KR20200047010A - Compositions comprising extract of Crataegi fructus and Lycopus lucidus for prevention or treatment of lipid-related cardiovascular diseases or obesity - Google Patents
Compositions comprising extract of Crataegi fructus and Lycopus lucidus for prevention or treatment of lipid-related cardiovascular diseases or obesity Download PDFInfo
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- KR20200047010A KR20200047010A KR1020180128949A KR20180128949A KR20200047010A KR 20200047010 A KR20200047010 A KR 20200047010A KR 1020180128949 A KR1020180128949 A KR 1020180128949A KR 20180128949 A KR20180128949 A KR 20180128949A KR 20200047010 A KR20200047010 A KR 20200047010A
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Abstract
Description
본 발명은 산사자 및 택란 추출물의 혼합물을 포함하는 지질 관련 심혈관 질환 또는 비만의 예방 또는 치료용 약학적 조성물 및 식품 조성물에 관한 것이다.The present invention relates to a pharmaceutical composition and a food composition for the prevention or treatment of lipid-related cardiovascular disease or obesity, comprising a mixture of Sansa and Taxane extracts.
동맥경화증은 동맥혈관 자체의 약화나 감염으로 인한 손상, 지단백(lipoprotein)으로 인한 콜레스테롤의 축적 등 여러 내인적, 외인적 요인으로 발생되는 것으로 알려져 있다. 동맥벽의 손상과 변성을 일으키는 복합적인 요인들이 서로 동맥경화 형성을 부추겨서 발병하게 하지만, 위험요인들 중 고혈압, 고지혈증, 흡연은 독립적으로 동맥경화를 일으킨다. 특히 동물성 지방의 과다섭취로 인한 혈액 속의 콜레스테롤 수치가 높은 고지혈증일 경우는 동맥 내막과 근육층 사이에 자리 잡은 식세포들이 더 많은 기름기를 세포질 속에 함유하게 되어 동맥벽에 지방이 축적된다.It is known that arteriosclerosis is caused by various endogenous and extrinsic factors such as weakening of the arterial vessels itself, damage caused by infection, and accumulation of cholesterol caused by lipoproteins. Although multiple factors that cause damage and degeneration of the arterial walls encourage the formation of atherosclerosis with each other, hypertension, hyperlipidemia and smoking among the risk factors independently cause atherosclerosis. Particularly in the case of hyperlipidemia with high cholesterol level in the blood due to excessive consumption of animal fat, phagocytes located between the lining of the arteries and the muscle layer contain more oil into the cytoplasm, thus accumulating fat in the artery walls.
한편, 고지혈증은 혈액 내에 유리 콜레스테롤, 콜레스테롤 에스테르, 인지질, 중성지방 등의 지방질이 비정상적으로 증가된 상태를 말한다. 고지혈증은 대개 그 자체가 증상을 나타내는 것은 아니지만, 혈액 내에 지방성분이 많으면 혈관 벽에 달라붙어 동맥경화를 일으키고, 이로 인해 관상동맥 심장질환이나 뇌혈관 질환, 말초혈관 폐쇄 등을 발생시킬 수 있다. 또한, 과도한 지방성분은 간조직에 쌓여 지방간을 유발할 수 있다.On the other hand, hyperlipidemia refers to a condition in which fats such as free cholesterol, cholesterol esters, phospholipids, and triglycerides are abnormally increased in the blood. Hyperlipidemia usually does not manifest itself, but if there is a large amount of fat in the blood, it sticks to the walls of blood vessels and causes arteriosclerosis, which can lead to coronary heart disease, cerebrovascular disease, and peripheral blood vessel occlusion. In addition, excessive fat components can accumulate in the liver tissue and cause fatty liver.
비만은 사람의 몸무게가 지나치게 많이 나가는 것을 통틀어 부르는 말로서 병리학적으로는 세계보건기구(WHO)에서 정한 이른바 표준 몸무게 기준치(Body mass index, BMI)가 30 이상인 경우를 일컫지만 한국에서는 25 이상이면 비만으로 진단한다. 비만은 체내에 지방이 과도하게 축적된 상태로써 지방 조직 내 지방세포의 수가 증가하거나 지방세포의 크기가 늘어나 지방이 증가하게 된다. 비만은 고혈압, 고지혈증, 심장질환, 당뇨병, 동맥경화, 지방간, 관절이상, 관절염, 성기능장애, 암 등 주요 질환을 유발하므로 더욱 더 중요한 질환으로 대두되고 있다. 체중이 정상체중보다 20% 증가되면 당뇨병 발병 가능성은 정상인의 10배로 증가한다. 또한 심장 및 폐기능이 약해져서 수명이 단축될 수도 있다. 고혈압, 당뇨병, 고콜레스테롤 혈증, 동맥경화증 등의 복합적인 요인들이 심장기능에 압박을 주어 심부전증에 빠지고 돌발사를 유발하기도 한다.Obesity is a term used to refer to a person's excessive weight, and pathologically refers to a case in which the so-called standard body weight index (BMI) established by the World Health Organization (WHO) is 30 or more. Diagnose. Obesity is a state in which fat is excessively accumulated in the body, and the number of fat cells in fat tissue increases or the size of fat cells increases, resulting in increased fat. Obesity is becoming more and more important because it causes major diseases such as hypertension, hyperlipidemia, heart disease, diabetes, arteriosclerosis, fatty liver, joint abnormalities, arthritis, sexual dysfunction, and cancer. If the body weight is increased by 20% than normal weight, the likelihood of developing diabetes increases 10 times as much as normal people. In addition, the heart and lung function may be weakened, which may shorten life. Complex factors such as hypertension, diabetes, hypercholesterolemia, and arteriosclerosis stress the heart function, leading to heart failure and sudden death.
혈중 지질 농도를 저하시키는 방법으로는 고지방 식이를 억제하는 식이요법, 운동요법 및 약물요법 등이 권장되고 있다. 그러나, 식이요법이나 운동요법은 엄격한 관리 및 실시가 곤란하며, 그 효과에 한계가 있는 경우가 많다. 현재까지 개발된 지질 농도 감소제로는 담즙산 결합 수지, HMG-CoA 환원효소 억제제, 네오마이신 등과 같은 콜레스테롤 함량을 저하시키는 약제 및 피브린산 유도체, 니코틴산 및 어유 등 중성지방 함량을 낮추는 약제들이 치료제로 이용되고 있다. 그러나, 이와 같은 약제들은 간 독성, 위장장해 및 암 발생 등과 같은 부작용이 있다.As a method of lowering the lipid concentration in the blood, diet, exercise therapy, and drug therapy that suppress a high fat diet are recommended. However, diet or exercise therapy is difficult to strictly manage and implement, and there are many cases where its effectiveness is limited. As the lipid concentration reducing agent developed to date, drugs that lower cholesterol content such as bile acid binding resin, HMG-CoA reductase inhibitor, neomycin, and drugs that lower triglyceride content, such as fibrinic acid derivatives, nicotinic acid, and fish oil, are used as therapeutic agents. have. However, these drugs have side effects such as liver toxicity, gastrointestinal disorders and cancer.
