KR20200089242A - Composition containing complex extracts for preventing, improving or treating dyslipidemia - Google Patents
Composition containing complex extracts for preventing, improving or treating dyslipidemia Download PDFInfo
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- KR20200089242A KR20200089242A KR1020200065108A KR20200065108A KR20200089242A KR 20200089242 A KR20200089242 A KR 20200089242A KR 1020200065108 A KR1020200065108 A KR 1020200065108A KR 20200065108 A KR20200065108 A KR 20200065108A KR 20200089242 A KR20200089242 A KR 20200089242A
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Abstract
Description
본 발명은 복합 추출물을 포함하는 혈행 개선용 조성물 등에 관한 것으로서, 더 상세하게는 생약재 복합 추출물의 혈전 형성 억제 효능, 혈중 콜레스테롤 저하 효능 등에 기초한 생약재 복합 추출물의 다양한 의약적 용도 또는 건강기능식품 요도에 관한 것이다.The present invention relates to a composition for improving blood circulation, including a complex extract, and more specifically, to a variety of medicinal uses or health functional food urethra of the herbal extract complex based on the effect of inhibiting thrombus formation of the herbal extract, blood cholesterol lowering effect, etc. will be.
최근 선진국뿐 아니라 식생활의 서구화로 인한 과다 영양섭취로 비만 인구의 증가와 함께 우리나라에서도 동맥경화증, 뇌출혈, 고혈압, 심장병, 뇌졸중, 뇌경색 등의 순환기 질환이 사망원인 1, 2위를 차지하고 있다. 이러한 성인병은 현대사회로 발전하면서 식생활 양식의 변화 및 내, 외부적인 환경 스트레스로 인해 중, 장년층에서 빈번하게 발생하고 있다. 또한, 다양한 원인에 의해 혈관이 막혀 상기 질병들이 발생할 수 있는데, 예를 들어 심장 혈관이 막힐 경우 심근 경색증이 일어날 수 있고, 뇌의 혈관이 막혔을 경우 뇌경색이 발병될 수 있다. 또한, 뇌경색이 계속 진행되면 뇌졸중 증세가 나타나 목숨을 잃게 될 수도 있다. 미국에서는 뇌졸중이 성인의 사망 원인 중 3번째로 높은 순위를 차지하고 있으며 운동성이 무력하게 되는 가장 큰 요인으로 알려져있다. 이들 질환의 주요 발병 원인은 혈전(thrombus)으로 알려져 있는데, 혈전이란 과잉된 혈소판 응집에 의해 매개 되는 병리현상으로 인식되고 있다. 또한, 혈전이 생기면 그 부분의 혈관이 좁아지거나 막혀 혈액 순환의 장애도 발생하게 된다. 또한, 혈중 콜레스테롤 또는 혈중 중성지방의 농도가 증가하면 혈액 순환의 장애가 발생할 수 있다.Recently, not only in developed countries, but also in Korea, with the increase in obesity due to over-nutrition due to the westernization of eating habits, circulatory diseases such as arteriosclerosis, brain hemorrhage, hypertension, heart disease, stroke, and cerebral infarction have ranked first and second in death. As these adult diseases develop into the modern society, they frequently occur in middle-aged and older adults due to changes in dietary habits and internal and external environmental stress. In addition, the diseases may be caused by blood vessels blocked by various causes, for example, when the cardiovascular vessels are blocked, myocardial infarction may occur, and when the blood vessels in the brain are blocked, cerebral infarction may occur. In addition, if the stroke continues, stroke symptoms may appear and result in loss of life. Stroke is the third highest cause of death in adults in the United States, and it is known to be the biggest contributor to disability. The main cause of these diseases is known as thrombus, which is recognized as a pathology mediated by excessive platelet aggregation. In addition, when a blood clot is formed, blood vessels in the portion are narrowed or blocked, and thus blood circulation is disturbed. In addition, an increase in the concentration of cholesterol or triglycerides in the blood may cause disorders in blood circulation.
따라서, 혈행 개선, 혈전 질환의 예방 또는 치료를 위해 혈전 형성을 억제하고 동시에 혈중 콜레스테롤 및 중성지방 농도 등을 효과적으로 조절할 수 있는 의약품 소재 또는 건강기능식품 소재에 관한 연구가 많이 수행되고 있다. 한편, 천연 식의약 소재는 경제 산업적으로 큰 의의를 가지며 대부분 인체에 부작용이 없으므로 혈행 개선에 효과가 있는 천연 식의약 소재 개발이 절실히 요구되고 있다.Accordingly, many researches have been conducted on pharmaceutical materials or health functional food materials that can inhibit blood clot formation and effectively control blood cholesterol and triglyceride concentrations to improve blood circulation and prevent or treat thrombotic diseases. On the other hand, natural food and medicine materials have great significance in the economic and industrial sector, and since most of them have no side effects on the human body, the development of natural food and medicine materials that are effective in improving blood circulation is urgently required.
혈행 개선 효과를 가지는 천연 식의약 소재와 관련하여, 대한민국 등록특허공보 제10-1404168호에는 참당귀(Angelica gigas) 에탄올 추출물의 부탄올 분획물을 유효성분으로 함유하는 혈전증 예방 또는 치료용 약학적 조성물이 개시되어 있다. 또한, 대한민국 공개특허공보 제10-2011-0125960호에는 백하수오(Cynanchum wilfordii) 에탄올 추출물을 유효성분으로 함유하는 혈전 감소용 약학 조성물이 개시되어 있다. 또한, 혈행 개선에 도움을 주는 은행잎 추출물 함유 제품이 상업적으로 시판되고 있다. 또한, 대한민국 공개특허공보 제10-2018-0042035호에는 참당귀(Angelica gigas) 추출물을 유효성분으로 함유하는 이상지질혈증 예방 또는 치료용 약학적 조성물이 개시되어 있다. 또한, 대한민국 공개특허공보 제10-2011-0125958호에는 백하수오(Cynanchum wilfordii) 에탄올 추출물을 유효성분으로 함유하는 혈중 콜레스테롤 저하용 약학 조성물이 개시되어 있다. 또한, 미국 공개특허공보 제2008/0254155호에는 은행잎 추출물을 유효성분으로 포함하는 혈중 콜레스테롤 저하용 조성물이 개시되어 있다.In connection with a natural food and drug material having an effect of improving blood circulation, Korean Patent Publication No. 10-1404168 discloses a pharmaceutical composition for preventing or treating thrombosis containing an butanol fraction of Angelica gigas ethanol extract as an active ingredient It is. In addition, Korean Patent Publication No. 10-2011-0125960 discloses a pharmaceutical composition for reducing thrombosis, which contains an extract of ethanol of Baekshou ( Cynanchum wilfordii ) as an active ingredient. In addition, products containing ginkgo biloba extract that help improve blood circulation are commercially available. In addition, Korean Patent Publication No. 10-2018-0042035 discloses a pharmaceutical composition for preventing or treating dyslipidemia containing Angelica gigas extract as an active ingredient. Further, in Republic of Korea-A-10-2011-0125958 call back sewage (Cynanchum wilfordii ) A pharmaceutical composition for lowering cholesterol in blood containing an ethanol extract as an active ingredient is disclosed . In addition, U.S. Patent Publication No. 2008/0254155 discloses a composition for lowering cholesterol in the blood that includes an extract of ginkgo biloba as an active ingredient.
