye extract containing the same, and when administered orally, It may be administered in divided doses from 1 to several times so as to be administered in an amount of preferably 0.01 to 100 mg, more preferably 0.1 to 50 mg per 1 kg of body weight per day based on the nool or the olivine extract containing the same. However, the dose of the kylenol or the extract containing it is not only the administration route of the pharmaceutical composition and the number of treatments, but also the patient's age, weight, health condition, sex, disease severity, diet and excretion rate, etc. Since the effective dose for is determined, considering these points, those of ordinary skill in the art can determine the appropriate effective dose according to the specific use for enhancing exercise performance of the kylenol or olivine extract containing the same. I will be able to. The pharmaceutical composition according to the present invention is not particularly limited in its formulation, route of administration, and method of administration as long as it exhibits the effects of the present invention.
본 발명의 운동수행능력 증강용 약학 조성물은 단독으로, 또는 수술, 방사선 치료, 호르몬 치료, 화학 치료 또는 생물학적 반응조절제를 사용하는 방법들과 병용하여 사용할 수 있다.The pharmaceutical composition for enhancing exercise performance of the present invention may be used alone or in combination with surgery, radiation therapy, hormone therapy, chemotherapy, or methods using a biological response modifier.
본 발명의 운동수행능력 증강용 약학 조성물은 또한 키레놀 또는, 희첨 추출물 또는 이의 분획물을 유효성분으로 포함하는 외용제의 제형으로 제공할 수 있다.The pharmaceutical composition for enhancing exercise performance of the present invention may also be provided in the form of a formulation for external use comprising kylenol or extract or a fraction thereof as an active ingredient.
본 발명의 운동수행능력 증강용 약학 조성물을 피부외용제로 사용하는 경우, 추가로 지방 물질, 유기 용매, 용해제, 농축제 및 겔화제, 연화제, 항산화제, 현탁화제, 안정화제, 발포제(foaming agent), 방향제, 계면활성제, 물, 이온형 유화제, 비이온형 유화제, 충전제, 금속이온봉쇄제, 킬레이트화제, 보존제, 비타민, 차단제, 습윤화제, 필수 오일, 염료, 안료, 친수성 활성제, 친유성 활성제 또는 지질 소낭 등 피부 외용제에 통상적으로 사용되는 임의의 다른 성분과 같은 피부 과학 분야에서 통상적으로 사용되는 보조제를 함유할 수 있다. 또한 상기 성분들은 피부 과학 분야에서 일반적으로 사용되는 양으로 도입될 수 있다.When using the pharmaceutical composition for enhancing exercise performance of the present invention as an external preparation for skin, additionally fatty substances, organic solvents, solubilizing agents, thickening and gelling agents, emollients, antioxidants, suspending agents, stabilizers, foaming agents , Fragrance, surfactant, water, ionic emulsifier, nonionic emulsifier, filler, sequestering agent, chelating agent, preservative, vitamin, blocker, wetting agent, essential oil, dye, pigment, hydrophilic activator, lipophilic activator or It may contain adjuvants commonly used in the field of dermatology, such as any other ingredients commonly used in skin external preparations such as lipid vesicles. In addition, the above ingredients may be introduced in an amount generally used in the field of dermatology.
본 발명의 운동수행능력 증강용 약학 조성물이 피부 외용제로 제공될 경우, 이에 제한되는 것은 아니나, 연고, 패취, 겔, 크림 또는 분무제 등의 제형일 수 있다.When the pharmaceutical composition for enhancing exercise performance of the present invention is provided as an external preparation for skin, it may be a formulation such as an ointment, a patch, a gel, a cream, or a spray, but is not limited thereto.
본 발명의 운동수행능력 증강용 조성물은 또한 식품 조성물일 수 있다. 식품 조성물은 식품 조성물은 기능성 식품(functional food), 영양 보조제(nutritional supplement), 건강식품(health food), 식품 첨가제(food additives) 및 사료 등의 모든 형태를 포함하며, 인간 또는 가축을 비롯한 동물을 취식대상으로 한다. 상기 유형의 식품 조성물은 당 업계에 공지된 통상적인 방법에 따라 다양한 형태로 제조할 수 있다.The composition for enhancing exercise performance of the present invention may also be a food composition. The food composition includes all forms such as functional food, nutritional supplement, healthy food, food additives, and feed, and contains humans or animals including livestock. It is targeted for eating. Food compositions of this type can be prepared in various forms according to conventional methods known in the art.
상기 유형의 식품 조성물은 당업계에 공지된 통상적인 방법에 따라 다양한 형태로 제조할 수 있다. 일반 식품으로는 이에 한정되지 않지만 음료(알콜성 음료 포함), 과실 및 그의 가공식품(예: 과일통조림, 병조림, 잼, 마아말레이드 등), 어류, 육류 및 그 가공식품(예: 햄, 소시지 콘비이프 등), 빵류 및 면류(예: 우동, 메밀국수, 라면, 스파게이트, 마카로니 등), 과즙, 각종 드링크, 쿠키, 엿, 유제품(예: 버터, 치이즈 등), 식용식물 유지, 마아가린, 식물성 단백질, 레토르트 식품, 냉동식품, 각종 조미료(예: 된장, 간장, 소스 등) 등에 상기 키레놀 또는 이를 함유하는 희첨 추출물을 첨가하여 제조할 수 있다. 또한, 영양보조제로는 이에 한정되지 않지만 캡슐, 타블렛, 환 등에 상기 키레놀 또는 이를 함유하는 희첨 추출물을 첨가하여 제조할 수 있다. 또한, 건강기능식품으로는 이에 한정되지 않지만 예를 들면, 상기 키레놀 또는 이를 함유하는 희첨 추출물 자체를 차, 쥬스 및 드링크의 형태로 제조하여 음용(건강음료)할 수 있도록 액상화, 과립화, 캡슐화 및 분말화하여 섭취할 수 있다. 또한, 상기 키레놀 또는 이를 함유하는 희첨 추출물을 식품 첨가제의 형태로 사용하기 위해서는 분말 또는 농축액 형태로 제조하여 사용할 수 있다. 또한, 상기 키레놀 또는 이를 함유하는 희첨 추출물과 운동수행능력 증강 효과가 있다고 알려진 공지의 활성 성분과 함께 혼합하여 조성물의 형태로 제조할 수 있다.Food compositions of this type can be prepared in various forms according to conventional methods known in the art. General foods include, but are not limited to, beverages (including alcoholic beverages), fruits and processed foods thereof (e.g., canned fruit, canned food, jam, marmalade, etc.), fish, meat and processed foods thereof (e.g. ham, sausage) Corn beef), bread and noodles (e.g. udon, buckwheat noodles, ramen, spagate, macaroni, etc.), fruit juice, various drinks, cookies, sweets, dairy products (e.g. butter, cheese, etc.), edible vegetable oil, margarine , Vegetable protein, retort food, frozen food, various seasonings (eg, soybean paste, soy sauce, sauce, etc.), and the like, can be prepared by adding the kylenol or a rare extract containing the same. In addition, as a nutritional supplement, it is not limited thereto, but may be prepared by adding the kylenol or a rare extract containing the same to capsules, tablets, pills, and the like. In addition, the health functional food is not limited thereto, but for example, the kylenol or the lychee extract containing the same is prepared in the form of tea, juice, and drink and liquefied, granulated, and encapsulated so that it can be consumed (healthy beverage). And it can be powdered and ingested. In addition, in order to use the kylenol or a rare extract containing the same in the form of a food additive, it may be prepared and used in the form of a powder or a concentrate. In addition, it can be prepared in the form of a composition by mixing with the kylenol or the heecheum extract containing the same and a known active ingredient known to have an effect of enhancing exercise performance.
본 발명의 운동수행능력 증강용 조성물이 건강음료 조성물로 이용되는 경우, 상기 건강음료 조성물은 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로 함유할 수 있다. 상술한 천연 탄수화물은 포도당, 과당과 같은 모노사카라이드; 말토스, 슈크로스와 같은 디사카라이드; 덱스트린, 사이클로덱스트린과 같은 폴리사카라이드; 자일리톨, 소르비톨, 에리트리톨 등의 당알콜일 수 있다. 감미제는 타우마틴, 스테비아 추출물과 같은 천연 감미제; 사카린, 아스파르탐과 같은 합성 감미제 등을 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 mL 당 일반적으로 약 0.01 내지 0.04 g, 바람직하게는 약 0.02 내지 0.03 g 이다.When the composition for enhancing exercise performance of the present invention is used as a health drink composition, the health drink composition may contain various flavors or natural carbohydrates as an additional component, such as a conventional beverage. The natural carbohydrates described above include monosaccharides such as glucose and fructose; Disaccharides such as maltose and sucrose; Polysaccharides such as dextrin and cyclodextrin; It may be a sugar alcohol such as xylitol, sorbitol, and erythritol. Sweeteners include natural sweeteners such as taumatin and stevia extract; Synthetic sweeteners such as saccharin and aspartame can be used. The proportion of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 mL of the composition of the present invention.
키레놀 또는 이를 함유하는 희첨 추출물은 운동수행능력 증강용 식품 조성물의 유효성분으로 함유될 수 있는데, 그 양은 운동수행능력 증강 작용을 달성하기에 유효한 양으로 특별히 한정되는 것은 아니나, 전체 조성물 총 중량에 대하여 0.01 내지 100 중량%인 것이 바람직하다. 본 발명의 식품 조성물은 키레놀 또는 이를 함유하는 희첨 추출물과 함께 운동수행능력 증강 효과가 있는 것으로 알려진 다른 활성 성분과 함께 혼합하여 제조될 수 있다.Kylenol or the extract containing it may be contained as an active ingredient of a food composition for enhancing exercise performance, the amount of which is not particularly limited to an amount effective to achieve the effect of enhancing exercise performance, but is based on the total weight of the total composition. It is preferably 0.01 to 100% by weight. The food composition of the present invention may be prepared by mixing with kylenol or other active ingredients known to have an effect of enhancing exercise performance together with a lychee extract containing the same.
상기 외에 본 발명의 건강식품은 여러 가지 영양제, 비타민, 전해질, 풍미제, 착색제, 펙트산, 펙트산의 염, 알긴산, 알긴산의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올 또는 탄산화제 등을 함유할 수 있다. 그 밖에 본 발명의 건강식품은 천연 과일주스, 과일주스 음료, 또는 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 혼합하여 사용할 수 있다. 이러한 첨가제의 비율은 크게 중요하진 않지만 본 발명의 조성물 100 중량부당 0.01 내지 0.1 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above, the health food of the present invention includes various nutrients, vitamins, electrolytes, flavoring agents, colorants, pectic acid, salts of pectic acid, alginic acid, salts of alginic acid, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, It may contain glycerin, alcohol, or a carbonating agent. In addition, the health food of the present invention may contain flesh for the manufacture of natural fruit juice, fruit juice beverage, or vegetable beverage. These ingredients may be used independently or in combination. Although the proportion of these additives is not very important, it is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.
