KR101556524B1 - Composition for thrombotic disease containing Vitis labruscana extract - Google Patents
Composition for thrombotic disease containing Vitis labruscana extract Download PDFInfo
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- KR101556524B1 KR101556524B1 KR1020140035464A KR20140035464A KR101556524B1 KR 101556524 B1 KR101556524 B1 KR 101556524B1 KR 1020140035464 A KR1020140035464 A KR 1020140035464A KR 20140035464 A KR20140035464 A KR 20140035464A KR 101556524 B1 KR101556524 B1 KR 101556524B1
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- South Korea
- Prior art keywords
- extract
- blood
- composition
- vitis
- leaf
- Prior art date
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- 239000000284 extract Substances 0.000 title claims abstract description 56
- 239000000203 mixture Substances 0.000 title claims abstract description 29
- 208000007536 Thrombosis Diseases 0.000 title claims abstract description 22
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Abstract
Description
본 발명은 비티스 라브루스카나의 잎 추출물을 포함하는 혈전 질환용 조성물 관한 것이다.The present invention relates to a composition for thrombotic diseases comprising a leaf extract of Vitislavus vulgaris.
혈액순환이란 혈액이 심장을 중심으로 혈관을 따라 신체를 순환하는 것으로 각 기관 및 조직에 산소와 영양을 공급하고 대사산물을 방출하며, 여러 내분비선에서 호르몬을 운반하여 특정기관의 기능을 조절하며 그밖에 체온조절, 삼투압조절, 수분조절 등의 기능을 수행하는 과정이다. Blood circulation means that blood circulates the body along the blood vessels around the heart, supplying oxygen and nutrients to each organ and tissues, releasing metabolites, transporting hormones from various endocrine glands to regulate the functions of specific organs, Regulation, osmotic pressure control, and moisture control.
혈액순환 장애란 심장에서 펌프되어 나온 혈액이 동맥, 모세혈관, 정맥을 거쳐 다시 심장으로 돌아오는데 혈관이 탄력을 잃고 내벽에 혈전이나 콜레스테롤 등이 침착되어 혈관 내강이 좁아져 혈액 순환이 원활히 이루어지지 못하는 것을 말한다. 혈액순환 장애는 손발이 차고 저림, 뒷목 당김, 어깨 결림, 기억력 감퇴, 무기력, 집중력 약화, 현기증 및 만성 피로 등을 유발하여 정상적인 생활을 어렵게 하며 이로 인해 고혈압, 동맥경화증, 심장병, 뇌졸중 등이 발생할 수 있으므로 예방 및 관리가 필요하다. Blood circulation disorder The blood that is pumped out from the heart returns to the heart through the arteries, capillaries, and veins. The blood vessels lose their elasticity and blood clots or cholesterol are deposited on the inner walls of the blood vessels. It says. Blood circulation disorder can cause normal life by causing limbs and limbs, pulling back, neck stiffness, loss of memory, lethargy, weakness of concentration, dizziness and chronic fatigue, resulting in hypertension, arteriosclerosis, heart disease, stroke Therefore, prevention and management are necessary.
생체 내에서 혈액은 응고 작용과 용해 작용이 균형을 이룸으로써 항상성을 유지하며 정상적인 상태에서는 그 흐름이 방해받지 않는다. 그러나 여러 가지 요인으로 이러한 평형 상태가 무너지면 혈액의 흐름이 방해를 받아 심혈관계 질환이 발생하게 된다. 혈관 내벽의 콜라겐이 노출되면 일차적으로 혈액 중의 혈소판이 점착(adhension) 및 활성화(activation)되고 혈소판에서 분비되는 세로토닌(serotonin), 아데노신 디포스페이트(adenosine dephosphate, ADP) 및 트롬복산 A2(Thromboxane A2) 등이 혈소판의 응집(aggregation)을 유도한다. 그 후 2차 과정으로 내인성 경로(intrinsic pathway), 외인성 경로(extrinsic pathway) 및 공통 경로(common pathway)의 혈액 응고계를 활성화시켜 급속히 혈전을 생성하게 된다. 과도하게 생성된 혈전은 혈관 벽에 붙어 굳어져서 혈류의 흐름을 방해하고 혈액의 점도를 낮추어 혈액순환을 원활하지 못하게 한다. 이로 인해 혈액 내 산소나 영양성분이 조직으로 전달되는 것에 지장을 준다. 또한 혈전이 혈류를 따라 이동하다가 심장이나 폐, 뇌의 혈관을 막게 되면 호흡곤란이나 객혈 등을 유발하며 심근경색이나 폐색전증, 뇌졸중 등 여러 형태의 질병을 야기한다. In vivo, blood maintains homeostasis by balancing coagulation and dissolution, and its flow is not interrupted under normal conditions. However, when these equilibrium conditions are broken down by various factors, blood flow is disturbed and cardiovascular disease occurs. When collagen on the inner wall of the blood vessel is exposed, platelets in the blood are firstly adhered to and activated and serotonin, adenosine dephosphate (ADP), and thromboxane A2 (thromboxane A2) secreted from platelets Induces aggregation of platelets. Then, the second step is to activate the blood coagulation system of the intrinsic pathway, the extrinsic pathway and the common pathway to rapidly produce the thrombus. Excessive blood clots build up on the walls of the blood vessels, blocking the flow of blood flow and lowering the viscosity of the blood, making the blood circulation unfavorable. This hinders the transfer of oxygen and nutrients into the tissue. In addition, when the blood clot moves along the blood stream and blocks the blood vessels of the heart, lung, and brain, it causes dyspnea and hemoptysis, and causes various types of diseases such as myocardial infarction, pulmonary embolism, and stroke.
현재 혈전 질환의 예방과 치료를 위해 혈전용해제, 항응고제, 항혈소판제 등이 사용되고 있으나 대표적인 항혈소판제제인 아스피린은 효과는 뛰어나지만 위장관 출혈과 소화성 궤양 등의 부작용을 일으킨다고 알려져 있다. 또한, 항응고제나 혈전용해제로 쓰이는 약물들은 대부분 경구 투여가 불가능하며, 혈전에 대한 선택성이 적어 장기 복용할 경우 용혈현상, 이상 면역반응 등 다양한 부작용을 나타낸다. 따라서 혈소판의 응집 및 혈액 응고를 억제시키거나 혈전을 용해시키는 작용함과 동시에 부작용을 최소화시키는 치료제 개발의 필요성이 대두되고 있다.Thrombolytic agents, anticoagulants, and antiplatelet agents are currently used for the prevention and treatment of thrombotic diseases. However, aspirin, a typical antiplatelet agent, is known to cause side effects such as gastrointestinal hemorrhage and peptic ulceration. In addition, drugs used as anticoagulants and thrombolytic agents are mostly not orally administered, and their selectivity to thrombosis is low. Thus, when they are taken for a long time, they exhibit various side effects such as hemolysis and abnormal immune response. Therefore, there is a need to develop therapeutic agents that inhibit platelet aggregation and blood coagulation, dissolve thrombi, and minimize side effects.