본 발명은 종래의 기술적 배경하에서 도출된 것으로서, 본 발명의 목적은 참당귀 추출물, 백수오 추출물 및 은행잎 추출물으로 이루어진 복합 추출물의 혈행 개선, 혈전 질환 예방, 개선 또는 치료 등과 같은 다양한 의약품 용도 또는 건강기능식품 용도를 제공하는데에 있다.The present invention is derived under the conventional technical background, the purpose of the present invention is a variety of pharmaceutical uses or health functions, such as blood circulation improvement, thrombotic disease prevention, improvement or treatment of a complex extract consisting of Angelica keiskei koidus extract, white sorghum extract and ginkgo biloba extract In providing food use.
본 발명의 발명자들은 합성 화학물질에 비해 안전성이 확보된 수많은 천연물을 대상으로 혈전 형성 억제 효능을 갖는 추출물을 개발하기 위하여 연구를 수행하였다. 그 결과, 참당귀 추출물, 백수오 추출물 및 은행잎 추출물으로 이루어진 복합 추출물이 시너지 작용에 의해 우수한 혈전 형성 억제 효능을 가지며 동시에 우수한 혈중 콜레스테롤 저하 효능 및 혈중 중성지방 저하 효능을 가진다는 점을 확인하고 본 발명을 완성하였다.The inventors of the present invention conducted a study to develop an extract having the efficacy of inhibiting thrombus formation against a large number of natural products that are secured in safety compared to synthetic chemicals. As a result, it was confirmed that the complex extract consisting of Angelica keiskei koidus extract, Baeksuo extract and Ginkgo biloba leaf extract has excellent thrombus formation inhibitory effect by synergy and at the same time has excellent blood cholesterol lowering effect and blood triglyceride lowering effect. Was completed.
상기 목적을 달성하기 위하여, 본 발명의 일 예는 참당귀 추출물, 백수오 추출물 및 은행잎 추출물로 이루어진 복합 추출물을 유효성분으로 포함하는 혈행 개선용 조성물을 제공한다.In order to achieve the above object, an example of the present invention provides a composition for improving blood circulation, which includes a complex extract composed of a true Angelica extract, a white sorghum extract, and a ginkgo biloba extract as an active ingredient.
상기 목적을 달성하기 위하여 본 발명의 일 예는 참당귀 추출물, 백수오 추출물 및 은행잎 추출물로 이루어진 복합 추출물을 유효성분으로 포함하는 혈전 질환 예방, 개선 또는 치료용 조성물을 제공한다.In order to achieve the above object, an example of the present invention provides a composition for preventing, improving or treating a thrombotic disease, comprising a complex extract composed of an Angelica keiskei kombu extract, a white sorghum extract and a ginkgo leaf extract as an active ingredient.
상기 목적을 달성하기 위하여, 본 발명의 일 예는 참당귀 추출물, 백수오 추출물 및 은행잎 추출물로 이루어진 복합 추출물을 유효성분으로 포함하는 이상지질혈증 예방, 개선 또는 치료용 조성물을 제공한다.In order to achieve the above object, an example of the present invention provides a composition for preventing, improving or treating dyslipidemia comprising a complex extract consisting of Angelica keiskei kombu extract, Baeksuo extract and Ginkgo biloba extract as an active ingredient.
상기 조성물은 바람직하게는 약학 조성물 또는 식품 조성물의 형태를 가진다.The composition preferably takes the form of a pharmaceutical composition or a food composition.
본 발명의 조성물은 참당귀 추출물, 백수오 추출물 및 은행잎 추출물로 이루어진 복합 추출물의 시너지 작용에 의해 우수한 혈전 형성 억제 효능을 가지며 동시에 우수한 혈중 콜레스테롤 저하 효능 및 혈중 중성지방 저하 효능을 가진다. 따라서 본 발명의 조성물은 혈행 개선, 혈전 질환, 이상지질혈증을 예방, 개선 또는 치료하기 위한 용도의 의약품, 건강기능식품으로 구현될 수 있다.The composition of the present invention has excellent thrombus formation inhibitory effect by synergistic action of a complex extract composed of a true Angelica extract, white sorghum extract, and ginkgo biloba extract, and at the same time, has excellent blood cholesterol lowering effect and blood triglyceride lowering effect. Therefore, the composition of the present invention can be embodied as a drug for the purpose of preventing, improving or treating blood circulation improvement, thrombotic disease, dyslipidemia, and health functional food.
도 1은 본 발명의 제조예 4에서 제조한 복합 추출물의 항산화 효능을 DPPH 시험법을 이용하여 분석한 결과이다.
도 2는 혈전증 유도 동물 모델을 이용한 복합 추출물의 항혈전 효능 평가 실험 결과를 보호율(Protection, %) 값으로 나타낸 것이다.
도 4는 비만 유도 동물 모델을 이용한 실험 결과 중 혈장 내 트리글리세리드(triglyceride) 함량을 나타낸 것이고, 도 5는 비만 유도 동물 모델을 이용한 실험 결과 중 혈장 내 총 콜레스테롤 함량을 나타낸 것이고, 도 6은 비만 유도 동물 모델을 이용한 실험 결과 중 혈장 내 LDL 콜레스테롤 함량을 나타낸 것이다.1 is a result of analyzing the antioxidant efficacy of the complex extract prepared in Preparation Example 4 of the present invention using a DPPH test method.
Figure 2 shows the results of the anti-thrombotic efficacy evaluation of the complex extract using a thrombosis-induced animal model as a protection (%) value.
FIG. 4 shows the triglyceride content in plasma among the experimental results using the obese-inducing animal model, FIG. 5 shows the total cholesterol content in plasma among the experimental results using the obese-inducing animal model, and FIG. 6 shows the obese-inducing animal Among the experimental results using the model, it shows the LDL cholesterol content in plasma.
이하, 본 발명에서 사용한 용어를 설명한다.Hereinafter, terms used in the present invention will be described.
본 발명에서 사용되는 용어 "약학적으로 허용가능한" 및 "식품학적으로 허용가능한"이란 생물체를 상당히 자극하지 않고 투여 활성 물질의 생물학적 활성 및 특성을 저해하지 않는 것을 의미한다.As used herein, the terms "pharmaceutically acceptable" and "foodly acceptable" mean not significantly stimulating the organism and not inhibiting the biological activity and properties of the active substance administered.
본 발명에서 사용되는 용어 "예방"은 본 발명의 조성물의 투여로 특정 질환(예를 들어, 혈전 질환)의 증상을 억제시키거나 진행을 지연시키는 모든 행위를 의미한다.As used herein, the term "prevention" refers to all actions that inhibit or delay the progression of symptoms of a specific disease (eg, thrombotic disease) by administration of a composition of the invention.
본 발명에서 사용되는 용어 "개선"은 치료되는 상태와 관련된 파라미터, 예를 들면 증상의 정도를 적어도 감소시키는 모든 행위를 의미한다.As used herein, the term "improvement" means any action that at least reduces the severity of parameters associated with the condition being treated, such as symptoms.
본 발명에서 사용되는 용어 "치료"는 본 발명의 조성물의 투여로 특정 질환(예를 들어, 혈전 질환)의 증상을 호전 또는 이롭게 변경시키는 모든 행위를 의미한다.As used herein, the term "treatment" means any action that improves or beneficially alters the symptoms of a particular disease (eg, thrombotic disease) by administration of the composition of the invention.
