KR20140146312A - A composition containing extract of saururi herba for the treatment of heart failure - Google Patents
A composition containing extract of saururi herba for the treatment of heart failure Download PDFInfo
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- KR20140146312A KR20140146312A KR20130068759A KR20130068759A KR20140146312A KR 20140146312 A KR20140146312 A KR 20140146312A KR 20130068759 A KR20130068759 A KR 20130068759A KR 20130068759 A KR20130068759 A KR 20130068759A KR 20140146312 A KR20140146312 A KR 20140146312A
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- KR
- South Korea
- Prior art keywords
- atrial
- composition
- pulse pressure
- heart failure
- extract
- Prior art date
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Abstract
Description
본 발명은 삼백초 추출물을 유효성분으로 함유하는, 심부전을 예방, 개선 또는 치료하는 조성물로써, 삼백초 추출물 미처리시 기준으로 맥압(pulse pressure)을 8~220%, 1회 심방 박출량(stroke volume)을 25~220% 상승시켜 심근을 수축시키는 효능을 보유하고 있다.The present invention relates to a composition for preventing, ameliorating or treating heart failure, which comprises Saururus chinensis extract as an active ingredient. The composition comprises 8 ~ 220% pulse pressure and 25 stroke volume Up to 220%, and has the ability to contract myocardium.
본 발명에 따른 조성물은, L-타입 Ca2 + 채널 통로 저해제인 니페디핀(nifedifine) 또는 딜티아젬(diltiazem)과 병용처리시에도 심근을 수축시키는 효능을 보유하고 있다.The composition according to the present invention has an effect of contraction of the myocardium even when it is used in combination with nifedifine or diltiazem which is an L-type Ca 2 + channel channel inhibitor.
본 발명에 따른 조성물은, 가토 심방 박동관류 모델 기준으로 농도 10-3 g/ml인 것을 기술적 특징으로 보유하고 있다.
The composition according to the present invention has a technical characteristic that the concentration is 10 < -3 > g / ml on the basis of the rabbit atrial rhythm perfusion model.
심장은 흉골을 기준으로 왼쪽에 2/3, 오른쪽에 1/3이 위치한 근육질의 인체 순환 기관으로, 주된 역할은 산소와 영양분을 싣고 있는 혈액을 전신의 각 부위에 순환시키는 펌프 기능과 심방이뇨호르몬(atrial natriuretic peptide, ANP)을 분비하는 내분비기능이다. The heart is a muscular circulation organ with 2/3 on the left side and 1/3 on the right side based on the sternum. Its main function is to pump the oxygenated and nutrient-bound blood to each part of the body, (atrial natriuretic peptide, ANP).
심장은 크게 왼쪽 부분과 오른쪽 부분으로 나뉜다. 오른쪽과 왼쪽에는 각각 2개의 심방과 2개의 심실이 있으며, 각 부분 사이에는 판막이 있다. 왼쪽 부분은 산소와 영양분을 실은 신선한 혈액을 뿜어내는 역할을 하며, 오른쪽 부분은 각 장기를 순환하여 심장으로 들어오는 노폐물과 이산화탄소를 실은 혈액을 폐로 순환시켜 다시 산소를 받아들이게 하는 역할을 한다. 혈액의 순환을 위해 1분에 60~80회 정도 심장근육이 수축한다.
The heart is largely divided into a left part and a right part. There are two atria and two ventricles on the right and left, respectively, and there is a valve between each part. The left part plays a role of fresh blood containing oxygen and nutrients, and the right part circulates the organs and circulates the waste containing carbon dioxide into the lungs to circulate the oxygen to the lungs. The heart muscle contracts about 60 to 80 times per minute for blood circulation.
심부전(heart failure)은 심장의 구조적 또는 기능적 이상으로 인해 심장이 혈액을 짜내는 수축 기능이나 받아들이는 이완기능이 감소하여 신체 각 조직에 필요한 혈액을 제대로 공급하지 못해 발생하는 질환군을 일컫는다. 심부전이 발생하는 원인으로는, 심장혈관질환, 심장근육 질환, 장기간 지속되는 심장 판막증, 심장 기형 및 고혈압 등이 있다. Heart failure refers to a group of diseases caused by structural or functional abnormalities of the heart that cause the heart to squeeze out blood or reduce the relaxation function it receives and fail to properly supply the blood needed for each tissue in the body. Causes of heart failure include cardiovascular disease, heart muscle disease, long-lasting cardiac valvular disease, cardiac malformations and hypertension.
심부전의 병태생리학적 기전은 좌심실 기능의 부전, 저하된 운동허용능력, 부종과 울혈을 동반하는 체액, 심실성 부정맥, 신경 내분비계의 자극, 심실 비대 및 재형성, 혈관수축이 복합되어 나타나며, 근본적으로는 심근 수축력의 저하가 원인이 된다.
The pathophysiological mechanism of heart failure is a combination of left ventricular dysfunction, decreased exercise tolerance, swelling and congestion associated with body fluid, ventricular arrhythmia, stimulation of the neuroendocrine system, ventricular hypertrophy and remodeling, and vasoconstriction. Is the cause of myocardial contractility.