현재 우리나라에서 가장 많이 재배되고 있는 포도 품종은 미국종 포도(Vitis labruca BAILEY)인 캠벨 얼리(Campbell early)이다. 미국 오하이오주에서 켐벨 씨가 무어 얼리(moore early)(Vitis labruca L.)에 벨비디어(belvidere)×머스캣 함부르크(muscat hamburg)(Vitis vinifera L.)를 교배하여 육성한 품종으로 1892년 선발 명명한 품종이며 우리나라에는 1908년 도입되었다. 미네랄이 풍부한 포도는 알칼리성 식품으로 전화당, 주석산, 구연산, 칼륨 및 철분 등과 비타민 A, B1, B2, D 등 영양이 풍부하여 피부미용, 소화불량, 식욕부진에 효과를 나타낸다고 보고되었다.Currently, the most cultivated grape variety in Korea is Campbell early ( Vitis labruca BAILEY). Campbell, in Ohio, USA, named a breed in 1892 for cultivating and breeding belvidere muscat hamburg ( Vitis vinifera L.) on moore early ( Vitis labruca L.) It was introduced in 1908 in Korea. Minerals rich in grapes are alkaline foods, such as phone sugar, tartaric acid, citric acid, potassium and iron, vitamins A, B1, B2, D and nutrition rich in skin beauty, indigestion and anorexia have been reported to be effective.
본 발명의 목적은 비티스 라브루스카나(Vitis labruscana B.) 잎의 물, 알코올 및 초산 중에서 선택된 1 종 이상의 용매의 추출물을 유효성분으로 포함하는, 혈전 질환의 예방 또는 치료용 약학적 조성물을 제공하는 것이다.The object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of thrombotic diseases comprising, as an active ingredient, an extract of at least one solvent selected from water, alcohol and acetic acid of Vitis labruscana B. leaf .
또한 본 발명의 목적은 비티스 라브루스카나 잎의 물, 알코올 및 초산 중에서 선택된 1 종 이상의 용매의 추출물을 유효성분으로 포함하는 혈전 질환의 예방 또는 개선용 식품 조성물을 제공하는 것이다.It is also an object of the present invention to provide a food composition for preventing or ameliorating a thrombotic disease, which comprises an extract of at least one solvent selected from water, alcohol and acetic acid of Vitislavus vulgaris leaves as an active ingredient.
상기와 같은 과제를 해결하기 위해, 본 발명은 비티스 라브루스카나 잎의 물, 알코올 및 초산 중에서 선택된 1 종 이상의 용매의 추출물을 유효성분으로 포함하는, 혈전 질환의 예방 또는 치료용 약학적 조성물을 제공한다.In order to solve the above-mentioned problems, the present invention provides a pharmaceutical composition for preventing or treating thrombotic diseases comprising, as an active ingredient, an extract of at least one solvent selected from water, alcohol and acetic acid of Vitislavus vulgaris leaves to provide.
또한 본 발명은 비티스 라브루스카나 잎의 물, 알코올 및 초산 중에서 선택된 1 종 이상의 용매의 추출물을 유효성분으로 포함하는 혈전 질환의 예방 또는 개선용 식품 조성물을 제공한다.
The present invention also provides a food composition for preventing or ameliorating a thrombotic disease comprising an extract of at least one solvent selected from the group consisting of water, alcohol and acetic acid of Vitislavus vulgaris leaves as an active ingredient.
이하, 본 발명에 대하여 보다 상세히 설명한다.Hereinafter, the present invention will be described in more detail.
본 발명은 비티스 라브루스카나 잎의 물, 알코올 및 초산 중에서 선택된 1 종 이상의 용매의 추출물을 유효성분으로 포함하는, 혈전 질환의 예방 또는 치료용 약학적 조성물을 제공한다.The present invention provides a pharmaceutical composition for preventing or treating thrombotic diseases, which comprises an extract of at least one solvent selected from the group consisting of water, alcohol and acetic acid of Vityslava bruscana leaf as an active ingredient.
상기 비티스 라브루스카나는 무어 얼리(Moore Early)(Vitis labrusca L.; 미국종)와 머스캣 함부르크(Muscat Hamburg)(Vitis vinifera L.; 유럽종)를 교배하여 육성한 품종으로 구미잡종에 속하며, 일반적으로 미국종에 분류하고 미국계의 재배 품종을 모두 포함하여, 일 예로 캠벨얼리, 델라웨어 및 나이애가라 등이 이에 속한다. The Vitis la Bruiskana is a cross breed of the Moore Early ( Vitis labrusca L.; American species) and Muscat Hamburg ( Vitis vinifera L.; European species) , Generally categorized in the United States and include all cultivated varieties of the United States, such as Campbell, Delaware and Niagara.
상기 비티스 라브루스카나 잎을 용매로 추출한 추출물의 경우, 다른 부위의 추출물 보다 혈전 질환의 예방 또는 치료 효과가 우수하다. In the case of the extract obtained by extracting the Vityslava brassica leaves with a solvent, the effect of preventing or treating thrombotic diseases is superior to that of the extract of other regions.
상기 추출물은 당업계의 통상적인 방법으로 하여 추출할 수 있으며, 물, 알코올, 초산 및 이들의 조합으로 이루어진 군에서 선택된 어느 하나의 용매를 이용할 수 있고, 바람직하게는 물, 알코올, 초산 및 이들의 조합으로 이루어진 군에서 선택된 어느 하나의 용매, 더욱 바람직하게는 50 부피% 알코올 수용액과 3 부피% 초산을 혼합하여 이용할 수 있다. The extract may be extracted by a conventional method in the art, and any one selected from the group consisting of water, alcohol, acetic acid, and combinations thereof may be used. Preferably, water, alcohol, acetic acid, , More preferably 50 vol% aqueous alcohol solution and 3 vol% acetic acid may be mixed and used.
본 발명의 추출물을 포함하는 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는, 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다.Examples of carriers, excipients and diluents that can be contained in the composition containing the extract of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium Cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.
상기 혈전 질환은 혈액 순환에 문제가 생겨 유발될 수 있는 질환이면 특별히 한정되지는 않으며, 특히, 본 발명에 따른 추출물은 뇌출혈, 뇌졸증, 뇌경색, 만성 동맥폐색증 및 이들의 조합으로 이루어지는 군으로부터 선택되는 어느 하나의 혈전 질환에 유용하게 사용될 수 있다.The thrombotic disease is not particularly limited as long as it is a disease that can be caused by a problem of blood circulation, and in particular, the extract according to the present invention is useful as a therapeutic agent for preventing or treating a hemorrhage, stroke, cerebral infarction, chronic arterial occlusion, And can be usefully used for one thrombotic disease.
본 발명에 따른 조성물은 혈전 형성을 수반하는 질환의 예방 및 치료를 위하여 단독으로, 또는 수술, 방사선 치료, 호르몬 치료, 화학 치료 및 생물학적 반응 조절제를 사용하는 방법들과 병용하여 사용할 수 있다.The composition according to the present invention can be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy and biological response modifiers for the prevention and treatment of diseases involving thrombus formation.
