KR101935199B1 - Composition Containning Diphlorethohydroxycarmalol for Improvement of Exercise Performance - Google Patents
Composition Containning Diphlorethohydroxycarmalol for Improvement of Exercise Performance Download PDFInfo
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- KR101935199B1 KR101935199B1 KR1020180063998A KR20180063998A KR101935199B1 KR 101935199 B1 KR101935199 B1 KR 101935199B1 KR 1020180063998 A KR1020180063998 A KR 1020180063998A KR 20180063998 A KR20180063998 A KR 20180063998A KR 101935199 B1 KR101935199 B1 KR 101935199B1
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- A—HUMAN NECESSITIES
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Abstract
Description
본 발명은 디플로르에토하이드록시카르마롤(Diphlorethohydroxycarmalol, Cas No. 138529-04-1, DPHC)를 이용한 운동 능력 개선용 조성물에 관한 것이다.The present invention relates to a composition for improving exercise capacity using dihydrofluorohydroxycarmalol (Cas No. 138529-04-1, DPHC).
골격근의 주된 역할은 골근육의 수축과 이완을 일으키는 것이며, 이 때 골격근 세포의 세포질 내 칼슘 이온이 골격근의 수축과 이완 과정을 매개하는 핵심적인 이차전달 물질로 작용한다. 칼슘 이온은 인체에서 세포 내외 중요한 역할을 하며 다양한 조직에서 적절한 기능을 유지하기 위해 세밀하게 조절된다. 세포 외 칼슘은 연골과 골격의 주요 구성분일 뿐만 아니라 심장과 근육에서는 흥분 수축 결합, 신경계에서는 시냅스 전달 등에 관여한다. 세포 내 칼슘은 세포 외 칼슘보다 10,000배 낮은 농도를 유지하면서 세포 분열, 근육 수축, 세포 이동, 막 전달과 분비 등에 있어서 신호 전달자로서 중요한 역할을 한다(Clin J Am Soc Nephrol. 2010. 5 Suppl 1:S23-30; Nephro Physiol. 2011. 118:22-7; Nat.Rev.Mol.Cell.Biol.2003.4:517-29).The main role of the skeletal muscle is to cause contraction and relaxation of the osseous muscles, where the intracellular calcium ions of the skeletal muscle cells act as a key secondary messenger that mediates the contraction and relaxation processes of the skeletal muscle. Calcium ions play an important role in the cell both inside and outside the cell and are carefully controlled to maintain proper function in various tissues. Extracellular calcium is not only a major component of the cartilage and skeleton, but also involved excitatory contraction in the heart and muscle, and synaptic transmission in the nervous system. Intracellular calcium plays an important role as a signal transducer in cell division, muscle contraction, cell migration, membrane transport, and secretion, while maintaining a concentration 10,000 times lower than extracellular calcium (Clin J Am Soc Nephrol. 2010. 5 Suppl 1: S23-30: Nephro Physiol., 2011. 118: 22-7; Nat. Rev. Mol. Cell. Biol. 2003: 4: 517-29).
안정시의 세포 내 유리 칼슘이온 농도는 세포 외액에 비해 매우 낮으나 신경 자극에 따른 근세포 막의 탈분극으로 세포 외액이나 세포 내 저장 장소로부터 칼슘이온이 유입 또는 유리되어 일정 수준에 이르면 근 수축이 유발되는 것으로 알려져 있다. 특히 골격근 수축은 근세포 밖의 칼슘을 제거하였을 때에도 오랫동안 지속되기 때문에 근육은 세포 내 중요한 칼슘 공급처인 것으로 여겨진다(Annul. Rev. Physiol. 1976. 38:293-313; Physio. Rev. 1977. 71-108).The concentration of free calcium ions in the cells at rest is much lower than that of the extracellular fluid, but it is known that muscle contraction is induced when the calcium ion is introduced or released from the extracellular fluid or the intracellular storage place due to depolarization of the muscle cell membrane by nerve stimulation have. In particular, skeletal muscle contraction is believed to be an important source of calcium in the cell because it lasts for a long time even when calcium is removed from muscle cells (Annul. Rev. Physiol., 1976. 38: 293-313; Physio. Rev. 1977. 71-108) .
또한 세포 내 증가된 칼슘은 미토콘드리아를 통한 호흡과 ATP 생산을 유도한다고 알려져 있다(Am J Physiol Cell Physiol. 2004. 287:817-833; Biochemistry. 2013. 52:2793-2809). 근육이 자극을 받으면, SR(sarcoplasmic reticulum) Ca2+ pumps(SERCA, 소세포체 표면에 존재하는 칼슘 펌프로, 세포질에 존재하는 칼슘을 소포체내로 이동시킴으로써 세포 내 칼슘농도 항상성을 조절한다)를 통해 칼슘이 SR 안으로 들어오고, 이로 인하여 액틴-미오신 결합이 형성되어 근육의 수축이 일어난다. 근 수축 후에는 ATP을 이용한 능동수송으로 칼슘은 다시 원위치(SR을 통한 세포 바깥)로 이동하게 되며, ATP가 미오신과 결합하면 액틴-미오신 결합은 끊어지고 근육은 이완하게 된다. It is also known that increased intracellular calcium induces respiration and ATP production through mitochondria (Am J Physiol Cell Physiol. 2004. 287: 817-833; Biochemistry. 2013. 52: 2793-2809). When muscle is stimulated, SR (sarcoplasmic reticulum) Ca2 + pumps (SERCA, a calcium pump on the surface of a small cell body, regulates calcium intracellular homeostasis by moving the cytoplasmic calcium into the endoplasmic reticulum) , Which leads to the formation of actin-myosin bonds and muscle contraction. After muscle contraction, active transport using ATP causes calcium to migrate back to its original position (outside the cell via SR), and when ATP binds to myosin, the actin-myosin bond breaks and the muscle relaxes.
이때 필요한 ATP의 생성은 이원질 시스템(phosphagen system), 해당과정(glycolysis), ATP 분해과정의 3가지 방법에 이루어 지며, 특히 운동할 때 필요한 포도당 생산의 가장 중요한 역할을 하는 것은 글루카곤 분비의 증가이다(J Clin Invest. 1984. 74(4):1404-13). 운동이 세포막에 발현되는 포도당 수용체4(GLUT4)의 수를 증가시키며 세포조직에서의 GLUT4의 농도도 증가시킨다는 보고가 있으며(JAMA. 1991. 266:1535-42; J Clin invest. 1979. 64:1011-15; Am J Physiol. 1987. 252:E170-175), 이는 운동 중 근육의 포도당 섭취가 증가하므로 ATP의 재생을 증가시켜 포도당 수송 속도를 증가시킨다는 주장을 뒷받침 한다. At this time, the production of ATP is carried out in three ways: the phosphagen system, glycolysis, and the ATP degradation process. Especially, the most important role of glucose production during exercise is increased secretion of glucagon (J Clin Invest 1984 74 (4): 1404-13). It has been reported that exercise increases the number of glucose receptor 4 (GLUT4) expressed in the cell membrane and increases the concentration of GLUT4 in the cell tissue (JAMA 1991, 266: 1535-42; J Clin Invest 1979. 64: 1011 -15; Am J Physiol. 1987. 252: E170-175), which supports the assertion that increased glucose uptake by increasing muscle glucose uptake during exercise increases regeneration of ATP.