심부전의 치료 약물로는 막 결합 효소인 AC를 활성화시켜 cAMP를 증가시켜 심근 수축력 항진을 유도하는 도부타민(dobutamine), 지톡신(digitoxin), 스트로판틴(strophanthin), 오우아바인(ouabain)과 같은 강심 배당체, 포스포디에스테라제(phosphodiesteraase) 억제제, 항고혈압제 등이 있다.Therapeutic drugs for heart failure include dobutamine, digitoxin, strophanthin, and ouabain, which activate cAMP by activating the membrane-binding enzyme AC to induce hyperactivity of myocardial contractility. Cardiac glycosides, phosphodiesterase inhibitors, and antihypertensive agents.
이러한 약물들은 장기간 복용시 부작용을 가져올 수 있는데, 예를 들어 심부전 약물치료의 근간으로 사용되어져 왔던 강심 배당체는 혈역학적으로 불안정한 환자에 대해 빠른 임상증상 호전과 혈역학적 안정을 가져올 수 있다는 큰 장점에도 불구하고, 부정맥, 심근허혈 및 심근 산소 소모량 증가 등에 연관된 부작용과 사망률 증가로 그 사용에 제한점이 있다.
These medications can cause side effects when taken over a long period of time. For example, cardiac glycosides, which have been used as the basis of heart failure medication, have a great advantage of rapidly improving clinical symptoms and hemodynamic stability in hemodynamically unstable patients And there are limitations in its use due to increased side effects and increased mortality associated with arrhythmia, myocardial ischemia, and increased myocardial oxygen consumption.
따라서 본 출원인은 천연 유래의 물질을 이용하여 부작용이 없으면서, 체액 및 심혈관계의 항상성 장애 질환과, 심근 수축 및 이완의 기능장애로 인한 질환을 예방, 개선 또는 치료할 수 있는 조성물을 안출하였다.
Therefore, the Applicant has found a composition which can prevent, ameliorate or treat diseases caused by dysfunction of the body fluid and cardiovascular homeostatic disorder and myocardial contraction and relaxation without any adverse effect using a substance derived from natural origin.
이하에서, 본 발명에 사용된 천연 소재인 삼백초에 관하여 간략히 설명한다.Hereinafter, Saururus chinensis, a natural material used in the present invention, will be briefly described.
삼백초(Saururi Herba seu Rhizoma)는 삼백초 과(Saururaceae)에 속한 다년생 초본인 삼백초(Saururus chinensis)의 뿌리와 전초로 우리 나라에서는 제주도에 자생하며, 각지에서 재배되고 있다. 7~8월에 채취된다. Saururi Herba seu Rhizoma is a perennial herb Saururus belonging to Saururaceae, chinensis ) is a root and outpost in our country. It grows in Jeju Island and is cultivated in various places. It is collected in July-August.
줄기는 원주형으로 길이 50~80 cm이며, 표면은 황백색으로 세로주름이 있다. 잎은 길이 5~15 cm, 너비 3~8 cm로 끝이 뾰족하고 가장자리는 밋밋하다. 잎에는 쿼세틴(quercetin), 쿼시트린(quercitrin), 이소쿼시트린(isoquercitrin), 쿼세틴-3-l-아라비노사이드(quercetin-3-l-aravinoside) 등이 함유되어 있다. The stem is cylindrical and 50 to 80 cm long. The surface is yellowish white with vertical wrinkles. Leaves are 5 ~ 15 cm long and 3 ~ 8 cm wide with sharp ends and flat edges. Leaves contain quercetin, quercitrin, isoquercitrin, quercetin-3-l-arabinoside, and the like.
전초에 함유된 정유의 주성분은 메틸-n-노닐케톤(methyl-n-nonylketone)이다.
The main component of the essential oil contained in the outpost is methyl-n-nonylketone.
본 발명과 관련된 선행 기술을 살펴보면, 대한민국 공개특허공보 제10-2006-0037066호에는 삼백초에서 추출한 글리세롤계 화합물을 유효성분으로 하는 심장순환계 질환의 예방 및 치료용 조성물에 관하여 기재되어 있다. In the prior art related to the present invention, Korean Patent Laid-Open Publication No. 10-2006-0037066 discloses a composition for prevention and treatment of a cardiovascular system disease comprising glycerol compound extracted from Saururus chinensis as an active ingredient.
상기 선행 기술에는 심근 수축력을 증가시키는 효능에 대해서는 기재되어 있지 않다.
The prior art does not describe the efficacy of increasing myocardial contractility.
본 발명의 목적은, 삼백초 추출물 미처리시 기준으로 맥압을 8~220%, 1회 심방 박출량을 25~220% 상승시켜 심근을 수축시키는 효능을 보유하는, 심부전을 예방, 개선 또는 치료하는 조성물을 제공하는데에 있다.The object of the present invention is to provide a composition for preventing, ameliorating or treating heart failure, which has the effect of increasing the pulse pressure by 8 to 220% and the amount of atrial pericardium by 25 to 220% .
본 발명의 목적은, L-타입 Ca2 + 통로 저해제인 니페디핀 또는 딜티아젬 처리 후에도 심근을 수축시키는 효능을 보유하는, 심부전을 예방, 개선 또는 치료하는 조성물을 제공하는데에 있다.Object of the present invention is to provide an L- type Ca 2 + channel inhibitor nifedipine or diltiazem treatment composition, prevention, improvement or treatment of heart failure to retain the efficacy of contraction of the myocardium after.