이에, 본 발명자들은 지질 관련 심혈관 질환 또는 비만을 예방 또는 치료하는 효과가 있으면서도 부작용이 적은 천연물을 찾고자 노력하였으며, 그 결과, 산사자 및 택란 추출물이 동맥 경화를 억제하고, 혈중 총 콜레스테롤 농도를 감소시키는 등 지질 관련 심혈관 질환 및 비만 개선에 효과가 있음을 확인함으로써 본 발명을 완성하였다. Accordingly, the present inventors tried to find a natural product that has an effect of preventing or treating lipid-related cardiovascular disease or obesity, but has fewer side effects, and as a result, the Sansa and Taxane extracts inhibit arteriosclerosis, reduce the total cholesterol concentration in the blood, etc. The present invention was completed by confirming that it is effective in improving lipid-related cardiovascular disease and obesity.
본 발명의 일 목적은 산사자 추출물 및 택란 추출물의 혼합물을 포함하는 지질 관련 심혈관 질환 또는 비만의 예방 또는 치료용 약학적 조성물을 제공하는 것이다.One object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of lipid-related cardiovascular diseases or obesity, comprising a mixture of Sansa extract and taxane extract.
본 발명의 다른 목적은 산사자 추출물 및 택란 추출물의 혼합물을 포함하는 지질 관련 심혈관 질환 또는 비만의 예방 또는 개선용 식품 조성물을 제공하는 것이다.Another object of the present invention is to provide a food composition for preventing or improving lipid-related cardiovascular disease or obesity, which comprises a mixture of Sansa extract and taxane extract.
상기 목적을 달성하기 위하여 본 발명의 일 양상은 산사자 추출물 및 택란 추출물의 혼합물을 포함하는 지질 관련 심혈관 질환 또는 비만의 예방 또는 치료용 약학적 조성물을 제공한다.In order to achieve the above object, an aspect of the present invention provides a pharmaceutical composition for the prevention or treatment of lipid-related cardiovascular disease or obesity, comprising a mixture of hawthorn extract and taxane extract.
산사자(Crataegi fructus)는 장미과 식물인 산사나무의 열매를 지칭하는 것으로서, 감기, 기침, 소화불량을 치료하는 약재로 알려져 있으며, 택란(Lycopus lucidus)은 습지나 물가에서 자라는 꿀풀과의 여러해살이풀로 산전산후의 여러 가지 병과 허로병, 쇠붙이에 다친 것, 옹종을 낫게 하며 타박상으로 생긴 어혈을 소멸시키는 약재로 알려져 있다. Crataegi fructus ( Crataegi fructus ) refers to the fruit of the hawthorn, a rose family, and is known as a medicine for treating colds, coughs, and indigestion. Lycopus lucidus is a perennial plant of honeysuckle that grows in wetlands and waters. It is known as a medicinal material that helps to cure blood and blood caused by bruises, as well as various diseases and prenatal illness, injuries to ironware, and remedy.
본 명세서에서 용어 "예방"은 본 발명에 따른 약학적 조성물의 투여에 의해 지질 관련 심혈관 질환 또는 비만 발병을 억제 또는 지연시키는 모든 행위를 의미하고, "치료"는 상기 약학적 조성물의 투여에 의해 지질 관련 심혈관 질환 또는 비만 발병의 의심 및 발병 개체의 증상이 호전되거나 이롭게 변경하는 모든 행위를 의미한다.As used herein, the term "prevention" refers to all actions that inhibit or delay the onset of lipid-related cardiovascular disease or obesity by administration of a pharmaceutical composition according to the present invention, and "treatment" refers to lipids by administration of the pharmaceutical composition. Suspicion of related cardiovascular disease or obesity and all actions that improve or beneficially alter the symptoms of the affected individual.
본 명세서에서 용어 "추출물"은 산사자 또는 택란을 적절한 추출용매로 추출하여 얻은 추출액을 의미하는 것으로, 추출처리에 의해 얻어지는 추출액, 추출액의 희석액 또는 농축액, 추출액을 건조하여 얻어지는 건조물, 이들의 조정제물 또는 정제물일 수 있으나, 이에 한정하지는 않는다. 본 발명에 따른 산사자 및 택란의 추출물은 당업계에 공지된 일반적인 추출방법, 분리 및 정제방법을 이용하여 제조할 수 있다. 상기 추출방법으로는 열탕 추출, 열수 추출, 냉침 추출, 환류 냉각 추출 또는 초음파 추출 등의 방법을 사용할 수 있으나, 이에 한정되지 않는다.As used herein, the term "extract" refers to an extract obtained by extracting an acidic acid or taxane with an appropriate extraction solvent, an extract obtained by an extraction process, a dilution or concentrate of an extract, a dried product obtained by drying the extract, a control agent thereof, or It may be a purified product, but is not limited thereto. The extract of sanja and taxane according to the present invention can be prepared using general extraction methods, separation and purification methods known in the art. The extraction method may include hot water extraction, hot water extraction, cold needle extraction, reflux cooling extraction, or ultrasonic extraction, but is not limited thereto.
본 발명에 있어서, 상기 추출물은 추출용매로 추출하거나 추출용매로 추출하여 제조한 추출물에 분획용매를 가하여 분획함으로써 제조할 수 있다. 상기 추출용매는 이에 제한되지는 않으나, 물, 유기용매 또는 이들의 혼합용매 등을 사용할 수 있으며, 상기 유기용매는 탄소수 1 내지 4의 알코올이나, 에틸아세테이트 또는 아세톤 등의 극성용매, 헥산 또는 디클로로메탄의 비극성용매 또는 이들의 혼합용매를 사용할 수 있다. 또한, 바람직하게는 물, 탄소수 1 내지 4의 알코올 또는 이들의 혼합용매를 사용할 수 있다. In the present invention, the extract may be prepared by extracting with an extraction solvent or by fractionating an extract prepared by extraction with an extraction solvent by adding a fractional solvent. The extraction solvent is not limited thereto, and water, an organic solvent, or a mixed solvent thereof may be used, and the organic solvent is an alcohol having 1 to 4 carbon atoms, a polar solvent such as ethyl acetate or acetone, hexane or dichloromethane. Non-polar solvents or mixed solvents of these can be used. In addition, preferably, water, an alcohol having 1 to 4 carbon atoms or a mixed solvent thereof can be used.
본 발명의 일 구체예에 따르면, 상기 산사자 추출물 및 택란 추출물은 열수 추출물일 수 있다.According to an embodiment of the present invention, the hawthorn extract and the taxane extract may be hot water extract.
본 발명의 일 구체예에 따르면, 상기 혼합물은 산사자 추출물 및 택란 추출물을 1:2 내지 2:1의 부피비로 혼합한 것일 수 있다.According to one embodiment of the present invention, the mixture may be a mixture of the Sansa extract and the taxane extract in a volume ratio of 1: 2 to 2: 1.
본 발명의 일 구체예에 따르면, 상기 심혈관 질환은 동맥경화, 고혈압, 심근경색, 뇌졸중, 고지혈증, 허혈성 심장 질환, 심장성 부정맥, 심부전, 협심증, 심내막염, 심장 판막 장애, 전도 장애, 및 허혈성 뇌혈관 질환으로 이루어진 군으로부터 선택되는 하나 이상일 수 있으나, 이에 한정하지는 않는다.According to one embodiment of the invention, the cardiovascular disease is atherosclerosis, hypertension, myocardial infarction, stroke, hyperlipidemia, ischemic heart disease, cardiac arrhythmia, heart failure, angina pectoris, endocarditis, heart valve disorder, conduction disorder, and ischemic cerebrovascular disease It may be one or more selected from the group consisting of diseases, but is not limited thereto.