또한, 운동시 근육과 간의 글리코겐 고갈은 피로의 주요 원인이며, 골격근의 ATP는 근수축시 미토콘드리아에서 생성되는 즉각적인 에너지원이다. 때문에, 세포실험 또는 실험동물의 간과 근육조직을 통한 골격근 내 글리코겐 함량 또는 근육 내 ATP 함량 측정은 운동수행능력 향상 기능성 평가의 바이오마커로 사용된다(대한민국 식약처, 2016, 건강기능식품 기능성 평가 가이드).In addition, glycogen depletion in muscles and liver during exercise is a major cause of fatigue, and skeletal muscle ATP is an immediate energy source in mitochondria when muscle contraction occurs. Therefore, measurement of glycogen content or intramuscular ATP content in skeletal muscle through liver experiments and muscle tissues in cell experiments or laboratory animals is used as a biomarker for exercise performance improvement functional evaluation (Korea Food Research Agency, 2016, Guide for Functional Evaluation of Health Functional Foods) .
이에, 본 발명은 디플로르에토하이드록시카르마롤(Diphlorethohydroxycarmalol, DPHC)이 근육 내로의 칼슘 유입을 촉진하고 글루코오스의 흡수를 유도하여 근수축을 유도하고 근육의 운동성을 증가시킬 수 있음을 제시한다.Accordingly, the present invention suggests that Diphlorethohydroxycarmalol (DPHC) promotes calcium influx into muscles and induces absorption of glucose to induce muscle contraction and increase muscle motility.
본 발명의 목적은 디플로르에토하이드록시카르마롤(Diphlorethohydroxycarmalol, DPHC)를 이용한 운동 능력 개선용 조성물을 제공하는 데 있다.It is an object of the present invention to provide a composition for improving athletic performance using dihydrofluorohydroxycarmalol (DPHC).
본 발명의 다른 목적이나 구체적인 목적은 이하에서 제시될 것이다.Other and further objects of the present invention will be described below.
본 발명자들은 아래의 실시예 및 실험예에서 확인되는 바와 같이, DPHC가 5일 분화한 근원세포인 C2C12를 이용한 생체외(In vitro) 실험에서 근수축과 운동성 향상에 필요한 칼슘 이온의 세포 내 흡수를 촉진하고 이러한 근수축 등에 필요한 에너지원인 글루코오스 흡수를 유도하며, 또 제브라피시를 이용한 동물실험에서도 마찬가지로 세포 내 칼슘 이온의 농도를 증가시키고 세포 내로의 글루코오스 유입을 유도함을 확인하였다. As shown in the following Examples and Experimental Examples, the present inventors have conducted intracellular absorption of calcium ions necessary for improving muscle contraction and motility in vitro using C2C12, a source cell differentiated by DPHC for 5 days, And to induce glucose uptake, which is an energy source required for such muscle contraction, and also to increase the intracellular calcium ion concentration and to induce glucose uptake into cells as in animal experiments using zebrafish.
전술한 바의 실험 결과를 고려할 때, 본 발명은 DPHC, 이의 프로드럭, 이의 수화물, 또는 이의 용매화물을 유효성분으로 포함하는 운동 능력 개선용 조성물에 관한 것이다.In view of the above-described experimental results, the present invention relates to a composition for improving exercise capacity comprising DPHC, a prodrug thereof, a hydrate thereof, or a solvate thereof as an active ingredient.
본 명세서에서, "프로드럭(prodrug)"은 어떤 약물을 화학적으로 변화시켜 물리적, 화학적 성질을 조절한 약물을 의미하며, 그 자체는 생리 활성을 나타내지 않지만 투여 후 체내에서 화학적 혹은 효소의 작용에 의해 원래의 약물로 바뀌어 약효를 발휘할 수 있는 약물을 의미한다.In the present specification, the term " prodrug " refers to a drug that chemically changes a drug to control its physical and chemical properties. Although the drug itself does not exhibit a physiological activity, the drug is chemically or enzymatically It means a drug that can be converted into the original drug and take its effect.
또 본 명세서에서 "수화물(hydrate)"은 물이 결합되어 있는 화합물을 의미하며, 물과 화합물 사이에 화학적인 결합력이 없는 내포 화합물을 포함하는 의미이다.In the present specification, the term "hydrate" means a compound having water bonded thereto, and it is meant to include an inclusion compound having no chemical bonding force between water and the compound.
또 본 명세서에서 "용매화물"은 용질의 분자나 이온과 용매의 분자나 이온 사이에 생긴 화합물을 의미한다.&Quot; Solvate " as used herein means a compound formed between a molecule or ion of a solute and a molecule or ion of a solvent.
또한 본 명세서에서 "유효성분"이란 단독으로 목적하는 활성을 나타내거나 또는 그 자체는 활성이 없는 담체와 함께 활성을 나타낼 수 있는 성분을 의미한다.The term " active ingredient " as used herein alone means an ingredient which exhibits the desired activity or which can exhibit activity together with a carrier which is itself inactive.
본 발명의 조성물에서 그 유효성분은 운동 능력 개선 효과 등 나타낼 수 있는 한, 용도, 제형 등에 따라 임의의 양(유효량)으로 포함될 수 있는데, 통상적인 유효량은 조성물 전체 중량을 기준으로 할 때 0.001 중량 % 내지 15 중량 % 범위 내에서 결정될 것이다. 여기서 "유효량"이란 그 적용 대상인 포유동물 바람직하게는 사람에게 의료 전문가 등의 제언에 의한 투여 기간 동안 본 발명의 조성물이 투여될 때, 운동 능력 개선 효과 등 의도한 의료적·약리학적 효과를 나타낼 수 있는, 본 발명의 조성물에 포함되는 유효성분의 양을 말한다. 이러한 유효량은 당업자의 통상의 능력 범위 내에서 실험적으로 결정될 수 있다.In the composition of the present invention, the active ingredient may be contained in an arbitrary amount (effective amount) as long as it exhibits the effect of improving exercise capacity, etc., and a typical effective amount is 0.001 wt% To 15% by weight. Herein, " effective amount " means a medical or pharmacological effect, such as an effect of improving athletic performance, when the composition of the present invention is administered to a mammal, preferably a human, Refers to the amount of active ingredient contained in the composition of the present invention. Such effective amounts can be determined experimentally within the ordinary skill of those skilled in the art.
본 발명의 조성물은 유효성분 이외에, 운동 능력 개선 효과 등의 상승·보강을 위하여 또는 피로 개선 활성 등 유사활성의 부가를 통한 복용이나 섭취의 편리성을 증진시키기 위하여, 당업계에서 이미 안전성이 검증되고 해당 활성을 갖는 것으로 공지된 임의의 화합물이나 천연 추출물을 추가로 포함할 수 있다. The composition of the present invention has already been proved to be safe in the art in order to increase or enhance the athletic performance improving effect or the like or to improve the convenience of taking or ingesting by adding similar activities such as fatigue improving activity May further comprise any compound or natural extract known to have that activity.