본 발명의 목적은, 가토 심방 박동관류 모델 기준으로 삼백초 추출물을 10-3 g/ml 함유하는, 심부전을 예방, 개선 또는 치료하는 조성물을 제공하는데에 있다.
It is an object of the present invention to provide a composition for preventing, ameliorating or treating heart failure, which contains 10 -3 g / ml of Saururus chinensis extract on the basis of the rabbit atrial rhythm perfusion model.
상기 목적을 달성하기 위하여, 본 발명은 삼백초 추출물 미처리시 기준으로 맥압을 8~220%, 1회 심방 박출량을 25~220% 상승시켜 심근을 수축시키는 효능을 보유하는, 심부전을 예방, 개선 또는 치료하는 조성물을 제공함으로써 기술적 과제를 해결하고자 한다. In order to achieve the above object, the present invention provides a method for preventing, ameliorating or treating heart failure, which has the effect of increasing the pulse pressure by 8 to 220% and the amount of atrial ejection by 25 to 220% To solve the technical problem.
본 발명은, L-타입 Ca2 + 통로 저해제인 니페디핀 또는 딜티아젬 처리 후에도 심근을 수축시키는 효능을 보유하는, 심부전을 예방, 개선 또는 치료하는 조성물을 제공함으로써 기술적 과제를 해결하고자 한다.The present invention to solve the L- type Ca 2 + channel inhibitor nifedipine or diltiazem process aspect by providing a composition for the prophylaxis, improvement or treatment of heart failure to retain the efficacy of contraction of the myocardium after.
또한 본 발명은, 삼백초 추출물을 가토 심방 박동관류 모델 기준으로 10-3 g/ml 함유하는, 심부전을 예방, 개선 또는 치료하는 조성물을 제공함으로써 기술적 과제를 해결하고자 한다.
The present invention also aims at solving the technical problem by providing a composition for preventing, ameliorating or treating heart failure, which contains 10-3 g / ml of Saururus chinensis extract on the basis of rabbit atrial pumping flow model.
본 발명이 약학적 조성물로 이용되기 위하여는 약제학적 분야에서의 공지의 방법에 의해 제조될 수 있으며, 그 자체 또는 약학적으로 허용되는 담체, 부형제, 희석제 등과 혼합하여 분말, 과립, 정제, 캡슐제 또는 주사제 등의 제형으로 제조되어 사용될 수 있다. 또한 이들은 경구 또는 비경구로 처리될 수 있다.In order to use the present invention as a pharmaceutical composition, it may be prepared by a known method in the pharmaceutical field, and may be mixed with the carrier itself, a pharmaceutically acceptable carrier, excipient, diluent or the like to prepare a powder, granule, Or injections, and the like. They may also be administered orally or parenterally.
본 발명에 따른 조성물의 유효 처리량은 체내에서 활성성분의 흡수도, 물활성화율 및 배설속도, 환자의 연령, 성별 및 상태, 치료할 질병의 중증 정도 등에 따라 적절히 선택될 수 있다.
The effective throughput of the composition according to the present invention may be appropriately selected depending on the degree of absorption of the active ingredient in the body, the rate of water activation and excretion, the age, sex and condition of the patient, severity of the disease to be treated,
본 발명에 따른 조성물을 이용하여 환, 과립, 음료, 타블렛, 캅셀 등의 제형을 제조할 수 있으며, 이 경우에 각 제형을 제조하기 위하여 처리제가 추가될 수 있음은 물론이다.
Formulations such as pills, granules, beverages, tablets, capsules and the like may be prepared using the composition according to the present invention, and in this case, a treatment agent may be added to prepare each formulation.
본 발명에 따른 조성물은, 식품용 조성물로 제공될 수 있으며, 각각의 조성물은 식품학적으로 허용되는 처리제를 이용하여 건강기능식품으로 제조하여 제공한다. 본 발명에 따른 조성물을 이용한 건강기능식품은, 기능성 음료, 건강보조식품, 차, 과자류 등과 같이 다양한 형태로 제공될 수 있다.
The composition according to the present invention can be provided as a food composition, and each composition is prepared and provided as a health functional food using a foodstuff acceptable processing agent. The health functional food using the composition according to the present invention may be provided in various forms such as functional beverage, health supplement, tea, confectionery, and the like.
본 발명에 따른 조성물은, 삼백초 추출물 미처리시 기준으로 맥압(pulse pressure)을 8~220%, 1회 심방 박출량(stroke volume)을 25~220% 상승시켜 심근을 수축시키는 효능을 보유하고 있다.The composition according to the present invention has an effect of shrinking myocardial muscle by increasing pulse pressure by 8 to 220% and stroke volume by 25 to 220% on the basis of untreated Saururus chinensis extract.
본 발명에 따른 조성물은, L-타입 Ca2 + 채널 통로 저해제인 니페디핀 또는 딜티아젬과 병용처리하였을시에도 심근을 수축시키는 효능을 보유하고 있다.The composition according to the present invention has an effect of contraction of the myocardium even when it is used in combination with nifedipine or diltiazem, which is an L-type Ca 2 + channel channel inhibitor.
본 발명에 따른 조성물은, 함유되는 삼백초 추출물의 농도를 가토 심방 박동관류 기준 10-3 g/ml으로 특정한 효능을 보유하고 있다.
The composition according to the present invention has a specific efficacy at a concentration of 10 -3 g / ml based on rabbit atrial perfusion based on the concentration of the Saururus chinensis extract contained therein.