본 명세서에서 용어 "지질 관련 심혈관 질환"은, 순환기 계통의 혈관 질환, 심장 질환 또는 뇌혈관 질환 등을 총칭하는 것을 의미한다. 순환기 계통의 혈관 질환은 혈액의 순환에 관여하는 심장을 포함한 대순환계와 소순환계의 여러 기관에 질병이 생기는 경우를 총칭하는 것을 의미하며, 심장 질환은 인체의 혈액 공급을 담당하고 있는 심장과 관련된 질환으로 허혈성 심장 질환, 심장성 부정맥, 심부전 등을 총칭하는 것을 의미한다. 허혈성 심장 질환은 대표적으로 협심증, 심근 경색증 등이 있으며, 관상 동맥의 질병이 진행함에 따라 심근에 대한 혈액 공급이 감소하거나 중단되기 때문에 발생하는 급성 또는 만성 심장 장애를 의미한다. 기타 심장 질환으로는 심내막염, 심장 판막 장애, 전도 장애, 심장성 부정맥, 또는 심부전 등이 있으며, 특히 심부전이란 정맥계를 거쳐서 심장에 되돌아오는 혈액을 심장이 충분히 구출할 수 없는 상태를 의미한다. 뇌혈관 질환은 뇌혈관의 이상에 의해 갑자기 발생하여 뇌기능 장애를 일으켜 쓰러지는 병을 의미하며, 발병 형태에 따라 두 개 내의 혈과 일부가 파손되어 출혈하는 출혈성과 혈관 속의 혈액 흐름이 나빠지거나 막히기도 하는 허혈성 뇌혈관 질환으로 구별될 수 있으나, 이에 제한되지 않는다.As used herein, the term "lipid-related cardiovascular disease" refers to a vascular disease of the circulatory system, a heart disease, or a cerebrovascular disease. Vascular diseases of the circulatory system refer to cases in which diseases occur in various organs of the large and small circulatory systems, including the heart, which are involved in the circulation of blood, and heart diseases are diseases related to the heart that is responsible for supplying blood to the human body. It refers to ischemic heart disease, cardiac arrhythmia, and heart failure. Ischemic heart disease typically includes angina pectoris, myocardial infarction, etc., and refers to an acute or chronic heart disorder that occurs because the blood supply to the myocardium decreases or stops as the disease of the coronary artery progresses. Other heart diseases include endocarditis, heart valve disorder, conduction disorder, cardiac arrhythmia, or heart failure. In particular, heart failure refers to a condition in which the heart cannot sufficiently rescue blood returning to the heart through the venous system. Cerebral vascular disease refers to a disease that occurs suddenly due to abnormalities in the cerebrovascular vessels, causing brain dysfunction, and the blood and part of the blood in the two are damaged depending on the type of outbreak, and bleeding and blood flow in the blood vessels become worse or blocked. It can be classified as ischemic cerebrovascular disease, but is not limited thereto.
본 발명의 일 구체예에 따르면, 상기 혼합물은 혈중 중성지방 및 총 콜레스테롤의 감소에 의해 비만 증상을 개선시키는 것일 수 있다.According to one embodiment of the invention, the mixture may be to improve obesity symptoms by reducing triglycerides and total cholesterol in the blood.
본 명세서에서 용어 "비만"은 체지방이 과도한 상태를 말하는 것으로, 임상적으로 체질량지수가 한국의 경우 25, 세계보건기구(WHO)에 의하면 30 이상인 경우를 의미한다. 일반적으로 체중이 정상치보다 높은 경우를 의미하지만 체중이 많이 나가지 않더라도 몸의 구성성분 중 체지방의 비율이 높은 경우 비만이라고 진단하며, 성인과 어린이 모두에서 발병하는 질환이다.In this specification, the term "obesity" refers to a condition in which body fat is excessive, and clinically means a body mass index of 25 in Korea and 30 or more according to the World Health Organization (WHO). In general, it means that the body weight is higher than the normal value, but it is diagnosed as obesity when the proportion of body fat among the components of the body is high even if the body weight does not go too much.
본 발명의 약학적 조성물은 약학적으로 허용 가능한 담체를 추가로 포함할 수 있다. 본 발명의 용어 "약학적으로 허용 가능한"이란 상기 조성물에 노출되는 세포나 인간에게 독성이 없는 특성을 나타내는 것을 의미한다. 상기 담체는 완충제, 보존제, 무통화제, 가용화제, 등장제, 안정화제, 기제, 부형제, 윤활제 등 당업계에 공지된 것이라면 제한없이 사용할 수 있다. 또한 본 발명의 약학적 조성물은 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있다. 나아가, 연고제, 로션제, 스프레이제, 패취제, 크림제, 산제, 현탁제, 겔제 또는 피부 외용제의 형태로 사용될 수 있다. 본 발명의 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로즈, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로즈, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다. 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다.The pharmaceutical composition of the present invention may further include a pharmaceutically acceptable carrier. The term "pharmaceutically acceptable" of the present invention means that it exhibits a property that is not toxic to cells or humans exposed to the composition. The carrier may be used without limitation as long as it is known in the art, such as buffers, preservatives, painless agents, solubilizers, isotonic agents, stabilizers, bases, excipients, lubricants. In addition, the pharmaceutical composition of the present invention is formulated in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories, and sterile injection solutions, respectively, according to a conventional method. You can. Furthermore, it can be used in the form of ointments, lotions, sprays, patch, creams, powders, suspensions, gels or external preparations for the skin. Carriers, excipients and diluents that may be included in the compositions of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In the case of formulation, it is prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents and surfactants.
경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 상기 자화지정 추출물 또는 자화지정, 도인, 계지, 및 감초 복합 추출물에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘 카보네이트(Calcium carbonate), 수크로즈(Sucrose) 또는 락토오스(Lactose), 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 마그네슘 스티레이트, 탈크 같은 윤활제들도 사용된다. 경구를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는 데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜(Propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 마크로골, 트윈(Tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다.Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and these solid preparations include at least one excipient in the magnetized designated extract or magnetized designated, doin, gyeji, and licorice complex extract. It is prepared by mixing starch, calcium carbonate, sucrose or lactose, gelatin, etc. In addition, lubricants such as magnesium stearate and talc are used in addition to simple excipients. Liquid preparations for oral use may include various excipients, such as wetting agents, humectants, sweeteners, fragrances, and preservatives, in addition to water and liquid paraffin, which are simple diluents commonly used for suspending agents, liquid solutions, emulsions, and syrups. have. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, and suppositories. As the non-aqueous solvent and suspension, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate may be used. Macrogol, Tween 61, cacao butter, laurin, glycerogelatin, etc. may be used as a base for suppositories.
본 발명의 일 실시예에 따른 약학적 조성물에 포함된 상기 산사자 추출물 및 택란 추출물의 혼합물의 함량은 특별히 이에 제한되지 않으나, 최종 조성물 총중량을 기준으로 0.01 내지 100 중량%, 보다 바람직하게는 1 내지 100 중량%의 함량으로 포함할 수 있다.The content of the mixture of the Sansaja extract and the taxane extract contained in the pharmaceutical composition according to an embodiment of the present invention is not particularly limited, but 0.01 to 100% by weight based on the total weight of the final composition, more preferably 1 to 100 It may be included in a content of weight percent.
