KR20160141986A - A composition comprising red ginseng and lactic acid bacteria for preventing, improving or treating vascular disease - Google Patents
A composition comprising red ginseng and lactic acid bacteria for preventing, improving or treating vascular disease Download PDFInfo
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- KR20160141986A KR20160141986A KR1020150077729A KR20150077729A KR20160141986A KR 20160141986 A KR20160141986 A KR 20160141986A KR 1020150077729 A KR1020150077729 A KR 1020150077729A KR 20150077729 A KR20150077729 A KR 20150077729A KR 20160141986 A KR20160141986 A KR 20160141986A
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- red ginseng
- lactic acid
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- vascular
- acid bacteria
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Abstract
Description
본 발명은 혈관질환을 예방, 개선 또는 치료하기 위한 조성물에 관한 것으로, 더욱 상세하게는 홍삼 및 유산균을 혼합하여 발효한 발효물을 유효성분으로 함유하는 조성물에 관한 것이다. The present invention relates to a composition for preventing, ameliorating or treating vascular diseases, and more particularly, to a composition containing fermented product fermented by mixing red ginseng and lactic acid bacteria as an active ingredient.
본 발명에 따른 조성물은, 고과당식이 랫드 모델에서 혈압을 강하시키는 효능, 혈관 병변을 완화시키는 효능 및 ICAM-1(intercellular adhesion molecule-1), VCAM-1(vascular cell adhesion molecule-1)과 ET-1(endothelin-1)의 발현을 감소시키는 효능을 보유하고 있다.
The composition according to the present invention is effective in lowering blood pressure, efficacy of alleviating vascular lesions, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) -1 < / RTI > (endothelin-1) expression.
최근 산업화에 따른 생활양식의 변화로 고혈압, 관상동맥질환, 죽상경화증 또는 고지혈증과 같은 혈관질환의 발생이 증가하고 있으며, 혈관질환을 일차적인 임상 결과로 하는 대사증후군의 유병율도 계속 증가하고 있는 실정이다.Recently, changes in lifestyle due to industrialization have increased the incidence of vascular diseases such as hypertension, coronary artery disease, atherosclerosis or hyperlipidemia, and the prevalence of metabolic syndrome which is the primary clinical result of vascular disease is also increasing .
위와 같은 혈관질환으로 인해, 단순 부종에서 혈관과 림프관의 염증, 혈관의 이상 수축 또는 팽창, 출혈, 혈전에 의한 폐색 등의 증상이 나타날 수 있다.
Due to these vascular diseases, simple edema can cause symptoms such as inflammation of blood vessels and lymph vessels, abnormal shrinkage or swelling of blood vessels, bleeding, and clogging due to thrombosis.
고지혈증이나 죽상경화증이 발생하면 혈압이 높아지게 되며, 이는 심혈관질환과 뇌혈관질환의 원인이 될 수 있다. 또한 혈관당뇨나 간장질환도 연계되어 각종 성인병이 발생하게 된다. When hyperlipidemia or atherosclerosis occurs, blood pressure increases, which can be a cause of cardiovascular disease and cerebrovascular disease. In addition, diabetes mellitus and liver disease are linked to various adult diseases.
이를 예방하기 위해서는, 혈압강하 및 혈관 염증의 예방 또는 치료가 중요하다고 할 수 있다.
In order to prevent this, blood pressure reduction and prevention or treatment of vascular inflammation are important.
그러나 종래에 사용되는 화학적 혈관 이완제 등의 치료제는, 생체 내에 내피 손상, 용혈, 급성 독성이나 어독성, 급성 신장염 또는 심장마비 등의 부작용을 초래하는 경우가 있었으며, 생산 공정이 까다로워 대량 생산이 용이하지 못하다는 문제점이 있었다.
However, conventionally used therapeutic agents such as chemical vasoconstrictors cause side effects such as endothelial damage, hemolysis, acute toxicity or fish toxicity, acute nephritis or heart attack in a living body, and the production process is difficult and mass production is easy There was a problem that it was not possible.
이에 본 출원인은 천연물을 이용함으로써 부작용이 없으며, 장기 복용하여도 독성이 없고, 혈관질환을 예방, 개선 또는 치료하는 데에 효과가 있는 본 발명을 안출하였다.
Accordingly, the present applicant has discovered the present invention, which is effective for preventing, ameliorating or treating vascular diseases without using side effects by using natural products, having no toxicity even if taken for a long time.
본 발명은 홍삼 및 유산균을 소재로 사용하는바, 홍삼 및 유산균에 대하여 간략하게 설명하고자 한다.
The present invention uses red ginseng and lactic acid bacteria as materials, and briefly describes red ginseng and lactic acid bacteria.
홍삼(紅蔘)은 수삼(水蔘, Panax ginseng C.A. Meyer)의 뿌리를 쪄서 말린 붉은 인삼을 말한다.Red ginseng (ginseng) ginseng (ginseng, Panax ginseng CA Meyer) refers to dried red ginseng steamed roots.