본 발명에 따른 조성물은 투여를 위해서 상기 기재한 유효성분 이외에 추가로 약재학적으로 허용 가능한 담체를 1종 이상 포함하여 제조할 수 있다. 약제학적으로 허용 가능한 담체는 식염수, 멸균수, 링거액, 완충 식염수, 덱스트로즈 용액, 말토 덱스트린 용액, 글리세롤, 알코올 및 이들 성분 중 1 성분 이상을 혼합하여 사용할 수 있으며, 필요에 따라 항산화제, 완충액, 정균제 등 다른 통상의 첨가제를 첨가할 수 있다. 또한 희석제, 분산제, 계면활성제, 결합제 및 윤활제를 부가적으로 첨가하여 수용액, 현탁액, 유탁액 등과 같은 주사용 제형, 환약, 캡슐, 과립 또는 정제로 제제화할 수 있다. 더 나아가 당 분야의 적정한 방법으로 또는 Remington's Pharmaceutical Science(최근판), Mack Publishing Company, Easton PA에 개시되어 있는 방법을 이용하여 각 질환에 따라 또는 성분에 따라 바람직하게 제제화할 수 있다.The composition according to the present invention may further comprise one or more pharmaceutically acceptable carriers in addition to the above-described effective ingredients for administration. The pharmaceutically acceptable carrier may be a mixture of saline, sterilized water, Ringer's solution, buffered saline, dextrose solution, maltodextrin solution, glycerol, alcohol and one or more of these components. If necessary, an antioxidant, , And other conventional additives such as a bacteriostatic agent may be added. In addition, diluents, dispersants, surfactants, binders, and lubricants may be additionally added to formulate into injectable solutions, pills, capsules, granules or tablets such as aqueous solutions, suspensions, emulsions and the like. Further, it can be suitably formulated according to each disease or ingredient, using appropriate methods in the art or by the method disclosed in Remington's Pharmaceutical Science (recent edition), Mack Publishing Company, Easton PA.
본 발명에 따른 조성물은 목적하는 방법에 따라 경구 투여하거나 비경구 투여(예를 들어, 정맥 내, 피하, 복강 내 또는 국소에 적용)할 수 있으며, 투여량은 환자의 체중, 연령, 성별, 건강상태, 식이, 투여시간, 투여방법, 배설률 및 질환의 중증도에 따라 그 범위가 다양하다. 본 발명에 따른 혼합 추출물의 일일 투여량은 25 내지 100 ㎎/㎏이며, 바람직하게는 100 ㎎/㎏이고, 하루 1회 내지 3회에 나눠 투여하는 것이 바람직하다.
The composition according to the present invention may be administered orally or parenterally (for example, intravenously, subcutaneously, intraperitoneally or topically) according to a desired method, and the dosage may be appropriately selected according to the weight, age, sex, The range varies depending on the condition, diet, time of administration, method of administration, excretion rate and severity of the disease. The daily dose of the mixed extract according to the present invention is 25 to 100 mg / kg, preferably 100 mg / kg, and is preferably administered once to three times a day.
또한 본 발명은 비티스 라브루스카나 잎의 물, 알코올 및 초산 중에서 선택된 1 종 이상의 용매의 추출물을 유효성분으로 포함하는 혈전 질환의 예방 또는 개선용 식품 조성물을 제공한다.The present invention also provides a food composition for preventing or ameliorating a thrombotic disease comprising an extract of at least one solvent selected from the group consisting of water, alcohol and acetic acid of Vitislavus vulgaris leaves as an active ingredient.
상기 추출물은 당업계의 통상적인 방법으로 하여 추출할 수 있으며, 물, 알코올, 초산 및 이들의 조합으로 이루어진 군에서 선택된 어느 하나의 용매를 이용할 수 있고, 바람직하게는 물, 알코올, 초산 및 이들의 조합으로 이루어진 군에서 선택된 어느 하나의 용매, 더욱 바람직하게는 50 부피% 알코올 수용액과 3 부피% 초산을 혼합하여 이용할 수 있다.The extract may be extracted by a conventional method in the art, and any one selected from the group consisting of water, alcohol, acetic acid, and combinations thereof may be used. Preferably, water, alcohol, acetic acid, , More preferably 50 vol% aqueous alcohol solution and 3 vol% acetic acid may be mixed and used.
본 발명에 따른 조성물은 혈액순환 장애로 인한 질병 개선을 목적으로 하는 건강식품에 첨가할 수 있으며, 본 발명의 추출물을 식품 첨가물로 사용할 경우, 상기 생약재를 혼합하여 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 유효 성분의 혼합양은 사용 목적(예방, 건강 또는 치료적 처치)에 따라 적합하게 결정될 수 있다. The composition according to the present invention can be added to a health food for the purpose of improving disease caused by a blood circulation disorder. When the extract of the present invention is used as a food additive, the herbal medicine may be mixed and added as it is, Can be used together, and can be suitably used according to a conventional method. The amount of the active ingredient to be mixed can be suitably determined according to the intended use (prevention, health or therapeutic treatment).
상기 식품의 종류에는 특별한 제한이 없다. 상기 물질을 첨가할 수 있는 식품의 예로는 육류, 소세지, 빵, 쵸컬릿, 캔디류, 스넥류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함하는 낙농제품, 각종 스프, 음료수, 차, 드링크제, 알콜 음료 및 비타민 복합제 등이 있으며, 통상적인 의미에서의 건강식품을 모두 포함한다.There is no particular limitation on the kind of the food. Examples of the food to which the above substance can be added include dairy products including meat, sausage, bread, chocolate, candy, snack, confectionery, pizza, ramen, other noodles, gums, ice cream, soups, , Alcoholic beverages and vitamin complexes, and includes all health foods in a conventional sense.
본 발명의 식품 보조 첨가제는 여러 가지 향미제 또는 천연 탄수화물 등을 사용할 수 있다. 상술한 천연 탄수화물은 포도당, 과당과 같은 모노사카라이드, 말토스, 슈크로스와 같은 디사카라이드, 및 덱스트린, 사이클로 덱스트린과 같은 폴리사카라이드, 자일리톨, 소르비톨, 에르트리톨 등의 당알콜이다. 감미제로서는 타우마틴, 스테비아 추출물과 같은 천연 감미제나, 사카린, 아스파르탐과 같은 합성 감미제 등을 사용할 수 있다.Various additives such as flavors or natural carbohydrates can be used as the food-aid additive of the present invention. The above-mentioned natural carbohydrates are sugar saccharides such as monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, xylitol, sorbitol and erythritol. Examples of sweeteners include natural sweeteners such as tau martin and stevia extract, synthetic sweeteners such as saccharin and aspartame, and the like.
상기 외에 본 발명에 따른 조성물은 여러가지 영양제, 비타민, 전해질, 풍미제, 착색제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 중점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있다. 그밖에 본 발명에 따른 조성물은 천연 과일쥬스, 과일쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다.In addition to the above, the composition according to the present invention may further contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloid concentrating agents, pH adjusting agents, stabilizers, preservatives, , A carbonating agent used in carbonated drinks, and the like. In addition, the composition according to the present invention may contain flesh for the production of natural fruit juice, fruit juice beverage and vegetable beverage. These components may be used independently or in combination.