이러한 화합물 또는 추출물에는 각국 약전(한국에서는 "대한민국약전"), 각국 건강기능식품공전(한국에서는 식약처 고시인 "건강기능식품 기준 및 규격"임) 등의 공정서에 실려 있는 화합물 또는 추출물, 의약품의 제조·판매를 규율하는 각국의 법률(한국에서는 "약사법"임)에 따라 품목 허가를 받은 화합물 또는 추출물, 건강기능식품의 제조·판매를 규율하는 각국 법률(한국에서는 「건강기능식품에관한법률」임)에 따라 기능성이 인정된 화합물 또는 추출물이 포함된다. 예컨대 한국 「건강기능식품에관한법률」에 따라 '운동 수행 능력 향상'으로 기능성이 인정된 마카 젤라틴화 분말, 크레아틴, 헛개나무 과병 추출 분말, 동충하초 발효 추출물 등과, '피로 개선'으로 기능성이 인정된 발효 생성 아미노산 복합물, 헛개나무 과병 추출물, 홍경천 추출물 등이 이러한 화합물 또는 추출물에 해당할 것이다.Such compounds or extracts include compounds or extracts listed in the official pamphlet of each country's pharmacopeia ("Korea Pharmacopoeia" in Korea), each country's health functional foods (in Korea, "Health Functional Food Standards and Specifications" (The "Act on Health Functional Foods" in Korea), which regulates the manufacture and sale of compounds or extracts and health functional foods approved by the respective countries in accordance with the laws of the respective countries ("Pharmaceutical Affairs Law" in Korea) &Quot;). ≪ / RTI > For example, in accordance with the Korean Health Functional Food Act, maca-gelatinized powder, which has been recognized as functional by improving exercise performance, creatine, extract powder of Houttuynia cordata, and fermented extract of Cordyceps, Fermentation-producing amino acid complexes, Hovenia japonica extracts, and Rhodiola extracts, and the like.
이러한 화합물 또는 천연 추출물은 본 발명의 조성물에 그 유효성분과 함께 하나 이상 포함될 수 있다.Such compounds or natural extracts may be included in the compositions of the present invention in combination with one or more of their active ingredients.
이러한 화합물 또는 추출물은 본 발명의 조성물에 그 유효성분과 함께 하나 이상 포함될 수 있다.Such compounds or extracts may be included in the composition of the present invention in combination with one or more thereof.
본 발명의 조성물은 구체적인 양태에 있어서 식품 조성물로서 파악할 수 있다.The composition of the present invention can be identified as a food composition in a specific embodiment.
본 발명의 식품 조성물은 어떠한 형태로도 제조될 수 있으며, 예컨대 차, 쥬스, 탄산음료, 이온음료 등의 음료류, 우유, 요구루트 등의 가공 유류(乳類), 껌류, 떡, 한과, 빵, 과자, 면 등의 식품류, 정제, 캡슐, 환, 과립, 액상, 분말, 편상, 페이스트상, 시럽, 겔, 젤리, 바 등의 건강기능식품 제제류 등으로 제조될 수 있다. 또 본 발명의 식품 조성물은 법률상·기능상의 구분에 있어서 제조?유통 시점의 시행 법규에 부합하는 한 임의의 제품 구분을 띨 수 있다. 예컨대 한국 "건강기능식품에관한법률"에 따른 건강기능식품이거나, 한국 "식품위생법"의 식품공전(식약처 고시 "식품의 기준 및 규격"임)상 각 식품유형에 따른 과자류, 두류, 다류, 음료류, 특수용도식품 등일 수 있다.The food composition of the present invention can be prepared in any form and can be used in various forms such as beverages such as tea, juice, carbonated beverage, ionic drink, processed milk such as milk and request route, gum, rice cake, Such as confectionery, cotton, etc., tablets, capsules, rings, granules, liquids, powders, flakes, pastes, syrups, gels, jellies, bars and the like. In addition, the food composition of the present invention may be classified into any product category as long as it meets the laws and regulations of the time of manufacture and distribution in the legal and functional category. For example, it is a health functional food according to the "Health Functional Food Act" in Korea or the food standard (standard and standard of food notices) of the Food Sanitation Act of Korea. Beverages, special-purpose foods, and the like.
본 발명의 식품 조성물에는 그 유효성분 이외에 식품첨가물이 포함될 수 있다. 식품첨가물은 일반적으로 식품을 제조, 가공 또는 보존함에 있어 식품에 첨가되어 혼합되거나 침윤되는 물질로서 이해될 수 있는데, 식품과 함께 매일 그리고 장기간 섭취되므로 그 안전성이 보장되어야 한다. 식품의 제조·유통을 규율하는 각국 법률(한국에서는 "식품위생법"임)에 따른 식품첨가물공전에는 안전성이 보장된 식품첨가물이 성분 면에서 또는 기능 면에서 한정적으로 규정되어 있다. 한국 식품첨가물공전(식약처 고시 "식품첨가물 기준 및 규격)에서는 식품첨가물이 성분 면에서 화학적 합성품, 천연 첨가물 및 혼합 제제류로 구분되어 규정되어 있는데, 이러한 식품첨가물은 기능 면에 있어서는 감미제, 풍미제, 보존제, 유화제, 산미료, 점증제 등으로 구분된다. The food composition of the present invention may contain food additives in addition to the active ingredients thereof. Food additives are generally understood to be substances that are added to foods and mixed or infiltrated into food in the manufacture, processing or preservation of food, and their safety must be ensured since they are ingested daily with food and for long periods of time. Food additives according to national laws regulating the manufacture and distribution of food (in Korea, the "Food Sanitation Act") are stipulated as safety-guaranteed food additives in terms of ingredients or function. In the Food Additives Ordinance of the Republic of Korea (Food Additives Standards and Standards), the food additives are classified into chemical compounds, natural additives, and mixed preparations in terms of ingredients. These food additives are classified into sweeteners, , Preservatives, emulsifiers, acidulants, and thickeners.
감미제는 식품에 적당한 단맛을 부여하기 위하여 사용되는 것으로, 천연의 것이거나 합성된 것 모두 본 발명의 식품 조성물에 사용할 수 있다. 바람직하게는 천연 감미제를 사용하는 경우인데, 천연 감미제로서는 옥수수 시럽 고형물, 꿀, 수크로오스, 프룩토오스, 락토오스, 말토오스 등의 당 감미제를 들 수 있다. The sweetener is used for imparting a sweet taste suitable for food, and both natural and synthetic sweeteners can be used in the food composition of the present invention. Preferably, natural sweeteners are used. Examples of natural sweeteners include sugar sweeteners such as corn syrup solids, honey, sucrose, fructose, lactose and maltose.