홍삼의 중요 성분으로는 백삼과 같이 배당체(glycosides), 인삼향성분(panacen), 폴리아세틸렌계 화합물, 함질소성분, 플라보노이드, 비타민(B군), 미량원소, 효소, 항산화 물질과 유기산 및 아미노산 등이 있다.Important components of red ginseng include glycosides, panacen, polyacetylenic compounds, nitrogenous compounds, flavonoids, vitamins (B group), trace elements, enzymes, antioxidants, organic acids and amino acids .
홍삼은 중추신경에 대해서 진정작용과 흥분작용이 있으며, 순환계에 작용하여 고혈압이나 동맥경화의 예방효과가 있다고 알려져 있다. 그외에도 혈당치(血糖値)를 저하시켜 주고, 간을 보호하며, 내분비계에 작용하여 성행동(性行動)이나 생식효과에 간접적으로 유효하게 작용하며, 항염(抗炎) 및 항종양작용(抗腫瘍作用)이 있고, 방사선에 대한 방어효과와 피부를 보호하며 부드럽게 하는 작용이 있다. Red ginseng has sedative and excitatory effects on the central nervous system and acts on the circulatory system to prevent hypertension and arteriosclerosis. In addition, it reduces the blood sugar level (blood sugar level), protects the liver, acts on the endocrine system and indirectly acts on sexual behavior (sexual behavior) and reproductive effect, and anti-inflammatory and anti- Tumor effect), radiation protection, skin protection and softening action.
또한 홍삼은 피로회복, 면역력 증진, 혈소판 응집 억제를 통한 혈액 흐름 개선에 관한 기능성이 인정되었다.
In addition, red ginseng has been recognized as functional for improvement of blood flow through fatigue recovery, immunity enhancement, and inhibition of platelet aggregation.
유산균(lactic acid bacteria)은 당류를 발효하여 에너지를 획득하고 다량의 락트산을 생성하는 세균을 이르는 것으로, 젖산균이라고도 한다. Lactic acid bacteria are lactic acid bacteria, which ferment saccharides to obtain energy and produce bacteria that produce large amounts of lactic acid.
유산균의 정의에 적합한 것은 Lactobacillus , Lactococcus , Leuconostoc , Pediococcus, Bifidobacterium 등의 균속이다. 형태적으로는 구균(Lactococcus , Pediococcus, Leuconostoc )과 간균( Lactobacillus , Bifidobacterim)으로 나누어지고 그람(Gram) 염색성은 양성이다. 어느 것이나 산소가 적은 환경에서 잘 발육하여 각종 당으로부터 락트산을 생성한다. 산에 내성을 나타내는 것이 많고 영양요구성은 매우 복잡하여 당류 이외에 많은 종류의 아미노산이나 비타민을 요구하며 균종, 균주에 따라 미량 영양소를 가하지 않으면 생육할 수 없는 것도 있다. Lactobacillus , Lactococcus , Leuconostoc , Pediococcus, and Bifidobacterium are suitable for the definition of lactic acid bacteria. It is divided into two types, Lactococcus , Pediococcus and Leuconostoc , and Lactobacillus and Bifidobacterim . Gram stain is positive. Both develop well in an environment of low oxygen and produce lactic acid from various sugars. Many of them show tolerance to acids, and their nutritional requirements are very complex. They require many kinds of amino acids and vitamins in addition to sugars. Some bacteria can not grow unless added with trace nutrients depending on the strain.
이중 Lactobacillus는 대표적인 유산균으로서 각종 발효식품에 사용되고, 또한 장관 상재 균총으로서 사람이나 동물의 건강과 중요한 관계가 있다.
Lactobacillus is a typical lactobacillus which is used in various fermented foods and also has an important relation with human and animal health as a superficial glutinous fungus.
한편, 본 발명과 관련된 선행문헌을 살펴보면 대한민국 등록특허공보 제10-1392204호에 홍삼, 당귀, 진피 및 녹차의 생약 추출물을 함유하는 혈관 질환의 예방 또는 치료용 조성물이 기재되어 있다.Meanwhile, Korean Patent Publication No. 10-1392204 discloses a composition for preventing or treating vascular diseases containing herbal extracts of red ginseng, angelica gingiva, dermis, and green tea in a prior art document related to the present invention.
더욱 상세히 상기 문헌에는 홍삼, 당귀, 진피 및 녹차의 생약 추출물을 함유하는 것을 특징으로 하는 동맥경화증, 협심증, 심근경색, 허혈성 심장질환, 뇌경색 및 뇌졸중에서 선택되는 혈관 질환의 예방 또는 치료용 조성물이 기재되어 있다.
More particularly, the present invention provides a composition for preventing or treating vascular diseases selected from arteriosclerosis, angina pectoris, myocardial infarction, ischemic heart disease, cerebral infarction and stroke, which comprises extracts of herbal medicine of red ginseng, .
또한 대한민국 등록특허공보 제10-1517836호에 홍삼 복합물을 유효성분으로 함유하는 죽상경화증의 예방, 개선 또는 치료를 위한 조성물이 기재되어 있다.Korean Patent Registration No. 10-1517836 discloses a composition for preventing, ameliorating or treating atherosclerosis containing an effective component of a complex of red ginseng.