본 발명에 따른 비티스 라브루스카나 잎 추출물은 혈소판 응집을 억제시키며 혈액 응고 시간과 출혈 시간을 연장시켜 혈액 순환을 개선시키는 효과가 있어, 동맥경화증, 뇌출혈, 뇌졸증, 뇌경색 등과 같이 혈액순환 장애에 의하여 유발되는 질환의 예방 및 치료에 유용하게 사용될 수 있다.The Vitis lavrescus leaf extract according to the present invention inhibits platelet aggregation and prolongs blood coagulation time and bleeding time to improve blood circulation and is useful for the treatment of blood circulation disorders such as arteriosclerosis, cerebral hemorrhage, stroke, And can be usefully used for the prevention and treatment of diseases caused.
도 1은 실시예 1 내지 5 및 은행잎(Ginkgo biloba) 추출물을 농도별로 쥐의 혈소판에 처리하여 혈소판 응집 저해 효과를 확인한 결과를 나타낸 도이다.
도 2는 실시예 1 내지 5, 은행잎(Ginkgo biloba) 추출물을 혈소판을 제거한 사람의 혈장에 농도별(0.1, 0.3 및 1 mg/mL)로 처리한 뒤, aPPT 시약을 처리하여 내인성 경로에 따른 응고 시간을 측정한 결과를 나타낸 도이다. 그래프의 세로축은 응고시간(sec)을 나타낸다.
도 3은 실시예 4, 실시예 5 및 은행잎 추출물을 농도별로 실험 동물에 경구 투여한 뒤 실험 동물의 혈소판 응집 억제능을 확인한 결과를 나타낸 도이다. 그래프의 새로축은 대조군에 대한 실험군의 응집된 정도의 상대값을 의미하고, 그래프의 가로축은 실험군인 비티스 라브루스카 및 은행잎 추출물 각각의 투여 용량(mg/kg)을 나타낸다.
도 4는 실시예 4, 실시예 5 및 은행잎 추출물을 실험동물에 농도별로 처리하여 실험 동물의 꼬리 출혈 시간을 측정한 결과를 나타낸 도이다. 그래프의 세로축은 대조군에 대한 실험군의 출혈시간의 상대값을 의미하고, 그래프의 가로축은 각 실험군을 나타낸다.FIG. 1 is a graph showing the results of confirming the inhibition of platelet aggregation by treating the platelets of mice of Examples 1 to 5 and Ginkgo biloba extract at various concentrations.
FIG. 2 is a graph showing the results of treatment of the extracts of Examples 1 to 5 and Ginkgo biloba with plasma (0.1, 0.3 and 1 mg / mL) in plasma of a platelet-removing human, followed by treatment with aPPT reagent, Fig. 5 is a graph showing a result of measuring time. The vertical axis of the graph represents the solidification time (sec).
FIG. 3 is a graph showing the results of confirming the ability of the experimental animals to inhibit platelet aggregation after oral administration of Example 4, Example 5 and Ginkgo biloba extract to experimental animals at different concentrations. The new axis of the graph represents the relative value of the degree of agglutination of the experimental group to the control group, and the abscissa of the graph represents the dose (mg / kg) of each of the experimental groups, Vitislavus vulgaris and Ginkgo biloba extract.
FIG. 4 is a graph showing the result of measuring the tail bleeding time of experimental animals by treating the extracts of Example 4, Example 5, The vertical axis of the graph represents the relative value of the bleeding time of the experimental group to the control group, and the horizontal axis of the graph represents each experimental group.
이하, 실시예는 오로지 본 발명을 보다 구체적으로 설명하기 위한 것으로서, 본 발명의 요지에 따라 본 발명의 범위가 이들 실시예에 의해 제한되지 않는다는 것은 본 발명이 속하는 기술분야에서 통상의 지식을 가진 자에게 있어서 자명할 것이다.
It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the spirit or scope of the present invention as defined by the appended claims. It will be obvious to you.
실시예. 비티스 라브루스카나 잎(Examples. Vitis la Bruiskana leaf ( Vitis labruscana Vitis labruscana B.)의 추출물 제조 B.) Extract preparation
추출용매의 종류 및 함량에 따른 비티스 라브루스카나 잎의 추출물을 수득하기 위해, 비티스 라브루스카나 잎의 추출을 하기와 같이 수행하였다.In order to obtain an extract of Vityslava brassica leaves according to the kind and content of the extracting solvent, extraction of Vityslava bruciana leaves was carried out as follows.
보다 구체적으로, 비티스 라브루스카나 잎을 물로 씻어 이물질을 제거한 후 건조하여 분쇄하였다. 상기 분쇄한 비티스 라브루스카나 잎을 이용하여 실시예 1 내지 5의 방법으로 비티스 라브루스카나 잎의 추출물을 수득하였다. More specifically, the leaves of Vitis la Bruciana were washed with water to remove foreign matters, followed by drying and pulverization. An extract of Vitysulla brucus canana leaves was obtained by the method of Examples 1 to 5 using the above-mentioned pulverized Vitislava bruscuna leaf.
실시예 1은 상기에서 분쇄한 비티스 라브루스카나 잎 100 g에 추출용매로 정제수 2 L를 가하였다. 90 ℃로 3시간 동안 2회 반복하여 환류 냉각 방식을 이용하여 비티스 라브루스카나 잎을 추출하였다. 상기 추출액을 여과한 후, 40℃의 수욕상에서 감압농축 및 건조하여 최종 비티스 라브루스카나 잎 추출물을 수득하였다. In Example 1, 2 L of purified water was added as an extraction solvent to 100 g of the B. t.bruskana leaf ground in the above. And the mixture was repeated twice at 90 캜 for 3 hours to extract the Vityslava brassica leaves using a reflux cooling method. The extract was filtered, concentrated under reduced pressure in a water bath at 40 ° C, and dried The final Vitis lavrescina leaf extract was obtained.
실시예 2는 추출용매로 정제수 및 3 부피%의 초산을 혼합한 것을 이용하는 방법 외에는 상기 실시예 1과 동일한 방법으로 추출물을 수득하였다. In Example 2, an extract was obtained in the same manner as in Example 1 except that purified water and 3% by volume of acetic acid were mixed as an extraction solvent.
실시예 3은 추출용매로 30 부피%의 알코올 수용액 및 3 부피%의 초산을 혼합한 것을 이용하는 방법 외에는 상기 실시예 1과 동일한 방법으로 추출물을 수득하였다. In Example 3, an extract was obtained in the same manner as in Example 1 except that 30% by volume of an alcohol aqueous solution and 3% by volume of acetic acid were mixed as an extraction solvent.
실시예 4는 추출용매로 50 부피%의 알코올 수용액을 혼합한 것을 이용하는 방법 외에는 상기 실시예 1과 동일한 방법으로 추출물을 수득하였다. Example 4 was obtained in the same manner as in Example 1 except that 50% by volume of an aqueous alcohol solution was used as the extraction solvent.