도 1은 심방 박동관류 모델 제작시의 설계도를 나타낸 도면이다.
도 2는 삼백초 추출물을 10-3 g/ml 처리하였을시의 맥압 및 1회 심방 박출량을 측정한 결과를 나타낸 그래프이다.
도 3은 삼백초 추출물을 10-4 g/ml 처리하였을시의 맥압 및 1회 심방 박출량을 측정한 결과를 나타낸 그래프이다.
도 4는 삼백초 추출물의 농도를 10-3 g/ml과 10-4 g/ml로 달리하여 처리하였을시의 맥압 및 1회 심방 박출량을 측정한 결과를 비교한 그래프이다.
도 5는 니페디핀을 단독처리하였을시 및 삼백초 추출물 10-3 g/ml과 니페디핀을 병용처리하였을시의 맥압 및 1회 심방 박출량의 변화를 측정한 결과를 나타낸 그래프이다.
도 6은 딜티아젬을 단독처리하였을시 및 삼백초 추출물 10-3 g/ml과 딜티아젬을 병용처리하였을시의 맥압 및 1회 심방 박출량의 변화를 측정한 결과를 나타낸 그래프이다.FIG. 1 is a view showing a design diagram at the time of manufacturing the atrial ventricular perfusion model.
FIG. 2 is a graph showing the results of measurement of the pulse pressure and the amount of one-time atrial ejection when the Saururus chinensis extract was treated at 10 -3 g / ml.
FIG. 3 is a graph showing the results of measurement of the pulse pressure and the amount of one-shot atrial discharge when the Saururus chinensis extract was treated at 10 -4 g / ml.
FIG. 4 is a graph comparing the results of measuring the pulse pressure and the amount of one-time atrial ejection when the concentration of Saururus chinensis extract was changed to 10 -3 g / ml and 10 -4 g / ml.
FIG. 5 is a graph showing the results of measurement of changes in pulse pressure and one-time ventricular ejection when nifedipine alone was treated and when 10 -3 g / ml of Saururus chinense extract and nifedipine were coadministered.
FIG. 6 is a graph showing the results of measurement of changes in pulse pressure and one-time ventricular ejection when diltiazem is administered alone and when 10-3 g / ml of Saururus chinense extract and diltiazem are coadministered.
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 실시예와 도면에 도시된 구성은 본 발명의 가장 바람직한 일실시예에 불과할 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 embodiments described in the present specification and the configurations shown in the drawings 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 It should be understood that water and variations may be present.
실시예Example
1. 삼백초 추출물을 유효성분으로 함유하는 심부전을 예방, 개선 또는 치료하는 조성물 1. A composition for preventing, ameliorating or treating heart failure containing Saururus chinensis extract as an active ingredient
삼백초(Saururi Herba seu Rhizoma)는 삼백초 과(Saururaceae)에 속한 다년생 초본인 삼백초(Saururus chinensis)의 뿌리와 전초이다. Saururi Herba seu Rhizoma is a perennial herb Saururus belonging to Saururaceae, chinensis ) is the root and outpost.
삼백초의 뿌리 및/또는 전초를 추출하여, 삼백초 추출물을 유효성분으로 함유하는 심부전을 예방, 개선 또는 치료하는 조성물을 제조한다.
The roots and / or outpones of Saururus chinense are extracted to prepare a composition for preventing, ameliorating or treating heart failure containing Saururus chinense extract as an active ingredient.
삼백초의 추출 방법에는 용매 추출법, 수증기 증류법, 이산화탄소 초임계 추출법, 수증기 증류법, 마이크로 웨이브 공정 추출법, 퍼콜레이션 추출법 등의 다양한 추출 방법이 사용될 수 있다. 바람직하게는 용매 추출법을 사용한다. 추출 시간 역시 달라질 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 can be used for the extraction of Saururus chinensis. Preferably, a solvent extraction method is used. The extraction time may also vary.
추출 용매 역시 다양한 용매가 사용될 수 있다. 추출 가능한 용매에는 물, 에탄올, 메탄올, 지방유, 글리세린, 마유, 플로필렌글리콜, 에테르, 클로르포름, 석유에테르, 헥산, 벤젠, 메틸렌클로라이드, 에틸아세테이트, 아세톤, 부탄올, 이소프로판올 등이 있다. 바람직하게는 물을 추출 용매로 사용한다.
A variety of solvents may also be used as the extraction solvent. Extractable solvents include water, ethanol, methanol, fatty oils, glycerin, mayo, flouroprene glycol, ether, chloroform, petroleum ether, hexane, benzene, methylene chloride, ethyl acetate, acetone, butanol and isopropanol. Preferably, water is used as the extraction solvent.
설계 조건에 따라, 추출 전후에 여과, 농축, 환류 추출 등의 과정이 추가될 수도 있다. Depending on the design conditions, filtration, concentration, reflux extraction, etc. may be added before and after the extraction.
농축 방법에는 증발 농축, 건조 농축 등의 다양한 방법이 사용될 수 있으며, 건조 방법에는 양건조법, 음건조법, 동결건조법, 열풍건조법 등의 다양한 건조 방법이 사용될 수 있다.
Various methods such as evaporation, concentration and drying can be used for the concentration method. Various drying methods such as a positive drying method, a negative drying method, a freeze drying method, a hot air drying method and the like can be used for the drying method.