이하, 본 발명을 실시예에 의해 상세히 설명한다. 단, 하기 실시예는 본 발명에 대한 이해를 돕기 위해 예시의 목적으로만 제공된 것일 뿐 본 발명의 범위가 이것들로만 한정되는 것은 아니다. 하기 실시예의 실험 결과는 평균 ± 표준편차로 표시하였으며, 통계적 분석은 t 검정을 사용하여 P 값이 0.05 또는 0.01 이하이면 유의성이 있는 것으로 평가하였다.Hereinafter, the present invention will be described in detail by examples. However, the following examples are provided for illustrative purposes only to aid understanding of the present invention, and the scope of the present invention is not limited thereto. The experimental results of the following examples were expressed as mean ± standard deviation, and statistical analysis was evaluated as having significance if the P value was 0.05 or 0.01 or less using a t test.
참조예Reference example 1: One: 키레놀(kirenol)물질Kirenol substance 정보 Information
명칭: Kirenol; Kirel; (1R,3S,4aS,4bS,7S,10aS)-1,2,3,4,4a,4b,5,6,7,9,10,10a-Dodecahydro-3-hydroxy-7-[(R)-1,2-dihydroxyethyl]-1,4a,7-trimethylphenanthrene-1-methanolName: Kirenol; Kirel; (1R,3S,4aS,4bS,7S,10aS)-1,2,3,4,4a,4b,5,6,7,9,10,10a-Dodecahydro-3-hydroxy-7-[(R) -1,2-dihydroxyethyl]-1,4a,7-trimethylphenanthrene-1-methanol
CAS No.: 52659-56-0CAS No.: 52659-56-0
[[ 실시예Example 1] One] 시게스벡키아Sigesbeckia 글라브레센스Glabresense 추출물의 제조 Preparation of extract
[실시예 1-1] 시게스벡키아 글라브레센스 에탄올 추출물의 제조[Example 1-1] Preparation of Ethanol Extract of Sigesbeckia Glabrecens
건조시킨 시게스벡키아 글라브레센스의 잎과 줄기를 믹서로 분쇄한 다음, 분쇄한 시게스벡키아 글라브레센스 시료 100 g을 에탄올 1 L에 넣고 50℃에서 60분간 교반하면서 추출하였다. 추출된 시료는 와트만(Whatman) 2번 여과지로 여과하고, 여과된 추출액을 진공 회전 농축기로 농축하여 용매성분을 제거함으로써 시게스벡키아 글라브레센스 에탄올 추출물을 얻었다.After pulverizing the dried leaves and stems of Sigesveccia glavresense with a mixer, 100 g of the crushed Sigesveccia glavresense sample was added to 1 L of ethanol and extracted with stirring at 50° C. for 60 minutes. The extracted sample was filtered through Whatman No. 2 filter paper, and the filtered extract was concentrated with a vacuum rotary concentrator to remove the solvent component to obtain an ethanol extract of Sigesbeckia Glabresense.
[실시예 1-2] 시게스벡키아 글라브레센스 열수 추출물의 제조[Example 1-2] Preparation of Sigesbeckia Glabrecens Hot Water Extract
건조시킨 시게스벡키아 글라브레센스의 잎과 줄기를 믹서로 분쇄한 다음, 분쇄한 시게스벡키아 글라브레센스 시료 100 g을 물 1 L에 넣고 100℃에서 4시간 교반하면서 추출하였다. 추출된 시료는 와트만 2번 여과지로 여과하고, 여과된 추출액을 진공 회전 농축기로 농축하여 용매성분을 제거함으로써 시게스벡키아 글라브레센스 열수 추출물을 얻었다.The dried leaves and stems of Sigesveccia Glabresense were pulverized with a mixer, and then 100 g of the crushed Sigesveccia Glabresense sample was added to 1 L of water and extracted with stirring at 100°C for 4 hours. The extracted sample was filtered through Whatman No. 2 filter paper, and the filtered extract was concentrated with a vacuum rotary concentrator to remove the solvent component, thereby obtaining a Sigesbeckia Glabrecens hot water extract.
[실시예 1-3] 시게스벡키아 글라브레센스 헥산 추출물의 제조[Example 1-3] Preparation of Sigesbeckia Glabrecens Hexane Extract
건조시킨 시게스벡키아 글라브레센스의 잎과 줄기를 믹서로 분쇄한 다음, 분쇄한 시게스벡키아 글라브레센스 시료 100 g을 헥산 1 L에 넣고 50℃에서 60분간 교반하면서 추출하였다. 추출된 시료는 와트만 2번 여과지로 여과하고, 여과된 추출액을 진공 회전 농축기로 농축하여 용매성분을 제거함으로써 시게스벡키아 글라브레센스 헥산 추출물을 얻었다.After pulverizing the dried leaves and stems of Sigesveccia glavresense with a mixer, 100 g of the pulverized Sigesveccia glavresense sample was added to 1 L of hexane and extracted with stirring at 50° C. for 60 minutes. The extracted sample was filtered through Whatman No. 2 filter paper, and the filtered extract was concentrated with a vacuum rotary concentrator to remove the solvent component, thereby obtaining a Sigesbeckia glavresense hexane extract.
[실시예 1-4] 시게스벡키아 글라브레센스 에틸아세테이트 추출물의 제조[Example 1-4] Preparation of Sigesbeckia Glabrecens Ethyl Acetate Extract
건조시킨 시게스벡키아 글라브레센스의 잎과 줄기를 믹서로 분쇄한 다음, 분쇄한 시게스벡키아 글라브레센스 시료 100 g을 에틸아세테이트 1 L에 넣고 50℃에서 60분간 교반하면서 추출하였다. 추출된 시료는 와트만 2번 여과지로 여과하고, 여과된 추출액을 진공 회전 농축기로 농축하여 용매성분을 제거함으로써 시게스벡키아 글라브레센스 에틸아세테이트 추출물을 얻었다.After pulverizing the dried leaves and stems of Sigesveccia glavresense with a mixer, 100 g of the pulverized Sigesveccia glavresense sample was added to 1 L of ethyl acetate and extracted with stirring at 50° C. for 60 minutes. The extracted sample was filtered through Whatman No. 2 filter paper, and the filtered extract was concentrated with a vacuum rotary concentrator to remove the solvent component, thereby obtaining a Sigesbeckia glavresense ethyl acetate extract.
[실시예 1-5] 시게스벡키아 글라브레센스 초고압 추출물의 제조[Example 1-5] Preparation of Sigesbeckia Glabrecens Ultra High Pressure Extract
건조시킨 시게스벡키아 글라브레센스의 잎과 줄기를 믹서로 분쇄한 다음, 분쇄한 시게스벡키아 글라브레센스 시료 1 g과 18% 에탄올 76 mL을 폴리에틸렌(polyethylene) 팩에 넣고 밀봉한 후 초고압 추출장치(Frescal MFP-7000; Mitsubishi Heavy Industries, Tokyo, Japan)를 이용하여 추출하였다. 초고압 추출 조건은 추출 압력이 320 MPa, 추출 시간은 5 min 이었다. 추출된 시료는 와트만 2번 여과지로 여과하고, 여과된 추출액을 진공 회전 농축기로 농축하여 용매성분을 제거함으로써 시게스벡키아 글라브레센스 초고압 추출물을 얻었다.After pulverizing the dried leaves and stems of Sigesveccia Glabresense with a mixer, put 1 g of the crushed Sigesveccia Glabresense sample and 76 mL of 18% ethanol into a polyethylene pack, sealed, and ultra-high pressure. It was extracted using an extraction device (Frescal MFP-7000; Mitsubishi Heavy Industries, Tokyo, Japan). In the ultra-high pressure extraction conditions, the extraction pressure was 320 MPa and the extraction time was 5 min. The extracted sample was filtered with Whatman No. 2 filter paper, and the filtered extract was concentrated with a vacuum rotary concentrator to remove the solvent component, thereby obtaining a Sigesbeckia Glabrecens ultra-high pressure extract.
[실시예 1-6] 시게스벡키아 글라브레센스 초임계 유체 추출물의 제조[Example 1-6] Preparation of Sigesbeckia Glabrecens Supercritical Fluid Extract
건조시킨 시게스벡키아 글라브레센스의 잎과 줄기를 믹서로 분쇄 한 다음, 분쇄한 시게스벡키아 글라브레센스 시료 1 g을 시료 카트리지에 충전하고 초임계 유체 추출 장치(SFX 3560, Isco Inc., Lincoln, NE, USA)를 이용하여 추출하였다. 초임계 유체 추출 조건은 추출 압력이 20 MPa, 추출 온도는 60℃, 초임계 이산화탄소의 유속은 60 mL/min, 추출 시간은 60 min이었다. 초임계 유체 추출이 완료되면, 추출 장치의 압력을 낮춰 초임계 유체 상태를 해제하여 시게스벡키아 글라브레센스 초임계 유체 추출물을 얻었다.After pulverizing the dried leaves and stems of Sigesveccia glavresense with a mixer, 1 g of the crushed Sigesveccia glavresense sample was filled into a sample cartridge, and a supercritical fluid extraction device (SFX 3560, Isco Inc. , Lincoln, NE, USA). The conditions for supercritical fluid extraction were: extraction pressure was 20 MPa, extraction temperature was 60°C, flow rate of supercritical carbon dioxide was 60 mL/min, and extraction time was 60 min. When the supercritical fluid extraction was completed, the pressure of the extraction device was lowered to release the supercritical fluid state to obtain a Sigesveccia glavresense supercritical fluid extract.