실시예 5는 추출용매로 50 부피%의 알코올 수용액 및 3 부피%의 초산을 혼합한 것을 이용하는 방법 외에는 상기 실시예 1과 동일한 방법으로 추출물을 수득하였다. In Example 5, an extract was obtained in the same manner as in Example 1 except that 50% by volume of an aqueous alcohol solution and 3% by volume of acetic acid were used as extraction solvents.
상기와 같이 추출한 결과, 실시예 1은 19.0%를, 실시예 2는 28.2%를, 실시예 3은 25.8%를, 실시예 4는 20.1%를, 실시예 5는 19.0%의 비티스 라브루스카나 잎 추출물 수득율이 나타남을 확인하였다.
As a result of the above extraction, it was found that 19.0% of Example 1, 28.2% of Example 2, 25.8% of Example 3, 20.1% of Example 4, 19.0% of Vitisla brucina Leaf extract yield was confirmed.
실험예 1. 비티스 라브루스카나 잎 추출물의 혈소판 응집 저해 효과 비교 측정EXPERIMENTAL EXAMPLE 1. Comparison of Platelet Aggregation Inhibitory Effect of Vitis lavrucina leaf Extract
상기 실시예 1 내지 5에 따라 수득한 비티스 라브루스카나 잎 추출물의 혈소판 응집 저해 효과를 비교 측정하기 위하여, 하기와 같은 실험을 수행하였다.In order to comparatively measure the platelet aggregation inhibitory effect of the Vityslava brassica leaf extract obtained according to Examples 1 to 5, the following experiment was conducted.
보다 구체적으로, 실험용 쥐(Rat)을 에테르(Ether)로 마취시키고, 항응고제인 3.2% 소듐 시트레이트(sodium citrate)와 상기 실험용 쥐의 혈액이 1:9 (v/v) 비율이 되도록 함유한 PT관을 이용하여 실험용 쥐의 복대동맥에서 채혈하였다. 상기 채혈한 혈액을 200×g에서 10분간 원심분리하여 상등액을 분리하고 혈소판 풍부 혈장(Platelet Rich Plasma, PRP)을 얻었다. 이후 상등액을 분리하고 남은 부분을 800×g에서 15분간 원심분리하고 상층액을 분리하여 혈소판이 거의 없는 혈청(platelet poor plasma, PPP)을 수득하였다. 이후 혈소판 세포 계수기(Horiba LC-660, Japan)를 이용하여 혈소판 수를 계측하고 상기 PPP를 이용하여 혈소판이 4×108 개/mL가 되도록 희석하였다. 혈소판은 저온에서 응집되므로 모든 실험은 상온에서 실시하였다. 쥐의 혈소판 응집 저해율은 전혈응집분석기(Aggregometer)(Chrono-log, Haver town, PA, USA)를 통해 탁도 측정법으로 확인하였다. 상기 PRP를 37℃에서 5분간 보존한 후, 상기 실시예 1에서 수득한 실시예 1 내지 5의 비티스 라브루스카나 잎 추출물 및 대조군으로서 혈행개선에 효과적이라고 알려진 은행잎(Ginkgo biloba) 추출물을 시료로 이용하여 0.1, 0.3 및 1 mg/mL 농도별로 처리하였다. 2분 후 혈소판 응집 유도 물질(Agonist)인 아데노신2인산(adenosine diphosphate, ADP)(5 ㎕)으로 유도하였으며 시료를 처리하지 않은 PRP를 정상군으로 하여 하기의 수학식 1과 같은 방법으로 나타내었다. 그 결과를 하기 표 1 및 도 1에 나타내었다.More specifically, the experimental rat (Rat) was anesthetized with ether, and a PT containing 3.2% sodium citrate, which is an anticoagulant, and the blood of the experimental rats at a ratio of 1: 9 (v / v) Blood was drawn from the abdominal artery of the experimental rats using a tube. The collected blood was centrifuged at 200 xg for 10 minutes to separate the supernatant and obtain platelet rich plasma (PRP). Then, the supernatant was separated and the remaining portion was centrifuged at 800 xg for 15 minutes and the supernatant was separated to obtain a platelet poor plasma (PPP). Platelet counts were then measured using a platelet cell counter (Horiba LC-660, Japan) and the platelets were diluted to 4 × 10 8 platelets / mL using the PPP. Platelets aggregated at low temperatures, so all experiments were performed at room temperature. The inhibition rate of platelet aggregation in rats was confirmed by turbidity measurement through Aggregometer (Chrono-log, Haver town, PA, USA). The PRP was preserved at 37 캜 for 5 minutes, and then the Vityslava brassica leaf extracts of Examples 1 to 5 obtained in Example 1 and a Ginkgo biloba extract known to be effective for improving blood circulation were used as a sample 0.1, 0.3, and 1 mg / mL, respectively. 2 minutes later, adenosine diphosphate (ADP) (5 μl), which is a platelet aggregation inducer (agonist), was induced. PRP not treated with the sample was expressed as a normal group and expressed by the following formula (1). The results are shown in Table 1 and Fig.
표 1 및 도 1에 나타낸 바와 같이, 0.1 mg/mL 농도로 처리하였을 때 ADP로 유도한 혈소판 응집 효과는 추출물의 농도에 차이가 있기는 하나, 실시예 1 내지 5 모두에서 나타났으며, 특히 실시예 5의 추출물의 경우 다른 처리구보다 약 2배 이상 높은 혈소판 응집 저해효과를 나타냄을 확인하였다. 따라서 비티스 라브루스카나 잎 추출물에 혈소판 응집효과가 있으나, 특히 추출용매를 실시예 5와 같이 한정하는 경우 현저히 우수한 저해 효과를 가짐을 확인하였다.
As shown in Table 1 and Fig. 1, the platelet aggregation effect induced by ADP when treated at a concentration of 0.1 mg / mL was found in all of Examples 1 to 5, though there was a difference in the concentration of the extracts. It was confirmed that the extract of Example 5 exhibited a platelet aggregation inhibitory effect about twice as high as that of the other treatments. Therefore, it was confirmed that the extract of Vitis lavrescina leaf has platelet aggregation effect, but especially when the extraction solvent is limited as in Example 5, it has a remarkably excellent inhibitory effect.
실험예 2. 실시예 1 내지 5에 의한 혈액응고 경로 확인Experimental Example 2: Confirmation of blood coagulation route according to Examples 1 to 5
실시예 1 내지 5의 처리에 의해 내인성 및 외인성 경로 중 어느 경로가 혈액 응고에 관여하는지 확인하기 위하여, 하기와 같은 실험을 수행하였다.
In order to determine which pathway of endogenous and exogenous pathways participates in blood coagulation by the treatment of Examples 1 to 5, the following experiment was conducted.