본 발명에서 사용되는 용어 "투여"는 임의의 적절한 방법으로 개체에 소정의 본 발명의 조성물을 제공하는 것을 의미한다. 이때, 개체는 본 발명의 조성물을 투여하여 특정 질환의 증상이 호전될 수 있는 질환을 가진 인간, 원숭이, 개, 염소, 돼지 또는 쥐 등 모든 동물을 의미한다.As used herein, the term "administration" means providing a subject composition of the present invention to an individual in any suitable way. At this time, the individual refers to all animals, such as humans, monkeys, dogs, goats, pigs, or rats, with diseases that may improve symptoms of a specific disease by administering the composition of the present invention.
본 발명에서 사용되는 용어 "약학적으로 유효한 양"은 의학적 치료에 적용 가능한 합리적인 수혜 또는 위험 비율로 질환을 치료하기에 충분한 양을 의미하며, 이는 개체의 질환의 종류, 중증도, 약물의 활성, 약물에 대한 민감도, 투여 시간, 투여 경로 및 배출비율, 치료기간, 동시에 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 결정될 수 있다.The term "pharmaceutically effective amount" used in the present invention means an amount sufficient to treat a disease at a reasonable benefit or risk ratio applicable to medical treatment, which is the type, severity, drug activity, drug of the individual. Sensitivity to, time of administration, route of administration and rate of discharge, duration of treatment, factors including concurrently used drugs, and other factors well known in the medical field can be determined.
이하, 본 발명을 상세하게 설명한다. 본 발명은 3가지 생약의 추출물로 이루어진 복합 추출물을 유효성분으로 포함하는 조성물을 포함한다. 상기 복합 추출물은 구체적으로 참당귀 추출물, 백수오 추출물 및 은행잎 추출물로 이루어진다. 본 발명의 조성물은 혈행 개선; 혈전 질환 예방, 개선 또는 치료; 이상지질혈증 예방, 개선 또는 치료 등과 같이 다양한 의약품 용도 또는 건강기능식품 용도로 사용될 수 있다.Hereinafter, the present invention will be described in detail. The present invention includes a composition comprising a complex extract consisting of extracts of three herbal medicines as an active ingredient. The complex extract is specifically composed of Angelica keiskei kombu extract, Baeksuo extract and ginkgo biloba extract. The composition of the present invention improves blood circulation; Preventing, improving or treating thrombotic diseases; It can be used for various medicines or health functional foods such as dyslipidemia prevention, improvement or treatment.
상기 참당귀(Angelica gigas)는 쌍떡잎식물 이판화군 산형화목 산형과에 속하는 여러해살이풀서, 그 뿌리를 약재로 쓴다. 상기 백수오(Cynanchum wilfordii)는 박주가리과(Asclepiadaceae) 백미꽃속(Cynanchum)에 속하는 덩굴성 여러해살이풀로서, 그 뿌리를 약재로 쓴다. 본 발명에서 참당귀 추출물 또는 백수오 추출물을 얻기 위한 식물의 부위는 뿌리, 줄기, 잎, 꽃, 씨앗 등 크게 제한되지 않으며 효능을 고려할 때 뿌리인 것이 바람직하다.The Angelica gigas is a perennial plant that belongs to the mountain type family of the mountain type tree, Ipanhwa-gun, and uses its roots as a medicinal material. The white snail ( Cynanchum wilfordii ) is a vine perennial plant belonging to the genus Cynanchum of the Asclepiadaceae family, and uses its roots as a medicinal material. In the present invention, the site of the plant for obtaining the Angelica keiskei koi extract or Baeksuo extract is not greatly limited such as roots, stems, leaves, flowers, seeds, and is preferably a root when considering efficacy.
본 발명에 따른 조성물의 유효성분인 복합 추출물은 다양한 방법으로 제조될 수 있다. 예를 들어, 상기 복합 추출물은 참당귀, 백수오 및 은행잎을 혼합한 후 여기에 추출 용매를 가하고 혼합 추출물을 추출하여 제조할 수도 있고, 다시 혼합 추출물에 탄소 수가 3 내지 8인 알코올을 가하고 분획하여 제조할 수도 있다. 또한, 상기 복합 추출물은 참당귀, 백수오 및 은행잎으로부터 각각 참당귀 추출물, 백수오 추출물 및 은행잎 추출물을 얻은 후 이들을 혼합하여 제조할 수도 있다. 구체적으로, 상기 복합 추출물을 구성하는 참당귀 추출물, 백수오 추출물 또는 은행잎 추출물은 당업계에 공지된 통상의 추출 방법, 예를 들어 용매 추출법을 사용하여 제조될 수 있다. 용매 추출법에 이용되는 추출 용매는 물, 탄소 수가 1 내지 4인 저급 알코올(예를 들면, 메탄올, 에탄올, 프로판올 및 부탄올) 또는 이들의 혼합물인 함수 저급 알코올, 프로필렌글리콜, 1,3-부틸렌글리콜, 글리세린, 아세톤, 디에틸에테르, 에틸 아세테이트, 부틸아세테이트, 디클로로메탄, 클로로포름, 헥산 및 이들의 혼합물로 구성된 군으로부터 선택될 수 있고, 이중 물, 알코올 또는 이들의 혼합물인 함수 알코올에서 선택되는 것이 바람직하고, 함수 알코올인 것이 더 바람직하다. 추출 용매로 물을 사용하는 경우 물은 열수인 것이 바람직하다. 또한, 추출 용매로 알코올을 사용하는 경우 알코올은 탄소 수가 1 내지 4인 저급 알코올인 것이 바람직하고, 저급 알코올은 메탄올 또는 에탄올에서 선택되는 것이 더 바람직하다. 또한, 추출 용매로 함수 알코올을 사용하는 경우 알코올 함량은 50~90%인 것이 바람직하고, 60~85%인 것이 더 바람직하다. 한편, 상기한 추출 용매뿐만 아니라, 다른 추출 용매를 이용하여도 실질적으로 동일한 효과를 나타내는 참당귀 추출물, 백수오 추출물 또는 은행잎 추출물이 얻어질 수 있다는 것은 당업자에게 자명한 것이다. 또한, 복합 추출물을 구성하는 참당귀 추출물, 백수오 추출물 또는 은행잎 추출물에는 상술한 추출 용매에 의한 추출물뿐만 아니라, 통상적인 다른 추출 방법을 통해 얻어진 추출물, 분획물, 정제물 및 발효 과정을 거친 추출물도 포함될 수 있다. 예를 들어, 이산화탄소를 이용한 초임계 유체 추출법(supercritical fluid extraction)에 의한 추출, 초음파를 이용한 추출법에 의한 추출, 일정한 분자량 컷-오프 값을 갖는 한외 여과막을 이용한 분리 또는 다양한 크로마토그래피(크기, 전하, 소수성 또는 친화성에 따른 분리를 위해 제작된 것)에 의한 분리, 각종 미생물의 발효 산물에 의한 추출 등, 추가적으로 실시된 다양한 정제 및 추출방법을 통해 얻어진 활성 분획도 본 발명의 추출물에 포함된다. 일반적으로 초임계 유체는 기체가 고온 고압 조건에서 임계점에 도달하였을 때 갖는 액체 및 기체의 성질을 지니고 있으며, 화학적으로 비극성 용매와 유사한 극성을 지니고 있으며 이러한 특성으로 인해 초임계 유체는 지용성 물질의 추출에 사용되고 있다(J. Chromatogr. A. 1998;479:200-205). 이산화탄소는 초임계 유체기기의 작동으로 압력 및 온도가 임계점까지 이르는 과정을 거치면서 액체 및 기체 성질을 동시에 지닌 초임계 유체가 되고 그 결과 지용성 용질에 대한 용해도가 증가한다. 초임계 이산화탄소가 일정량의 시료를 함유한 추출 용기를 통과하게 되면 시료에 함유된 지용성 물질은 초임계 이산화탄소에 추출되어 나온다. 지용성 물질을 추출한 후 추출 용기에 남아있는 시료에 다시 소량의 공용매가 함유된 초임계 이산화탄소를 흘려 통과시키면 순수한 초임계 이산화탄소만으로는 추출되지 않았던 성분들이 추출되어 나오게 할 수 있다. 본 발명의 초임계 추출법에 사용되는 초임계 유체는 초임계 이산화탄소 또는 이산화탄소에 추가적으로 공용매를 혼합한 혼합유체를 사용함으로써 효과적으로 유효 성분을 추출할 수 있다. 이러한 공용매로 클로로포름, 에탄올, 메탄올, 물, 에틸아세테이트, 헥산 및 디에틸에테르로 이루어진 군에서 선택되는 1종 또는 2종 이상의 혼합물을 사용할 수 있다. 추출된 시료는 대부분 이산화탄소를 함유하고 있는데 이산화탄소는 실온에서 공기 중으로 휘발되고, 공용매는 감압증발기로 제거할 수 있다. 또한, 상기 초음파 추출법은 초음파 진동에 의해 발생되는 에너지를 이용하는 추출방법으로, 초음파가 수용성 용매 속에서 시료에 포함된 불용성인 용매를 파괴시킬 수 있으며, 이때 발생되는 높은 국부온도로 인하여 주위에 위치하는 반응물 입자들의 운동에너지를 크게 하기 때문에 반응에 필요한 충분한 에너지를 얻게 되고, 초음파 에너지의 충격효과로 높은 압력을 유도하여 시료에 함유된 물질과 용매의 혼합 효과를 높여주어 추출 효율을 증가시키게 된다. 초음파 추출법에 사용할 수 있는 추출용매는 클로로포름, 에탄올, 메탄올, 물, 에틸아세테이트, 헥산 및 디에틸 에테르로 이루어진 군에서 선택되는 1종 또는 2종 이상의 혼합물을 사용할 수 있다. 추출된 시료는 진공 여과하여 여과액을 회수한 후 감압증발기로 제거하고, 동결 건조하는 통상의 추출물 제조방법을 통해 추출물을 얻을 수 있다. 또한, 복합 추출물을 구성하는 참당귀 추출물, 백수오 추출물 또는 은행잎 추출물은 발효과정을 거친 추출물도 포함하는데, 예를 들어 참당귀의 발효 추출물은 다음과 같이 제조할 수 있다. 참당귀를 100~500 메쉬 정도로 미세하게 파쇄한 다음 통상적인 미생물용 배양액을 지모 농도가 1~50g/L가 되도록 첨가하고 여기에 효모 균주 또는 유산균 등의 미생물을 10,000~100,000 cfu/L의 양으로 첨가한다. 이후, 30~37℃의 배양 온도, 5~7의 pH와 같은 통상적인 미생물 배양조건으로 로 호기적 또는 혐기(anaerobic)적인 상태에서 약 5일 내지 10일간 배양한다. 이후, 숙성 및 여과를 통해 참당귀의 발효 추출물을 얻을 수 있다. 