여기에서, 삼백초 추출물의 농도는 가토 심방 박동관류 모델 기준으로 10-3 g/ml이며, 바람직하게는 ±20% 범위 내, 즉 0.8×10-3~1.2×10-3 g/ml의 농도 범위 내에서 선택될 수 있다. 넓게는 10-4 g/ml에서 세포독성이 없는 농도 범위 내까지 선택될 수도 있다.
Here, the concentration of Saururus chinensis extract is 10 -3 g / ml, preferably within a range of ± 20%, that is, in a concentration range of 0.8 × 10 -3 to 1.2 × 10 -3 g / ml ≪ / RTI > And may be selected within a concentration range that is not cytotoxic at a wide range of 10 -4 g / ml.
바람직하게, 삼백초 추출물을 약학적 조성물로 사용하기 위하여는 약학적으로 허용되는 첨가물이 추가될 수 있고, 건강기능식품으로 사용하기 위하여 식품학적으로 허용되는 첨가물이 추가될 수 있음은 물론이다.
Preferably, to use the Saururus chinensis extract as a pharmaceutical composition, a pharmaceutically acceptable additive may be added, and a pharmaceutically acceptable additive may be added for use as a health functional food.
실험예Experimental Example
1. 삼백초 추출물의 농도에 따른 맥압 및 1회 심방 박출량의 변화(1) 1. Changes in pulse pressure and atrial ejection fraction according to the concentration of Saururus chinensis extract (1)
본 실험은 삼백초 추출물의 농도에 따른 맥압 및 1회 심방 박출량의 변화를 알아보기 위하여 실행되었다.
This study was conducted to investigate the effects of spermatozoa extract concentration and pulse pressure It was carried out to see the change.
(1) 실험 과정(1) Experimental process
도 1은 심방 박동관류 모델 제작시의 설계도를 나타낸 도면이다.
FIG. 1 is a view showing a design diagram at the time of manufacturing the atrial ventricular perfusion model.
1) 심방 박동관류 모델 제작1) Model of atrial pumping
① 실험동물로서 뉴질랜드 화이트계 가토 1.82 kg를 사용하였다. 가토에 케타민(Ketamine)-HCl(50 mg/kg, i.v.)을 처리하여 마취시킨 직후 개흉하여 출혈시키고 심장을 적출하였다.1.82 kg of New Zealand white rape was used as an experimental animal. The rabbits were treated with ketamine-HCl (50 mg / kg, i.v.) and immediately anesthetized, bleeding was performed, and the heart was harvested.
② 적출된 심장을 산소가 포함된 34℃의 생리식염수에 옮겨놓고 좌측 심방을 분리하였다.② The extracted heart was transferred to physiological saline solution at 34 ℃ containing oxygen and the left atrium was separated.
③ PE(Polyethylene)관 3개를 심방 내부에 매몰시켜 만든 외경 4 mm의 투명한 캐뉼라(canula)를 심방에 고정하였다. 이 때, 2.5 mm 깊이까지 위치하도록 고정하였다. PE관 3개 중 한 개는 영양액을 심방내로 주입하는 용도, 다른 한 개는 관류액의 유출을 측정하는 용도, 또다른 한 개는 심방 내부의 압력을 측정하는데 사용하였다. ③ A 4 mm outer diameter canula (canula) made of 3 polyethylene (PE) tubes embedded in the atrium was fixed to the atrium. At this time, it was fixed so as to be located up to a depth of 2.5 mm. One of the three PE tubes was used to inject the nutrient solution into the atrium, the other to measure the flow of the perfusion solution, and the other to measure the pressure inside the atrium.
캐뉼라에는 눈금을 새겼으며 캐뉼라 내부에는 전기 자극을 주기 위해 백금선을 매몰하였다.The cannula was scribed and platinum wire was buried in the cannula to provide electrical stimulation.
④ 캐뉼라가 고정된 심방을 곧바로 3의 이중 관류장치에 옮겨 고정하고 0.3~0.5 ms, 30~40V의 전기 자극으로 적당히 자극하였다. ④ The atrium with fixed cannula was immediately transferred to a 3-pass double perfusion device and stimulated with electric stimulation of 0.3 ~ 0.5 ms and 30 ~ 40V.
관류장치 내에는 관류액과 동일한 조성의 용액 3 ㎖를 주입하였으며, 산소를 관류장치 내부의 실리콘 관으로 공급하였다. 또한 관류액을 계속 박동주입 펌프(1㎖/min)로 주입하였다.In the perfusion device, 3 ml of the same solution as the perfusion solution was injected, and oxygen was supplied to the silicon tube inside the perfusion device. The perfusate was also continuously infused with a beating infusion pump (1 ml / min).
관류액은 HEPES 완충액으로서, 118 NaCl, 4.7 KCl, 2.5 CaCl2, 1.2 MgCl2, 25 NaHCO3, 10 glucose, 10 HEPES 및 0.1%의 우혈청 알부민 (bovine serum albumin, BSA)으로 조성되었고 mM 단위이며, pH는 7.4이다.The perfusion solution was composed of 118 NaCl, 4.7 KCl, 2.5 CaCl 2 , 1.2 MgCl 2 , 25 NaHCO 3 , 10 glucose, 10 HEPES and 0.1% bovine serum albumin (BSA) , and the pH is 7.4.