실험예 2-1. 외인성 경로에 따른 응고 시간 측정Experimental Example 2-1. Measurement of coagulation time by extrinsic pathway
보다 구체적으로, 혈소판을 완전히 제거한 사람의 혈장을 미리 37℃에서 가열시키고 상기 실시예 1에서 수득한 실시예 1 내지 5의 비티스 라브루스카나 잎 추출물 및 대조군인 은행잎 추출물 시료를 처리하여 5분간 보관하였다. 그 후 상기 37℃로 가온해 둔 PT reagent(TECO, Germany)를 빠르게 분주한 후 타이머를 눌러서 응고가 일어날 때까지의 시간을 코어귤로미터(coagulometer)(Coatron M4, Germany)를 이용하여 프로트롬빈 타임(Prothrombin time, PT)을 측정하여 평균±표준편차로 나타내었다. 그 결과를 하기 표 2에 나타내었다. More specifically, plasma of a person completely removed from the platelets was heated at 37 ° C in advance, treated with Vitoslava brassica leaf extracts of Examples 1 to 5 obtained in Example 1 and a control group of Ginkgo biloba extract, and stored for 5 minutes Respectively. Then, PT reagent (TECO, Germany) heated to 37 ° C was quickly dispensed, and the time until coagulation was achieved by pressing the timer was measured using a core coagulometer (Coatron M4, Germany) (Prothrombin time, PT) were measured and expressed as the mean ± standard deviation. The results are shown in Table 2 below.
표 2에 나타낸 바와 같이, 상기와 같이 정상군과 비교했을 때 모든 실험군에서 프로트롬빈 타임(PT)의 변화는 거의 없음을 확인하였다.As shown in Table 2, it was confirmed that there was almost no change in the prothrombin time (PT) in all the experimental groups as compared with the normal group.
따라서, 은행잎이나 실시예 1 내지 5의 비티스 라브루스카나 잎 추출물 모두 외인성 응고인자에는 거의 영향을 미치지 않음을 확인하였다.
Thus, it was confirmed that Ginkgo biloba and Vitilus brucus leaf extracts of Examples 1 to 5 had little effect on exogenous coagulation factors.
실험예 2-2. 내인성 경로에 따른 응고 시간 측정Experimental Example 2-2. Measurement of coagulation time by intrinsic pathway
보다 구체적으로, 혈소판을 완전히 제거한 사람의 혈장을 미리 37℃에서 가열시키고 상기 실시예 1에서 수득한 실시예 1 내지 5의 비티스 라브루스카나 잎 추출물 및 대조군인 은행잎 추출물 시료를 처리하여 5분간 보관하였다. 여기에 37℃로 가온해 둔 aPTT reagent(TECO, Germany)를 분주한 후 다시 5분간 배양하였다. 그 후 칼슘클로라이드 용액(CaCl2)을 빠르게 분주하고 타이머를 눌러서 응고가 일어날 때까지의 시간을 코어큘로미터(Coatron M4, Germany)를 이용하여 활성트롬보플라스틴 시간(activated partial thromboplastin time, aPTT)을 측정하여 평균±표준편차로 나타내었다. 그 결과를 표 3 및 도 2에 나타내었다.More specifically, plasma of a person completely removed from the platelets was heated at 37 ° C in advance, treated with Vitoslava brassica leaf extracts of Examples 1 to 5 obtained in Example 1 and a control group of Ginkgo biloba extract, and stored for 5 minutes Respectively. The aPTT reagent (TECO, Germany), which had been heated to 37 ° C, was added thereto, followed by further incubation for 5 minutes. Then, the calcium chloride solution (CaCl 2 ) was quickly dispensed and the time until the coagulation was achieved by pressing the timer was measured using an activated partial thromboplastin time (aPTT) using a coacron meter (Coatron M4, Germany) ) Were measured and expressed as the mean ± standard deviation. The results are shown in Table 3 and FIG.
표 3 및 도 2에 나타낸 바와 같이, 비티스 라브루스카나 잎 추출물을 처리한 농도 1 mg/mL으로 처리했을 때 정상군과 비교하여 내인성 응고 기전에 의한 혈액응고 시간이 증가하는 것을 확인 하였고, 특히 실시예 5의 경우 혈액 응고 시간이 은행잎 추출물 및 실시예 1 내지 4에 비해 유의적으로 증가함을 확인하였다. As shown in Table 3 and FIG. 2, when the treatment was carried out at a concentration of 1 mg / mL treated with Vitis lavrucina leaf extract, the blood coagulation time due to the endogenous coagulation mechanism was increased compared with the normal group, It was confirmed that the blood coagulation time of Example 5 was significantly increased compared to that of Ginkgo biloba extract and Examples 1 to 4.
따라서, 이를 통해 비티스 라브루스카나 잎 추출물이 내인성 인자가 관여하는 aPTT 시간을 증가시켜 혈액 응고를 억제하는 효과를 가지는 것을 확인하였으며 특히 실시예 5의 혈액 응고 억제능이 현저히 우수함을 확인하였다.
Therefore, it was confirmed that the Vittyla brucus canana leaf extract has an effect of inhibiting blood coagulation by increasing the aPTT time in which the endogenous factor participates. In particular, it was confirmed that the blood coagulation inhibitory ability of Example 5 is remarkably excellent.
실험예 3. 실험동물에서 혈소판 응집 억제능 평가Experimental Example 3. Assessment of inhibition of platelet aggregation in experimental animals
실험예 3-1. 실험동물에서 비티스 라브루스카나 잎 추출물의 혈행 개선 효과Experimental Example 3-1. Improvement of blood circulation of Vitis lavrucina leaf extract in experimental animals
상기 실시예 1 및 2의 in vitro 실험에서 가장 효과가 뛰어난 실시예 4 및 5를 이용하여 실험동물에서 혈행 개선 효과를 확인하였다.Using Examples 4 and 5, which are most effective in the in vitro experiments of Examples 1 and 2, blood circulation improvement effect was confirmed in the experimental animals.