한편, 본 발명의 약학적 조성물은 약학적으로 유효한 양으로 투여될 수 있다. 본 발명의 용어 "투여"란, 적절한 방법으로 개체에게 소정의 물질을 도입하는 것을 의미하며 상기 조성물의 투여 경로는 목적 조직에 도달할 수 있는 한 어떠한 일반적인 경로를 통하여 투여될 수 있다. 복강 내 투여, 정맥 내 투여, 근육 내 투여, 피하 투여, 피내 투여, 경구 투여, 국소 투여, 비 내 투여, 폐 내 투여, 직장 내 투여될 수 있으나, 이에 제한되지는 않는다.Meanwhile, the pharmaceutical composition of the present invention may be administered in a pharmaceutically effective amount. The term "administration" of the present invention means to introduce a predetermined substance into an individual in an appropriate manner, and the route of administration of the composition can be administered through any general route as long as it can reach the target tissue. Intraperitoneal administration, intravenous administration, intramuscular administration, subcutaneous administration, intradermal administration, oral administration, topical administration, intranasal administration, intrapulmonary administration, rectal administration, but are not limited thereto.
상기 용어 "개체"란 지질 관련 심혈관 질환 또는 비만이 발병하였거나 발병할 수 있는 인간을 포함한 쥐, 생쥐, 가축 등의 모든 동물을 의미한다. 바람직하게는, 인간을 포함한 포유동물일 수 있다.The term "individual" refers to all animals, such as rats, mice, livestock, including humans, who may or may have developed lipid-related cardiovascular disease or obesity. Preferably, it can be a mammal, including a human.
상기 용어 "약학적으로 유효한 양"이란 의학적 치료에 적용 가능한 합리적인 수혜/위험 비율로 질환을 치료하기에 충분하며 부작용을 일으키지 않을 정도의 양을 의미하며, 유효 용량 수준은 환자의 성별, 연령, 체중, 건강상태, 질병의 종류, 중증도, 약물의 활성, 약물에 대한 민감도, 투여 방법, 투여 시간, 투여 경로, 및 배출 비율, 치료 기간, 배합 또는 동시에 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 당업자에 의해 용이하게 결정될 수 있다. 바람직하게 본 발명의 자화지정 추출물 또는 자화지정, 도인, 계지, 및 감초 복합 추출물을 포함하는 약학적 조성물은 1일 0.0001 내지 1000 ㎎/체중 ㎏으로, 바람직하게는 0.001 내지 500 ㎎/체중 ㎏으로 투여할 수 있다. 투여는 상기 권장 투여량을 하루에 한 번 투여할 수도 있고, 수 회 나누어 투여할 수도 있다.The term "pharmaceutically effective amount" means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment and does not cause side effects, and the effective dose level is the patient's sex, age, and weight Good for factors and other medical fields, including health, health condition, type of disease, severity, drug activity, sensitivity to the drug, administration method, administration time, route of administration, and rate of discharge, duration of treatment, combination or drug used concurrently It can be readily determined by those skilled in the art according to known factors. Preferably, the pharmaceutical composition comprising the magnetized designated extract of the present invention or the magnetized designated, doin, gyeji, and licorice complex extract is administered at 0.0001 to 1000 mg / kg body weight per day, preferably at 0.001 to 500 mg / kg body weight per day. can do. The administration may be the above-mentioned recommended dose once a day, or may be divided into several times.
본 발명의 산사자 추출물 및 택란 추출물의 혼합물은 천연 한약재를 원료로 하므로 일반적인 합성 화합물에 비하여 부작용이 덜할 수 있으므로 안전하게 사용될 수 있다.Since the mixture of the Sansaja extract and the Taxane extract of the present invention uses natural herbal ingredients as raw materials, it can be used safely because it has less side effects than general synthetic compounds.
본 발명의 다른 양상은 산사자 추출물 및 택란 추출물의 혼합물을 포함하는 지질 관련 심혈관 질환 또는 비만의 예방 또는 개선용 식품 조성물을 제공한다.Another aspect of the present invention provides a food composition for preventing or improving lipid-related cardiovascular disease or obesity, comprising a mixture of hawthorn extract and taxane extract.
본 명세서에서 용어 "개선"은 상기 조성물의 투여로 지질관련 심혈관 질환 또는 비만의 증세가 호전 또는 이롭게 변경되는 모든 행위를 의미한다.As used herein, the term "improvement" means any action in which the symptoms of lipid-related cardiovascular disease or obesity are improved or beneficially altered by administration of the composition.
본 발명에 따른 산사자 추출물 및 택란 추출물의 혼합물을 이용한 식품 조성물은 기능성 식품(functional food), 영양보조제(nutritional supplement), 건강식품(health food) 및 식품첨가제(food additives) 등의 모든 형태를 포함한다. 상기 유형들은 당업계에 공지된 통상적인 방법에 따라 다양한 형태로 제조할 수 있다.The food composition using the mixture of the Sansa extract and the taxane extract according to the present invention includes all forms of functional food, nutritional supplement, health food and food additives. . These types can be prepared in various forms according to conventional methods known in the art.
예를 들면, 건강식품으로는 본 발명의 식품 조성물 자체를 차, 쥬스 및 드링크의 형태로 제조하여 음용하도록 하거나, 과립화, 캡슐화 및 분말화하여 섭취할 수 있다. 또한 본 발명의 식품 조성물은 체지방 감소, 콜레스테롤 개선, 혈압강하의 효과가 있다고 알려진 공지의 물질 또는 활성 성분과 함께 혼합하여 조성물의 형태로 제조할 수 있다.For example, as a health food, the food composition itself of the present invention may be prepared in the form of tea, juice, and drink for drinking or granulated, encapsulated, and powdered. In addition, the food composition of the present invention can be prepared in the form of a composition by mixing with a known substance or active ingredient known to have an effect of reducing body fat, improving cholesterol, and lowering blood pressure.
또한 기능성 식품으로는 음료(알콜성 음료 포함), 과실 및 그의 가공식품(예를 들어, 과일 통조림, 병조림, 잼, 마말레이드 등), 어류, 육류 및 그 가공식품(예를 들어, 햄, 소시지콘비프 등), 빵류 및 면류(예를 들어, 우동, 메밀국수, 라면, 스파게티, 마카로니 등), 과즙, 각종 드링크, 쿠키, 엿, 유제품(예를 들어, 버터, 치즈 등), 식용식물유지, 마아가린, 식물성 단백질, 레토르트 식품, 냉동식품, 각종 조미료(예를 들어, 된장, 간장, 소스 등) 등에 본 발명의 식품 조성물을 첨가하여 제조할 수 있다.In addition, functional foods include beverages (including alcoholic beverages), fruits and processed foods thereof (e.g., canned fruits, canned fruits, jams, marmalades, etc.), fish, meat, and processed foods (e.g. ham, sausage corn beef) Etc.), breads and noodles (e.g., udon, buckwheat noodles, ramen, spaghetti, macaroni, etc.), juice, various drinks, cookies, syrup, dairy products (e.g. butter, cheese, etc.), edible vegetable oil, margarine , Vegetable protein, retort food, frozen food, various seasonings (eg, miso, soy sauce, sauce, etc.) can be prepared by adding the food composition of the present invention.