상기 문헌에는 홍삼 추출물, 천마 추출물, 적하수오 추출물 및 상엽 추출물을 혼합한 홍삼 복합물을 유효성분으로 함유하는 조성물로서, 상기 홍삼 복합물은 홍삼 추출물 300 중량부 기준으로, 천마 추출물 100 중량부, 적하수오 추출물 100 중량부 및 상엽 추출물 100 중량부를 혼합하여 제조되고, 상기 조성물은 체내에서 항산화 작용을 하는 효능, 체내에서 항염증 작용을 하는 효능, 혈관 내 CRP(C 반응 단백)를 감소시키는 효능, 혈관 내 평활근의 비후 및 내피세포의 비정상적 비대를 억제하는 효능, 혈관 내의 VCAM-1(vascular cell adhesion molecule), ICAM-1(intercellular adhesion molecule)과 E-selection을 감소시키는 효능 및 혈관 내 PPAR-γ를 증가시키는 효능을 보유하는 것을 특징으로 하는 죽상경화증의 예방 또는 개선을 위한 건강기능식품 조성물이 기재되어 있다.
The above red ginseng complex comprises 300 parts by weight of a red ginseng extract, 100 parts by weight of a ginseng extract, 100 parts by weight of a red ginseng extract, a red ginseng extract, And 100 parts by weight of the leaf extract, wherein the composition has an antioxidative effect in the body, an anti-inflammatory effect in the body, an effect of reducing vascular CRP (C reactive protein), a vascular smooth muscle (Vascular cell adhesion molecule), ICAM-1 (intercellular adhesion molecule) and E-selection, and an increase in intravascular PPAR-gamma Or a pharmaceutically acceptable salt thereof. The present invention also relates to a health functional food composition for preventing or ameliorating atherosclerosis.
논문에서는, 경희대학교 동서의학대학원 동서의학과 학위논문(박사) '홍삼 투여에 따른 혈관변화 및 혈관에 영향을 주는 혈액학적 지표에 대한 연구'에 홍삼의 투여가 혈관 이완 촉진 및 혈관염증 반응 억제에 대해 효과가 있다는 내용이 기재되어 있다.
In the thesis, the dissertation of Professor Dong Sung Medical Dept. of Dongseo Medical School, Kyung Hee University, "The study on the hematological index that affects blood vessel changes and blood vessels according to administration of red ginseng" It is said that the effect is effective.
그러나 상기 선행문헌들에는 본 발명의 소재 중 홍삼만이 포함되어 있으며, 홍삼 및 유산균의 혼합발효에 의한 상승효과에 대해서는 알 수 없다는 문제점이 있다.
However, the above-mentioned prior arts contain only red ginseng among the materials of the present invention, and there is a problem that the synergistic effect of mixed germination of red ginseng and lactic acid bacteria can not be known.
본 발명에서 해결하고자 하는 과제는 혈관질환을 예방, 개선 또는 치료하기 위한 조성물로서, 홍삼 및 유산균을 혼합하여 발효한 발효물을 유효성분으로 함유하는 조성물을 제공하는 데에 있다. A problem to be solved by the present invention is to provide a composition containing a fermented product fermented by mixing red ginseng and lactic acid bacteria as an active ingredient, for preventing, improving or treating vascular diseases.
본 발명에서 해결하고자 하는 과제는 고과당식이 랫드 모델에서 혈압을 강하시키는 효능, 혈관 병변을 완화시키는 효능 및 ICAM-1(intercellular adhesion molecule-1), VCAM-1(vascular cell adhesion molecule-1)과 ET-1(endothelin-1)의 발현을 감소시키는 효능을 보유하는 조성물을 제공하는 데에 있다.
The present invention has been made to solve the above-mentioned problems, and it is an object of the present invention to provide a method for reducing blood pressure, efficacy for alleviating vascular lesions, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule- ET-1 < / RTI > (endothelin-1).
본 발명은 홍삼 및 유산균을 혼합하여 발효한 발효물을 유효성분으로 함유하는 혈관질환을 예방, 개선 또는 치료하기 위한 조성물을 제공함으로써 기술적 과제를 해결하고자 한다.The present invention aims to solve the technical problem by providing a composition for preventing, ameliorating or treating vascular diseases containing fermented product fermented by mixing red ginseng and lactic acid bacteria as an effective ingredient.
본 발명은 고과당식이 랫드 모델에서 혈압을 강하시키는 효능, 혈관 병변을 완화시키는 효능 및 ICAM-1(intercellular adhesion molecule-1), VCAM-1(vascular cell adhesion molecule-1)과 ET-1(endothelin-1)의 발현을 감소시키는 효능을 보유하는 혈관질환을 예방, 개선 또는 치료하기 위한 조성물을 제공함으로써 기술적 과제를 해결하고자 한다.
The present invention relates to a method for reducing blood pressure and reducing vascular lesions in a high-fructose diet rat model, and a method for inhibiting angiotensin-converting enzyme (ICAM-1), vascular cell adhesion molecule- -1 < / RTI > expression in a mammal, including a mammal, a human, a mammal, and a human.
본 발명에 따른 조성물은, 고과당식이 랫드 모델에서 혈압을 강하시키고, 혈관 내 평활근의 비후 및 내피세포의 비정상적 비대 등의 혈관 병변을 완화시키며, ICAM-1(intercellular adhesion molecule-1), VCAM-1(vascular cell adhesion molecule-1) 및 ET-1(endothelin-1)의 발현을 감소시키는 효능을 보유하고 있다.