보다 구체적으로, 실험용 쥐(Rat)는 7주령(무게 300-320 g) 수컷을 오리엔트 바이오(Orient Bio, Seong-nam si, Korea)로부터 공급받아 사육실 온도는 22±2℃, 습도는 40~60%를 유지하고, 오전 6시와 오후 6시를 기준으로 밤낮의 주기가 12시간이 되도록 하였다. 표준 사료와 물은 자유롭게 접근할 수 있도록 하여 1주일간 환경에 적응시킨 후 실험을 진행하였다. 은행잎 추출물(비교예)과 실시예 4, 실시예 5를 물에 녹여 1주일간 매일 동일한 시간에 경구로 1일 1회 투여하였다. 실험 마지막 날, 쥐를 에테르로 마취시키고, 항응고제로 3.2% 소듐 시트레이트를 혈액과 1:9 (v/v) 비율이 되도록 함유한 PT관을 이용하여 복대동맥으로부터 채혈하였다. 얻어진 혈액을 200×g에서 10분간 원심분리하여 상등액을 분리하여 PRP를 준비하였고 남은 부분은 800×g에서 15분간 원심분리하여 상층액을 분리하여 PPP를 얻었다. 이후 혈소판 세포 계수기(Horiba LC-660, Japan)를 이용하여 혈소판 수를 계측하고 PPP를 이용하여 혈소판이 4×108 개/mL이 되도록 희석하였다. 혈소판은 저온에서 응집되므로 모든 실험은 상온에서 실시하였다. 쥐의 혈소판 응집 저해율은 전혈응집분석기(Chrono-log, Haver town, PA, USA)를 통해 탁도 측정법으로 확인하였다. 실험동물에서 분리한 PRP를 37℃에서 2분간 보존한 후 혈소판 응집 유도 물질인 ADP(5 ㎕)으로 유도하였으며 시료를 경구투여하지 않은 실험동물의 PRP를 정상군으로 하여 상기 수학식 1과 같은 방법으로 나타내었다. 그 결과를 표 4 및 도 3에 나타내었다.More specifically, male rats (7 weeks old, weighing 300-320 g) were supplied from Orient Bio (Seong-nam si, Korea), and the temperature of the feeding room was 22 ± 2 ℃ and the humidity was 40 ~ 60 , And the night and day cycle was 12 hours at 6:00 am and 6:00 pm. The standard feed and water were freely accessible and adapted to the environment for one week before the experiment. Ginkgo biloba extract (Comparative Example) and Example 4 and Example 5 were dissolved in water and administered orally once a day at the same time every day for one week. On the last day of the experiment, rats were anesthetized with ether and blood was drawn from the abdominal aorta using a PT tube containing 3.2% sodium citrate as an anticoagulant in a ratio of 1: 9 (v / v) to blood. The obtained blood was centrifuged at 200 × g for 10 minutes, and the supernatant was separated to prepare PRP. The remaining portion was centrifuged at 800 × g for 15 minutes, and the supernatant was separated to obtain PPP. Platelet counts were then measured using a platelet cell counter (Horiba LC-660, Japan) and diluted to 4 × 10 8 platelets / mL using PPP. Platelets aggregated at low temperatures, so all experiments were performed at room temperature. The inhibition rate of platelet aggregation in rats was confirmed by turbidity measurement through a whole blood coagulation analyzer (Chrono-log, Haver town, PA, USA). The PRP isolated from the experimental animals was preserved at 37 ° C for 2 minutes and then induced with ADP (5 μl) as a platelet aggregation inducer. The PRP of the experimental animals without oral administration of the sample was used as the normal group, Respectively. The results are shown in Table 4 and FIG.
표 4 및 도 3에 나타낸 바와 같이, 실험동물에 1주일간 투여하였을 때 ADP에 의한 혈소판 응집률이 실시예 5의 경우 은행잎 추출물(비교예) 및 실시예 4보다 약 1.5배 이상 ADP로 유도한 혈소판 응집을 억제 효과가 우수한 것을 확인하였다. 따라서, in vivo 상에서도 실시예 5의 추출물이 다른 추출물보다 현저히 우수한 효과를 가짐을 확인하였다.
As shown in Table 4 and FIG. 3, platelet aggregation rate by ADP for 1 week in experimental animals was significantly higher than that of Example 5 in comparison with Ginkgo biloba extract (Comparative Example) and ADP-induced platelets It was confirmed that the effect of suppressing aggregation was excellent. Therefore, it was confirmed that the extract of Example 5 had remarkably superior effects than other extracts in vivo .
실험예 3-2. 비티스 라브루스카나 잎이 실험동물의 꼬리 출혈에 미치는 영향 비교 분석Experimental Example 3-2. Comparison of the effects of Vitis lavrescan leaf on tail bleeding in experimental animals
혈소판과 혈액 응고 인자들에 의한 지혈 마개를 형성하는 능력을 측정하기 위하여, 실험 동물의 꼬리 출혈 시간을 하기와 같이 측정하였다.To measure the ability of platelets and blood clotting factors to form a hemostatic plug, the tail bleeding time of the experimental animals was measured as follows.
보다 구체적으로, 일주일간 투약한 실험용 쥐를 럼푼(20 mg/kg)과 케타민(75 mg/kg)의 혼합액을 복강 주사하여 마취시켰다. 그 후 체온이 내려가지 않게 하여 쥐를 편평한 곳에 두고 꼬리가 수직으로 늘어지게 한 후 끝에서 3 mm를 잘라 37℃가 유지되는 생리식염수에 담가 피를 흘리는 시간을 측정하였다. 30초 이상 혈액이 나오지 않으면 지혈이 된 것으로 보고 최대 20분까지 출혈 시간을 관찰하였다. 그 결과를 표 5 및 도 4에 나타내었다.More specifically, experimental rats dosed for one week were anesthetized by intraperitoneal injection of a mixture of rumun (20 mg / kg) and ketamine (75 mg / kg). Thereafter, the mice were placed on a flat surface so that the temperature was not lowered, the tail was vertically slackened, and 3 mm was cut from the tip, and the time for which the blood was soaked in physiological saline maintained at 37 ° C was measured. Bleeding time was observed for up to 20 minutes if blood was not taken for more than 30 seconds. The results are shown in Table 5 and FIG.
표 5 및 도 4에 나타낸 바와 같이, 실험동물에 1주일간 투여하였을 때 실시예 4 투여군은 농도에 따른 출혈 시간의 변화가 거의 없었다. 그러나 실시예 5를 투여하였을 때 농도에 따라 유의적으로 출혈 시간이 증가하였으며 50 및 100 mg/kg 농도로 투여 시, 실시예 4 및 은행잎 추출물 투여군(비교예) 보다 약 1.5배 이상 더 출혈 시간 연장에 효과적임을 확인하였다. As shown in Table 5 and FIG. 4, when administered to experimental animals for one week, there was almost no change in bleeding time according to the concentration in Example 4 administration group. However, when the administration of Example 5 was performed, the bleeding time was significantly increased depending on the concentration. When administered at 50 and 100 mg / kg, the bleeding time was extended about 1.5 times or more more than that of Example 4 and the Ginkgo biloba extract- .
따라서, 본 발명에 따른 비티스 라브루스카나 잎 추출물을 이용한 혈행 개선용 조성물은 부작용 없이 ADP에 의한 혈소판 응집을 억제시키며 in vivo 상에서도 혈액 응고 시간과 출혈 시간을 연장시켜 혈액 순환을 개선시키는 효능이 다른 추출물보다 현저히 우수함을 확인하였다.
Therefore, the composition for improving blood circulation using the Vitis lavrucus leaf extract according to the present invention inhibits platelet aggregation caused by ADP without side effects and has an effect of improving blood circulation by prolonging blood clotting time and bleeding time in vivo Extracts.
제제예 1. 약학적 조성물의 제조 Formulation Example 1. Preparation of a pharmaceutical composition
1-1. 산제의 제조1-1. Manufacture of Powder
비티스 라브루스카나의 잎 추출물 20 mg Leaf Extract of
유당 100 mg
탈크 10 mgTalc 10 mg
상기의 성분들을 혼합하고 기밀포에 충진하여 산제를 제조한다.
The above components are mixed and filled in airtight bags to prepare powders.
1-2. 정제의 제조1-2. Manufacture of tablets
비티스 라브루스카나의 잎 추출물 10 mgLeaf extract of Vitesse Bruiskana 10 mg
옥수수전분 100 mg
유당 100 mg
스테아린산 마그네슘 2 mgMagnesium stearate 2 mg
상기의 성분들을 혼합한 후 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조한다.