⑤ 심방 내의 압력 변동은 파워 랩(Power Lab)/8sp (모델 ML 785, AD 인스트루먼트, 호주)을 이용하여 지속적으로 측정하였다. (5) Pressure fluctuations in the atria were continuously measured using a Power Lab / 8sp (model ML 785, AD Instrument, Australia).
⑥ 1회 심방 박출량은 심방의 이완기와 수축기 때 캐뉼라 내의 물기둥의 변화를 측정함으로써 측정되었다.
⑥ One atrial ejection fraction was measured by measuring changes in the water column in the cannula during atrial diastole and systolic period.
2) 삼백초 추출물 처리시의 맥압 및 1회 심방 박출량의 변화 측정2) Measurement of changes in pulsation pressure and atrial ejection during treatment with Saururus chinensis extract
심방 박동관류 모델을 4개 그룹 준비하여, 2개 그룹에는 측정 시작 6분 후에 삼백초 추출물 10-3 g/ml, 10-4 g/ml를 처리하고 맥압을 측정하였다. Four groups of atrial ventricular perfusion models were prepared and the two groups were treated with 10 -3 g / ml and 10 -4 g / ml of Saururus chinensis
나머지 2개 그룹 또한 측정 시작 6분 후에 삼백초 추출물 10-3 g/ml, 10-4 g/ml를 처리하고 1회 심방 박출량을 측정하였다. The remaining two groups were also treated with 10 -3 g / ml and 10 -4 g / ml of Saururus chinensis extract at the beginning of the measurement and the amount of atrial ejection was measured once.
측정은 삼백초 추출물 처리 42분 후까지 실행되었으며, 6분 단위로 측정하였다.
Measurements were carried out up to 42 minutes after treatment with Saururus chinensis extract and measured in 6 minute increments.
(2) 실험 결과(2) Experimental results
도 2는 삼백초 추출물을 10-3 g/ml 처리하였을시의 맥압 및 1회 심방 박출량을 측정한 결과를 나타낸 그래프이다.FIG. 2 is a graph showing the results of measurement of the pulse pressure and the amount of one-time atrial ejection when the Saururus chinensis extract was treated at 10 -3 g / ml.
도 3은 삼백초 추출물을 10-4 g/ml 처리하였을시의 맥압 및 1회 심방 박출량을 측정한 결과를 나타낸 그래프이다.
FIG. 3 is a graph showing the results of measurement of the pulse pressure and the amount of one-shot atrial discharge when the Saururus chinensis extract was treated at 10 -4 g / ml.
삼백초 추출물 10-3 g/ml 처리군과 10-4 g/ml 처리군을 비교해 본 결과, 삼백초 추출물 10-3 g/ml 처리군에서는 맥압 및 1회 심방 박출량이 지속적인 증가 양상을 보였다. The extract was three hundred seconds 10 -3 g / ml treatment group with 10 -4 g / ml treatment group compared to the results, in the Houttuynia cordata extract 10 -3 g / ml treatment group pulse pressure and stroke volume is constant once the atrial aspect of this increase.
삼백초 추출물 10-4 g/ml 처리군에서는 시간이 경과함에 따라 맥압 및 1회 심방 박출량이 감소하여, 대조군과 유사한 정도로 변화하는 것을 확인할 수 있었다.The Houttuynia cordata extract 10 -4 g / ml treatment group with the lapse of time as the pulse pressure, and once the atrial cardiac output decreases, and it was confirmed that the change in extent is similar to the control group.
이로써, 삼백초 추출물 10-3 g/ml 이상 처리시 맥압 및 1회 심방 박출량, 즉 심근 수축을 증가시킨다는 결론을 도출할 수 있다.
Thus, it can be concluded that the treatment of Saururus chinensis extract at 10 -3 g / ml or more increases pulse pressure and one-time atrial ejection, that is, myocardial contraction.
실험예Experimental Example
2. 삼백초 추출물의 농도에 따른 맥압 및 1회 심방 박출량의 변화(2) 2. Changes in pulse pressure and one-time atrial ejection according to the concentration of Saururus chinensis extract (2)
본 실험은 실험예 1에서 실행된 삼백초 추출물의 농도에 따른 맥압 및 1회 심방 박출량의 변화를 더 확실히 알아보기 위하여 실행되었다.
The present experiment was conducted in the same manner as in Experimental Example 1 except that the pulse pressure and the amount of one-time atrial ejection It was implemented to learn more about changes.
(1) 실험 과정(1) Experimental process
1) 심방 박동관류 모델 제작1) Model of atrial pumping
실험예 1에 기재된 과정과 동일하게 실행되었다.
The same procedure as described in Experimental Example 1 was carried out.
2) 삼백초 추출물의 농도에 따른 맥압 및 1회 심방 박출량의 변화 측정2) Measurement of change in pulse pressure and atrial ejection fraction according to the concentration of Saururus chinensis extract
심방 박동관류 모델을 3개 그룹 준비하여 그룹 각각에 미처리, 삼백초 추출물 10-3 g/ml, 10-4 g/ml를 처리하고 맥압의 변화량을 측정하였으며, 나머지 2개 그룹 또한 삼백초 추출물 10-3 g/ml, 10-4 g/ml를 처리하고 1회 심방 박출량의 변화량을 측정하였다.