The composition according to the present invention lowers blood pressure in a hyperfumine diet rat model, alleviates vascular lesions such as hypertrophy of the intravascular smooth muscle and abnormal hypertrophy of endothelial cells, and inhibits intercellular adhesion molecule-1 (ICAM-1), VCAM- 1 (vascular cell adhesion molecule-1) and ET-1 (endothelin-1).
도 1은 고과당식이 랫드 모델에서 시료 처리에 따른 혈압변화를 나타낸 그래프이다.
도 2는 고과당식이 랫드 모델에서 시료 처리에 따른 흉부대동맥의 혈관 죽종 형성을 관찰한 사진이다.
도 3은 고과당식이 랫드 모델에서 시료 처리에 따른 흉부대동맥의 내막-중막의 길이 변화를 나타낸 그래프이다.
도 4는 고과당식이 랫드 모델에서 시료 처리에 따른 ICAM-1의 발현 정도를 측정한 사진 및 그래프이다.
도 5는 고과당식이 랫드 모델에서 시료 처리에 따른 VCAM-1의 발현 정도를 측정한 사진 및 그래프이다.
도 6은 고과당식이 랫드 모델에서 시료 처리에 따른 ET-1의 발현 정도를 측정한 사진 및 그래프이다. FIG. 1 is a graph showing changes in blood pressure according to a sample treatment in a high-fructose diet rat model.
FIG. 2 is a photograph showing blood vessel atherogenesis of the thoracic aorta according to the sample treatment in a high fructose diet rat model.
FIG. 3 is a graph showing changes in the length of the intima-media of the thoracic aorta according to the sample treatment in a hyperglycemic rat model.
FIG. 4 is a photograph and a graph showing the degree of expression of ICAM-1 according to a sample treatment in a high-fructose diet rat model.
FIG. 5 is a photograph and a graph showing the degree of expression of VCAM-1 according to a sample treatment in a high-fructose diet rat model.
FIG. 6 is a photograph and a graph showing the degree of expression of ET-1 according to the sample treatment in a high-fructose diet rat model.
본 명세서 및 청구범위에 사용된 용어나 단어는 통상적이거나 사전적인 의미로 한정해서 해석되어서는 안 되며, 발명자는 그 자신의 발명을 가장 최선의 방법으로 설명하기 위해 용어의 개념을 적절하게 정의할 수 있다는 원칙에 입각하여 본 발명의 기술적 사상에 부합하는 의미와 개념으로 해석되어야만 한다.
The terms and words used in the present specification and claims should not be construed as limited to ordinary or dictionary terms and the inventor may properly define the concept of the term in order to best describe its invention It should be construed as meaning and concept consistent with the technical idea of the present invention.
따라서 본 명세서에 기재된 실험예와 참고예는 본 발명의 가장 바람직한 일실시예에 불과한 뿐이고 본 발명의 기술적 사상을 모두 대변하는 것은 아니므로, 본 출원시점에 있어서 이들을 대체할 수 있는 다양한 균등물과 변형예들이 있을 수 있음을 이해하여야 한다.
Therefore, the experimental examples and the reference examples described in the present specification are merely the most preferred embodiments of the present invention and are not intended to represent all of the technical ideas of the present invention. Therefore, various equivalents and variations Examples should be understood.
실시예Example
1. 홍삼 및 유산균을 함유하는 조성물 1. Composition containing red ginseng and lactic acid bacteria
본 발명에 따른 혈관질환을 예방, 개선 또는 치료하기 위한 조성물은 홍삼 및 유산균을 혼합하여 발효한 발효물을 유효성분으로 함유하는 조성물로서, 제조 과정을 살펴보면 다음과 같다.
The composition for preventing, ameliorating or treating vascular diseases according to the present invention comprises a fermented product fermented by mixing red ginseng and lactic acid bacteria as an active ingredient. The preparation process will be described below.
1) 홍삼 및 유산균을 혼합한다.1) Red ginseng and lactic acid bacteria are mixed.
이때 홍삼은 가공하지 않은 상태의 것을 사용할 수도 있고, 조분쇄한 것을 사용할 수도 있다. 또한 유산균과 혼합하여 발효하기 전, 홍삼이 멸균되어 사용될 수도 있다.
At this time, red ginseng may be used in the unprocessed state, or may be ground. In addition, red ginseng can be sterilized before fermentation by mixing with lactic acid bacteria.
상기 유산균은 락토바실러스(Lactobacillus), 류코노스톡(Leuconostoc), 엔테로코커스(Enterococcus), 비피도박테리움(Bifidobacterium) 및 스트렙토코커스(Streptococcus) 중에서 선택된 어느 하나 이상의 유산균을 사용할 수 있다.
The lactic acid bacteria can use the Lactobacillus bacteria (Lactobacillus), flow Pocono stock (Leuconostoc), Enterococcus (Enterococcus), Bifidobacterium (Bifidobacterium) and any one or more lactic acid bacteria selected from Streptococcus (Streptococcus).
홍삼 및 유산균의 혼합 비율은 홍삼 100 중량부 기준으로 유산균 0.1~50 중량부가 혼합될 수 있다.