풍미제는 맛이나 향을 좋게 하기 위한 용도로 사용되는 것으로, 천연의 것과 합성된 것 모두 사용될 수 있다. 바람직하게는 천연의 것을 사용하는 경우이다. 천연의 것을 사용할 경우에 풍미 이외에 영양 강화의 목적도 병행할 수 있다. 천연 풍미제로서는 사과, 레몬, 감귤, 포도, 딸기, 복숭아 등에서 얻어진 것이거나 녹차잎, 둥굴레, 대잎, 계피, 국화 잎, 자스민 등에서 얻어진 것일 수 있다. 또 인삼(홍삼), 죽순, 알로에 베라, 은행 등에서 얻어진 것을 사용할 수 있다. 천연 풍미제는 액상의 농축액이나 고형상의 추출물일 수 있다. 경우에 따라서 합성 풍미제가 사용될 수 있는데, 합성 풍미제로서는 에스테르, 알콜, 알데하이드, 테르펜 등이 이용될 수 있다. Flavors are used to improve taste and flavor, and natural and synthetic flavors can be used. Preferably, a natural one is used. When using natural ones, the purpose of nutritional fortification can be performed in addition to the flavor. Examples of natural flavoring agents include those obtained from apples, lemons, citrus fruits, grapes, strawberries, peaches, and the like, or those obtained from green tea leaves, Asiatica, Daegu, Cinnamon, Chrysanthemum leaves and Jasmine. Also, those obtained from ginseng (red ginseng), bamboo shoots, aloe vera, banks and the like can be used. The natural flavoring agent may be a liquid concentrate or a solid form of extract. If desired, a synthetic flavor agent may be used. As the synthetic flavor agent, esters, alcohols, aldehydes, terpenes and the like may be used.
보존제로서는 소르브산칼슘, 소르브산나트륨, 소르브산칼륨, 벤조산칼슘, 벤조산나트륨, 벤조산칼륨, EDTA(에틸렌디아민테트라아세트산) 등이 사용될 수 있고, 또 유화제로서는 아카시아검, 카르복시메틸셀룰로스, 잔탄검, 펙틴 등이 사용될 수 있으며, 산미료로서는 연산, 말산, 푸마르산, 아디프산, 인산, 글루콘산, 타르타르산, 아스코르브산, 아세트산, 인산 등이 사용될 수 있다. 산미료는 맛을 증진시키는 목적 이외에 미생물의 증식을 억제할 목적으로 식품 조성물이 적정 산도로 되도록 첨가될 수 있다. 점증제로서는 현탁화 구현제, 침강제, 겔형성제, 팽화제 등이 사용될 수 있다.As the preservative, calcium sorbate, sodium sorbate, potassium sorbate, calcium benzoate, sodium benzoate, potassium benzoate, EDTA (ethylenediaminetetraacetic acid) and the like can be used, and as the emulsifier, acacia gum, carboxymethyl cellulose, xanthan gum, pectin And acidulant, malic acid, fumaric acid, adipic acid, phosphoric acid, gluconic acid, tartaric acid, ascorbic acid, acetic acid, phosphoric acid and the like may be used as the acidulant. The acidulant may be added so that the food composition has a proper acidity for the purpose of inhibiting the growth of microorganisms other than the purpose of enhancing the taste. Examples of the thickening agent include suspending agents, sedimentation agents, gel-forming agents, bulking agents and the like.
본 발명의 식품 조성물은 전술한 바의 식품첨가물 이외에, 기능성과 영양성을 보충·보강할 목적으로 당업계에 공지되고 식품첨가물로서 안정성이 보장된 생리활성 물질이나 미네랄류를 포함할 수 있다.The food composition of the present invention may contain physiologically active substances or minerals which are known in the art and which are stable as a food additive, for the purpose of supplementing and reinforcing the functionality and nutrition, in addition to the above-mentioned food additives.
그러한 생리활성 물질로서는 녹차 등에 포함된 카테킨류, 비타민 B1, 비타민 C, 비타민 E, 비타민 B12 등의 비타민류, 토코페롤, 디벤조일티아민 등을 들 수 있으며, 미네랄류로서는 구연산칼슘 등의 칼슘 제제, 스테아린산마그네슘 등의 마그네슘 제제, 구연산철 등의 철 제제, 염화크롬, 요오드칼륨, 셀레늄, 게르마늄, 바나듐, 아연 등을 들 수 있다. Examples of such physiologically active substances include catechins contained in green tea and the like, vitamins such as vitamin B1, vitamin C, vitamin E and vitamin B12, tocopherol, dibenzoyl thiamine, etc. Examples of minerals include calcium preparations such as calcium citrate, magnesium stearate , Iron preparations such as iron citrate, chromium chloride, potassium iodide, selenium, germanium, vanadium, zinc and the like.
본 발명의 식품 조성물에는 전술한 바의 식품첨가물이 제품 유형에 따라 그 첨가 목적을 달성할 수 있는 적량으로 포함될 수 있다.The food composition of the present invention may contain an appropriate amount of the above-mentioned food additives according to the product type so as to achieve the purpose of addition thereof.
본 발명의 식품 조성물에 포함될 수 있는 기타의 식품첨가물과 관련하여서는 각국 법률에 따른 식품공전이나 식품첨가물공전을 참조할 수 있다.With regard to other food additives that may be included in the food composition of the present invention, reference may be made to the Food Code or the Food Additive Code of the respective country.
본 발명의 조성물은 다른 구체적인 양태에 있어서는 약제학적 조성물로 파악될 수 있다.In another specific embodiment, the composition of the present invention can be identified as a pharmaceutical composition.
본 발명의 약제학적 조성물은 유효성분 이외에 약제학적으로 허용되는 담체를 포함하여 당업계에 공지된 통상의 방법으로 투여 경로에 따라 경구용 제형 또는 비경구용 제형으로 제조될 수 있다. 여기서 "약제학적으로 허용되는" 의미는 유효성분의 활성을 억제하지 않으면서 적용(처방) 대상이 적응 가능한 이상의 독성을 지니지 않는다는 의미이다.The pharmaceutical composition of the present invention may be prepared into oral formulations or parenteral formulations according to the route of administration by conventional methods known in the art, including pharmaceutically acceptable carriers in addition to the active ingredient. The term " pharmaceutically acceptable " as used herein means that the application (prescribing) subject does not have the above-mentioned toxicity that is adaptable without inhibiting the activity of the active ingredient.
본 발명의 약제학적 조성물이 경구용 제형으로 제조될 경우, 적합한 담체와 함께 당업계에 공지된 방법에 따라 분말, 과립, 정제, 환제, 당의정제, 캡슐제, 액제, 겔제, 시럽제, 현탁액, 웨이퍼 등의 제형으로 제조될 수 있다. 이때 약제학적으로 허용되는 적합한 담체의 예로서는 락토스, 글루코오스, 슈크로스, 덱스트로스, 솔비톨, 만니톨, 자일리톨 등의 당류, 옥수수 전분, 감자 전분, 밀 전분 등의 전분류, 셀룰로오스, 메틸셀룰로오스, 에틸셀룰로오스, 나트륨 카르복시메틸셀룰로오스, 하이드록시프로필메틸셀룰로오스 등의 셀룰로오스류, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 마그네슘 스테아레이트, 광물유, 맥아, 젤라틴, 탈크, 폴리올, 식물성유 등을 들 수 있다. 제제화활 경우 필요에 따라 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 및/또는 부형제를 포함하여 제제화할 수 있다.When the pharmaceutical composition of the present invention is prepared into an oral formulation, it may be formulated into powder, granules, tablets, pills, sugar tablets, capsules, solutions, gels, syrups, suspensions, wafers And the like. Examples of suitable pharmaceutically acceptable carriers include sugars such as lactose, glucose, sucrose, dextrose, sorbitol, mannitol, xylitol, starch such as corn starch, potato starch and wheat starch, cellulose, methylcellulose, ethylcellulose, Cellulose derivatives such as sodium carboxymethyl cellulose and hydroxypropylmethyl cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, magnesium stearate, mineral oil, malt, gelatin, talc, And the like. In case of formulation, a diluent such as a filler, an extender, a binder, a wetting agent, a disintegrant, a surfactant, and / or an excipient may be formulated according to need.