백수오의 발효 추출물 또는 은행잎의 발효효 추출물도 동일한 과정을 거쳐 제조될 수 있다.The complex extract, which is the active ingredient of the composition according to the present invention, can be prepared by various methods. For example, the composite extract may be prepared by mixing the Angelica keiskei, white snails and ginkgo biloba and adding an extracting solvent thereto and extracting the mixed extract, again adding and fractionating alcohol having 3 to 8 carbons to the mixed extract. It can also be manufactured. In addition, the composite extract may be prepared by obtaining a true Angelica extract, a white sorghum extract, and a ginkgo biloba extract, respectively, from a true Angelica, white sorghum, and ginkgo leaf. Specifically, the Angelica extract, Baeksuo extract, or Ginkgo biloba extract constituting the complex extract may be prepared using a conventional extraction method known in the art, for example, a solvent extraction method. The extraction solvent used in the solvent extraction method is water, lower alcohol having 1 to 4 carbon atoms (for example, methanol, ethanol, propanol and butanol) or a mixture thereof, hydrous lower alcohol, propylene glycol, 1,3-butylene glycol. , Glycerin, acetone, diethyl ether, ethyl acetate, butyl acetate, dichloromethane, chloroform, hexane, and mixtures thereof, and may be selected from water, alcohols, or mixtures thereof. It is more preferable that it is hydrous alcohol. When water is used as the extraction solvent, water is preferably hot water. In addition, when alcohol is used as the extraction solvent, the alcohol is preferably a lower alcohol having 1 to 4 carbon atoms, and the lower alcohol is more preferably selected from methanol or ethanol. In addition, when using hydrous alcohol as the extraction solvent, the alcohol content is preferably 50 to 90%, and more preferably 60 to 85%. On the other hand, it is apparent to those skilled in the art that, in addition to the above-described extraction solvent, a true Angelica extract, white sorghum extract, or ginkgo biloba extract, which exhibits substantially the same effect, can be obtained using other extraction solvents. In addition, the extract of the Angelica Angelica constituting the complex extract, the extract of Baeksuo or Ginkgo biloba, as well as the extract by the above-mentioned extraction solvent, include extracts, fractions, purified products obtained through other conventional extraction methods, and extracts that have undergone a fermentation process. Can. For example, extraction by supercritical fluid extraction using carbon dioxide, extraction by ultrasonic extraction, separation using an ultrafiltration membrane having a constant molecular weight cut-off value, or various chromatography (size, charge, The active fraction obtained through various purification and extraction methods additionally performed, such as separation by hydrophobicity or affinity), separation by fermentation products of various microorganisms, is also included in the extract of the present invention. In general, supercritical fluids have the properties of liquids and gases that the gas has when it reaches a critical point under high temperature and high pressure conditions, and have a chemically polarity similar to a non-polar solvent. Due to these characteristics, supercritical fluids are used for extraction of fat-soluble materials. Used (J. Chromatogr. A. 1998; 479:200-205). Carbon dioxide becomes a supercritical fluid having both liquid and gaseous properties through the process of pressure and temperature reaching a critical point through the operation of a supercritical fluid device, and as a result, solubility in fat-soluble solute increases. When the supercritical carbon dioxide passes through an extraction container containing a certain amount of sample, the fat-soluble substance contained in the sample is extracted from the supercritical carbon dioxide. After extracting the fat-soluble substance, passing the supercritical carbon dioxide containing a small amount of the co-solvent back to the sample remaining in the extraction container may allow components not extracted with pure supercritical carbon dioxide to be extracted. The supercritical fluid used in the supercritical extraction method of the present invention can effectively extract an active ingredient by using supercritical carbon dioxide or a mixed fluid in which a co-solvent is additionally mixed with carbon dioxide. As such a co-solvent, one or two or more mixtures selected from the group consisting of chloroform, ethanol, methanol, water, ethyl acetate, hexane and diethyl ether can be used. Most of the extracted sample contains carbon dioxide, which is volatilized into the air at room temperature, and the co-solvent can be removed by a vacuum evaporator. In addition, the ultrasonic extraction method is an extraction method that uses energy generated by ultrasonic vibration, and ultrasonic waves can destroy insoluble solvents contained in a sample in a water-soluble solvent, and are located around due to the high local temperature generated at this time. Since the kinetic energy of the reactant particles is increased, sufficient energy necessary for the reaction is obtained, and high pressure is induced by the impact effect of ultrasonic energy to increase the mixing effect of the substance and the solvent contained in the sample, thereby increasing extraction efficiency. As the extraction solvent that can be used for the ultrasonic extraction method, one or a mixture of two or more selected from the group consisting of chloroform, ethanol, methanol, water, ethyl acetate, hexane and diethyl ether can be used. The extracted sample can be vacuum filtered to recover the filtrate, then removed with a vacuum evaporator, and an extract can be obtained through a conventional extract preparation method of freeze drying. In addition, the extract of the Angelica constituting the complex extract, the extract of Baeksuo or Ginkgo biloba also includes the extract that has undergone the fermentation process. For example, the fermented extract of the Angelica can be prepared as follows. Finely shredded Angelica Angelica to a size of about 100 to 500 mesh, and then added a conventional culture medium for microorganisms so that the jimo concentration is 1 to 50 g/L, and microorganisms such as yeast strains or lactic acid bacteria are added in an amount of 10,000 to 100,000 cfu/L. Add. Subsequently, the cells are cultured for about 5 to 10 days in aerobic or anaerobic conditions under normal microbial culture conditions such as a culture temperature of 30 to 37°C and a pH of 5 to 7. Then, fermentation extract of Angelica Angelica can be obtained through aging and filtration. The fermented extract of Baeksuo or the fermented extract of ginkgo biloba can also be prepared through the same process.