The mixing ratio of red ginseng and lactic acid bacteria may be 0.1 to 50 parts by weight of lactic acid bacterium based on 100 parts by weight of red ginseng.
2) 혼합물을 발효한다.2) Ferment the mixture.
혼합물의 발효는 각각 30~50℃에서 12~72시간 동안 수행될 수 있으며, 교반하며 발효될 수도 있다. Fermentation of the mixture may be carried out at 30 to 50 ° C for 12 to 72 hours, respectively, and may be fermented with stirring.
설계 조건에 따라 발효 온도 및 발효 시간은 조절될 수 있으며, 발효 균주가 생장하기에 적합한 환경이면 충분하다.
Depending on the design conditions, the fermentation temperature and fermentation time can be controlled and an environment suitable for the fermentation of the fermentation strain is sufficient.
상기 유산균에 의해 발효된 발효물은 약용성분의 추출 효율이 증가하고, 체내에서의 흡수가 용이해진다.
The fermentation product fermented by the above-mentioned lactic acid bacteria increases the extraction efficiency of the medicinal component and facilitates absorption in the body.
3) 발효물을 추출한다. 3) Extract the fermented product.
발효물을 추출하여 본 발명에 따른 조성물을 제조한다.The fermentation product is extracted to prepare a composition according to the present invention.
추출 방법에는 용매 추출법, 수증기 증류법, 이산화탄소 초임계 추출법, 수증기 증류법, 마이크로 웨이브 공정 추출법, 퍼콜레이션 추출법 등의 다양한 추출방법이 사용될 수 있으며, 바람직하게는 용매 추출법을 이용할 수 있다.
Various extraction methods such as a solvent extraction method, a steam distillation method, a carbon dioxide supercritical extraction method, a steam distillation method, a microwave process extraction method and a percolation extraction method may be used as the extraction method, and a solvent extraction method may be preferably used.
용매 추출시, 추출 용매 또한 다양한 용매가 사용될 수 있다. In solvent extraction, extraction solvents and various solvents may be used.
추출 가능한 용매에는 물, 에탄올, 메탄올, 지방유, 글리세린, 마유,플로필렌글리콜, 에테르, 클로르포름, 석유에테르, 헥산, 벤젠, 메틸렌클로라이드, 에틸아세테이트, 아세톤, 부탄올 및 이소프로판올 등이 있으며, 설계 조건에 따라 추출 온도, 추출 시간, 용매의 양 및 잔류 성분 처리 방식 등을 달리하여 처리할 수 있다.
Extractable solvents include water, ethanol, methanol, fatty oil, glycerin, mayo, propylene glycol, ether, chloroform, petroleum ether, hexane, benzene, methylene chloride, ethyl acetate, acetone, butanol and isopropanol. Depending on the extraction temperature, the extraction time, the amount of the solvent, and the method of treating the residual components, the treatment can be performed.
본 발명에 따른 조성물에 있어서, 홍삼 및 유산균을 혼합발효한 발효물의 추출물 투여 농도는, 고과당식이 랫드 모델 기준으로 1일 20~300 mg/kg일 수 있으며, 바람직하게는 1일 250 mg/kg일 수 있다.
In the composition according to the present invention, the concentration of the extract of the fermented product mixed with fermented red ginseng and lactic acid bacteria may be 20 to 300 mg / kg per day on the basis of the high fructose diet rat model, preferably 250 mg / kg per day Lt; / RTI >
설계 조건에 따라 상기 기재된 공정 외에도 여과, 농축, 추출 등의 공정이 반복 실행될 수 있으며, 각 공정 전후에 발효, 냉동 등의 기타 공정이 추가로 실행될 수도 있다.
In addition to the processes described above, filtration, concentration, extraction, and the like may be repeatedly performed in accordance with design conditions, and other processes such as fermentation and freezing may be performed before and after each process.
참조예Reference Example
1. 실험모델 준비 1. Preparation of experimental model
1) 고과당식이 랫드 모델1) High fructose diet rat model
고과당식이 랫드 모델로 혈관질환을 유발시켜 실험에 활용하였다.A high fructose diet rat model was used to induce vascular disease.
고과당식이 랫드 모델은 Research Diets사의 high fructose 사료를 약 9주간 투여하여 구축하였으며, 상기 사료에는 60%의 fructos가 포함되어 있었다.
A high fructose diet rat model was constructed by administering Research Diets high fructose diet for about 9 weeks, and the feed contained 60% fructos.
2) 시료 투여2) Sample administration
홍삼+유산균 추출물은 상기 실시예 1에 따라 제조되었으며, 1일 250 mg/kg씩 투여하였고, 비교군으로 홍삼 추출물을 제조하여 실험에 사용하였으며, 1일 250 mg/kg씩 투여하였다.The extracts of red ginseng and lactic acid bacterium were prepared according to the above Example 1, 250 mg / kg per day, and the red ginseng extract was prepared as a comparative group and administered at a dose of 250 mg / kg per day.
각각 9주 동안 상기 high fructose 사료와 동시에 랫드에 투여하였다.
Were administered to the rats simultaneously with the high fructose diet for 9 weeks each.