본 발명의 약제학적 조성물이 비경구용 제형으로 제조될 경우, 적합한 담체와 함께 당업계에 공지된 방법에 따라 점안제, 주사제, 경피 투여제, 비강 흡입제, 좌제의 형태로 제제화될 수 있다. 점안제로 제제화활 경우 적합한 담체로서는 멸균수, 식염수, 5% 덱스트로스 같은 등장 용액 등을 사용할 수 있으며 필요에 따라 염화벤잘코늄, 메필파라벤, 에틸파라벤 등을 방부 목적으로 첨가할 수 있다. 주사제로 제제화할 경우 적합한 담체로서는 멸균수, 에탄올, 글리세롤이나 프로필렌 글리콜 등의 폴리올 또는 이들의 혼합물을 사용할 수 있으며, 바람직하게는 링거 용액, 트리에탄올 아민이 함유된 PBS(phosphate buffered saline)나 주사용 멸균수, 5% 덱스트로스 같은 등장 용액 등을 사용할 수 있다. 경피 투여제로 제제화할 경우 연고제, 크림제, 로션제, 겔제, 외용액제, 파스타제, 리니멘트제, 에어롤제 등의 형태로 제제화할 수 있다. 비강 흡입제의 경우 디클로로플루오로메탄, 트리클로로플루오로메탄, 디클로로테트라플루오로에탄, 이산화탄소 등의 적합한 추진제를 사용하여 에어로졸 스프레이 형태로 제제화할 수 있으며, 좌제로 제제화할 경우 그 기제로는 위텝솔(witepsol), 트윈(tween) 61, 폴리에틸렌글리콜류, 카카오지, 라우린지, 폴리옥시에틸렌 소르비탄 지방산 에스테르류, 폴리옥시에틸렌 스테아레이트류, 소르비탄 지방산 에스테르류 등을 사용할 수 있다.When the pharmaceutical composition of the present invention is prepared into a parenteral dosage form, it may be formulated in the form of eye drops, injections, transdermal drug delivery, nasal aspirates, suppositories according to methods known in the art together with suitable carriers. In the case of formulation with eyedrops, sterile water, saline, isotonic solution such as 5% dextrose may be used. If necessary, benzalkonium chloride, mepilparaben, ethylparaben and the like may be added for preservative purposes. As the carrier suitable for injection preparation, sterilized water, ethanol, polyol such as glycerol or propylene glycol, or a mixture thereof, may be used, and preferably, a solution of Ringer's solution, phosphate buffered saline containing triethanolamine or sterilized by injection Water, or isotonic solution such as 5% dextrose may be used. When formulated with a transdermal preparation, it can be formulated in the form of ointments, creams, lotions, gels, external liquids, pastes, liniments, and air-lozenges. The nasal inhalant may be formulated in the form of an aerosol spray using a suitable propellant such as dichlorofluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide, etc. When formulated as a suppository, witepsol, tween 61, polyethylene glycols, cacao butter, laurin, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene stearates, and sorbitan fatty acid esters.
약제학적 조성물의 구체적인 제제화와 관련하여서는 당업계에 공지되어 있으며, 예컨대 문헌[Remington's Pharmaceutical Sciences(19th ed., 1995)] 등을 참조할 수 있다. 상기 문헌은 본 명세서의 일부로서 간주 된다.The formulation of pharmaceutical compositions is well known in the art and can be found, for example, in Remington ' s Pharmaceutical Sciences (19th ed., 1995). This document is considered part of this specification.
본 발명의 약제학적 조성물의 바람직한 투여량은 환자의 상태, 체중, 성별, 연령, 환자의 중증도, 투여 경로에 따라 1일 0.001mg/kg ~ 10g/kg 범위, 바람직하게는 0.001mg/kg ~ 1g/kg 범위일 수 있다. 투여는 1일 1회 또는 수회로 나누어 이루어질 수 있다. 이러한 투여량은 어떠한 측면으로든 본 발명의 범위를 제한하는 것으로 해석되어서는 아니 된다. The preferred dosage of the pharmaceutical composition of the present invention is 0.001 mg / kg to 10 g / kg per day, preferably 0.001 mg / kg to 1 g / day, depending on the patient's condition, body weight, sex, age, / kg < / RTI > The administration can be carried out once or several times a day. Such dosages should in no way be construed as limiting the scope of the invention.
전술한 바와 같이, 본 발명에 따르면 디플로르에토하이드록시카르마롤(Diphlorethohydroxycarmalol, DPHC)를 이용한 운동 능력 개선용 조성물을 제공할 수 있다. 본 발명의 조성물은 식품 또는 약품으로 제품화될 수 있다. As described above, according to the present invention, it is possible to provide a composition for improving exercise capacity using dihydrofluorohydroxycarmalol (DPHC). The composition of the present invention can be commercialized as food or medicine.
도 1은 5일 분화된 근원세포인 C2C12에서 DPHC가 세포 내 칼슘 이온(Ca2+) 농도를 상승시킴을 보여주는 결과이다.
도 2는 5일 분화된 근원세포인 C2C12에서 DPHC가 글루코오스의 흡수를 유도함을 보여주는 결과이다.
도 3은 제브라피시 배아에서의 DPHC의 독성 데스트 결과이다.
도 4는 DPHC가 제브라피시 세포 내 칼슘 이온(Ca2+) 농도를 상승시킴을 보여주는 결과이다.
도 5는 DPHC가 제브라피시 근육 내로의 글루코오스 유입을 유도함을 보여주는 결과이다. FIG. 1 shows that DPHC increases intracellular calcium ion (Ca2 +) concentration in C2C12, which is a 5-day differentiated source cell.
FIG. 2 is a graph showing that DPHC induces glucose uptake in C2C12, a 5-day differentiated source cell.
Figure 3 shows the toxicity results of DPHC in zebrafish embryos.
Figure 4 shows that DPHC increases the calcium ion (Ca < 2 + >) concentration in zebrafish cells.
Figure 5 shows that DPHC induces glucose uptake into the zebrafish muscle.
이하 본 발명을 실시예를 설명한다. 그러나 본 발명의 범위가 이러한 실시예에 한정되는 것은 아니다.Hereinafter, embodiments of the present invention will be described. However, the scope of the present invention is not limited to these embodiments.