본 발명에 따른 식품 조성물의 바람직한 함유량으로는 이에 한정되지 않지만 바람직하게는 최종적으로 제조된 식품 총 중량 중 0.01 내지 50중량% 이다. 본 발명의 식품 조성물을 식품 첨가제의 형태로 사용하기 위해서는 분말 또는 농축액 형태로 제조하여 사용할 수 있다.The preferred content of the food composition according to the present invention is not limited to this, but is preferably from 0.01 to 50% by weight of the total weight of the food finally produced. In order to use the food composition of the present invention in the form of a food additive, it may be prepared and used in the form of a powder or a concentrate.
또한, 본 발명의 식품 조성물은 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상기 탄수화물은 포도당, 과당과 같은 모노사카라이드, 말토스, 슈크로스와 같은 디사카라이드 및 덱스트린, 사이클로덱스트린과 같은 폴리사카라이드, 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 감미제로서는 타우마틴, 스테비아 추출물과 같은 천연 감미제나, 사카린, 아스파르탐과 같은 합성 감미제 등을 사용할 수 있다.In addition, the food composition of the present invention may contain various flavoring agents, natural carbohydrates, and the like, as additional components, like a conventional beverage. The carbohydrates are monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, and polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As the sweetener, natural sweeteners such as taumatin and stevia extract, synthetic sweeteners such as saccharin and aspartame can be used.
본 발명의 산사자 및 택란 추출물의 혼합물은 지질 관련 심혈관계 질환 또는 비만을 효과적으로 예방, 치료 또는 개선시킬 수 있다.The mixture of Sansa and Taxane extracts of the present invention can effectively prevent, treat or improve lipid related cardiovascular disease or obesity.
도 1은 산사자 열수 추출물(CE), 택란 열수 추출물(LE), 산사자 및 택란의 열수 추출물의 혼합물(CL1, CL2, CL3)의 처리에 따른 혈관내피세포에서의 단핵구의 흡착정도를 나타내는 그래프이다.
도 2는 TNF-α를 처리한 혈관내피세포에서 CL1 처리군의 THP-1 단핵구 부착 억제 효과를 확인한 결과이다.
도 3은 TNF-α를 처리한 혈관내피세포에서 CL2 처리군의 THP-1 단핵구 부착 억제 효과를 확인한 결과이다.
도 4는 TNF-α를 처리한 혈관내피세포에서 CL1 또는 CL2 처리군의 VCAM-1 및 ICAM-1의 단백질 발현 정도를 확인한 웨스턴 블롯 결과이다.
도 5는 TNF-α를 처리한 혈관내피세포에서 CL1 처리군의 VCAM-1, ICAM-1, MCP-1, eNOS의 유전자 발현 수준을 확인한 실시간 RT-PCR 분석 결과이다.
도 6은 TNF-α를 처리한 혈관내피세포에서 CL2 처리군의 VCAM-1, ICAM-1, MCP-1, eNOS의 유전자 발현 수준을 확인한 실시간 RT-PCR 분석 결과이다.
도 7은 TNF-α를 처리한 혈관내피세포에서 CL1 또는 CL2 처리군의 NF-κB 핵 내 이동 및 IκBα의 분해 여부를 확인한 결과이다.
도 8은 TNF-α를 처리한 혈관내피세포에서 CL1 또는 CL2 처리군의 ERK, JNK, p38의 활성을 확인한 결과이다.
도 9는 산사자 열수 추출물(CE), 택란 열수 추출물(LE), 산사자 및 택란의 열수 추출물의 혼합물(CL1, CL2, CL3)의 처리에 따른 고지혈증 유도 마우스의 혈중 중성지방 농도 변화를 나타낸 그래프이다.
도 10은 산사자 열수 추출물(CE), 택란 열수 추출물(LE), 산사자 및 택란의 열수 추출물의 혼합물(CL1, CL2, CL3)의 처리에 따른 고지혈증 유도 마우스의 혈중 총 콜레스테롤 농도 변화를 나타낸 그래프이다.1 is a graph showing the degree of adsorption of monocytes in vascular endothelial cells according to the treatment of a mixture (CL1, CL2, CL3) of a hot water extract of Sansaja (CE), a hot water extract of Taxan (LE), and a hot water extract of Sansaja and Taxan.
Figure 2 is a result confirming the inhibitory effect of TH1-1 monocyte adhesion of the CL1 treatment group in TNF-α-treated vascular endothelial cells.
Figure 3 is a result confirming the inhibitory effect of TH2-1 monocyte adhesion of the CL2 treatment group in TNF-α-treated vascular endothelial cells.
4 is a Western blot result confirming the protein expression level of VCAM-1 and ICAM-1 in CL1 or CL2 treated groups in TNF-α-treated vascular endothelial cells.
Figure 5 is a real-time RT-PCR analysis results confirming the gene expression level of VCAM-1, ICAM-1, MCP-1, eNOS of CL1 treatment group in TNF-α-treated vascular endothelial cells.
Figure 6 is a real-time RT-PCR analysis results confirming the gene expression level of VCAM-1, ICAM-1, MCP-1, eNOS of CL2 treatment group in TNF-α-treated vascular endothelial cells.
7 is a result confirming whether the CL1 or CL2 treated group in the NF-κB nucleus moves and decomposes IκBα in TNF-α-treated vascular endothelial cells.
8 is a result confirming the activity of ERK, JNK, p38 of CL1 or CL2 treatment group in TNF-α-treated vascular endothelial cells.
FIG. 9 is a graph showing changes in triglyceride concentration in the blood of hyperlipidemia-induced mice according to treatment of a mixture (CL1, CL2, CL3) of a hot water extract of Sansaja (CE), a hot water extract of Taxan (LE), and a hot water extract of Sansaja and Taxan.
10 is a graph showing changes in total cholesterol concentration in the blood of hyperlipidemia-inducing mice according to treatment of a mixture (CL1, CL2, CL3) of a hot water extract of Sansaja (CE), a hot water extract of Taxan (LE), and a hot water extract of Sansaja and Taxan.
이하 하나 이상의 구체예를 실시예를 통하여 보다 상세하게 설명한다. 그러나, 이들 실시예는 하나 이상의 구체예를 예시적으로 설명하기 위한 것으로 본 발명의 범위가 이들 실시예에 한정되는 것은 아니다.Hereinafter, one or more specific examples will be described in more detail through examples. However, these examples are intended to illustrate one or more embodiments by way of example, and the scope of the present invention is not limited to these examples.
실시예Example 1 : 산사자 및 1: Sansa and 택란Taklan 추출물의 제조 Preparation of extract
산사자 및 택란 추출물을 제조하기 위하여, 하기와 같은 방법으로 열수 추출하였다. 산사자 300 g, 택란 300 g을 각각 3L의 생수와 함께 약탕기에 넣고 1시간 동안 침적시킨 다음, 4시간 동안 가열하여 추출하였다. 이후, 각각의 추출물을 여과망으로 여과한 후, 감압농축기로 농축하여 실험에 사용하였다.In order to prepare an extract of hawthorn and taxane, hot water was extracted as follows. 300 g of mountain lion and 300 g of taxane were placed in a water bath together with 3 L of bottled water, and then immersed for 1 hour, followed by extraction by heating for 4 hours. Subsequently, each extract was filtered through a filter screen, and then concentrated using a vacuum concentrator for use in the experiment.