고혈압은 대부분의 대사증후군 환자에게 나타나며 이는 심장질환이나 뇌혈관질환에 있어서 가장 위험한 인자 중 하나이다. Hypertension is seen in most people with metabolic syndrome, which is one of the most dangerous factors in heart disease and cerebrovascular disease.
그러므로 양성대조군으로 사용된 약물은 안지오텐신 수용체 길항제 (ARB; Angiotensin receptor blocker) 계열로서 임상에서 많이 사용되는 AT type II receptor antagonist Losartan을 사용하였으며, 1일 30 mg/kg씩 9주 동안 상기 high fructose 사료와 동시에 랫드에 투여하였다.
Therefore, the drug used as a positive control was the AT type II receptor antagonist Losartan, which is used in clinical practice as an angiotensin receptor blocker (ARB), and was administered at a dose of 30 mg / kg per day for 9 weeks to the high fructose diet At the same time, they were administered to the rats.
실험예Experimental Example
1. 혈압 변화 측정 1. Measurement of blood pressure change
1-1. 실험 과정1-1. Experimental course
수축기 평균 혈압은 automatic sphygmotonography (Mutomachi Kikai, Tokyo, Japan)을 이용하여 랫드 꼬리 동맥에서 측정하였다. 각 개체마다 최소 8번 혈압을 측정하고, 그 중 5 mmHg 내에 있는 5번의 측정값을 평균값으로 이용하였다.
Systolic mean blood pressure was measured in rat tail artery using automatic sphygmotonography (Mutomachi Kikai, Tokyo, Japan). Blood pressure was measured at least 8 times for each subject, and 5 measurements within 5 mmHg were used as mean values.
1-2. 실험 결과1-2. Experiment result
도 1은 고과당식이 랫드 모델에서 시료 처리에 따른 혈압변화를 나타낸 그래프이다.
FIG. 1 is a graph showing changes in blood pressure according to a sample treatment in a high-fructose diet rat model.
고과당식이 및 약물 투여 전 혈압을 측정한 결과, 각 군이 유의성 있는 차이를 보이지는 않았다. There was no significant difference between the groups in terms of blood pressure before and after high fructose diet and drug administration.
그러나 고과당식이 및 약물 투여를 시작한 후(3주) 혈압을 측정한 결과, Control군을 제외한 나머지 군에서 혈압의 상승경향을 나타내었다. However, blood pressure was measured after the initiation of high fructose diet and drug administration (3 weeks). As a result, blood pressure was increased in the rest of the control group.
또한 6주와 9주째 혈압을 측정한 결과, Control군과 high fructose군에서 유의성 있는 차이를 보였으며, 홍삼 추출물과 홍삼+유산균 추출물을 투여한 군은 high fructose군과 비교하여 유의성 있게 혈압이 감소한 것을 확인할 수 있었다.
In addition, blood pressure at 6 and 9 weeks showed a significant difference in the control and high fructose groups. In the group treated with red ginseng extract and red ginseng + lactic acid bacterium, blood pressure was significantly decreased compared with the high fructose group I could confirm.
실험예Experimental Example
2. 혈관 병변 확인 2. Check for vascular lesions
2-1. 실험 과정2-1. Experimental course
적출된 흉부대동맥 조직을 10% 포르말린(ph 7.4)에 3일간 고정시킨 후 조직 내에 남아있는 포르말린을 제거하였다. The extracted thoracic aortic tissue was fixed in 10% formalin (pH 7.4) for 3 days, and the remaining formalin was removed.
50% 알코올에서부터 100% 알코올까지 농도 상승 순으로 탈수하고 xylen으로 치환하였으며, 파라핀 침투과정을 거친 후 포매하여 블록을 제작하였다. Dehydrated in the order of increasing concentration from 50% alcohol to 100% alcohol, substituted with xylen, embedded in paraffin, and embedded.
준비된 파라핀 블록을 회전형 박절기(microtome; Thermo Electron Corporation, Pittsburg, PA)를 사용하여 4-5 um으로 박절 후 slide에 부착하여 사용하였다.
The prepared paraffin blocks were attached to the slides after 4-5 μm separation using a microtome (Thermo Electron Corporation, Pittsburg, Pa.).
흉부대동맥의 형태학적인 변화를 보기 위하여 헤마토실린-에오신 염색(Hematoxylin-eosin staining)을 수행하였으며, 광학현미경에서 흉부대동맥을 400배 시야에서 관찰한 후 사진 촬영하였다.
Hematoxylin-eosin staining was performed to observe the morphologic changes of the thoracic aorta, and the thoracic aorta was photographed after observing the thoracic aorta at 400-fold visual field under an optical microscope.
2-2. 실험 결과2-2. Experiment result
도 2는 고과당식이 랫드 모델에서 시료 처리에 따른 흉부대동맥의 혈관 죽종 형성을 관찰한 사진이며, 도 3은 고과당식이 랫드 모델에서 시료 처리에 따른 흉부대동맥의 내막-중막의 길이 변화를 나타낸 그래프이다.
FIG. 2 is a photograph showing blood vessel atherogenesis of the thoracic aorta according to the sample treatment in a hyperglycemic-type rat model, and FIG. 3 is a graph showing changes in the intima-media thickness of the thoracic aorta according to the sample treatment in a hyperglycemic- to be.