<실시예> DPHC의 운동수행능력 향상 활성 실험EXAMPLES Experiments to improve exercise performance of DPHC
1. 실험 방법1. Experimental Method
1.1 생체 외(in vitro) 실험1.1 In vitro experiments
1.1.1 C2C12 세포 배양과 분화1.1.1 C2C12 cell culture and differentiation
마우스 유래 근원세포인 C2C12 세포(ATCC, Manassas, VA, USA)는 10% FBS와 항생제가 포함된 DMEM(Dulbeccos Modified Eagle's Media) 배지에 현탁하여 37℃, 5% CO2 조건에서 배양기에서 배양했다. 세포 밀도가 80%가 되면, C2C12세포는 2% 마혈청(horse serum)과 저농도 글루코오스가 포함된 DMEM 배지에서 5일 동안 분화시켰으며 배지는 3일마다 교체하였다. 분화된 세포는 저농도의 글루코오스가 포함된 무혈청 DMEM 배지에서 12시간 동안 혈청 기아 상태(starvation)를 유지시키고, PBS 용액으로 세척한 후, 저농도의 글루코오스가 포함된 새로운 무혈청 DMEM 배지에서 24시간 동안 시료(DPHC)와 반응시켰다.C2C12 cells (ATCC, Manassas, Va., USA) were suspended in DMEM (Dulbeccos Modified Eagle's Media) medium containing 10% FBS and antibiotics and cultured in an incubator at 37 ° C and 5% CO2. When the cell density reached 80%, C2C12 cells were differentiated for 5 days in DMEM medium containing 2% horse serum and low glucose, and the medium was changed every 3 days. The differentiated cells were maintained in serum-free DMEM medium containing low glucose for 12 hours, washed with PBS solution, and cultured in fresh serum-free DMEM medium containing low glucose for 24 hours And reacted with a sample (DPHC).
1.1.2 C2C12 세포에서 Fluo4를 이용한 세포 내 칼슘 농도 측정1.1.2 Measurement of intracellular calcium concentration using Fluo4 in C2C12 cells
세포 내 칼슘 농도는 칼슘 민감성 프로브 Fluo4를, 칼슘 미포함된 1X PSS 버퍼(140mM 염화나트륨, 5.9mM 염화칼륨, 1.8mM 염화마그네슘, 10mM HEPES, 11.5mM 글루코오스, 1.2mM 인산수소나트륨, 5mM 탄산수소나트륨 포함 생리식염수)에 희석하여 사용하였다. C2C12세포를 Fluo4와 37℃에서 30분간 반응시키고, 0.1% BSA가 포함된 1X PSS 버퍼를 첨가하였다. 처음 5분 동안의 기저 형광을 기록하고, 0.1% 소혈청 알부민과 함께 1X PSS 버퍼를 처리하거나 DPHC를 농도별(10, 100, 300 및 1000 ㎍/ml)로 처리하였다. 10분 동안 형광을 다시 기록한 후, 세포에 바로 고농도 포타슘 용액(100mM KCl), 칼슘(2mM CaCl2)이 포함된 1X PSS 버퍼(0.1% BSA 포함))를, 0.1% 소혈청 알부민과 함께 첨가하여, 세포막 전압을 탈분극시켜 칼슘 통로를 활성화 시켰다. 시간에 따른 형광 강도를 현미경으로 관찰하였다(이때 형광 강도는 세포내 칼슘 이온 농도를 반영한다).The intracellular calcium concentration was determined by incubating the calcium-sensitive probe Fluo4 in a physiological saline solution containing 1 mM PSS buffer (140 mM sodium chloride, 5.9 mM potassium chloride, 1.8 mM magnesium chloride, 10 mM HEPES, 11.5 mM glucose, 1.2 mM sodium hydrogen phosphate, ). C2C12 cells were reacted with Fluo4 at 37 ° C for 30 minutes and 1 × PSS buffer containing 0.1% BSA was added. Baseline fluorescence was recorded for the first 5 minutes, treated with 1X PSS buffer with 0.1% bovine serum albumin, or treated with DPHC (10, 100, 300 and 1000 ug / ml). After re-recording the fluorescence for 10 minutes, the cells were immediately added with 1X PSS buffer (with 0.1% BSA) containing 0.1% bovine serum albumin and high concentration of potassium solution (100 mM KCl), calcium (2 mM CaCl2) The cell membrane voltage was depolarized to activate the calcium channel. Fluorescence intensity with time was observed with a microscope (fluorescence intensity reflects intracellular calcium ion concentration).
1.1.3 C2C12 세포의 당 흡수 측정1.1.3 Measurement of glucose uptake by C2C12 cells
근원세포 C2C12의 당 흡수는 2-NBDG((2-(N-(7-Nitrobenz-2 oxa-1,3-diazol-4-yl)Amino)-2-Deoxyglucose)를 이용한 분석법(2NBDG assay, Diabetes technology & therapeutics, 2011, 13(7):743-751)으로 마이크로플레이트 측정기(microplate reader)를 이용하여 측정하였다. 분화된 세포에 10μM 농도의 형광물질인 2-NBDG(2-[N-(7-160 nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose)를 처리한 후, 37℃에서 24시간 동안 반응시켰다. 그리고 난 후, PBS로 두번 세척하고 무혈청 배지를 추가한 후, 마이크로플레이트 측정기(microplate reader)에서 여기 파장 485nm, 방출 파장 530nm에서 형광 강도를 측정하였다. 세포에 의해 2-NBDG가 흡수되면, 2-NBDG는 비형광성 유도체로 전환되기 때문에 형광 감소를 정량함에 의해 당 흡수를 측정할 수 있다. The glucose uptake of the source cell C2C12 was assayed using the 2NBDG assay, a method using 2-NBDG ((2- (N- (7-Nitrobenz-2 oxa-1,3-diazol- 2-NBDG (2- [N- (7-N, N-dimethylaminopyridine)], a fluorescent substance at a concentration of 10 μM, was added to the differentiated cells using a microplate reader. The reaction was carried out for 24 hours at 37 ° C. After that, the cells were treated with PBS twice with PBS After washing and adding serum-free medium, the fluorescence intensity was measured at 485 nm excitation wavelength and 530 nm emission wavelength in a microplate reader. When 2-NBDG was absorbed by the cells, 2-NBDG was converted into a non- The glucose uptake can be measured by quantifying fluorescence reduction.
1.2 동물실험1.2 Animal experiments
성체 제브라피시(Zebrafish)는 시중(제주 아쿠라이룸, 제주도, 한국)에서 구입하여 실험에 사용하였으며, 28.5±1℃ 온도 및 14/10시간 명암 주기 조건의 3.5L 아크릴 탱크에서 관리하며 1일 2회 식이(Tetra GmgH D-49304 Melle, made in Germany)를 급여하였다. 실험은 제주대학교 동물실험윤리위원회의 승인하에 이루어졌다.The zebrafish was purchased from the city (Jeju Island, Jeju Island, Korea) and used in the experiment. The zebrafish was maintained in a 3.5L acrylic tank at 28.5 ± 1 ℃ and 14/10 hour shading condition. (Tetra GmgH D-49304 Melle, made in Germany). The experiment was conducted with the approval of the Ethical Committee for Animal Experiments at Cheju National University.
1.2.1 제브라피시 배아에서 DPHC의 독성 테스트1.2.1 Toxicity testing of DPHC in zebrafish embryos
독성이 없는 DPHC의 농도를 확인하고자 제브라피시 배아에 대해 생존율을 평가하였다. 수정 후 4시간이 경과한 배아(n=15)를, 배아 배지(60 ppm의 염을 포함하는 증류수) 950㎕와 DPHC(0.01, 0.1, 1, 및 10㎍/㎖) 50㎕이 함유된 12 웰 플레이트의 각 웰에 옮기고, 수정 후 168시간 동안 DPHC에 노출된 제브라피시 배아의 생존율을 측정하였다.Survival rates were evaluated for zebrafish embryos to determine the concentration of DPHC without toxicity. The embryo (n = 15), which had lapsed 4 hours after fertilization, was transfected with 950 ㎕ of embryo medium (distilled water containing 60 ppm salt) and 12 쨉 l of DPHC (0.01, 0.1, 1 and 10 / / Were transferred to each well of the well plate and the survival rate of the zebrafish embryo exposed to DPHC for 168 hours after the fertilization was measured.