[실시예 1-7] 시게스벡키아 글라브레센스 아임계 유체 추출물의 제조[Example 1-7] Preparation of Sigesbeckia Glabrecens Subcritical Fluid Extract
건조시킨 시게스벡키아 글라브레센스의 잎과 줄기를 믹서로 분쇄 한 다음, 분쇄한 시게스벡키아 글라브레센스 시료 1 g을 증류수 10 mL에 넣고 아임계 유체 추출 장치(DIONEX Accelerated Solvent Extractor 100, DIONEX co., USA)를 이용하여 추출하였다. 아임계 유체 추출 조건은 추출 압력 0.5 MPa, 추출 온도 240℃, 추출 시간 20분의 조건하에서 아임계 추출을 수행하였다. 추출된 시료는 와트만 2번 여과지로 여과하고, 여과된 추출액을 -40℃에서 동결 건조하여 시게스벡키아 글라브레센스 아임계 유체 추출물을 얻었다.After crushing the dried leaves and stems of Sigesveccia glavresense with a mixer, add 1 g of the crushed Sigesveccia glavresense sample to 10 mL of distilled water, and add a subcritical fluid extraction device (DIONEX Accelerated
[[ 실시예Example 2] 2] 시게스벡키아Sigesbeckia 푸베센스Fuvesense 추출물의 제조 Preparation of extract
[실시예 2-1] 시게스벡키아 푸베센스 에탄올 추출물의 제조[Example 2-1] Preparation of Ethanol Extract of Sigesbeckia Fuvesense
건조시킨 시게스벡키아 글라브레센스의 잎과 줄기를 믹서로 분쇄한 다음, 분쇄한 시게스벡키아 글라브레센스 시료 100 g을 에탄올 1 L에 넣고 50℃에서 60분간 교반하면서 추출하였다. 추출된 시료는 와트만(Whatman) 2번 여과지로 여과하고, 여과된 추출액을 진공 회전 농축기로 농축하여 용매성분을 제거함으로써 시게스벡키아 푸베센스 에탄올 추출물을 얻었다.After pulverizing the dried leaves and stems of Sigesveccia glavresense with a mixer, 100 g of the crushed Sigesveccia glavresense sample was added to 1 L of ethanol and extracted with stirring at 50° C. for 60 minutes. The extracted sample was filtered through Whatman No. 2 filter paper, and the filtered extract was concentrated with a vacuum rotary concentrator to remove the solvent component, thereby obtaining an ethanol extract of Sigesbeckia fuvesense.
[실시예 2-2] 시게스벡키아 푸베센스 열수 추출물의 제조[Example 2-2] Preparation of Sigesbeckia Fuvesense Hot Water Extract
건조시킨 시게스벡키아 푸베센스 의 잎과 줄기를 믹서로 분쇄한 다음, 분쇄한 시게스벡키아 푸베센스 시료 100 g을 물 1 L에 넣고 100℃에서 4시간 교반하면서 추출하였다. 추출된 시료는 와트만 2번 여과지로 여과하고, 여과된 추출액을 진공 회전 농축기로 농축하여 용매성분을 제거함으로써 시게스벡키아 푸베센스 열수 추출물을 얻었다.The dried leaves and stems of Sigesveccia fuvesense were pulverized with a mixer, and then 100 g of the pulverized Sigesveccia fuvesenses sample was added to 1 L of water and extracted with stirring at 100°C for 4 hours. The extracted sample was filtered through Whatman No. 2 filter paper, and the filtered extract was concentrated with a vacuum rotary concentrator to remove the solvent component, thereby obtaining a Sigesbeckia fuvesense hot water extract.
[실시예 2-3] 시게스벡키아 푸베센스 헥산 추출물의 제조[Example 2-3] Preparation of hexane extract of Sigesbeckia fuvesense
건조시킨 시게스벡키아 푸베센스 의 잎과 줄기를 믹서로 분쇄한 다음, 분쇄한 시게스벡키아 푸베센스 시료 100 g을 헥산 1 L에 넣고 50℃에서 60분간 교반하면서 추출하였다. 추출된 시료는 와트만 2번 여과지로 여과하고, 여과된 추출액을 진공 회전 농축기로 농축하여 용매성분을 제거함으로써 시게스벡키아 푸베센스 헥산 추출물을 얻었다.After crushing the dried leaves and stems of Sigesveccia fuvesenses with a mixer, 100 g of the pulverized Sigesveccia fuvesenses sample was added to 1 L of hexane and extracted while stirring at 50° C. for 60 minutes. The extracted sample was filtered through Whatman No. 2 filter paper, and the filtered extract was concentrated with a vacuum rotary concentrator to remove the solvent component, thereby obtaining a Sigesveccia fuvesense hexane extract.
[실시예 2-4] 시게스벡키아 푸베센스 에틸아세테이트 추출물의 제조[Example 2-4] Preparation of Sigesbeckia fuvesense ethyl acetate extract
건조시킨 시게스벡키아 푸베센스 의 잎과 줄기를 믹서로 분쇄한 다음, 분쇄한 시게스벡키아 푸베센스 시료 100 g을 에틸아세테이트 1 L에 넣고 50℃에서 60분간 교반하면서 추출하였다. 추출된 시료는 와트만 2번 여과지로 여과하고, 여과된 추출액을 진공 회전 농축기로 농축하여 용매성분을 제거함으로써 시게스벡키아 푸베센스 에틸아세테이트 추출물을 얻었다.The dried leaves and stems of Sigesveccia fuvesense were pulverized with a mixer, and then 100 g of a pulverized Sigesveccia fuvesense sample was added to 1 L of ethyl acetate and extracted with stirring at 50° C. for 60 minutes. The extracted sample was filtered through Whatman No. 2 filter paper, and the filtered extract was concentrated with a vacuum rotary concentrator to remove the solvent component, thereby obtaining a Sigesveccia fuvesense ethyl acetate extract.
[실시예 2-5] 시게스벡키아 푸베센스 초고압 추출물의 제조[Example 2-5] Preparation of Sigesbeckia Fuvesense Ultra High Pressure Extract
건조시킨 시게스벡키아 푸베센스의 잎과 줄기를 믹서로 분쇄한 다음, 분쇄한 시게스벡키아 푸베센스 시료 1 g과 18% 에탄올 76 mL을 폴리에틸렌(polyethylene) 팩에 넣고 밀봉한 후 초고압 추출장치(Frescal MFP-7000; Mitsubishi Heavy Industries, Tokyo, Japan)를 이용하여 추출하였다. 초고압 추출 조건은 추출 압력이 320 MPa, 추출 시간은 5 min 이었다. 추출된 시료는 와트만 2번 여과지로 여과하고, 여과된 추출액을 진공 회전 농축기로 농축하여 용매성분을 제거함으로써 시게스벡키아 푸베센스 초고압 추출물을 얻었다.After pulverizing the dried leaves and stems of Sigesveccia fuvesenses with a mixer, 1 g of the crushed Sigesveccia fuvesenses sample and 76 mL of 18% ethanol are put in a polyethylene pack and sealed, followed by an ultra-high pressure extraction device. (Frescal MFP-7000; Mitsubishi Heavy Industries, Tokyo, Japan) was used to extract. In the ultra-high pressure extraction conditions, the extraction pressure was 320 MPa and the extraction time was 5 min. The extracted sample was filtered through Whatman No. 2 filter paper, and the filtered extract was concentrated with a vacuum rotary concentrator to remove the solvent component, thereby obtaining a Sigesveccia fuvesense ultra-high pressure extract.
[실시예 2-6] 시게스벡키아 푸베센스 초임계 유체 추출물의 제조[Example 2-6] Preparation of Sigesbeckia Fuvesense Supercritical Fluid Extract
건조시킨 시게스벡키아 푸베센스의 잎과 줄기를 믹서로 분쇄 한 다음, 분쇄한 시게스벡키아 푸베센스 시료 1 g을 시료 카트리지에 충전하고 초임계 유체 추출 장치(SFX 3560, Isco Inc., Lincoln, NE, USA)를 이용하여 추출하였다. 초임계 유체 추출 조건은 추출 압력이 50 MPa, 추출 온도는 40℃, 초임계 이산화탄소의 유속은 60 mL/min, 추출 시간은 60 min이었다. 초임계 유체 추출이 완료되면, 추출 장치의 압력을 낮춰 초임계 유체 상태를 해제하여 시게스벡키아 푸베센스 초임계 유체 추출물을 얻었다.After pulverizing the dried leaves and stems of Sigesveccia fuvesenses with a mixer, 1 g of the pulverized Sigesveccia fuvesenses sample is filled into a sample cartridge, and a supercritical fluid extraction device (SFX 3560, Isco Inc., Lincoln) , NE, USA). Supercritical fluid extraction conditions were: extraction pressure 50 MPa,
[실시예 2-7] 시게스벡키아 푸베센스 아임계 유체 추출물의 제조[Example 2-7] Preparation of Sigesveccia fuvesense subcritical fluid extract
건조시킨 시게스벡키아 푸베센스의 잎과 줄기를 믹서로 분쇄 한 다음, 분쇄한 시게스벡키아 푸베센스 시료 1 g을 증류수 10 mL에 넣고 아임계 유체 추출 장치(DIONEX Accelerated Solvent Extractor 100, DIONEX co., USA)를 이용하여 추출하였다. 아임계 유체 추출 조건은 추출 압력 5 MPa, 추출 온도 90℃, 추출 시간 15분의 조건하에서 아임계 추출을 수행하였다. 추출된 시료는 와트만 2번 여과지로 여과하고, 여과된 추출액을 -40℃에서 동결 건조하여 시게스벡키아 푸베센스 아임계 유체 추출물을 얻었다.After crushing the dried leaves and stems of Sigesveccia fuvesenses with a mixer, 1 g of the crushed Sigesveccia fuvesenses sample is added to 10 mL of distilled water and a subcritical fluid extractor (DIONEX Accelerated
[[ 실시예Example 3] 3] 시게스벡키아Sigesbeckia 오리엔탈리스Orientalis 추출물의 제조 Preparation of extract
[실시예 3-1] 시게스벡키아 오리엔탈리스 에탄올 추출물의 제조[Example 3-1] Preparation of Ethanol Extract of Sigesbeckia Orientalis
건조시킨 시게스벡키아 오리엔탈리스의 잎과 줄기를 믹서로 분쇄한 다음, 분쇄한 시게스벡키아 오리엔탈리스 시료 100 g을 에탄올 1 L에 넣고 50℃에서 60분간 교반하면서 추출하였다. 추출된 시료는 와트만(Whatman) 2번 여과지로 여과하고, 여과된 추출액을 진공 회전 농축기로 농축하여 용매성분을 제거함으로써 시게스벡키아 오리엔탈리스 에탄올 추출물을 얻었다.After pulverizing the dried leaves and stems of Siges Veckia Orientalis with a mixer, 100 g of the ground Siges Veckia Orientalis sample was added to 1 L of ethanol and extracted while stirring at 50° C. for 60 minutes. The extracted sample was filtered through Whatman No. 2 filter paper, and the filtered extract was concentrated with a vacuum rotary concentrator to remove the solvent component to obtain an ethanol extract of Sigesbeckia Orientalis.
[실시예 3-2] 시게스벡키아 오리엔탈리스 열수 추출물의 제조[Example 3-2] Preparation of Sigesbeckia Orientalis Hot Water Extract
건조시킨 시게스벡키아 오리엔탈리스의 잎과 줄기를 믹서로 분쇄한 다음, 분쇄한 시게스벡키아 오리엔탈리스 시료 100 g을 물 1 L에 넣고 100℃에서 4시간 교반하면서 추출하였다. 추출된 시료는 와트만 2번 여과지로 여과하고, 여과된 추출액을 진공 회전 농축기로 농축하여 용매성분을 제거함으로써 시게스벡키아 오리엔탈리스 열수 추출물을 얻었다.The dried leaves and stems of Siges Beckia Orientalis were pulverized with a mixer, and then 100 g of the ground Siges Beckia Orientalis sample was added to 1 L of water and extracted with stirring at 100°C for 4 hours. The extracted sample was filtered through Whatman No. 2 filter paper, and the filtered extract was concentrated with a vacuum rotary concentrator to remove the solvent component, thereby obtaining a Sigesbeckia Orientalis hot water extract.