실험 결과, 고과당식이 랫드 모델을 이용한 혈관 병변 대사증후군 모델의 흉부대동맥에서 혈관 죽종 형성은 관찰되지 않았으나, 내막-중막의 길이로 내피조직이 손상되었음을 확인하였으며, 이는 평활근의 비후 및 내피세포의 비정상적 비대, 즉 초기 죽상경화증을 나타낸다고 할 수 있다.
As a result, vascular atheromatosis was not observed in the thoracic aorta of the vascular lesion metabolic syndrome model using a high fructose diet rat model, but the endothelial tissue was damaged by the length of the intima-media, indicating that the thickening of smooth muscle and abnormal endothelial cells Hypertrophy, that is, early atherosclerosis.
홍삼 추출물과 홍삼+유산균 추출물을 투여한 군에서는, 혈관 손상 정도가 감소한 것을 확인할 수 있었다.
In the group treated with red ginseng extract and red ginseng + lactic acid bacterium extract, the degree of vascular injury was decreased.
실험예Experimental Example
3. 혈관질환 연관 인자의 발현 측정 3. Expression of vascular disease-related factors
3-1. 실험 과정3-1. Experimental course
1) 혈관 염증 인자의 발현 측정1) Expression of vascular inflammatory factor
혈관 염증 인자인 ICAM-1(intercellular adhesion molecule-1) 및 VCAM-1(vascular cell adhesion molecule-1)의 발현 정도를 측정하기 위해 면역화학조직 염색(Immunohistochemistry staining)을 수행하였으며, 광학현미경으로 발현 정도를 400배 시야에서 관찰한 후 사진 촬영하였다.Immunohistochemistry staining was performed to measure the expression levels of ICAM-1 (intercellular adhesion molecule-1) and VCAM-1 (vascular cell adhesion molecule-1), which are vascular inflammatory factors, Were photographed after observing at 400x field of view.
또한 혈장을 3000 rpm으로 20분 동안 원심분리한 후, ELISA kit를 이용하여 측정하였다.
Plasma was also centrifuged at 3000 rpm for 20 minutes and then measured using an ELISA kit.
2) 혈관 수축 인자의 발현 측정2) Measurement of expression of vasoconstrictor
흉부대동맥 내 혈관 수축 변화를 알아보기 위하여 혈관 수축 인자인 ET-1(endothelin-1)의 발현 정도를 측정하였으며, 실험 방법은 3-1의 1)과 동일한 과정으로 수행되었다.
The expression level of ET-1 (endothelin-1), a vasoconstrictor, was measured in order to investigate the changes in vasoconstriction in the thoracic aorta. The experimental procedure was the same as that in 1) of 3-1.
3-2. 실험 결과3-2. Experiment result
도 4는 고과당식이 랫드 모델에서 시료 처리에 따른 ICAM-1의 발현 정도를 측정한 사진 및 그래프이며, 도 5는 고과당식이 랫드 모델에서 시료 처리에 따른 VCAM-1의 발현 정도를 측정한 사진 및 그래프이다.
FIG. 4 is a photograph and a graph showing the degree of expression of ICAM-1 according to a sample treatment in a high-fructose diet rat model, and FIG. 5 is a graph showing the degree of expression of VCAM-1 in the high- And graphs.
ICAM-1(intercellular adhesion molecule-1)은, CD(항원)이라고도 하며, 분자량이 9만인 막관통성 단백질이다. 혈관내피세포, 상피세포, 조혈계 세포 등에 널리 분포하는 면역글로불린상과(IgSF)에 속하는 대표적인 접착분자인데, 주로 백혈구상의 β2인테그린 LFA-1과 2가 금속 양이온 의존성으로 결합한다. ICAM-1 (intercellular adhesion molecule-1), also called CD (antigen), is a transmembrane protein with a molecular weight of 90,000. (IgSF), which is widely distributed in vascular endothelial cells, epithelial cells, hematopoietic cells, and the like, and mainly binds to leucocyte β2 integrin LFA-1 in a divalent metal cation-dependent manner.
ICAM-1의 발현은, TNF-α 등의 염증성 사이토카인, 활성산소 등의 자극을 유도하고, 백혈구의 혈관 외 유출, 항원제시세포에 의한 T세포의 활성화 등에 관여하여 염증 병태 형성에 중요한 역할을 한다.
Expression of ICAM-1 plays an important role in the inflammatory state by inducing stimulation of inflammatory cytokines such as TNF-α, active oxygen, leukocyte extravasation and activation of T cells by antigen presenting cells do.
또한 VCAM-1(vascular cell adhesion molecule-1)은, 인터류킨1, 종양괴사인자α, 인터페론γ, 인터류킨4 등 염증성 사이토키닌이나 리포다당에 의해 24~48시간을 정점으로 발현이 유도되는 세포접착분자로서, 면역글로불린슈퍼패밀리족에 속하고, 3종류의 동형(isoform)이 존재한다. In addition, VCAM-1 (vascular cell adhesion molecule-1) is a cell adhesion molecule that induces expression at the peak of 24 to 48 hours by inflammatory cytokinins or lipopolysaccharides such as
생체에서는 염증부위에 나타나는 활성화혈관 내피세포 외에 가슴샘과 골수의 스트로마세포, 비장배(胚) 중심의 수상세포, 골격근에 발현한다. 또한 인테그린 α4β1에 결합하고, 염증부위로의 림프구 침윤, 줄기세포와 스트로마세포의 접착, 근관 형성 등에 관여한다.