실시예Example 2 : 산사자 및 2: Sansa and 택란Taklan 추출물의 항동맥경화 효과 확인 Confirmation of anti-atherosclerotic effect of extract
실시예Example 2-1 : 혈관내피세포에서의 단핵구의 흡착 감소 효과 2-1: Effect of reducing the adsorption of monocytes in vascular endothelial cells
단핵구와 T-세포와 같은 면역세포들은 체내 혈관 내에서 염증이나 혈관의 손상부위를 인지하여 셀렉틴(Selectin)이라는 세포부착 물질을 통해 혈관세포에 흡착하여 혈관 내부로 침투한다. 그 결과, 염증 반응 및 동맥 경화 단계가 가속화되는 현상을 보이게 된다. 본 실험에서는 산사자 추출물, 택란 추출물 또는 이들의 혼합물이 혈관내피세포에서 단핵구 흡착의 억제하는지 여부를 확인하였다.Immune cells, such as monocytes and T-cells, penetrate into the blood vessels by recognizing inflammation or damage to blood vessels in the body's blood vessels, adsorbing on blood vessel cells through a cell attachment substance called Selectin. As a result, the inflammatory reaction and the arteriosclerosis step is accelerated. In this experiment, it was confirmed whether the Sansaja extract, the Taxane extract, or a mixture thereof inhibits monocyte adsorption in vascular endothelial cells.
상기 실시예 1에서 제조한 산사자 추출물(CE), 택란 추출물(LE), 산사자 추출물과 택란 추출물을 각각 0.5:1(CL1), 1:1(CL2), 1:0.5(CL3)의 부피비로 혼합한 추출물을 준비하고, 혈관내피세포(HUVEC)에 TNF-α를 처리한 후, 10 μM의 형광물질(BCECF-AM, 2',7'-Bis-(2-Carboxyethyl)-5-(and-6)-Carboxyfluorescein, Acetoxymethyl Ester)을 37℃에서 40분 동안 반응시키고, THP-1 세포와 함께 37℃에서 배양하였다.The Sansaja extract (CE), the Taxan extract (LE), the Sansaja extract and the Taxan extract prepared in Example 1 were 0.5: 1 (CL1), 1: 1 (CL2), respectively. Prepare a mixed extract at a volume ratio of 1: 0.5 (CL3), treat TNF-α on vascular endothelial cells (HUVEC), and then 10 μM fluorescent material (BCECF-AM, 2 ', 7'-Bis- ( 2-Carboxyethyl) -5- (and-6) -Carboxyfluorescein, Acetoxymethyl Ester) was reacted at 37 ° C for 40 minutes, and cultured at 37 ° C with THP-1 cells.
그 결과, 도 1에서 보는 바와 같이, 대조군에서는 THP-1 세포와 HUVEC이 결합하여 형광물질의 농도가 증가하였으나, LE, CL1, CL2 처리군에서는 이러한 현상이 농도 증가에 따라 감소하여 최대 농도에서 32%, 49%, 26% 정도 감소시키는 것을 확인하였다. 또한, CL1 또는 CL2 처리군에서 THP-1 세포의 흡착 정도를 비교한 결과, 처리 농도가 증가할수록 THP-1 세포의 부착 정도가 감소함을 확인할 수 있었다(도 2 및 도.3).As a result, as shown in FIG. 1, in the control group, THP-1 cells and HUVEC were combined to increase the concentration of the fluorescent substance, but in the LE, CL1, and CL2 treatment groups, this phenomenon decreased as the concentration increased, resulting in a maximum concentration of 32. %, 49% and 26%. In addition, as a result of comparing the degree of adsorption of THP-1 cells in the CL1 or CL2 treatment group, it was confirmed that the degree of adhesion of THP-1 cells decreased as the treatment concentration increased (FIGS. 2 and 3).
실시예 2-2 : 혈관내피세포에서의 Example 2-2: In vascular endothelial cells TNFTNF -α에 의해 발현되는 -expressed by α 세포간Intercellular 부착물질의 발현 억제 효과 Effect of suppressing the expression of adhesion substances
본 실험에서는 CL1 또는 CL2의 처리가 혈관내피세포에서 세포간 부착물질인 VCAM-1과 ICAM-1 단백질의 발현에 어떠한 영향을 미치는지 웨스턴 블롯 분석을 통해 확인하였다.In this experiment, it was confirmed by Western blot analysis that the treatment of CL1 or CL2 affects the expression of the intercellular adhesion substances VCAM-1 and ICAM-1 proteins in vascular endothelial cells.
도 4에서 보는 바와 같이, 혈관내피세포에 TNF-α를 처리한 대조군에서는 VCAM-1과 ICAM-1의 발현이 증가되었으나, CL1 또는 CL2를 처리하였을 때, 처리한 농도가 증가함에 따라 VCAM-1 및 ICAM-1의 발현이 억제됨을 확인할 수 있었다.As shown in FIG. 4, in the control group treated with TNF-α on vascular endothelial cells, expression of VCAM-1 and ICAM-1 was increased, but when treated with CL1 or CL2, VCAM-1 as the concentration increased. And it was confirmed that the expression of ICAM-1 is suppressed.
실시예 2-3 : Example 2-3: 세포간Intercellular 부착물질, 케모카인( Attachment substance, chemokine ( chemokine)의chemokine) 발현 억제 효과 및 Expression suppression effect and eNOSeNOS 발현 상승 효과 Synergistic effect
CL1 또는 CL2의 세포간 부착물질 조절 능력을 mRNA 수준에서 확인하기 위해, real time RT-PCR로 정량화 하였다. 그 결과, 도 5에서 보는 바와 같이, 혈관내피세포에 TNF-α를 처리하였을 때, 세포간 부착물질과 케모카인과 사이토카인의 발현이 현저하게 증가되었으나, CL1을 처리한 군에서는 VCAM-1, ICAM-1, IL-1β, MCP-1의 발현이 CL1의 처리 농도가 증가함에 따라 억제되었으며, 혈관의 이완에 관여하는 eNOS는 CL1의 처리 농도 증가에 따라 상승하는 것으로 확인되었다(도 5).In order to check the ability of CL1 or CL2 to regulate the adhesion between the cells at the mRNA level, it was quantified by real time RT-PCR. As a result, as shown in FIG. 5, when TNF-α was treated with vascular endothelial cells, the expression of intercellular adhesion substances, chemokines and cytokines was significantly increased, but in the group treated with CL1, VCAM-1, ICAM Expression of -1, IL-1β, and MCP-1 was suppressed as the treatment concentration of CL1 increased, and eNOS involved in the relaxation of blood vessels was confirmed to increase as the treatment concentration of CL1 increased (FIG. 5).