1.2.2. 제브라피시 배아에서 flou4를 이용한 세포 내 칼슘 농도 측정1.2.2. Measurement of intracellular calcium concentration using flou4 in zebrafish embryos
제브라피시 배아의 세포 내 칼슘 농도 측정은, 칼슘 민감성 Fluo4 프로브를 이용하여 측정하였다. 제브라피시 배아를 Fluo4와 28.5±1℃ 온도에서 30분 동안 반응시킨 후, DPHC(0.6, 3, 및 6㎍/ml)를 처리하였다. 칼슘의 세포 내 진입을 억제시키기 위해 칼슘 킬레이트제인 BAPTA-AM 0.1mM를 fluo4 처리하기 전 1시간 동안 미리 반응시켰다. 실험군은 무처리군(N), Fluo4 단독 처리군(F), DPHC 단독 처리군(0.6, 3, 및 6 ㎍/ml), Fluo4와 DPHC 처리군(0.6, 3, 및 6 ㎍/ml), Fluo4와 BAPTA-AM 그리고 DPHC 처리군(6 ㎍/ml)으로 구성하였다.The intracellular calcium concentration of the zebrafish embryo was measured using a calcium-sensitive Fluo4 probe. The zebrafish embryos were reacted with Fluo4 at 28.5 ± 1 ° C for 30 minutes and then treated with DPHC (0.6, 3, and 6 μg / ml). To inhibit the intracellular entry of calcium, 0.1 mM calcium BAPTA-AM was reacted for 1 hour before the fluo4 treatment. In the experimental group, the treatment group (N), Fluo4 alone treatment group (F), DPHC alone treatment group (0.6, 3, and 6 ㎍ / ml), Fluo4 and DPHC treated groups (0.6, Fluo4 and BAPTA-AM and DPHC-treated group (6 ㎍ / ml).
1.2.3. 혈중 글루코오스 레벨 측정1.2.3. Blood glucose level measurement
야생형 성체 제브라피시를 2mg/ml의 알록산(alloxan)에 1시간 동안 반응시킨 후, 인슐린이 없는 상태에서 1% 글루코오스에 1시간 반응시켰다. 이후 반응용액을 물로 바꾸고 1시간 동안 반응시킨 후, DPHC, 메트포르민(Metformin), BAPTA-AM을 90분 동안 처리하였다. 실험군은 무처리군, 알록산 처리군(control), 알록산과 DPHC(0.3㎍/g body weight) 처리군, 알록산과 메트포르민(5㎍/g body weight) 처리군, 알록산과 BAPTA-AM(3㎍/g body weight) 처리군, 및 알록산과 BAPTA-AM(3㎍/g body weight) 그리고 DPHC(0.3㎍/g body weight) 처리군으로 구성하였다.The wild-type adult zebrafish was reacted with 2 mg / ml of alloxan for 1 hour and reacted with 1% glucose for 1 hour in the absence of insulin. Then, the reaction solution was changed to water and reacted for 1 hour. Then, DPHC, metformin and BAPTA-AM were treated for 90 minutes. The experimental group was divided into three groups: untreated group, alooxan treated group, alooxan treated with DPHC (0.3 μg / g body weight), alooxan and metformin (5 μg / g body weight) treated group, alloxan and BAPTA- / g body weight), and alloxan, BAPTA-AM (3 μg / g body weight) and DPHC (0.3 μg / g body weight).
2. 실험 결과2. Experimental results
2.1 C2C12세포의 세포 내 칼슘이온 레벨 측정 결과2.1 Intracellular calcium ion level measurement of C2C12 cells
5일 분화된 C2C12 세포에서, DPHC에 의한 세포 내 칼슘 이온 증가를 측정하여 결과를 도 1에 나타내었다. DPHC에 의한 세포 내 칼슘 이온 농도 증가 확인을 위해 5일간 분화한 C2C12 세포에 24시간 DPHC를 처리하여 15분 동안 칼슘 이온의 농도를 확인한 결과, DPHC 처리에 의하여 농도 의존적으로 유의한 세포 내 칼슘 이온 농도의 증가가 관찰 되었다.In 5 day-differentiated C2C12 cells, intracellular calcium ion increase by DPHC was measured and the results are shown in Fig. In order to confirm the increase of intracellular calcium ion concentration by DPHC, C2C12 cells differentiated for 5 days were treated with DPHC for 24 hours and the concentration of calcium ion was observed for 15 minutes. As a result, the intracellular calcium ion concentration Was observed.
2.2 C2C12세포의 당 흡수 측정 결과2.2 Results of glucose uptake assay of C2C12 cells
분화된 C2C12 세포에서, DPHC에 의한 글루코오스 흡수능을 측정하여 결과를 도 2에 나타내었다. 도 2을 참조하여 보면, DPHC를 24시간 처리한 C2C12 세포 내의 글루코오스 흡수가 DPHC의 처리 농도에 의존적으로 유의하게 증가함을 알 수 있다. 이는 DPHC가 근세포의 수축과 관련하여 에너지 공급을 필요한 포도당의 흡수를 촉진할 수 있음을 보여주는 결과라 할 수 있다. In the differentiated C2C12 cells, the ability of glucose uptake by DPHC was measured and the results are shown in Fig. Referring to FIG. 2, it can be seen that the glucose uptake in C2C12 cells treated with DPHC for 24 hours is significantly increased depending on the treatment concentration of DPHC. This is a result of showing that DPHC can accelerate the absorption of glucose required for energy supply in relation to contraction of muscle cells.
2.3 제브라피시 배아에서의 DPHC 독성 테스트 결과2.3 DPHC toxicity test results in zebrafish embryos
독성이 없는 DPHC의 농도를 확인하고자 제브라피시 배아에 대해 생존율을 평가하고 그 결과를 도 3에 나타내었다. 도 3에서 보여지는 바와 같이 1㎍/ml 이하에서 약 90% 이상의 생존율을 보였다.Survival rates were evaluated for zebrafish embryos to determine the concentration of DPHC without toxicity, and the results are shown in FIG. As shown in FIG. 3, the survival rate was about 90% or more at 1 μg / ml or less.