[실시예 3-3] 시게스벡키아 오리엔탈리스 헥산 추출물의 제조[Example 3-3] Preparation of hexane extract of Sigesbeckia Orientalis
건조시킨 시게스벡키아 오리엔탈리스의 잎과 줄기를 믹서로 분쇄한 다음, 분쇄한 시게스벡키아 오리엔탈리스 시료 100 g을 헥산 1 L에 넣고 50℃에서 60분간 교반하면서 추출하였다. 추출된 시료는 와트만 2번 여과지로 여과하고, 여과된 추출액을 진공 회전 농축기로 농축하여 용매성분을 제거함으로써 시게스벡키아 오리엔탈리스 헥산 추출물을 얻었다.The dried leaves and stems of Siges Beckia Orientalis were pulverized with a mixer, and then 100 g of the ground Siges Beckia Orientalis sample was added to 1 L of hexane and extracted while stirring at 50° C. for 60 minutes. The extracted sample was filtered through Whatman No. 2 filter paper, and the filtered extract was concentrated with a vacuum rotary concentrator to remove the solvent component, thereby obtaining a Sigesbeckia Orientalis hexane extract.
[실시예 3-4] 시게스벡키아 오리엔탈리스 에틸아세테이트 추출물의 제조[Example 3-4] Preparation of Sigesbeckia Orientalis Ethyl Acetate Extract
건조시킨 시게스벡키아 오리엔탈리스의 잎과 줄기를 믹서로 분쇄한 다음, 분쇄한 시게스벡키아 오리엔탈리스 시료 100 g을 에틸아세테이트 1 L에 넣고 50℃에서 60분간 교반하면서 추출하였다. 추출된 시료는 와트만 2번 여과지로 여과하고, 여과된 추출액을 진공 회전 농축기로 농축하여 용매성분을 제거함으로써 시게스벡키아 오리엔탈리스 에틸아세테이트 추출물을 얻었다.The dried leaves and stems of Siges Beckia Orientalis were pulverized with a mixer, and then 100 g of the ground Siges Beckia Orientalis sample was added to 1 L of ethyl acetate and extracted while stirring at 50° C. for 60 minutes. The extracted sample was filtered through Whatman No. 2 filter paper, and the filtered extract was concentrated with a vacuum rotary concentrator to remove the solvent component, thereby obtaining a Sigesbeckia Orientalis ethylacetate extract.
[실시예 3-5] 시게스벡키아 오리엔탈리스 초고압 추출물의 제조[Example 3-5] Preparation of Sigesbeckia Orientalis Ultra High Pressure Extract
건조시킨 시게스벡키아 오리엔탈리스의 잎과 줄기를 믹서로 분쇄한 다음, 분쇄한 시게스벡키아 오리엔탈리스 시료 1 g과 18% 에탄올 76 mL을 폴리에틸렌(polyethylene) 팩에 넣고 밀봉한 후 초고압 추출장치(Frescal MFP-7000; Mitsubishi Heavy Industries, Tokyo, Japan)를 이용하여 추출하였다. 초고압 추출 조건은 추출 압력이 320 MPa, 추출 시간은 5 min 이었다. 추출된 시료는 와트만 2번 여과지로 여과하고, 여과된 추출액을 진공 회전 농축기로 농축하여 용매성분을 제거함으로써 시게스벡키아 오리엔탈리스 초고압 추출물을 얻었다.After pulverizing the dried leaves and stems of Siges Beckia Orientalis with a mixer, put 1 g of the crushed Siges Veckia Orientalis sample and 76 mL of 18% ethanol into a polyethylene pack, sealed, and then ultra-high pressure extraction device (Frescal MFP-7000; Mitsubishi Heavy Industries, Tokyo, Japan) was used to extract. In the ultra-high pressure extraction conditions, the extraction pressure was 320 MPa and the extraction time was 5 min. The extracted sample was filtered through Whatman No. 2 filter paper, and the filtered extract was concentrated with a vacuum rotary concentrator to remove the solvent component, thereby obtaining a Sigesbeckia Orientalis ultra-high pressure extract.
[실시예 3-6] 시게스벡키아 오리엔탈리스 초임계 유체 추출물의 제조[Example 3-6] Preparation of Sigesbeckia Orientalis Supercritical Fluid Extract
건조시킨 시게스벡키아 오리엔탈리스의 잎과 줄기를 믹서로 분쇄 한 다음, 분쇄한 시게스벡키아 오리엔탈리스 시료 1 g을 시료 카트리지에 충전하고 초임계 유체 추출 장치(SFX 3560, Isco Inc., Lincoln, NE, USA)를 이용하여 추출하였다. 초임계 유체 추출 조건은 추출 압력이 40 MPa, 추출 온도는 50℃, 초임계 이산화탄소의 유속은 60 mL/min, 추출 시간은 60 min이었다. 초임계 유체 추출이 완료되면, 추출 장치의 압력을 낮춰 초임계 유체 상태를 해제하여 시게스벡키아 오리엔탈리스 초임계 유체 추출물을 얻었다.The dried leaves and stems of Sigesveccia Orientalis are pulverized with a mixer, and then 1 g of the pulverized Sigesveccia Orientalis sample is filled into a sample cartridge and a supercritical fluid extraction device (SFX 3560, Isco Inc., Lincoln). , NE, USA). Supercritical fluid extraction conditions were:
[실시예 3-7] 시게스벡키아 오리엔탈리스 아임계 유체 추출물의 제조 [Example 3-7] Preparation of Sigesbeckia Orientalis Subcritical Fluid Extract
건조시킨 시게스벡키아 오리엔탈리스의 잎과 줄기를 믹서로 분쇄 한 다음, 분쇄한 시게스벡키아 오리엔탈리스 시료 1 g을 증류수 10 mL에 넣고 아임계 유체 추출 장치(DIONEX Accelerated Solvent Extractor 100, DIONEX co., USA)를 이용하여 추출하였다. 아임계 유체 추출 조건은 2.5 MPa, 추출 온도 150℃, 추출 시간 15분의 조건하에서 아임계 추출을 수행하였다. 추출된 시료는 와트만 2번 여과지로 여과하고, 여과된 추출액을 -40℃에서 동결 건조하여 시게스벡키아 오리엔탈리스 아임계 유체 추출물을 얻었다.After pulverizing the dried leaves and stems of Sigesveccia Orientalis with a mixer, 1 g of the crushed Sigesveccia Orientalis sample is added to 10 mL of distilled water and a subcritical fluid extractor (DIONEX Accelerated
[[ 실시예Example 4] 4] 키레놀의Kylenol 분리 및 구조결정 Separation and structure determination
[실시예 4-1] 키레놀의 분리[Example 4-1] Isolation of kylenol
상기 실시예 3-1에서 얻은 농축된 시게스벡키아 오리엔탈리스 에탄올 추출물을 실리카겔이 충진된 컬럼에 적재하고 에틸아세테이트, 메탄올을 10:0.5(v/v)의 비율로 혼합한 용매시스템을 이용하여 분취하였다. 상기 분취 순서에 따라서 총 7개의 분획으로 나누어 각각의 분획을 농축 건조하였다. 7개의 분획 중 6번 분획(분획 6)을 RP-18 역상컬럼 크로마토그래피(Lichroprep RP-18 25~40um, Merck&Co., Whitehouse Station, NJ, USA)를 이용하여 전개 용매 10% 에틸아세테이트로 분취하였다. 상기 분취 순서에 따라서 총 2개의 분획으로 나누어 각각의 분획을 농축 건조하였다. 상기 2개의 분획 중 2번 분획(분획 6-2)을 농축 건조하고 다시 RP-18 역상컬럼 크로마토그래피 이용하여 전개 용매 20% 에틸아세테이트로 분취하였다. 상기 분취 순서에 따라서 총 3개의 분획으로 나누어 각각의 분획을 농축 건조하였다. 최종적으로 3개의 분획 중 2번 분획(분획 6-2-2)을 농축 건조시켜 순수한 단일 활성 물질을 분리하였다.Using a solvent system in which the concentrated Sigesbeckia Orientalis ethanol extract obtained in Example 3-1 was loaded on a column filled with silica gel and ethyl acetate and methanol were mixed in a ratio of 10:0.5 (v/v). Aliquoted. According to the preparative sequence, it was divided into a total of 7 fractions, and each fraction was concentrated and dried. Fraction 6 of the 7 fractions (fraction 6) was fractionated with 10% ethyl acetate as a developing solvent using RP-18 reverse phase column chromatography (Lichroprep RP-18 25-40um, Merck&Co., Whitehouse Station, NJ, USA). . According to the preparative sequence, a total of two fractions were divided and each fraction was concentrated to dryness. Of the two fractions, fraction 2 (fraction 6-2) was concentrated to dryness, and fractionated with 20% ethyl acetate as a developing solvent using RP-18 reverse phase column chromatography. According to the preparative sequence, it was divided into three fractions, and each fraction was concentrated to dryness. Finally, fraction 2 of the three fractions (fraction 6-2-2) was concentrated to dryness to separate a pure single active substance.
[실시예 4-2] 키레놀의 구조결정[Example 4-2] Structure determination of kylenol
상기 실시예 4-1에서 분리된 단일 활성물질의 구조결정을 위하여 1H-NMR 스펙트럼과 13C-NMR 스펙트럼을 각각 500 MHz 와 125 MHz(용매: MeOH)에서 측정하였다. 수득된 1H-NMR 스펙트럼과 13C-NMR 스펙트럼의 결과를 토대로 1H1H의 상관관계와 1H13C의 상관관계를 측정하기 위하여 1H1H COSY 스펙트럼과 1H13C HSQC 스펙트럼을 측정하고, 탄소공명을 통해 나오는 파장으로 각각의 탄소 신호를 구별하여 그 결과를 측정하였다.In order to determine the structure of the single active material isolated in Example 4-1, 1 H-NMR spectrum and 13 C-NMR spectrum were measured at 500 MHz and 125 MHz (solvent: MeOH), respectively. The 1 H 1 H COSY spectrum and 1 H 13 C HSQC spectra in order to obtain the 1 H-NMR measurement of correlation between the spectrum and the 13 C-NMR correlation of the 1 H 1 H on the basis of the result of the spectrum related to the 1 H 13 C relationships It was measured, and the result was measured by discriminating each carbon signal by the wavelength emitted through the carbon resonance.