또한, CL2를 처리한 군에서는 VCAM-1의 발현은 100 μg/ml에서 유의적인 억제효과를 나타내었고, ICAM-1은 CL2를 50 μg/ml과 100 μg/ml의 농도로 처리한 군에서 유의성을 나타내었지만, MCP-1은 큰 효과가 나타나지 않았다. 한편, eNOS는 경우 저농도에서 유의적인 상승효과를 나타냈지만, 고농도에서는 큰 효과가 나타나지 않았다(도 6). In addition, in the group treated with CL2, expression of VCAM-1 showed a significant inhibitory effect at 100 μg / ml, and ICAM-1 was significant in the group treated with CL2 at concentrations of 50 μg / ml and 100 μg / ml. , But did not show a significant effect on MCP-1. On the other hand, eNOS showed a significant synergistic effect at low concentrations, but did not show a large effect at high concentrations (FIG. 6).
결과적으로 산사자 및 택란 추출물의 혼합물은 동맥경화발생에 영향을 주는 유발물질들, 즉, 세포간 부착물질 및 케모카인의 발현을 조절할 수 있어 동맥경화발생 억제에 기여할 수 있을 것으로 판단되며, 특히 CL1은 CL2에 비해 동맥경화 억제 효과가 우수함을 확인할 수 있었다.As a result, it is determined that the mixture of the Sansa and the taklan extracts can contribute to the suppression of atherosclerosis by controlling the expression of inducers that affect atherosclerosis, i.e., intercellular adhesion substances and chemokines, especially CL1 is CL2 It was confirmed that the effect of suppressing arteriosclerosis was superior.
실시예 2-4 : Example 2-4: NFNF -- κBκB p65의 p65 핵내Nuclear 이동 및 Move and II κκ Bα의Bα 인산화, 분해 억제 효과 Phosphorylation and decomposition inhibitory effect
상기 실시예에서 확인한 다양한 염증 유발에 대한 산사자 및 택란 추출물의 혼합물인 CL1과 CL2의 억제 효과가 어떤 작용기작에 의해 일어나는지를 알아보기 위해, 가장 대표적인 전사인자인 NF-κB의 활성을 확인하였다.In order to find out by what action mechanism the inhibitory effect of CL1 and CL2, which is a mixture of Sansa and Taxane extracts, against various inducing inflammations identified in the above Examples, the activity of NF-κB, the most representative transcription factor, was confirmed.
통상적으로 NF-κB의 활성을 조절할 수 있는 단백질인 IκBα의 변화를 살펴보았는데, 혈관내피세포에 TNF-α를 처리하면, 5분 후에 IκBα는 인산화가 일어나면서 분해된다. 이후 30분 정도에는 IκBα가 다시 재생되어 1시간 정도 지나면 원상복귀가 된다. 따라서, 본 실험에서는 5~20분 사이의 IκBα 변화를 관찰하였다. Normally, changes in IκBα, a protein that can regulate the activity of NF-κB, were examined. When TNF-α is treated on vascular endothelial cells, IκBα is degraded after phosphorylation occurs after 5 minutes. After 30 minutes, IκBα is regenerated again, and after about an hour, it returns to its original state. Therefore, in this experiment, IκBα changes between 5 and 20 minutes were observed.
도 7에서 보는 바와 같이, TNF-α 처리에 의하여 IκBα는 5분 이후에 인산화와 분해현상이 관찰되었으며(대조군), CL1 또는 CL2는 TNF-α 처리 후 5분까지 IκBα의 분해를 억제하였을 뿐, 시간이 지날수록 IκBα의 단백질 가수분해(proteolysis)를 억제하지는 못하는 것으로 확인되었다. As shown in FIG. 7, phosphorylation and decomposition of IκBα was observed after 5 minutes by TNF-α treatment (control), and CL1 or CL2 inhibited the degradation of IκBα until 5 minutes after TNF-α treatment. Over time, it was confirmed that protein proteolysis of IκBα was not inhibited.
한편, NF-κB p65는 처음에는 IκBα와 결합되어 세포질 내에서 비활성 상태로 존재하고 있다가 TNF-α와 같은 자극을 받게 되면 IκBα의 분해로 인해 자유로이 핵 내로 이동하게 되며, 이후 타겟 유전자에 결합되어 염증유발인자를 생성하게 된다. 혈관내피세포에 TNF-α를 처리하면, 10분 정도 후에 TNF-α를 처리하지 않은 군과 비교될 정도로 많은 양의 NF-κB p65가 핵내로 이동이 시작된다. 도 7에서 보는 바와 같이, 이러한 시간 증가에 따른 NF-κB p65의 핵내 이동을 CL1 또는 CL2가 억제함으로써 NF-κB 활성을 억제하는 것을 확인할 수 있었다.On the other hand, NF-κB p65 initially binds to IκBα and remains inactive in the cytoplasm, and upon stimulation such as TNF-α, it is freely moved into the nucleus due to decomposition of IκBα, and then is bound to the target gene It produces inflammatory factors. When TNF-α is treated with vascular endothelial cells, a large amount of NF-κB p65 begins to move into the nucleus after about 10 minutes, compared to the group not treated with TNF-α. As shown in FIG. 7, it was confirmed that CL1 or CL2 inhibits NF-κB activity by inhibiting intranuclear movement of NF-κB p65 with increasing time.
실시예 2-5 :혈관내피세포에서의 MAPK 활성 조절Example 2-5: MAPK activity regulation in vascular endothelial cells
상기 실시예 2-4에서 확인한 바와 같이, 산사자 및 택란 추출물의 혼합물은 다양한 염증유발인자들의 발현을 조절할 수 있는데, 그 작용기작은 NF-κB가 관여하는 것으로 확인되었다. 이에, 추가적인 세포내 신호전달을 찾기 위해 대표적인 신호전달 인자인 MAPK 신호전달을 살펴보았다. As confirmed in Example 2-4, the mixture of Sansaja and Taxan extract can control the expression of various inflammatory factors, and the mechanism of action was confirmed to be involved in NF-κB. Therefore, we looked at MAPK signaling, a representative signaling factor, to find additional intracellular signaling.
도 8에서 보는 바와 같이, CL1 또는 CL2의 처리는 TNF-α에 의해 인산화되는 3종의 MAPK(ERK, JNK, p38)를 농도 의존적으로 억제함을 확인할 수 있었으며, 특히, CL1 처리군은 ERK와 JNK MAPK의 억제 효과가 더 우수한 것으로 확인되었다. 이러한 결과는 산사자 및 택란 추출물의 혼합물이 상당 부분 NF-κB의 신호전달을 조절함과 동시에 3종의 MAPK를 조절함으로써 다양한 염증유발인자들의 발현을 조절함을 나타낸다.As shown in FIG. 8, it was confirmed that the treatment of CL1 or CL2 inhibited concentration-dependently three kinds of MAPK (ERK, JNK, p38) phosphorylated by TNF-α, and in particular, the CL1 treatment group was treated with ERK. It was confirmed that the inhibitory effect of JNK MAPK is better. These results indicate that the mixture of the Sansa and the taxane extracts significantly regulates the signaling of NF-κB and at the same time regulates the expression of various inflammatory factors by controlling three MAPKs.