2.4 제브라피시의 DPHC에 의한 세포 내 칼슘 농도 변화 측정 결과2.4 Measurement of intracellular calcium concentration by zebrafish DPHC
DPHC에 의한 제브라피시 배아 세포 내 칼슘 변화를 fluo4로 관찰한 결과를 도 4에 나타내었다. 도 4을 참조하여 보면, 무처리군(N)과 비교하였을 때 Fluo4 처리군(F)은 복부 주의로 유의적인 차이가 있음을 확인하였으나, DPHC만을 처리한 실험군은 무처리군(N) 또는 Fluo4 처리군(F)과 비교하여 특별한 변화가 나타내지 않았다(도 4의 왼쪽). 이는 DPHC에 의한 형광 변화는 없음을 의미한다. 그리고 DPHC와 Fluo4을 함께 처리군 실험군은 Fluo4 처리군(F)과 비교하여 형광의 유의적인 증가가 관찰됨에 따라 세포 내 Ca2+ 농도가 DPHC 처리로 인해 증가하였음을 알 수 있고, 또 칼슘 킬레이트제인 BAPTA-AM를 DPHC와 함께 처리한 경우는 세포 내 Ca2+ 유입이 억제됨에 따라 형광이 감소하였음을 확인할 수 있다(도 4의 오른쪽).Fig. 4 shows the results of observing calcium change in zebrafish embryo cells by DPHC with fluo4. 4, when compared to the non-treated group (N), it was confirmed that the Fluo4 treated group (F) was significantly different from that of the abdominal group. However, in the DPHC treated group, There was no specific change compared with the treatment group (F) (left side of FIG. 4). This means that there is no fluorescence change by DPHC. In addition, DPHC and Fluo4 treatment groups showed a significant increase in fluorescence as compared with Fluo4 treatment group (F), indicating that the intracellular Ca2 + concentration was increased due to DPHC treatment, and that the calcium chelating agent BAPTA- When AM was treated with DPHC, the intracellular Ca < 2 + > inflow was inhibited, indicating that fluorescence decreased (right side of FIG. 4).
2.5 제브라시피의 DPHC에 의한 혈중 글루코오스 변화 측정 결과2.5 Results of measurement of blood glucose change by zebrafish DPHC
DPHC가, 세포 내 칼슘 이온 농도 상승에 따라, 근수축 등에 필요한 에너지원인 글루코오스 흡수를 유도하는지 확인하기 위해, 알록산 처리에 의해 인슐린 분비가 감소된 제브라피시 성체에 글루코오스를 주입하여 DPHC에 의한 근육 내로의 글루코오스 유입 유도 여부를 혈중 농도로 확인한 결과를, 도 5에 나타내었다. 에너지원인 글루코오스의 혈중 농도의 감소는 근육 등의 조직으로의 포도당 유입이 지표로 알려져 있다(Diabetes 30 (1981) 1000-1007; Biochemical and Biophysical Research Communications 420 (2012) 576-581; Nat. Rev. Mol. Cell Biol. 7 (2006) 85-96; Eur. J. Cell Biol. 87 (2008) 337-351).In order to confirm that DPHC induces glucose uptake, which is an energy source necessary for muscle contraction and the like, in accordance with an increase in intracellular calcium ion concentration, glucose is injected into the zebrafish adduct with reduced insulin secretion by alloying treatment, The results of confirming the induction of the glucose uptake by the blood concentration are shown in Fig. Reduced blood glucose levels in energy sources are known to be indicative of glucose uptake into tissues such as muscle (Diabetes 30 (1981) 1000-1007; Biochemical and Biophysical Research Communications 420 (2012) 576-581; Nat. Rev. Mol Cell Biol 7 (2006) 85-96; Eur., J. Cell Biol 87 (2008) 337-351).
알록산을 처리한 제브라피시 성체의 혈중 글루코오스는 DPHC를 처리할 경우 유의적으로 감소하였으며, 이러한 효과는 혈당 조절을 위해 시중에 사용되는 메트포르민(metformin)과 비교하였을 때 유사한 수준로 나타났다. 특히 이는 DPHC의 처리 농도가 0.3㎍/g임을 고려할 때, 메트포르민의 처리 농도인 5㎍/g보다 16.7배 낮은 농도로 유사한 수준의 글루코오스 세포 내 유입 유도 효과를 기대할 수 있음을 의미한다. Glucose in the zebras administrated with alloxan was significantly decreased when treated with DPHC, and this effect was similar to that of metformin used for the control of blood sugar. Especially, considering that the treatment concentration of DPHC is 0.3 μg / g, it means that the effect of inducing a similar level of intracellular glucose uptake can be expected at a concentration of 16.7 times lower than 5 μg / g of metformin treatment.
또한 DPHC의 글루코오스 유입 유도 효과가 세포 내 칼슘 농도의 상승과 관련이 있는지 확인하기 위해, 칼슘 킬레이트제인 BAPTA-AM을 함께 처리한 결과, 알록산 처리군과 BAPTA-AM 처리군 및 DPHC와 BAPTA-AM 처리군 사이에 혈중 글루코오스의 농도가 큰 차이가 없음이 관찰되어, DPHC에 의해 세포 내 칼슘 농도가 상승함에 의해 제브라피시 성체의 글루코오스 흡수가 촉진되었음을 확인할 수 있다.In addition, in order to confirm whether the DPHC-induced effect of glucose uptake was related to the increase of intracellular calcium concentration, the calcium chelating agent BAPTA-AM was treated together with the aloxic acid treatment group, BAPTA-AM treatment group and DPHC and BAPTA- There was no significant difference in the blood glucose concentration between the treatment groups, and it was confirmed that the intracellular calcium concentration was increased by DPHC, thereby accelerating the glucose uptake of the zebrafish adult.
Claims (3)
A composition for improving athletic performance comprising di-fluoroethoxycarumrol, a solvate thereof or a hydrate thereof as an active ingredient.
상기 조성물은 식품 조성물인 것을 특징으로 하는 운동 능력 개선용 조성물.
The method according to claim 1,
Wherein the composition is a food composition.
상기 조성물은 약제학적 조성물인 것을 특징으로 하는 운동 능력 개선용 조성물.
The method according to claim 1,
Wherein the composition is a pharmaceutical composition.
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| US16/192,216 US20190367437A1 (en) | 2018-06-04 | 2018-11-15 | Novel Compound Hexadecaphlorethol Isolated From Ishige Okamurae And Use Thereof |
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| KR101964080B1 (en) * | 2018-06-04 | 2019-04-01 | 제주대학교 산학협력단 | Composition for Improvement of Exercise Performance Using Novel Compound hexadecaphlorethol Isolated from Ishige okamurae |
| KR102317113B1 (en) * | 2021-04-28 | 2021-10-22 | 제주대학교 산학협력단 | Compostion for Improving Muscle Strength or Muscular Atrophy Using an Extract of Ishige okamurae or Diphlorethohydroxycarmalol |
| CN116369249A (en) * | 2023-01-13 | 2023-07-04 | 四川轻化工大学 | Construction method of zebra fish enteritis model |
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| Diphlorethohydroxycarmalol induces calcium-dependent glucose uptake of muscle in in-vitro and in-vivo models, 한국수산과학회 2018년도 춘계학술대회, 97-97(2018.5.)* |
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| KR101964080B1 (en) * | 2018-06-04 | 2019-04-01 | 제주대학교 산학협력단 | Composition for Improvement of Exercise Performance Using Novel Compound hexadecaphlorethol Isolated from Ishige okamurae |
| KR102317113B1 (en) * | 2021-04-28 | 2021-10-22 | 제주대학교 산학협력단 | Compostion for Improving Muscle Strength or Muscular Atrophy Using an Extract of Ishige okamurae or Diphlorethohydroxycarmalol |
| CN116369249A (en) * | 2023-01-13 | 2023-07-04 | 四川轻化工大学 | Construction method of zebra fish enteritis model |
| CN116369249B (en) * | 2023-01-13 | 2024-05-17 | 四川轻化工大学 | Construction method of zebra fish enteritis model |
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