In vivo, activated vascular endothelial cells appear in inflamed areas, and are expressed in stromal cells of the thymus and bone marrow, dendritic cells in the center of the spleen (embryo), and skeletal muscle. It also binds to integrin α4β1, is involved in lymphocyte infiltration into inflammatory sites, adhesion of stem cells and stromal cells, and root canal formation.
실험 결과, Control군과 비교하여 high fructose군에서 ICAM-1 및 VCAM-1의 발현이 증가하였다. 이로써 high fructose diet로 인하여 혈관 염증 손상이 진행된다는 것을 알 수 있었다.The expression of ICAM-1 and VCAM-1 was increased in the high fructose group compared to the control group. This suggests that the high fructose diet promotes vascular inflammation damage.
그러나 Losartan 투여군, 홍삼 추출물 투여군 및 홍삼+유산균 추출물 투여군에서는, high fructose군에 비하여 ICAM-1 및 VCAM-1의 발현 정도가 모두 유의성 있게 감소하였다.
However, the levels of ICAM-1 and VCAM-1 were significantly decreased in the Losartan group, the red ginseng extract group, and the red ginseng + lactic acid bomb extract group, compared with the high fructose group.
도 6은 고과당식이 랫드 모델에서 시료 처리에 따른 ET-1의 발현 정도를 측정한 사진 및 그래프이다.
FIG. 6 is a photograph and a graph showing the degree of expression of ET-1 according to the sample treatment in a high-fructose diet rat model.
ET-1(endothelin-1)은 혈관 수축 인자로서, 혈관을 수축시키고 혈압을 증가시키며, 심장에 산소 공급량을 감소시키는 단백질이다.ET-1 (endothelin-1) is a vasoconstrictor, a protein that contracts blood vessels, increases blood pressure, and reduces oxygen supply to the heart.
이러한 ET-1이 증가 되면 심장 질환의 위험성이 높아진다(Psychosomatic Medicine 2002;64:707-713).
Increased ET-1 increases the risk of heart disease (Psychosomatic Medicine 2002; 64: 707-713).
실험 결과, High fructose군은 control군에 비해 ET-1의 발현이 현저하게 증가하였으나, 홍삼 추출물과 홍삼+유산균 추출물을 투여한 군에서는 그 발현 정도가 high fructose군에 비하여 ET-1의 발현 정도가 유의성 있게 감소한 것을 볼 수 있었다.In the high fructose group, the expression of ET-1 was significantly higher than that of the control group, but the expression level of ET-1 was higher in the group treated with the red ginseng extract and red ginseng + lactic acid bacterium Respectively.
Claims (5)
A composition for preventing, improving or treating vascular diseases containing red ginseng and lactic acid bacteria as an active ingredient.
상기 조성물은 홍삼 및 유산균을 혼합하여 발효한 발효물을 유효성분으로 함유하되,
상기 발효물을 추출한 추출물의 투여 농도는, 고과당식이 랫드 모델 기준으로 1일 20~300 mg/kg인 것을 특징으로 하는 혈관질환을 예방, 개선 또는 치료하기 위한 조성물.
The method according to claim 1,
Wherein the composition contains a fermented product obtained by mixing red ginseng and lactic acid bacteria as an active ingredient,
The composition for preventing, ameliorating or treating a vascular disease is characterized in that the concentration of the extract obtained by extracting the fermented product is 20 to 300 mg / kg per day on the basis of a high fructose diet rat model.
상기 혈관질환은 고혈압, 관상동맥질환, 죽상경화증 및 고지혈증인 것을 특징으로 하는 혈관질환을 예방, 개선 또는 치료하기 위한 조성물.
The method according to claim 1,
Wherein the vascular disease is hypertension, coronary artery disease, atherosclerosis, and hyperlipidemia.
상기 조성물은 고과당식이 랫드 모델에서 혈압을 강하시키고, 혈관 내 평활근의 비후 및 내피세포의 비정상적 비대 등의 혈관 병변을 완화시키며, ICAM-1(intercellular adhesion molecule-1), VCAM-1(vascular cell adhesion molecule-1) 및 ET-1(endothelin-1)의 발현을 감소시키는 효능을 보유하는 것을 특징으로 하는 혈관질환을 예방, 개선 또는 치료하기 위한 조성물.
The method according to claim 1,
The composition reduces the blood pressure in the hyperglycemic rat model and alleviates vascular lesions such as hypertrophy of the intravascular smooth muscle and abnormal hypertrophy of the endothelial cells and inhibits vascular lesions such as intercellular adhesion molecule-1 (ICAM-1), vascular cell 1, and endothelin-1 in a mammal, comprising administering to the mammal an effective amount of a compound of the present invention.
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KR20210009732A (en) * | 2019-07-17 | 2021-01-27 | 주식회사 리바이오 | Composition comprising Salvia miltiorrhiza and red ginseng biotransformation extract for improving, preventing and treating of cardiovascular disease |
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