본 발명에 따른 조성물에서 유효성분인 복합 추출물을 구성하는 참당귀 추출물, 백수오 추출물 및 은행잎 추출물의 혼합비는 크게 제한되지 않는다. 예를 들어, 상기 복합 추출물 내에서 참당귀 추출물, 백수오 추출물 및 은행잎 추출물의 중량비는 1 : (0.5~2) : (0.5~2) 에서 선택될 수 있고, 시너지 작용을 고려할 때 1 : (0.6~1.5) : (0.6~1.5)에서 선택되는 것이 바람직하고, 1 : (0.8~1.2) : (0.8~1.2)에서 선택되는 것이 더 바람직하다.In the composition according to the present invention, the mixing ratio of the Angelica kerosene extract, Baeksu-o extract and Ginkgo biloba extract constituting the complex extract as an active ingredient is not significantly limited. For example, the weight ratio of Angelica keiskei koidus extract, Baeksuo extract and Ginkgo biloba extract in the complex extract may be selected from 1: (0.5~2): (0.5~2), and considering synergistic action, 1:(0.6 ~1.5): It is preferably selected from (0.6-1.5), and more preferably selected from 1: (0.8-1.2): (0.8-1.2).
본 발명의 조성물에서 유효성분으로 사용되는 복합 추출물은 참당귀 추출물, 백수오 추출물 및 은행잎 추출물의 병용에 의한 시너지 작용에 의해 우수한 혈전 형성 억제 효능을 가지며 동시에 우수한 혈중 콜레스테롤 저하 효능 및 혈중 중성지방 저하 효능을 가진다. 따라서, 본 발명의 조성물은 혈행 개선, 혈전 질환, 이상지질혈증을 예방, 개선 또는 치료하기 위한 용도의 의약품, 건강기능식품으로 구현될 수 있다. 또한, 본 발명의 조성물에서 유효성분으로 사용되는 복합 추출물은 라디칼 소거 활성이 우수하여 항산화용 조성물의 성분으로도 사용될 수 있다. 또한, 본 발명의 조성물에서 유효성분으로 사용되는 복합 추출물은 비만을 예방, 개선 또는 치료하기 위한 조성물의 성분으로도 사용될 수 있다. 또한, 본 발명의 조성물에서 유효성분으로 사용되는 복합 추출물은 대사증후군을 예방, 개선 또는 치료하기 위한 조성물의 성분으로도 사용될 수 있다. 상기 대사증후군은 비만과 함께 고지혈증, 심혈관 질환, 고혈압 또는 동맥경화증에서 선택되는 1종 이상의 질환이 동시에 발생하는 질환이다.The complex extract used as an active ingredient in the composition of the present invention has excellent thrombus formation inhibitory effect by synergistic action of the combination of Angelica keiskei kombu extract, Baeksuo extract and Ginkgo biloba extract, and at the same time has excellent blood cholesterol lowering effect and blood triglyceride lowering effect Have Therefore, the composition of the present invention can be implemented as a medicine for the purpose of preventing, improving or treating blood circulation improvement, thrombotic disease, dyslipidemia, and health functional food. In addition, the complex extract used as an active ingredient in the composition of the present invention has excellent radical scavenging activity and can also be used as a component of an antioxidant composition. In addition, the complex extract used as an active ingredient in the composition of the present invention may be used as a component of a composition for preventing, improving or treating obesity. In addition, the complex extract used as an active ingredient in the composition of the present invention may be used as a component of a composition for preventing, improving or treating metabolic syndrome. The metabolic syndrome is a disease in which at least one disease selected from hyperlipidemia, cardiovascular disease, hypertension or arteriosclerosis occurs simultaneously with obesity.
본 발명에서 혈전 질환은 혈전에 의해 발생하는 질환으로서 그 종류가 크게 제한되지 않으며, 예를 들어 동맥 혈전증, 정맥 혈전증, 폐동맥 색전증, 만성정맥 허혈, 하지 정맥류, 심부 정맥 혈전증, 동맥경화증, 뇌출혈, 뇌졸증 및 뇌경색으로 이루어진 군에서 선택되는 어느 하나 이상일 수 있다.In the present invention, thrombotic disease is a disease caused by thrombi, and its type is not greatly limited, for example, arterial thrombosis, venous thrombosis, pulmonary embolism, chronic venous ischemia, lower extremity varicose veins, deep venous thrombosis, arteriosclerosis, cerebral hemorrhage, stroke And it may be any one or more selected from the group consisting of cerebral infarction.