또한 상기 분리된 단일물질의 질량분석을 위해 측정한 FAB-MS를 측정하였다. 본 화합물은 FAB-MS에서 [M]가 m/z 338.48에서 관측되어 분자량이 338.48로 판명되었고, 분자식 C20H34O4였다.In addition, FAB-MS measured for mass spectrometry of the isolated single substance was measured. This compound was found to have a molecular weight of 338.48 as [M] was observed at m/z 338.48 in FAB-MS, and had a molecular formula of C 20 H 34 O 4 .
이상의 1H-NMR, 13C-NMR, 및 FAB-MS에 대한 결과와 기존에 발표된 연구보고(Wang J.P. et al., Pharmacogn. Mag., 8:149-155, 2012)를 비교 분석하여 동정한 결과, 상기에서 분리된 단일물질은 하기 화학식 2로 표시되는 키레놀(kirenol) 화합물로 확인되었다.The above 1 H-NMR, 13 C-NMR, and FAB-MS results were identified by comparative analysis and previously published research reports (Wang JP et al., Pharmacogn. Mag., 8:149-155, 2012). As a result, the single substance isolated above was identified as a kirenol compound represented by the following formula (2).
[화학식 2][Formula 2]
[ 실시예 5] 운동수행능력에 관여하는 주요 유전자 PGC - 1α의 단백질 발현 증가효과 [ Example 5] Effect of increasing protein expression of PGC - 1α, a major gene involved in exercise performance
[실시예 5-1] 키레놀 또는 이를 함유하는 시게스벡키아 글라브레센스 에탄올 추출물, 시게스벡키아 푸베센스 에탄올 추출물, 시게스벡키아 오리엔탈리스 에탄올 추출물의 운동수행능력 증강 효과[Example 5-1] The effect of enhancing exercise performance of Sigesveccia glavresense ethanol extract, Sigesveccia fuvesense ethanol extract, and Sigesveccia orientalis ethanol extract containing chilenol or the same
근육 세포인 L6 미오블라스트(myoblast; American Type Culture Collection, Manassas, VA, USA)를 10% fetal bovine serum (FBS; Hyclone, Logan, UT, USA)과 100 U/mL 페니실린, 100 ug/mL 스트렙토마이신(Gibco, Grand Island, NY, USA)이 함유된 Dulbecco?s modified Eagle?s media (DMEM; Hyclone)에서 배양하였다. L6 세포에 상기 실시예 1-1에서 제조한 시게스벡키아 글라브레센스 에탄올 추출물, 실시예 2-1에서 제조한 시게스벡키아 푸베센스 에탄올 추출물, 실시예 3-1에서 제조한 시게스벡키아 오리엔탈리스 에탄올 추출물을 10 ppm 농도로 처리하였다. 또한, L6 세포에 상기 실시예 4에서 제조한 키레놀을 10 μM 농도로 처리하였다. 이 때, 시료 대신 0.01% DMSO를 처리한 군을 대조군으로 하였다. 24시간 경과 후 L6 세포를 프로테나제 억제자 칵테일(proteinase inhibitor cocktail; Sigma-Aldrich, St. Louis, MO, USA)이 포함된 RIPA (ELPIS-Biotech, Daejeon, Korea)완충용액으로 용해시켰다. 상기 시료를 5분간 끓인 후, 동량의 단백질(20 ug)을 10% SDS-PAGE로 전기영동하여 분리하였다. 전기영동 후 분리된 단백질들을 니트로셀룰로스 막으로 전달하고 웨스턴 블롯을 수행하였다. 1차 항체에 반응시킨 다음 Tris-buffered saline containing 0.1% Tween 20 (TBST)를 이용하여 10분간 3회 세척하였다. 이때, 본 발명에서 사용된 1차 항체의 종류와 희석률은 1:1000이다. 2차 항체반응은 상기 1차 항체반응을 수행한 막에 2차 항체(anti-rabbit horseradish)를 넣고 상온에서 2시간 동안 반응하였다. 이때 2차 항체의 희석률은 1:5000으로 하였다. 단백질 밴드는 ECL 웨스턴 블롯 검출 시약(western blotting detection reagents; Amersham, Tokyo, Japan)을 사용하여 발색하여 운동수행능력에 관여하는 주요 유전자 PGC-1α의 단백질 발현을 확인하였으며, α-튜불린(α-tubulin)으로 단백질 로딩량이 일정함을 나타내었다. Muscle cells, L6 myoblast (American Type Culture Collection, Manassas, VA, USA), 10% fetal bovine serum (FBS; Hyclone, Logan, UT, USA), 100 U/mL penicillin, 100 ug/mL streptomycin (Gibco, Grand Island, NY, USA) was cultured in Dulbecco's modified Eagle's media (DMEM; Hyclone). To L6 cells, the Sigesbeckia glavresense ethanol extract prepared in Example 1-1, the Sigesbeckia fuvesense ethanol extract prepared in Example 2-1, and the Sigesbekki prepared in Example 3-1 A Orientalis ethanol extract was treated at a concentration of 10 ppm. In addition, the L6 cells were treated with the kylenol prepared in Example 4 at a concentration of 10 μM. At this time, the group treated with 0.01% DMSO instead of the sample was used as a control. After 24 hours, L6 cells were lysed with RIPA (ELPIS-Biotech, Daejeon, Korea) buffer solution containing proteinase inhibitor cocktail (Sigma-Aldrich, St. Louis, MO, USA). After boiling the sample for 5 minutes, the same amount of protein (20 ug) was separated by electrophoresis by 10% SDS-PAGE. After electrophoresis, the separated proteins were transferred to a nitrocellulose membrane and Western blot was performed. After reacting with the primary antibody, it was washed three times for 10 minutes using Tris-buffered saline containing 0.1% Tween 20 (TBST). At this time, the type and dilution rate of the primary antibody used in the present invention is 1:1000. In the secondary antibody reaction, a secondary antibody (anti-rabbit horseradish) was added to the membrane in which the primary antibody reaction was performed and reacted at room temperature for 2 hours. At this time, the dilution rate of the secondary antibody was 1:5000. The protein band was colored using ECL western blotting detection reagents (Amersham, Tokyo, Japan) to confirm the protein expression of PGC-1α, a major gene involved in exercise performance, and α-tubulin (α- tubulin) showed a constant protein loading.
그 결과 도 1에 나타낸 바와 같이 키레놀 또는 이를 함유하는 시게스벡키아 글라브레센스 에탄올 추출물, 시게스벡키아 푸베센스 에탄올 추출물, 시게스벡키아 오리엔탈리스 에탄올 추출물 처리에 따라 운동수행능력에 관여하는 주요 유전자 PGC-1α의 단백질 발현량이 증가함을 알 수 있었다.As a result, as shown in FIG. 1, the treatment of Sigesveccia glavresense ethanol extract, Sigesveccia fuvesense ethanol extract, and Sigesveccia orientalis ethanol extract containing chilenol or the same is involved in exercise performance. It was found that the protein expression level of the major gene PGC-1α increased.
이러한 결과는, 본 발명의 키레놀, 이를 함유하는 희첨 추출물 또는 이의 분획물이 PGC-1α의 단백질 발현량의 증가를 통하여 운동수행능력을 증강하는 활성이 있음을 의미한다.These results indicate that the kylenol of the present invention, the extract of olivine extract containing the same, or a fraction thereof has the activity of enhancing exercise performance through an increase in the protein expression level of PGC-1α.
[실시예 5-2] 시게스벡키아 오리엔탈리스 초고압 추출물의 운동수행능력 증강 효과[Example 5-2] The effect of enhancing exercise performance of Sigesbeckia Orientalis ultra-high pressure extract
상기 실시예 3-5에서 제조한 시게스벡키아 오리엔탈리스 초고압 추출물을 10, 20, 40 ppm 농도로 상기 실시예 9-1과 동일한 방법으로 근육 세포에 처리하였다.The Sigesbeckia Orientalis ultra-high pressure extract prepared in Example 3-5 was treated on muscle cells in the same manner as in Example 9-1 at concentrations of 10, 20, and 40 ppm.
그 결과 도 2에 나타낸 바와 같이 키레놀을 함유하는 시게스벡키아 오리엔탈리스 초고압 추출물 처리에 따라 운동수행능력에 관여하는 주요 유전자 PGC-1α의 단백질의 발현량이 증가함을 알 수 있었다.As a result, as shown in FIG. 2, it was found that the expression level of the protein of PGC-1α, a major gene involved in exercise performance, was increased according to the treatment of the Sigesbeckia Orientalis ultra-high pressure extract containing kylenol.
이러한 결과는, 본 발명의 키레놀, 이를 함유하는 희첨 추출물 또는 이의 분획물이 PGC-1α의 단백질 발현량의 증가를 통하여 운동수행능력을 증강하는 활성이 있음을 의미한다.These results indicate that the kylenol of the present invention, the extract of olivine extract containing the same, or a fraction thereof has the activity of enhancing exercise performance through an increase in the protein expression level of PGC-1α.
[실시예 5-3] 희첨 에틸아세테이트 추출물의 운동수행능력 증강 효과[Example 5-3] Effect of enhancing exercise performance of lye ethyl acetate extract
상기 실시예 1-4에서 제조한 시게스벡키아 글라브레센스 에틸아세테이트 추출물, 상기 실시예 2-4에서 제조한 시게스벡키아 푸베센스 에틸아세테이트 추출물, 상기 실시예 3-4에서 제조한 시게스벡키아 오리엔탈리스 에틸아세테이트 추출물을 10 ppm 농도로 상기 실시예 5-1과 동일한 방법으로 근육 세포에 처리하였다.Sigesveccia glavresense ethyl acetate extract prepared in Example 1-4, Sigesveccia fuvesense ethyl acetate extract prepared in Example 2-4, and Siges prepared in Example 3-4 Beccia orientalis ethylacetate extract was treated to muscle cells in the same manner as in Example 5-1 at a concentration of 10 ppm.
ECL 웨스턴 블롯 검출 시약(western blotting detection reagents; Amersham, Tokyo, Japan)을 사용하여 PGC-1α 단백질 밴드를 발색하였으며, G;BOX EF imaging system (Syngene, Cambridge, UK)을 이용하여 발색된 단백질 밴드의 density를 측정하였다. 이 때 대조군 단백질 밴드의 density를 100%로 하여, 시료를 처리한 실험군의 상대적인 단백질 밴드의 density를 백분율(%)로 나타내었다.The PGC-1α protein band was developed using ECL western blotting detection reagents (Amersham, Tokyo, Japan), and the protein band developed using the G;BOX EF imaging system (Syngene, Cambridge, UK). The density was measured. At this time, the density of the control protein band was set to 100%, and the density of the relative protein band of the experimental group treated with the sample was expressed as a percentage (%).
그 결과를 하기 표 1에 나타내었다.The results are shown in Table 1 below.