Atrial beats perfusion model, the three groups prepared in Houttuynia cordata extract 10 in the untreated group, respectively, -3 g / ml, 10 -4 g / ml , and the treatment were measured and the amount of change in pulse pressure, and the remaining two groups also Houttuynia cordata extract 10-3 g / ml, 10 -4 g / ml, and the change in atrial ejection fraction was measured once.
(2) 실험 결과(2) Experimental results
도 4는 삼백초 추출물의 농도를 10-3 g/ml과 10-4 g/ml로 달리하여 처리하였을시의 맥압 및 1회 심방 박출량을 측정한 결과를 비교한 그래프이다.
FIG. 4 is a graph comparing the results of measuring the pulse pressure and the amount of one-time atrial ejection when the concentration of Saururus chinensis extract was changed to 10 -3 g / ml and 10 -4 g / ml.
실험 결과, 삼백초 추출물은 맥압 및 1회 심방 박출량을 농도의존적으로 유의성있게 증가시켰다. 삼백초 추출물 10-3 g/ml 처리군과 10-4 g/ml 처리군을 비교해 본 결과, 특히 삼백초 추출물 10-3 g/ml 처리군에서 맥압 및 1회 심방 박출량이 확연히 높았다. As a result of the experiment, Saururus chinensis extract significantly increased the pulse pressure and the one atrial ventricular output in a concentration dependent manner. Houttuynia cordata extract 10 -3 g / ml treatment group with 10 -4 g / ml compared to the group treated with the present results, particularly Houttuynia cordata extract 10 -3 g / ml treatment group, pulse pressure, and once the atrial cardiac output was higher significantly in.
삼백초 추출물 10-4 g/ml 처리군에서는 대조군보다는 맥압 및 1회 심방 박출량이 약간 높았다. 삼백초 추출물 10-4 g/ml 처리군의 맥압의 변화량은 8△%였으며, 1회 심방 박출량 변화량은 25△%였다.At 10 -4 g / ml of Saururus chinensis extract, pulse pressure and one atrial output were slightly higher than the control group. The amount of change in the pulse pressure of the Houttuynia cordata extract 10 -4 g / ml treatment group was 8 △%, 1 times atrial stroke volume variation was 25% △.
삼백초 추출물 10-3 g/ml 처리군의 맥압의 변화량은 220△%였으며, 1회 심방 박출량의 변화량 또한 220△%였다.The change in the pulse pressure of the Saururus chinensis extract treated with 10 -3 g / ml was 220 △%, and the change of the atrial ejection amount was also 220 △%.
이로써, 삼백초 추출물은 맥압 및 1회 심방 박출량을 증가시킨다는 결론을 도출할 수 있다.
As a result, it can be concluded that Saururus chinensis extract increases pulse pressure and one atrial ejection.
실험예Experimental Example
3. 삼백초 추출물의 심근 수축 유발 효능 3. Myocardial contraction inducing activity of Saururus chinensis extract
일반적인 심근 수축 기전은 L-타입 Ca2 + 채널 통로(L-type Ca channel pathway)을 경유하여 일어나며, L-타입 Ca2 + 채널 저해제로 널리 사용되는 약물은 니페디핀(nifedifine)과 딜티아젬(diltiazem)이다.Typical myocardial contraction mechanism of L- type Ca + 2 channel passage (L-type Ca channel pathway) takes place by way of a, L- type Ca 2 + drug which is widely used as a channel inhibitor nifedipine (nifedifine) and diltiazem (diltiazem )to be.
본 실험은 앞서 언급한 두 종류의 L-타입 Ca2 + 채널 저해제를 전처리하여 L-타입 Ca2 + 채널 통로를 비활성화한 후, 삼백초 추출물과 두 종류의 L-타입 Ca2 + 채널 저해제를 병용처리하여 맥압과 1회 심방 박출량의 변화를 측정, 삼백초 추출물의 심근 수축 유발 효능을 알아보기 위하여 실행되었다.
This experiment aforementioned two types of L- type Ca 2 + and then to the pre-treatment channel inhibitors disable L- type Ca + 2 channel path, together with the Houttuynia cordata extract two types of L- type Ca 2 + channel inhibitor treatment The changes of pulse pressure and 1 atrial output were measured and the effect of Saururus chinensis extract on myocardial contractility was investigated.
(1) 실험 과정(1) Experimental process
1) 심방 박동관류 모델 제작1) Model of atrial pumping
실험예 1에 기재된 과정과 동일하게 실행되었다.
The same procedure as described in Experimental Example 1 was carried out.
2) 니페디핀 또는 딜티아젬 전처리시 및 삼백초 추출물과 니페디핀 또는 딜티아젬 병용처리시의 맥압 및 1회 심방 박출량의 변화 비교2) Comparing changes in pulse pressure and one-time atrial ejection during pretreatment of nifedipine or diltiazem and in combination with nifedipine or diltiazem treatment
심방 박동관류 모델을 4개 그룹 준비하여 2개 그룹에는 측정 시작 6분 후에 니페디핀 1 uM을 처리한 후, 측정 시작 24분 후에 삼백초 추출물 10-3 g/ml과 니페디핀 1 uM을 병용처리하였다. Four groups of atrial ventricular perfusion models were prepared. Two groups were treated with 1 μM of
나머지 2개 그룹에는 측정 시작 6분 후에 딜티아젬 1 uM을 처리한 후, 측정 시작 24시간 후에 삼백초 추출물 10-3 g/ml, 딜티아젬 1 uM을 병용처리하였다. 이들 4개 그룹의 맥압 및 1회 심방 박출량을 측정하였다. The remaining two groups were treated with 1 uM of
측정은 삼백초 추출물 처리 60분 후까지 실행되었으며, 6분 단위로 측정하였다.