본 발명에서 이상지질혈증은 혈중에 총콜레스테롤, LDL콜레스테롤, 중성지방이 증가된 상태거나 HDL콜레스테롤이 감소된 상태를 말하며, 고지혈증, 고콜레스테롤혈증 및 고중성지방혈증으로 이루어진 군에서 선택되는 어느 하나 이상일 수 있다. 상기 고지혈증란 혈중에 콜레스테롤과 중성지방을 포함한 지질이 증가된 상태를 말한다. 고지혈증은 비록 증상을 나타내지 않을지라도 동맥경화나 심근경색과 같은 관상동맥질환의 위험을 증가시킬 수가 있다. 상기 고콜레스테롤혈증이란 혈중에 콜레스테롤이 증가된 상태로 총콜레스테롤과 LDL콜레스테롤이 높게 나타난다. 상기 고중성지방혈증이란 혈중에 중성지방이 증가된 상태를 말한다.In the present invention, dyslipidemia refers to a condition in which total cholesterol, LDL cholesterol, and triglycerides are increased or HDL cholesterol is decreased in the blood, and any one or more selected from the group consisting of hyperlipidemia, hypercholesterolemia and hypertriglyceridemia. Can. The hyperlipidemia refers to a state in which lipids including cholesterol and triglycerides are increased in the blood. Hyperlipidemia may increase the risk of coronary artery disease, such as arteriosclerosis or myocardial infarction, although it does not exhibit symptoms. The hypercholesterolemia is a condition in which cholesterol is increased in the blood, and total cholesterol and LDL cholesterol are high. The hypertriglyceridemia refers to a state in which triglycerides are increased in the blood.
본 발명의 복합 추출물을 유효성분으로 포함하는 조성물은 사용 목적 내지 양상에 따라 약학 조성물, 식품 첨가제, 식품 조성물(특히 건강기능식품), 또는 사료 첨가제 등으로 구체화될 수 있고, 조성물 내에서의 복합 추출물의 함량도 조성물의 구체적인 형태, 사용 목적 내지 양상에 따라 다양한 범위에서 조정될 수 있다.The composition comprising the complex extract of the present invention as an active ingredient may be embodied as a pharmaceutical composition, a food additive, a food composition (especially a health functional food), or a feed additive depending on the purpose or aspect of use, and a complex extract in the composition The content of can also be adjusted in various ranges depending on the specific form of the composition, purpose of use, and aspect.
본 발명의 약학 조성물에서 유효성분인 복합 추출물의 함량은 크게 제한되지 않으며, 예를 들어 조성물 총 중량을 기준으로 0.1~99 중량%, 바람직하게는 0.5~50 중량%, 더 바람직하게는 1~30 중량%일 수 있다. 또한, 본 발명의 약학 조성물은 복합 추출물 외에 약학적으로 허용가능한 담체, 부형제 또는 희석제와 같은 첨가제를 더 포함할 수 있다. 본 발명의 약학 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다. 또한, 본 발명의 약학 조성물은 복합 추출물 외에 혈행 개선; 혈전 질환 예방, 개선 또는 치료; 이상지질혈증 예방, 개선 또는 치료 효과를 갖는 공지의 유효 성분을 1종 이상 더 함유할 수 있다. 본 발명의 약학 조성물은 통상의 방법에 의해 경구 투여를 위한 제형 또는 비경구 투여를 위한 제형으로 제제화될 수 있고, 제제화할 경우 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제될 수 있다. 경구 투여를 위한 고형 제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형 제제는 유효성분인 복합 추출물에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트(Calcium carbonate), 수크로스(Sucrose), 락토오스(Lactose) 또는 젤라틴 등을 섞어 조제될 수 있다. 또한, 단순한 부형제 이외에 마그네슘 스티레이트 탈크 같은 윤활제들도 사용될 수 있다. 경구 투여를 위한 액상 제제로는 현탁제, 내용액제, 유제 및 시럽제 등이 해당되는데 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, 동결건조제제, 좌제가 포함될 수 있다. 비수성용제, 현탁용제로는 프로필렌글리콜(Propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다. 더 나아가 당 분야의 적정한 방법으로 또는 Remington's Pharmaceutical Science(최근판), Mack Publishing Company, Easton PA에 개시되어 있는 방법을 이용하여 각 질환에 따라 또는 성분에 따라 바람직하게 제제화할 수 있다. 본 발명의 약학 조성물은 목적하는 방법에 따라 인간을 포함한 포유류에 경구 투여되거나 비경구 투여될 수 있으며, 비경구 투여 방식으로는 피부 외용, 복강내주사, 직장내주사, 피하주사, 정맥주사, 근육내 주사 또는 흉부내 주사 주입방식 등이 있다. 본 발명의 약학 조성물의 투여량은 약학적으로 유효한 양이라면 크게 제한되지 않으며, 환자의 체중, 연령, 성별, 건강상태, 식이, 투여시간, 투여방법, 배설율 및 질환의 중증도에 따라 그 범위가 다양하다. 본 발명의 약학 조성물의 통상적인 1일 투여량은 크게 제한되지 않으며, 예를 들어 유효성분인 복합 추출물을 기준으로 할 때 1 내지 1000 ㎎/㎏에서 선택될 수 있고, 10 내지 500 ㎎/㎏에서 선택되는 것이 바람직하고, 50 내지 250 ㎎/㎏에서 선택되는 것이 더 바람직하다. 본 발명의 약학 조성물의 투여 횟수도 크게 제한되지 않으며, 예를 들어 하루 1회 또는 수회로 나누어 투여될 수 있다.The content of the complex extract as an active ingredient in the pharmaceutical composition of the present invention is not significantly limited, for example, 0.1 to 99% by weight, preferably 0.5 to 50% by weight, more preferably 1 to 30 based on the total weight of the composition. Weight percent. In addition, the pharmaceutical composition of the present invention may further include additives such as a pharmaceutically acceptable carrier, excipient or diluent in addition to the complex extract. Carriers, excipients and diluents that may be included in the pharmaceutical 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 addition, the pharmaceutical composition of the present invention improves blood circulation in addition to the complex extract; Preventing, improving or treating thrombotic diseases; It may further contain one or more known active ingredients having the effect of preventing, improving or treating dyslipidemia. The pharmaceutical composition of the present invention may be formulated into a formulation for oral administration or a formulation for parenteral administration by a conventional method, and when formulated, a filler, a bulking agent, a binder, a wetting agent, a disintegrant, a surfactant, etc. It can be prepared using diluents or excipients. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc.These solid preparations include at least one excipient such as starch, calcium carbonate, water, etc. It can be prepared by mixing Sucrose, Lactose, or gelatin. In addition, lubricants such as magnesium stearate talc may be used in addition to simple excipients. Liquid preparations for oral administration include suspending agents, intravenous solutions, emulsions, and syrups. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, can be included. have. Formulations for parenteral administration may include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, and suppositories. As the non-aqueous solvent and the suspension solvent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate may be used. As a base for suppositories, witepsol, macrogol, tween 61, cacao butter, laurin butter, and glycerogelatin may be used. Furthermore, it can be preferably formulated in accordance with each disease or ingredient using methods disclosed in Remington's Pharmaceutical Science (Recent Edition), Mack Publishing Company, Easton PA, or by appropriate methods in the art. The pharmaceutical composition of the present invention may be administered orally or parenterally to mammals, including humans, according to the desired method, and the parenteral administration methods include external application to the skin, intraperitoneal injection, intrarectal injection, subcutaneous injection, intravenous injection, and muscle. Intra-injection or intra-thoracic injection. The dosage of the pharmaceutical composition of the present invention is not particularly limited as long as it is a pharmaceutically effective amount, and the range thereof depends on the patient's weight, age, sex, health condition, diet, administration time, administration method, excretion rate and disease severity. Varies. The typical daily dosage of the pharmaceutical composition of the present invention is not greatly limited, and can be selected from 1 to 1000 mg/kg, for example, based on the complex extract as an active ingredient, and from 10 to 500 mg/kg It is preferably selected, and more preferably 50 to 250 mg/kg. The number of times of administration of the pharmaceutical composition of the present invention is also not greatly limited, and can be administered, for example, once or several times a day.