상기 표 1에 나타낸 바와 같이 시게스벡키아 글라브레센스 에틸아세테이트 추출물, 시게스벡키아 푸베센스 에틸아세테이트 추출물, 시게스벡키아 오리엔탈리스 에틸아세테이트 추출물이 운동수행능력에 관여하는 주요 유전자 PGC-1α의 단백질 발현량을 증가시킴을 알 수 있었다.As shown in Table 1 above, the Sigesveccia glavresense ethyl acetate extract, the Sigesveccia fuvesense ethyl acetate extract, and the Sigesveccia orientalis ethylacetate extract are the main genes PGC-1α involved in exercise performance. It was found that the protein expression level was increased.
이러한 결과는, 본 발명의 키레놀, 이를 함유하는 희첨 추출물 또는 이의 분획물이 PGC-1α의 단백질 발현량의 증가를 통하여 운동수행능력을 증강하는 활성이 있음을 의미한다.These results indicate that the kylenol of the present invention, the extract of olivine extract containing the same, or a fraction thereof has the activity of enhancing exercise performance through an increase in the protein expression level of PGC-1α.
[실시예 5-4] 희첨 초임계 및 아임계 추출물의 운동수행능력 증강 효과[Example 5-4] Effect of enhancing exercise performance of supercritical and subcritical extracts of Heechoum
상기 실시예 1-6과 실시예 1-7에서 제조한 시게스벡키아 글라브레센스 초임계 및 아임계 추출물, 상기 실시예 2-6과 실시예 2-7에서 제조한 시게스벡키아 푸베센스 초임계 및 아임계 추출물, 상기 실시예 3-6과 실시예 3-7에서 제조한 시게스벡키아 오리엔탈리스 초임계 및 아임계 추출물을 20 ppm 농도로 상기 실시예 5-1과 동일한 방법으로 근육 세포에 처리하였다. 다음, 실시예 5-3과 동일한 방법으로 대조군 단백질 밴드의 density를 100%로 하여, 시료를 처리한 실험군의 상대적인 단백질 밴드의 density를 백분율(%)로 나타내었다.Sigesveccia glavresense supercritical and subcritical extracts prepared in Examples 1-6 and 1-7, Sigesveccia fuvesenses prepared in Examples 2-6 and 2-7 Supercritical and subcritical extracts, Sigesveccia Orientalis supercritical and subcritical extracts prepared in Examples 3-6 and 3-7 were used in the same manner as in Example 5-1 at a concentration of 20 ppm. The cells were treated. Next, in the same manner as in Example 5-3, the density of the control protein band was set to 100%, and the density of the relative protein band of the experimental group treated with the sample was expressed as a percentage (%).
그 결과를 하기 표 2에 나타내었다.The results are shown in Table 2 below.
상기 표 2에 나타낸 바와 같이 시게스벡키아 글라브레센스, 시게스벡키아 푸베센스, 시게스벡키아 오리엔탈리스 초임계 및 아임계 추출물은 운동수행능력에 관여하는 주요 유전자 PGC-1α의 단백질 발현량을 증가시킴을 알 수 있었다.As shown in Table 2 above, the Sigesveccia glavresense, Sigesveccia fuvesense, and Sigesveccia orientalis supercritical and subcritical extracts are protein expression levels of PGC-1α, a major gene involved in exercise performance. It can be seen that it increases.
이러한 결과는, 본 발명의 키레놀, 이를 함유하는 희첨 추출물 또는 이의 분획물이 PGC-1α의 단백질 발현량의 증가를 통하여 운동수행능력을 증강하는 활성이 있음을 의미한다.These results indicate that the kylenol of the present invention, the extract of olivine extract containing the same, or a fraction thereof has the activity of enhancing exercise performance through an increase in the protein expression level of PGC-1α.
[실시예 5-5] 시게스벡키아 오리엔탈리스 에탄올 추출물의 분획물의 운동수행능력 증강 효과[Example 5-5] Effect of Enhancing Exercise Performance of Fractions of Sigesbeckia Orientalis Ethanol Extract
상기 실시예 4-1에서 제조한 시게스벡키아 오리엔탈리스 에탄올 추출물의 에틸아세테이트와 메탄올의 10:0.5(v/v) 혼합 용매에 대한 분획물 6을 20 ppm 농도로 상기 실시예 5-1과 동일한 방법으로 근육 세포에 처리하였다. 다음, 실시예 5-3과 동일한 방법으로 대조군 단백질 밴드의 density를 100%로 하여, 시료를 처리한 실험군의 상대적인 단백질 밴드의 density를 백분율(%)로 나타내었다.The fraction 6 of the ethanol extract of Sigesbeckia Orientalis prepared in Example 4-1 in a 10:0.5 (v/v) mixed solvent of ethyl acetate and methanol was the same as in Example 5-1 at a concentration of 20 ppm. The muscle cells were treated by the method. Next, in the same manner as in Example 5-3, the density of the control protein band was set to 100%, and the density of the relative protein band of the experimental group treated with the sample was expressed as a percentage (%).
그 결과 시게스벡키아 오리엔탈리스 에탄올 추출물의 분획물의 대조군에 대한 상대 density는 168%로서, 시게스벡키아 오리엔탈리스 에탄올 추출물의 분획물이 운동수행능력에 관여하는 주요 유전자 PGC-1α의 단백질 발현량을 증가시킴을 알 수 있었다.As a result, the relative density of the fractions of the Sigesveccia orientalis ethanol extract relative to the control was 168%, and the fractions of the Sigesveccia orientalis ethanol extract showed the protein expression level of PGC-1α, a major gene involved in exercise performance. It can be seen that it increases.
이러한 결과는 이러한 결과는, 본 발명의 키레놀, 이를 함유하는 희첨 추출물 또는 이의 분획물이 PGC-1α의 단백질 발현량의 증가를 통하여 운동수행능력을 증강하는 활성이 있음을 의미한다.These results indicate that the kylenol of the present invention, the olivine extract containing the same, or a fraction thereof has an activity of enhancing exercise performance through an increase in the protein expression level of PGC-1α.
[[ 실시예Example 6] 6] 정상식이Normal diet 동물 모델에서 운동수행능력 향상 효과 확인 Confirmation of the effect of improving exercise performance in animal models
[실시예 6-1] 실험동물 식이[Example 6-1] Diet for experimental animals
4주령된 C57BL/6 수컷 마우스를 1주일간 적응시키고 식이는 정상식이(Research Diets D12450B, 10% kcal from fat, New Brunswick, NJ, USA)를 제공 하였으며, 체중을 기초로 무작위적으로 군을 배치하여 각각 5마리씩 총 3군으로 나누어 실험에 이용하였다. 실험군으로는 상기 실시예 4에서 제조한 키레놀, 상기 실시예 3-1에서 제조한 시게스벡키아 오리엔탈리스 에탄올 추출물을 각각 0.25% 카르복시메틸셀룰로오스(carboxymetylcellulose)에 현탁하여 시게스벡키아 오리엔탈리스 에탄올 추출물 250 mg/day/kg체중의 투여농도로 1일 1회씩 6주 동안 일정한 시간에 경구투여 하였고, 대조군은 동일량의 0.25% 카르복시메틸셀룰로오스만을 경구투여 하였다. 시료를 투여한 마우스의 식이량과 개체의 무게를 1주일 마다 측정하였다.Four-week-old C57BL/6 male mice were acclimated for 1 week, and a normal diet (Research Diets D12450B, 10% kcal from fat, New Brunswick, NJ, USA) was provided, and groups were randomly arranged based on body weight. Each of 5 animals was divided into 3 groups and used in the experiment. As an experimental group, the Chilenol prepared in Example 4 and the Sigesbeckia Orientalis ethanol extract prepared in Example 3-1 were suspended in 0.25% carboxymetylcellulose, respectively, and Sigesbeckia Orientalis ethanol. The extract was administered orally once a day at an administration concentration of 250 mg/day/kg body weight for 6 weeks for 6 weeks, and the control group was orally administered only the same amount of 0.25% carboxymethylcellulose. The dietary amount of the mice to which the sample was administered and the weight of the individual were measured every week.
[실시예 6-2] 운동수행능력 향상효과[Example 6-2] Effect of improving exercise performance
6주간 시료를 투여한 후 트레이드밀(treadmill)을 이용하여 운동수행능력을 평가하였다. 운동수행능력 평가는 경사도 5°에서 25 ㎝/초 속도로 20분, 30 ㎝/초 속도로 20분, 33 ㎝/초의 속도로 20분, 36 ㎝/초 속도로 20분, 36 ㎝/초 속도로 15분, 경사도 10°에서 38 ㎝/초 속도로 15분, 그리고 41 ㎝/초 속도로 지칠 때까지 달리도록 구성하여 실험동물의 최대운동수행능력을 측정하였다. 최대 운동수행능력의 결정시점은 운동수행 시작 후 실험동물이 트레드밀 속도를 10초 이상 따라잡지 못하는 현상이 발생하거나 전기 충격의 누적수가 5분 안에 100회를 넘는 시점으로 정의하였다. 최대운동수행능력은 실험동물의 운동거리(running distance)와 운동시간(running time)으로 측정하였다. 대조군과 시게스벡키아 오리엔탈리스 에탄올 추출물 투여군의 t검정을 실시하여 실험결과에 대한 유의성을 검증하였으며, 통계학적으로 유의한 차이를 보였다 (**p<0.01).After administration of the sample for 6 weeks, exercise performance was evaluated using a treadmill. Exercise performance evaluation was performed at a slope of 5° at 25 cm/sec speed for 20 minutes, 30 cm/sec speed for 20 minutes, 33 cm/sec speed for 20 minutes, 36 cm/sec speed for 20 minutes, and 36 cm/sec speed. It was configured to run for 15 minutes at a speed of 15 minutes at a slope of 10° at a speed of 38 cm/second, and at a speed of 41 cm/second until exhaustion, and the maximum motor performance of the experimental animals was measured. The time point for determining the maximum exercise performance was defined as the time point when the experimental animal could not keep up with the treadmill speed for more than 10 seconds after the exercise performance started or the cumulative number of electric shocks exceeded 100 times within 5 minutes. The maximum exercise performance was measured by the running distance and running time of the experimental animal. The significance of the experimental results was verified by performing a t-test between the control group and the Sigesbeckia Orientalis ethanol extract-administered group, and there was a statistically significant difference (**p<0.01).
그 결과 도 3에 나타난 바와 같이, 대조군과 비교하여 키레놀을 함유하는 시게스벡키아 오리엔탈리스 에탄올 추출물을 투여한 군에서 운동수행능력이 증가함을 확인하였다(a: 운동 거리, b: 운동 시간).As a result, as shown in FIG. 3, it was confirmed that the exercise performance increased in the group administered with the Sigesbeckia Orientalis ethanol extract containing kylenol compared to the control group (a: exercise distance, b: exercise time ).