실시예 3 : 마우스 모델에서 산사자 및 택란 추출물의 항고지혈증 효과 확인Example 3: Confirmation of antihyperlipidemic effect of Sansa and Taxane extract in mouse model
실시예 3-1 : Poloxamer-407 유발 고지혈증 모델Example 3-1: Poloxamer-407 induced hyperlipidemia model
본 실험을 위하여 사용된 C57BL/6J(6주령, 수컷, 18~22 g)는 대한바이오링크(Korea)에서 구입하였다. 실험동물은 2주간의 안정기를 가지면서 순화를 시켰으며, 안정기 동안 모든 실험군에는 일반 사료(㈜퓨리나, Korea)를 자유식이 하였다. 동물 사육실의 조건은 일반 동물 사육 시스템(conventional system)으로 22±2 ℃, 1일 중 12시간은 200-300 Lux로 조명하고, 12시간 동안 모든 빛을 차단하였다.C57BL / 6J (6 weeks old, male, 18-22 g) used for this experiment was purchased from Daehan Biolink (Korea). The experimental animals were purified with a two-week stabilization period, and during the stabilization period, all the experimental groups were fed free diet (Purina, Korea). The conditions of the animal breeding room are general animal breeding systems (22 ± 2 ° C), 12 hours of the day were illuminated with 200-300 Lux, and all light was blocked for 12 hours.
생리 식염수에 용해시킨 poloxamer-407 (300 mg/1mL/kg 기준으로 1/2 양씩)을 마우스에 1회 피하 투여하여 고지혈증을 유발시키고, 산사자 및 택란 추출물의 혼합물(0.5:1, 1:1, 1:0.5, v/v)을 농도별로 하루에 두 번 경구 투여한 다음, 24시간 후 채혈하고 중성지방(triglyceride) 및 총 콜레스테롤(total cholesterol) 수치를 측정하였다. 한편, 실험의 효과를 극대화하기 위하여, 고지혈증 유발 농도는 150mg/1mL/kg(150T)로 설정하였다.The poloxamer-407 dissolved in physiological saline (1/2 dose based on 300 mg / 1 mL / kg) was subcutaneously administered to the mouse once to induce hyperlipidemia, and a mixture of Sansa and Taxane extract (0.5: 1, 1: 1, 1: 0.5, v / v) was administered orally twice a day for each concentration, and then, after 24 hours, blood was collected and triglyceride and total cholesterol levels were measured. On the other hand, in order to maximize the effect of the experiment, the hyperlipidemia-inducing concentration was set to 150 mg / 1 mL / kg (150T).
실시예 3-2 : 고지혈증 유도 마우스 모델에서 산사자와 택란 추출물의 효능 평가Example 3-2: Evaluation of efficacy of Sansaja and Taxane extract in hyperlipidemia-induced mouse model
산사자 추출물 단독군(100 mg/kg), 택란 추출물 단독군(100 mg/kg), 산사자와 택란 추출물의 혼합물(100 mg/kg) 비율별(0.5:1, 1:1, 1:0.5, v/v, 각각 CL1, CL2, CL3로 표기함)로 샘플을 준비하여 poloxamer-407 (150 mg/1mL/kg 기준) 동물 모델(n=6)에서 효능을 확인하였다. 양성 대조군으로는 Atorvastatin(50 mg/kg)을 사용하였다.Sansaja extract alone group (100 mg / kg), taxane extract alone group (100 mg / kg), mixture of Sansaza and taxane extract (100 mg / kg) by ratio (0.5: 1, 1: 1, 1: 0.5, v / v, CL1, CL2, and CL3, respectively, to prepare samples and confirm efficacy in the poloxamer-407 (150 mg / 1 mL / kg standard) animal model (n = 6). Atorvastatin (50 mg / kg) was used as a positive control.
도 9에서 보는 바와 같이, poloxamer-407 대조군 그룹에 비해 산사자 추출물 단독군(CE), 택란 추출물 단독군(LE)의 중성지방의 감소 효과는 크지 않았으나, 산사자와 택란 추출물의 혼합물(CL2)은 통계적으로 유의하게 중성지방을 감소시키는 것으로 확인하였다(P*<0.05).As shown in FIG. 9, compared to the poloxamer-407 control group, the effect of reducing triglycerides in the Sansa extract alone group (CE) and the Taxan extract alone group (LE) was not significant, but the mixture of the Sansaza and Taxan extract (CL2) was statistical. It was confirmed to significantly reduce triglyceride (P * <0.05).
또한, 산사자 단독군(CE)과 택란 단독군(LE)와 비교할 때, 총 콜레스테롤의 감소 효과는 산사자 및 택란 추출물의 혼합물(CL1 및 CL2) 처리군에서 통계적으로 유의하게 나타났다(P**<0.01, P*<0.05)(도 10).In addition, when compared with the Sansa alone group (CE) and the Taxan alone group (LE), the effect of reducing total cholesterol was statistically significant in the treatment group (CL1 and CL2) of the Sansa and Taxan extract (P ** <0.01). , P * <0.05) (FIG. 10).
이제까지 본 발명에 대하여 그 바람직한 실시예들을 중심으로 살펴보았다. 본 발명이 속하는 기술 분야에서 통상의 지식을 가진 자는 본 발명이 본 발명의 본질적인 특성에서 벗어나지 않는 범위에서 변형된 형태로 구현될 수 있음을 이해할 수 있을 것이다. 그러므로 개시된 실시예들은 한정적인 관점이 아니라 설명적인 관점에서 고려되어야 한다. 본 발명의 범위는 전술한 설명이 아니라 특허청구범위에 나타나 있으며, 그와 동등한 범위 내에 있는 모든 차이점은 본 발명에 포함된 것으로 해석되어야 할 것이다.So far, the present invention has been focused on the preferred embodiments. Those skilled in the art to which the present invention pertains will understand that the present invention can be implemented in a modified form without departing from the essential characteristics of the present invention. Therefore, the disclosed embodiments should be considered in terms of explanation, not limitation. The scope of the present invention is shown in the claims rather than the foregoing description, and all differences within the equivalent range should be interpreted as being included in the present invention.
Claims (6)
A pharmaceutical composition for the prevention or treatment of lipid-related cardiovascular disease or obesity, comprising a mixture of hawthorn extract and taxane extract.
The composition of claim 1, wherein the Sansaja extract and the Taxane extract are hot water extracts.
The composition of claim 1, wherein the mixture is a mixture of Sansa extract and Taxan extract in a volume ratio of 1: 2 to 2: 1.
According to claim 1, wherein the cardiovascular disease is atherosclerosis, hypertension, myocardial infarction, stroke, hyperlipidemia, ischemic heart disease, cardiac arrhythmia, heart failure, angina, endocarditis, heart valve disorder, conduction disorder, and ischemic cerebrovascular disease The composition is one or more selected from the group.
The composition of claim 1, wherein the mixture improves obesity symptoms by reducing triglycerides and total cholesterol in the blood.
A food composition for preventing or improving lipid-related cardiovascular disease or obesity, comprising a mixture of hawthorn extract and taxane extract.
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KR101910317B1 (en) * | 2018-01-31 | 2018-10-19 | 경북대학교 산학협력단 | Composition for preventing, treating or improving obesity comprising extracts of Lycopus lucidus Turcz. |
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KR100787175B1 (en) | 2006-06-02 | 2007-12-21 | 동국대학교 산학협력단 | A herbal mixture extract comprising Atractylodis Rhizoma Alba, Gastrodia elata, Aurantii nobilis pericarpium, Poria cocos, Crataegur, Siegesbeckia glabrescens Makino, and food supplement comprising the same for prevention and treatment of Arteriosclerosis |
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