본 발명의 식품 조성물에서 유효성분인 복합 추출물의 함량은 크게 제한되지 않으며, 조성물 총 중량을 기준으로 0.01~50 중량%, 바람직하게는 0.1~25 중량%, 더 바람직하게는 0.5~10 중량%일 수 있다. 본 발명의 식품 조성물은 환제, 분말, 과립, 침제, 정제, 캡슐, 또는 액제 등의 형태를 포함하며, 구체적인 식품의 예로는 육류, 소시지, 빵, 초콜릿, 캔디류, 스넥류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 차, 기능수, 드링크제, 알코올음료 및 비타민 복합제 등이 있으며, 통상적인 의미에서의 건강식품을 모두 포함한다. 본 발명의 식품 조성물은 유효성분인 복합 추출물 외에 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 또한, 본 발명의 식품 조성물은 여러 가지 영양제, 비타민, 전해질, 풍미제, 착색제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 그 밖에 본 발명의 식품 조성물은 천연 과일주스, 과일주스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분들은 독립적으로 또는 혼합하여 사용할 수 있다. 상술한 천연 탄수화물은 포도당, 과당과 같은 모노사카라이드, 말토스, 슈크로스와 같은 디사카라이드, 및 덱스트린, 사이클로덱스트린과 같은 폴리사카라이드, 자일리톨, 소르비톨, 에리트리톨 등의 당알코올이다. 향미제로는 타우마틴, 스테비아 추출물과 같은 천연 향미제나 사카린, 아스파르탐과 같은 합성 향미제 등을 사용할 수 있다.The content of the complex extract as an active ingredient in the food composition of the present invention is not significantly limited, and is 0.01 to 50% by weight, preferably 0.1 to 25% by weight, more preferably 0.5 to 10% by weight based on the total weight of the composition Can. Food composition of the present invention includes a form of pills, powders, granules, needles, tablets, capsules, or liquids, and examples of specific foods include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, Other dairy products including noodles, gums, and ice creams, various soups, beverages, teas, functional waters, drinks, alcoholic beverages, and vitamin complexes are all included. The food composition of the present invention may contain various flavoring agents or natural carbohydrates as an additional component in addition to the complex extract as an active ingredient. In addition, the food composition of the present invention, various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohol , Carbonic acid used in carbonated beverages, and the like. In addition, the food composition of the present invention may contain flesh for the preparation of natural fruit juice, fruit juice beverages and vegetable beverages. These ingredients can be used independently or in combination. The above-mentioned natural carbohydrates are monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, and polysaccharides such as dextrin and cyclodextrin, sugar alcohols such as xylitol, sorbitol and erythritol. As the flavoring agent, natural flavoring agents such as taumatin and stevia extract or synthetic flavoring agents such as saccharin and aspartame may be used.
이하, 본 발명을 실시예를 통하여 보다 구체적으로 설명한다. 다만, 하기 실시예는 본 발명의 기술적 특징을 명확하게 예시하기 위한 것 일뿐, 본 발명의 보호범위를 한정하는 것은 아니다.Hereinafter, the present invention will be described in more detail through examples. However, the following examples are only for clearly illustrating the technical features of the present invention, and are not intended to limit the protection scope of the present invention.
1. 참당귀 추출물, 1. Angelica extract, 백수오Baek Su-oh 추출물, 은행잎 추출물 및 복합 추출물의 제조 Preparation of extract, ginkgo biloba extract and complex extract
제조예 1 : 참당귀 추출물의 제조Preparation Example 1: Preparation of Angelica Angelica extract
경동 약재 시장에서 구입한 건조된 참당귀(Angelica gigas)의 지하부를 분쇄하여 분말화 하였다. 이후, 참당귀 분말 시료에 약 5배의 70% 주정을 첨가하고 80℃에서 약 4 hr 동안 2회 추출한 후 여과하였다. 이후, 여과된 추출액을 감압 조건하에서 농축하고 동결건조하여 참당귀 추출물을 수득하였다. 참당귀 추출물의 수율은 약 32% 이었다.The ground part of dried Angelica gigas purchased from the Gyeongdong Herb Market was ground and powdered. Thereafter, about 5 times 70% alcohol was added to the Angelica keiskei koid powder sample, extracted twice at 80° C. for about 4 hr, and then filtered. Thereafter, the filtered extract was concentrated under reduced pressure and freeze-dried to obtain an Angelica keiskei koidz extract. The yield of Angelica keiskei koidz was about 32%.
제조예 2 : 백수오 추출물의 제조Preparation Example 2: Preparation of Baeksuo extract
경동 약재 시장에서 구입한 건조된 백수오(Cynanchum wilfordii)를 분쇄하여 분말화 하였다. 이후, 백수오 분말 시료에 약 5배의 70% 주정을 첨가하고 80℃에서 약 4 hr 동안 2회 추출한 후 여과하였다. 이후, 여과된 추출액을 감압 조건하에서 농축하고 동결건조하여 백수오 추출물을 수득하였다. 백수오 추출물의 수율은 약 29.2% 이었다.The dried white sorghum ( Cynanchum wilfordii ) purchased from the Gyeongdong Herb Market was ground and powdered. Then, about 5 times as much as 70% alcohol was added to the baeksuo powder sample and extracted twice at 80° C. for about 4 hr, followed by filtration. Then, the filtered extract was concentrated under reduced pressure and freeze-dried to obtain a white shou extract. The yield of Baeksuo extract was about 29.2%.
제조예 3 : 은행잎 추출물의 제조Preparation Example 3: Preparation of ginkgo biloba extract
경동 약재 시장에서 구입한 건조된 은행잎(Ginko biloba leaves)를 분쇄하여 분말화 하였다. 이후, 은행잎 분말 시료에 약 5배의 70% 주정을 첨가하고 80℃에서 약 4 hr 동안 2회 추출한 후 여과하였다. 이후, 여과된 추출액을 감압 조건하에서 농축하고 동결건조하여 은행잎 추출물을 수득하였다. 은행잎 추출물의 수율은 약 27.3% 이었다.Dried Ginkgo biloba leaves purchased at the Gyeongdong Herb Market were ground and powdered. Thereafter, about 5 times 70% alcohol was added to the ginkgo biloba powder sample, extracted twice at 80° C. for about 4 hr, and then filtered. Thereafter, the filtered extract was concentrated under reduced pressure and lyophilized to obtain ginkgo biloba extract. The yield of ginkgo biloba extract was about 27.3%.
제조예 4 : 복합 추출물의 제조Preparation Example 4: Preparation of complex extract
제조예 1에서 제조한 참당귀 추출물, 제조예 2에서 제조한 백수오 추출물 및 제조예 3에서 추출한 은행잎 추출물을 1:1:1의 중량비로 혼합하여 복합 추출물을 제조하였다.A mixture extract was prepared by mixing the Angelica keiskei koidz extract prepared in Preparation Example 1, Baekshou extract prepared in Preparation Example 2, and ginkgo biloba extract extracted from Preparation Example 3 in a weight ratio of 1:1:1.