이러한 결과는 본 발명의 키레놀, 이를 함유하는 희첨 추출물 또는 이의 분획물이 운동수행능력을 효율적으로 증강하는 효과가 있음을 의미한다.These results imply that the kylenol of the present invention, the extract or fractions thereof containing the same, has the effect of effectively enhancing exercise performance.
[실시예 6-3] 희첨 열수 추출물에 대한 운동수행능력 증가 효과 [Example 6-3] Effect of Increasing Exercise Performance on Heechoum Hot Water Extract
상기 실시예 6-1과 실시예 6-2와 동일한 방법으로 상기 실시예 1-2에서 제조한 시게스벡키아 글라브레센스 열수 추출물, 상기 실시예 2-2에서 제조한 시게스벡키아 푸베센스 열수 추출물, 상기 실시예 3-2에서 제조한 시게스벡키아 오리엔탈리스 열수 추출물에 대한 운동시간을 각각 측정하였다.In the same manner as in Example 6-1 and 6-2, the Shigesveccia glavresense hot-water extract prepared in Example 1-2, and the Shigesveccia fuvesense prepared in Example 2-2. Exercise times were measured for the hot water extract and the Siges Beckia Orientalis hot water extract prepared in Example 3-2, respectively.
그 결과를 하기 표 3에 나타내었다.The results are shown in Table 3 below.
그 결과 상기 표 3에 나타낸 바와 같이 대조군에 비해 시게스벡키아 글라브레센스 열수 추출물, 시게스벡키아 푸베센스 열수 추출물, 시게스벡키아 오리엔탈리스 열수 추출물에 의해 운동시간이 각각 유의적으로 증가함을 알 수 있었다(p<0.01).As a result, as shown in Table 3 above, exercise time was significantly increased by the Sigesveccia glavresense hot water extract, Sigesveccia fuvesense hot water extract, and Sigesbeckia orientalis hot water extract, respectively, compared to the control group. Was found (p<0.01).
이러한 결과는, 본 발명의 키레놀, 이를 함유하는 희첨 추출물 또는 이의 분획물이 운동수행능력을 효율적으로 증강하는 효과가 있음을 의미한다.These results mean that the kylenol of the present invention, the extract or a fraction thereof containing the same, has the effect of effectively enhancing exercise performance.
[ 실시예 7] 고지방식이로 유도된 비만 동물 모델에서 운동수행능력 향상 효과 확인 [Example 7] to improve physical performance in an animal model of obesity induced by a high fat effect confirmed
[실시예 7-1] 실험동물 식이[Example 7-1] Diet for experimental animals
4주령된 C57BL/6 수컷 마우스를 1주일간 적응시키고 비만을 유도하기 위해 고지방 식이(Research Diets D12492, 60% kcal from fat)를 6주간 공급하여 비만을 유도 시킨 다음, 각각 5마리씩 총 2군으로 임의적으로 나누어 상기 실시예 10-1과 동일한 방법으로 비만동물 모델에 경구투여하였다.Four-week-old C57BL/6 male mice were adapted for 1 week and fed a high-fat diet (Research Diets D12492, 60% kcal from fat) for 6 weeks to induce obesity. Divided into and administered orally to an obese animal model in the same manner as in Example 10-1.
[실시예 7-2] 운동수행능력 향상효과[Example 7-2] Effect of improving exercise performance
고지방식이로 유도된 비만동물 모델을 이용하여 상기 실시예 10-2와 동일한 방법으로 운동수행능력 평가하였다. 실험결과는 고지방식이 대조군과 고지방식이 시게스벡키아 오리엔탈리스 에탄올 추출물 투여군의 t검정을 실시하여 그 유의성을 검증하였으며, 통계학적으로 유의한 차이를 보였다(**p<0.01).Exercise performance was evaluated in the same manner as in Example 10-2 using an obese animal model induced by a high fat diet. As for the experimental results, a t-test was performed between the high-fat diet control group and the high-fat diet-treated Sigesbeckia Orientalis ethanol extract group to verify their significance, and there was a statistically significant difference (**p<0.01).
그 결과 도 4에 나타난 바와 같이, 고지방식이 대조군과 비교하여 고지방식이 시게스벡키아 오리엔탈리스 에탄올 추출물을 투여한 군에서 운동수행능력이 증가함을 확인하였다(a: 운동 거리, b: 운동 시간).As a result, as shown in FIG. 4, it was confirmed that exercise performance increased in the group administered with the ethanol extract of Sigesbeckia Orientalis in the high-fat diet compared to the control group in the high-fat diet (a: exercise distance, b: exercise time).
이러한 결과는 본 발명의 키레놀, 이를 함유하는 희첨 추출물 또는 이의 분획물이 비만 모델에서 운동수행능력을 효율적으로 증강하는 효과가 있음을 의미한다.These results imply that the kylenol of the present invention, the extract or fraction thereof containing the same, has the effect of effectively enhancing exercise performance in an obesity model.
[ 실시예 8] 동물 모델의 근육조직에서 운동능력향상과 관련된 유전자의 단백질 발현 증진 효과 [ Example 8] Effect of enhancing protein expression of genes related to exercise capacity improvement in muscle tissue of an animal model
실시예 6-1의 정상식이 마우스와 실시예 7-1의 고지방식이 마우스로부터 종아리 근육(calf muscle)을 적출한 후, 웨스턴 블랏(western blot)을 통해 p-AMPK, SIRT1, PGC-1α, PPARδ의 단백질 발현을 확인하였으며, α-튜불린으로 단백질 로딩량이 일정함을 나타내었다. After extracting the calf muscle from the normal diet mouse of Example 6-1 and the high fat diet mouse of Example 7-1, p-AMPK, SIRT1, PGC-1α, and Protein expression of PPARδ was confirmed, and it was shown that the amount of protein loading with α-tubulin was constant.
그 결과 도5에 나타낸 바와 같이 시게스벡키아 오리엔탈리스 추출물이 정상식이 모델과 고지방식이 모델에서 모두 운동능력향상과 관련된 유전자인 p-AMPK, SIRT1, PGC-1α, PPARδ의 단백질 발현량을 증가시킴을 알 수 있었다.As a result, as shown in Fig. 5, Sigesbeckia orientalis extract increased the protein expression levels of p-AMPK, SIRT1, PGC-1α, and PPARδ, genes related to exercise performance improvement in both the normal diet model and the high fat diet model. I could see Sikkim.
이러한 결과는, 본 발명의 키레놀, 이를 함유하는 희첨 추출물 또는 이의 분획물이 동물 모델에서 운동능력향상과 관련된 유전자의 단백질 발현을 증가시켜 운동수행능력을 효율적으로 증가하는 효과가 있음을 의미한다.These results indicate that the kylenol of the present invention, the extract of olivine extract containing the same, or a fraction thereof has the effect of efficiently increasing the exercise performance by increasing the protein expression of the gene related to the improvement of exercise performance in an animal model.
[ 실시예 9] 동물 모델의 근육조직에서 미토콘드리아 생합성과 관련된 유전자 발현 증진 효과 [ Example 9] Effect of enhancing gene expression related to mitochondrial biosynthesis in muscle tissue of an animal model
실시예 6-1의 정상식이 마우스와 실시예 7-1의 고지방식이 마우스로부터 종아리 근육(calf muscle)을 적출한 후, RT-PCR을 통해 PGC-1α, NRF-1, ERRα, Tfam의 mRNA 발현을 확인하였다. 종아리 근육으로부터 TRIzol시약(Invitrogen, Carlsbad, CA, USA)을 사용하여 총 RNA를 수확하여 역전사시킨 후, RT-PCR 분석을 다음과 같이 수행하였다. 먼저 cDNA 합성을 위해 상기 RNA를 역전사 효소로 역전사시켰다. RT-PCR은 다음의 특정 프라이머로 수행하였다:After extracting the calf muscle from the normal diet mouse of Example 6-1 and the high fat diet mouse of Example 7-1, mRNA of PGC-1α, NRF-1, ERRα, Tfam through RT-PCR Expression was confirmed. Total RNA was harvested and reverse transcribed from calf muscle using a TRIzol reagent (Invitrogen, Carlsbad, CA, USA), and then RT-PCR analysis was performed as follows. First, for cDNA synthesis, the RNA was reverse transcribed with a reverse transcriptase. RT-PCR was performed with the following specific primers:
PGC-1αPGC-1α
서열번호 1: 5'-ATGTGTCGCCTTCTTGCTCT-3' (Forward primer)SEQ ID NO: 1: 5'-ATGTGTCGCCTTCTTGCTCT-3' (Forward primer)
서열번호 2: 5'-ATCTACTGCCTGGGGACCTT-3' (Reverse primer)SEQ ID NO: 2: 5'-ATCTACTGCCTGGGGACCTT-3' (Reverse primer)
ERRαERRα
서열번호 3: 5'-GCTGGTGGTTGAACCTGAGA-3' (Forward primer)SEQ ID NO: 3: 5'-GCTGGTGGTTGAACCTGAGA-3' (Forward primer)
서열번호 4: 5'-GGGCTAACACCCTATGCCAG-3' (Reverse primer)SEQ ID NO: 4: 5'-GGGCTAACACCCTATGCCAG-3' (Reverse primer)
NRF-1:NRF-1:
서열번호 5: 5'-TGGACCCAAGCATTACGGAC-3' (Forward primer)SEQ ID NO: 5: 5'-TGGACCCAAGCATTACGGAC-3' (Forward primer)
서열번호 6: 5'-GGTCATTTCACCGCCCTGTA-3' (Reverse primer)SEQ ID NO: 6: 5'-GGTCATTTCACCGCCCTGTA-3' (Reverse primer)
Tfam:Tfam:
서열번호 7: 5'-TCGCCTGTCAGCCTTATCTG-3' (Forward primer)SEQ ID NO: 7: 5'-TCGCCTGTCAGCCTTATCTG-3' (Forward primer)
서열번호 8: 5'-CCGGGCTTCCTTCTCTAAC-3' (Reverse primer)SEQ ID NO: 8: 5'-CCGGGCTTCCTTCTCTAAC-3' (Reverse primer)
β-액틴:β-actin:
서열번호 9: 5'-TAACCAACTGGGACGATATG-3' (Forward primer)SEQ ID NO: 9: 5'-TAACCAACTGGGACGATATG-3' (Forward primer)
서열번호 10: 5'-ATACAGGGACAGCACAGCCT-3' (Reverse primer)SEQ ID NO: 10: 5'-ATACAGGGACAGCACAGCCT-3' (Reverse primer)
그 결과 도 6에 나타낸 바와 같이, 시게스벡키아 오리엔탈리스 추출물이 정상식이 모델과 고지방식이 모델에서 미토콘드리아 생합성 유전자인 PGC-1α, NRF-1, ERRα, Tfam의 mRNA 발현량을 증가시킴을 확인할 수 있었다.As a result, as shown in FIG. 6, it was confirmed that the Sigesbeckia orientalis extract increased the mRNA expression levels of mitochondrial biosynthesis genes PGC-1α, NRF-1, ERRα, and Tfam in the normal diet model and the high fat diet model. Could.