After mixing the above components, tablets are prepared by tableting according to the usual preparation method of tablets.
1-3. 캡슐제의 제조1-3. Preparation of capsules
비티스 라브루스카나의 잎 추출물 10 mgLeaf extract of Vitesse Bruiskana 10 mg
결정성 셀룰로오스 3 mgCrystalline cellulose 3 mg
락토오스 14.8 mgLactose 14.8 mg
마그네슘 스테아레이트 0.2 mgMagnesium stearate 0.2 mg
통상의 캡슐제 제조방법에 따라 상기의 성분을 혼합하고 젤라틴 캡슐에 충전하여 캡슐제를 제조한다.
The above components are mixed according to a conventional capsule preparation method and filled in gelatin capsules to prepare capsules.
1-4. 주사제의 제조1-4. Injection preparation
비티스 라브루스카나의 잎 추출물 10 mgLeaf extract of Vitesse Bruiskana 10 mg
만니톨 180 mg180 mg mannitol
주사용 멸균 증류수 2974 mgSterile sterilized water for injection 2974 mg
Na2HPO42H2O 26 mgNa 2 HPO 4 2H 2 O 26 mg
통상의 주사제의 제조방법에 따라 1 앰플당 (2 ml) 상기의 성분 함량으로 제조한다.
(2 ml) per 1 ampoule in accordance with the usual injection preparation method.
1-5. 액제의 제조1-5. Manufacture of liquid agent
비티스 라브루스카나의 잎 추출물 20 mgLeaf Extract of
이성화당 10 g10 g per isomer
만니톨 5 g5 g mannitol
정제수 적량Purified water quantity
통상의 액제의 제조방법에 따라 정제수에 각각의 성분을 가하여 용해시키고 레몬향을 적량 가한 다음 상기의 성분을 혼합한 다음 정제수를 가하여 전체를 정제수를 가하여 전체 100 ml로 조절한 후 갈색병에 충진하여 멸균시켜 액제를 제조한다.
Each component was added and dissolved in purified water according to the usual liquid preparation method, and the lemon flavor was added in an appropriate amount. Then, the above components were mixed, and purified water was added thereto. The whole was added with purified water to adjust the total volume to 100 ml, And sterilized to prepare a liquid preparation.
제제예 2. 식품 조성물의 제조Formulation Example 2. Preparation of Food Composition
2-1. 건강식품의 제조2-1. Manufacture of health food
비티스 라브루스카나의 잎 추출물 100 mgVitesse
비타민 혼합물 적량Vitamin mixture quantity
비타민 A 아세테이트 70 ㎍ 70 [mu] g of vitamin A acetate
비타민 E 1.0 mgVitamin E 1.0 mg
비타민 B1 0.13 mgVitamin B1 0.13 mg
비타민 B2 0.15 mg0.15 mg of vitamin B2
비타민 B6 0.5 mgVitamin B6 0.5 mg
비타민 B12 0.2 ㎍ 0.2 [mu] g vitamin B12
비타민 C 10 mgVitamin C 10 mg
비오틴 10 ㎍ Biotin 10 μg
니코틴산아미드 1.7 mgNicotinic acid amide 1.7 mg
엽산 50 ㎍ 50 ㎍ of folic acid
판토텐산 칼슘 0.5 mgCalcium pantothenate 0.5 mg
무기질 혼합물 적량Mineral mixture quantity
황산제1철 1.75 mg1.75 mg of ferrous sulfate
산화아연 0.82 mg0.82 mg of zinc oxide
탄산마그네슘 25.3 mgMagnesium carbonate 25.3 mg
제1인산칼륨 15 mgPotassium monophosphate 15 mg
제2인산칼슘 55 mgSecondary calcium phosphate 55 mg
구연산칼륨 90 mgPotassium citrate 90 mg
탄산칼슘 100 mg
염화마그네슘 24.8 mgMagnesium chloride 24.8 mg
상기의 비타민 및 미네랄 혼합물의 조성비는 비교적 건강식품에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 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.
Although the composition ratio of the above-mentioned vitamin and mineral mixture is comparatively mixed with a composition suitable for health food as a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional method for producing healthy foods , Granules can be prepared and used in the manufacture of health food compositions according to conventional methods.
2-2. 건강음료의 제조2-2. Manufacture of health drinks
비티스 라브루스카나의 잎 추출물 100 mgVitesse
비타민 C 15 gVitamin C 15 g
비타민 E(분말) 100 gVitamin E (powder) 100 g
젖산철 19.75 g19.75 g of ferrous lactate
산화아연 3.5 g3.5 g of zinc oxide
니코틴산아미드 3.5 gNicotinic acid amide 3.5 g
비타민 A 0.2 gVitamin A 0.2 g
비타민 B1 0.25 gVitamin B1 0.25 g
비타민 B2 0.3 gVitamin B2 0.3 g
물 정량Water quantification
통상의 건강음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1시간 동안 85℃에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 2 l 용기에 취득하여 밀봉 멸균한 뒤 냉장 보관한 다음 본 발명의 건강음료 조성물 제조에 사용한다.The above components were mixed according to a conventional health drink manufacturing method, and the mixture was stirred and heated at 85 DEG C for about 1 hour. The solution thus prepared was filtered and sterilized in a sterilized 2 liter container, It is used in the production of the health beverage composition of the invention.
상기 조성비는 비교적 기호음료에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만 수요계층이나, 수요국가, 사용용도 등 지역적, 민족적 기호도에 따라서 그 배합비를 임의로 변형 실시하여도 무방하다.
Although the compositional ratio is relatively mixed with a component suitable for a favorite drink, it is also possible to arbitrarily modify the compounding ratio according to the regional or national preference such as the demand class, the demanding country, and the use purpose.
Claims (5)
Prevention or prevention of thrombotic diseases comprising an extract of Vitis labruscana B. leaf extracted with a mixed solvent containing 40 to 60% by volume of alcohol and 1 to 5% by volume of acetic acid as an active ingredient. A pharmaceutical composition for therapeutic use.
상기 혈전 질환은 동맥경화증, 뇌출혈, 뇌졸증, 뇌경색, 만성 동맥폐색증 및 이들의 조합으로 이루어지는 군으로부터 선택되는 어느 하나인, 혈전 질환의 예방 또는 치료용 약학적 조성물.The method according to claim 1,
Wherein the thrombotic disease is any one selected from the group consisting of arteriosclerosis, cerebral hemorrhage, stroke, cerebral infarction, chronic arterial occlusion, and combinations thereof.
Prevention or prevention of thrombotic diseases comprising an extract of Vitis labruscana B. leaf extracted with a mixed solvent containing 40 to 60% by volume of alcohol and 1 to 5% by volume of acetic acid as an active ingredient. Food composition for improvement.
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Non-Patent Citations (2)
Title |
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Journal of medicinal food, 2012, 15(10), pp.936-944 |
한국식품영양과학회지, 2013, 42(11), pp.1736-1743* |
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