Measurements were carried out up to 60 minutes after treatment with Saururus chinensis extract and measured in 6 minute increments.
(2) 실험 결과(2) Experimental results
도 5는 니페디핀을 단독처리하였을시 및 니페디핀과 삼백초 추출물 10-3 g/ml 을 처리하였을시의 맥압 및 1회 심방 박출량의 변화를 측정한 결과를 나타낸 그래프이다.FIG. 5 is a graph showing the results of measurement of changes in pulse pressure and one-time atrial ejection when nifedipine alone was treated and when 10 -3 g / ml of nifedipine and Saururus chinense extract were treated.
도 6은 딜티아젬을 단독처리하였을시 및 딜티아젬과 삼백초 추출물 10-3 g/ml과을 처리하였을시의 맥압 및 1회 심방 박출량의 변화를 측정한 결과를 나타낸 그래프이다.
FIG. 6 is a graph showing the results of measuring changes in pulse pressure and one-time atrial ejection when diltiazem was treated alone and when diltiazem and Saururus chinense extract were treated with 10 -3 g / ml.
실험 결과, 니페디핀을 전처리하였을시에는 36분 동안, 딜티아젬을 전처리하였을시에는 24분 동안 맥압 및 1회 심방 박출량이 감소되는 것을 볼 수 있다. 즉, 심근 수축이 감소됨을 볼 수 있다.Experimental results show that the pretreatment of nifedipine reduces pulse pressure and one time of atrial expulsion for 36 minutes and pretreatment of diltiazem for 24 minutes. In other words, myocardial contraction is reduced.
또한, 니페디핀 또는 딜티아젬을 전처리한 후 삼백초 추출물과 니페디핀, 또는 삼백초 추출물과 딜티아젬을 병용처리하였을시에는 맥압 및 1회 심방 박출량이 실험예 1에서 삼백초 추출물을 단독처리하였을시와 거의 동일한 정도로 증가함을 볼 수 있다. 즉, 심근 수축이 다시 증가함을 볼 수 있다.
In addition, when the nifedipine or diltiazem was pretreated and the Saururus chinensis extract and the nifedipine or Saururus chinensis extract were combined with diltiazem, the pulse pressure and the one atrial discharge were almost the same as those in the case of the Saururus chinensis extract alone in Experimental Example 1 Of the total. In other words, myocardial contraction is increased again.
정리하여 보면, L-타입 Ca2 + 채널 통로 저해제인 니페디핀 또는 딜티아젬을 심방 박동관류 모델에 전처리하였을시에는 심근 수축이 감소하였으나, 그 후 니페디핀과 삼백초 추출물 또는 딜티아젬과 삼백초 추출물을 처리하였을시에는 다시 심근 수축이 증가하였다.In summary, pretreatment of the L-type Ca 2 + channel channel inhibitor, nifedipine or diltiazem, with the atrial stroke perfusion model resulted in a decrease in myocardial contractility, but subsequent treatment of nifedipine and Saururus chinensis extract or Diltiazem and Saururus chinensis extract , Myocardial contraction increased again.
따라서 삼백초 추출물은 니페디핀 또는 딜티아젬과 병용처리시에도 심근 수축을 증가시키는 효능이 있다는 결론을 도출할 수 있다.Therefore, it can be concluded that Saururus chinensis extract has the effect of increasing myocardial contractility even in combination with nifedipine or diltiazem.
또한, 삼백초 추출물은 일반적인 심근 수축 기전인 L-타입 Ca2 + 채널 통로를 경유하지 않고 다른 기전을 통해 심근 수축을 유발한다는 결론을 유추할 수 있다. Also, Houttuynia cordata extract can derive a conclusion that cause myocardial contraction via other mechanisms without going through the normal myocardial contraction mechanism of L- type Ca + 2 channel passage.
Claims (5)
A composition for preventing, ameliorating, or treating heart failure, comprising Saururus chinensis extract as an active ingredient.
상기 조성물은 맥압(pulse pressure) 및 1회 심방 박출량(stroke volume)을 상승시키는 효능을 보유하는 것을 특징으로 하는, 심부전을 예방, 개선 또는 치료하는 조성물.
The method according to claim 1,
Wherein the composition has the effect of increasing pulse pressure and stroke volume. ≪ RTI ID = 0.0 > 11. < / RTI >
상기 조성물은 삼백초 추출물 미처리시 기준으로 맥압을 8~220% 상승시키며, 1회 심방 박출량을 25~220% 상승시키는 것을 특징으로 하는, 심부전을 예방, 개선 또는 치료하는 조성물.
The method of claim 2,
The composition according to any one of claims 1 to 5, wherein the composition is used for preventing, ameliorating or treating heart failure, wherein the heart rate is increased by 8 to 220% and the atrial output is increased by 25 to 220%.
상기 조성물의 농도는 가토 심방 박동관류 모델 기준으로 10-3 g/ml인 것을 특징으로 하는, 심부전을 예방, 개선 또는 치료하는 조성물.
The method according to claim 1,
Wherein the concentration of said composition is 10 < -3 > g / ml based on a rabbit atrial pacing model.
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