이러한 결과는, 본 발명의 키레놀, 이를 함유하는 희첨 추출물 또는 이의 분획물이 미토콘드리아 생합성을 증가시켜 운동수행능력을 효율적으로 증강하는 효과가 있음을 의미한다.These results mean that the kylenol of the present invention, the olivine extract containing the same, or a fraction thereof increases mitochondrial biosynthesis to effectively enhance exercise performance.
이하, 본 발명에 따른 키레놀 또는 이를 함유하는 희첨 추출물을 유효성분으로 함유하는 운동수행능력 증강용 식품류 및 의약품의 제조예를 설명하나, 본 발명은 이를 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다. 상기 운동수행능력 증강 효과가 우수한 키레놀 또는 이를 함유하는 희첨 추출물을 가지고 하기와 같은 조성성분 및 조성비에 따라 제조예 1 내지 2의 운동수행능력 증강용 식품 및 의약품 조성물을 통상적인 방법에 따라서 제조하였다.Hereinafter, examples of preparation of foods and pharmaceuticals for enhancing exercise performance containing kylenol according to the present invention or a lychee extract containing the same as an active ingredient will be described, but the present invention is not intended to limit this, but is intended to be described in detail to be. The food and pharmaceutical compositions for enhancing exercise performance of Preparation Examples 1 to 2 were prepared according to the following compositions and composition ratios with kylenol having excellent exercise performance enhancing effect or lychee extract containing the same, according to a conventional method. .
[제조예 1] 식품의 제조[Production Example 1] Preparation of food
[제조예 1-1] 건강식품의 제조[Production Example 1-1] Preparation of health food
상기 실시예 1내지 3의 희첨 추출물 또는 키레놀 1000 mg, 비타민 A 아세테이트 70 ug, 비타민 E 1.0 mg, 비타민 B1 0.13 mg, 비타민 B2 0.15 mg, 비타민 B6 0.5 mg, 비타민 B12 0.2 ug, 비타민 C 10 mg, 비오틴 10 ug, 니코틴산아미드 1.7 mg, 엽산 50 ug, 판토텐산 칼슘 0.5 mg, 황산제1철 1.75 mg, 산화아연 0.82 mg, 탄산마그네슘 25.3 mg, 제1인산칼륨 15 mg, 제2인산칼슘 55 mg, 구연산칼륨 90 mg, 탄산칼슘 100 mg, 염화마그네슘 24.8 mg를 혼합하여 제조할 수 있으며, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상의 건강식품 제조방법에 따라 상기의 성분을 혼합한 다음, 과립을 제조하고, 통상의 방법에 따라 건강식품 조성물 제조에 사용할 수 있다.Examples 1 to 3 of the extract or kylenol 1000 mg, vitamin A acetate 70 ug, vitamin E 1.0 mg, vitamin B1 0.13 mg, vitamin B2 0.15 mg, vitamin B6 0.5 mg, vitamin B12 0.2 ug,
[제조예 1-2] 건강음료의 제조[Production Example 1-2] Preparation of health drink
상기 실시예 1내지 3의 희첨 추출물 또는 키레놀 1000 mg, 구연산 1000 mg, 올리고당 100 g, 매실농축액 2 g, 타우린 1 g에 정제수를 가하여 전체 900 ml 통상의 건강음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1시간동안 85에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 2 L용기에 취득하여 밀봉 멸균한 뒤 냉장 보관한 다음 건강음료 조성물 제조에 사용할 수 있다.Purified water was added to the dilution extract of Examples 1 to 3 or 1000 mg of kylenol, 1000 mg of citric acid, 100 g of oligosaccharide, 2 g of plum concentrate, and 1 g of taurine, and the above ingredients were added according to a conventional health drink manufacturing method. After mixing, stirring and heating at 85 for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2 L container, sealed and sterilized, and then stored in a refrigerator, and then used for preparing a health drink composition.
[제조예 1-3] 츄잉껌[Production Example 1-3] Chewing gum
껌 베이스 20 중량%, 설탕 76.9 중량%, 향료 1 중량% 및 물 2 중량% 와 상기 실시예 1내지 3의 희첨 추출물 또는 키레놀 0.1 중량%를 배합하여 통상의 방법으로 츄잉껌을 제조하였다.A chewing gum was prepared by a conventional method by combining 20% by weight of gum base, 76.9% by weight of sugar, 1% by weight of flavor, 2% by weight of water, and 0.1% by weight of the lean extract or kylenol of Examples 1 to 3.
[제조예 1-4] 캔디[Production Example 1-4] Candy
설탕 60 중량%, 물엿 39.8 중량% 및 향료 0.1 중량%와 상기 실시예 3-5의 희첨 추출물 또는 키레놀 0.1 중량%를 배합하여 통상의 방법으로 캔디를 제조하였다.
[제조예 1-5] 비스켓[Production Example 1-5] Biscuit
박력 1급 25.59 중량%, 중력 1급 22.22 중량%, 정백당 4.80 중량%, 식염 0.73 중량%, 포도당 0.78 중량%, 팜쇼트닝 11.78 중량%, 암모늄 1.54 중량%, 중조 0.17 중량%, 중아황산나트륨 0.16 중량%, 쌀가루 1.45 중량%, 비타민 B 0.0001 중량%, 밀크향 0.04 중량%, 물 20.6998 중량%, 전지분유 1.16 중량%, 대용분유 0.29 중량%, 제1인산칼슘 0.03 중량%, 살포염 0.29 중량% 및 분무유 7.27 중량%와 상기 실시예 1내지 3의 희첨 추출물 또는 키레놀 중량%를 배합하여 통상의 방법으로 비스켓을 제조하였다.
[제조예 2 - 의약품][Production Example 2-Pharmaceuticals]
[제조예 2-1] 산제[Production Example 2-1] Powder
상기 실시예 1내지 3의 희첨 추출물 또는 키레놀 50 mg, 결정셀룰로오즈 2 g을 혼합한 후 통상의 산제 제조방법에 따라서 기밀포에 충진하여 산제를 제조하였다.After mixing the diluted extract of Examples 1 to 3 or 50 mg of kylenol and 2 g of crystalline cellulose, the powder was prepared by filling it in an airtight cloth according to a conventional powder preparation method.
[제조예 2-2] 정제[Production Example 2-2] Tablet
상기 실시예 1내지 3의 희첨 추출물 또는 키레놀 50 mg, 결정셀룰로오즈 400 mg, 스테아린산 마그네슘 5 mg을 혼합한 후 통상의 정제 제조방법에 따라서 타정하여 정제를 제조하였다.Tablets were prepared by mixing the diluted extract of Examples 1 to 3 or 50 mg of kylenol, 400 mg of crystalline cellulose, and 5 mg of magnesium stearate, followed by tableting according to a conventional tablet preparation method.
[제조예 2-3] 캡슐제[Production Example 2-3] Capsule
상기 실시예 1내지 3의 희첨 추출물 또는 키레놀 30 mg, 유청단백질 100 mg, 결정셀룰로오즈 400 mg, 스테아린산 마그네슘 6 mg을 혼합한 후 통상의 캡슐제 제조방법에 따라서 젤라틴 캡슐에 충전하여 캡슐제를 제조하였다.After mixing the dilution extract or kylenol of Examples 1 to 3, 30 mg,
[제조예 2-4] 주사제[Production Example 2-4] Injection
통상의 주사제 제조방법에 따라 활성성분을 주사용 증류수에 용해하고 pH를 약 7.5로 조절한 다음 상기 실시예 3-5의 키레놀 100 mg, 주사용 증류수, pH 조절제를 혼합하여 2 ml 용량의 앰플에 충진하고 멸균시켜서 주사제를 제조하였다.According to a conventional injection preparation method, the active ingredient was dissolved in distilled water for injection and the pH was adjusted to about 7.5, and then 100 mg of kylenol of Example 3-5, distilled water for injection, and a pH adjusting agent were mixed in a 2 ml ampoule. Filled in and sterilized to prepare an injection.
<110> University-Industry Foundation, Yonsei University <120> Composition for increase of exercise capacity comprising kirenol or extract of Sigesbeckia spp. <130> P15U16C0849 <150> KR 2014-0079538 <151> 2014-06-27 <160> 10 <170> KopatentIn 2.0 <210> 1 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> PGC-1alpha forward primer <400> 1 atgtgtcgcc ttcttgctct 20 <210> 2 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> PGC-1alpha reverse primer <400> 2 atctactgcc tggggacctt 20 <210> 3 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> ERR alpha forward primer <400> 3 gctggtggtt gaacctgaga 20 <210> 4 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> ERR alpha reverse primer <400> 4 gggctaacac cctatgccag 20 <210> 5 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> NRF-1 forward primer <400> 5 tggacccaag cattacggac 20 <210> 6 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> NRF-1 reverse primer <400> 6 ggtcatttca ccgccctgta 20 <210> 7 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Tfam forward primer <400> 7 tcgcctgtca gccttatctg 20 <210> 8 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> Tfam reverse primer <400> 8 ccgggcttcc ttctctaac 19 <210> 9 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> beta actin forward primer <400> 9 taaccaactg ggacgatatg 20 <210> 10 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> beta actin reverse primer <400> 10 atacagggac agcacagcct 20 <110> University-Industry Foundation, Yonsei University <120> Composition for increase of exercise capacity comprising kirenol or extract of Sigesbeckia spp. <130> P15U16C0849 <150> KR 2014-0079538 <151> 2014-06-27 <160> 10 <170> KopatentIn 2.0 <210> 1 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> PGC-1alpha forward primer <400> 1 atgtgtcgcc ttcttgctct 20 <210> 2 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> PGC-1alpha reverse primer <400> 2 atctactgcc tggggacctt 20 <210> 3 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> ERR alpha forward primer <400> 3 gctggtggtt gaacctgaga 20 <210> 4 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> ERR alpha reverse primer <400> 4 gggctaacac cctatgccag 20 <210> 5 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> NRF-1 forward primer <400> 5 tggacccaag cattacggac 20 <210> 6 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> NRF-1 reverse primer <400> 6 ggtcatttca ccgccctgta 20 <210> 7 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Tfam forward primer <400> 7 tcgcctgtca gccttatctg 20 <210> 8 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> Tfam reverse primer <400> 8 ccgggcttcc ttctctaac 19 <210> 9 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> beta actin forward primer <400> 9 taaccaactg ggacgatatg 20 <210> 10 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> beta actin reverse primer <400> 10 atacagggac agcacagcct 20
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