2. 복합 추출물의 항산화 효능 분석2. Analysis of antioxidant efficacy of complex extracts
제조예 4에서 제조한 복합 추출물의 항산화 효능을 DPPH 시험법을 이용하여 측정하였다. 먼저, 빛을 파단한 상태에서 DPPH(1,1-diphenyl-2-2hydrazyl)를 0.1 mM 농도가 되도록 methanol에 녹여 DPPH(1,1-diphenyl-2-2hydrazyl) 시약을 준비하였다. The antioxidant efficacy of the complex extract prepared in Preparation Example 4 was measured using the DPPH test method. First, DPPH (1,1-diphenyl-2-2hydrazyl) reagent was prepared by dissolving DPPH (1,1-diphenyl-2-2hydrazyl) in methanol to a concentration of 0.1 mM in the light-ruptured state.
이후, DPPH(1,1-diphenyl-2-2hydrazyl) 시약에 제조예 4에서 제조한 복합 추출물을 각각 50 ㎍/㎖, 100 ㎍/㎖, 500 ㎍/㎖ 및 1000 ㎍/㎖의 농도로 첨가하고 빛을 차단한 조건에서 20분 동안 반응시킨 후, 마이크로플레이트 판독기(Microplate reader)를 이용하여 517 ㎚의 파장에서 흡광도를 측정하였다. 한편, 양성 대조군으로 DPPH(1,1-diphenyl-2-2hydrazyl) 시약에 아스코르브산(Ascorbic acid)을 100 ㎍/㎖의 농도로 첨가하였다. 이후, 하기 수학식 1을 이용하여 DPPH 라디칼 소거능(DPPH radical scavenging activity, %)을 산출하였다.Thereafter, the complex extracts prepared in Preparation Example 4 were added to DPPH (1,1-diphenyl-2-2hydrazyl) reagent at concentrations of 50 µg/ml, 100 µg/ml, 500 µg/ml, and 1000 µg/ml, respectively. After reacting for 20 minutes under the condition of blocking the light, absorbance was measured at a wavelength of 517 nm using a microplate reader. Meanwhile, as a positive control, ascorbic acid was added to a DPPH (1,1-diphenyl-2-2hydrazyl) reagent at a concentration of 100 µg/ml. Thereafter, DPPH radical scavenging activity (%) was calculated using
[수학식 1][Equation 1]
도 1은 본 발명의 제조예 4에서 제조한 복합 추출물의 항산화 효능을 DPPH 시험법을 이용하여 분석한 결과이다. 도 1에서 X축의 'Control(+)'는 양성 대조군을 나타내고 'ACG-1 extract'는 제조예 4에서 제조한 복합 추출물을 나타낸다. 또한, 제조예 4에서 제조한 복합 추출물의 항산화 효능 분석 결과를 하기의 표 1에 나타내었다.1 is a result of analyzing the antioxidant efficacy of the complex extract prepared in Preparation Example 4 of the present invention using a DPPH test method. In FIG. 1,'Control(+)' of the X-axis represents a positive control, and'ACG-1 extract' represents a composite extract prepared in Preparation Example 4. In addition, the results of the antioxidant efficacy analysis of the composite extract prepared in Preparation Example 4 are shown in Table 1 below.
(㎍/㎖)IC 50 of complex extracts
(Μg/ml)
3. 복합 추출물의 혈소판 응집 3. Platelet aggregation of complex extracts 억제능Restraint 측정 Measure
제조예 4에서 제조한 복합 추출물의 인체 유래 혈소판 응집 억제능을 Aggregometer(Chrono-Log Co., Ltd., Havertown, PA, USA)를 이용한 탁도 측정법으로 측정하였다. 먼저, 제조예 1에서 제조한 참당귀 추출물, 제조예 2에서 제조한 백수오 추출물, 제조예 3에서 제조한 은행잎 추출물 및 제조예 4에서 제조한 복합 추출물을 각각 1% DMSO 용액에 다양한 농도별로 용해하여 시료 용액을 제조하였다. 이후, 인체 유래 혈소판을 37℃에서 3분 동한 배양한 후 시료 용액을 처리하고 혈소판 응집 유도 물질인 콜라겐으로 응집을 유도하였으며, 6분 동안 혈소판 응집률을 측정하였다. 하기 표 2에 제조예 1에서 제조한 참당귀 추출물, 제조예 2에서 제조한 백수오 추출물, 제조예 3에서 제조한 은행잎 추출물 및 제조예 4에서 제조한 복합 추출물의 혈소판 응집 억제능 측정 결과를 나타내었다.The ability of the complex extract prepared in Preparation Example 4 to inhibit platelet aggregation derived from the human body was measured by a turbidity measurement method using an Aggregometer (Chrono-Log Co., Ltd., Havertown, PA, USA). First, the Angelica Angelica extract prepared in Preparation Example 1, Baeksuo Extract prepared in Preparation Example 2, Ginkgo Leaf Extract prepared in Preparation Example 3, and the complex extract prepared in Preparation Example 4 are each dissolved in various concentrations in 1% DMSO solution. To prepare a sample solution. Thereafter, the human-derived platelets were incubated for 3 minutes at 37° C., and then the sample solution was processed and aggregation was induced with collagen, a platelet aggregation-inducing substance, and the platelet aggregation rate was measured for 6 minutes. Table 2 below shows the results of measuring platelet aggregation inhibitory ability of Angelica keiskei koidz extract prepared in Preparation Example 1, Baeksuo extract prepared in Preparation Example 2, ginkgo biloba extract prepared in Preparation Example 3, and the composite extract prepared in Preparation Example 4 .
상기 표 2에서 보이는 바와 같이 제조예 4에서 제조한 복합 추출물을 처리하는 경우 동일 농도 기준의 참당귀 추출물, 백수오 추출물 및 은행잎 추출물을 각각 단독으로 처리하는 경우에 비해 전체적으로 혈소판 응집률이 매우 낮았다. 이러한 결과는 참당귀 추출물, 백수오 추출물 및 은행잎 추출물의 병용에 의해 혈소판 응집 억제에 대한 시너지 작용이 발생한 것에서 기인한 것으로 사료된다.As shown in Table 2, when treating the composite extract prepared in Preparation Example 4, the platelet aggregation rate was very low overall compared to the case where the Angelica keiskei koidus extract, Baeksuo extract, and Ginkgo biloba extract were treated alone. These results are thought to be attributable to the synergistic action of platelet aggregation inhibition by the combination of Angelica keiskei koidus extract, Baeksuo extract and Ginkgo biloba extract.
4. 혈전증 유도 동물 모델을 이용한 복합 추출물의 4. Combination of complex extracts using thrombosis-induced animal models 항혈전Antithrombosis 효능 평가 Efficacy evaluation
5주령 수컷 ICR계 마우스(25-30 g 내외)를 라온바이오로부터 구입하였다. 구입한 마우스에 사료와 물을 충분히 공급하면서 1주일 동안 순화사육을 거쳐 실험에 사용하였다. 사육 환경 조건으로 23±2℃ 온도, 55±15% 상대습도, 시간당 10 내지 20회의 환기, 12 hr의 조명시간(08:00 점등, 20:00 소등), 150 내지 300 Lux의 조도 조건을 사용하였다. 혈전증 유도 동물 모델 실험은 Diminno 등의 실험방법에 의거하여 수행하였다. 구체적으로, 혈소판 응집 유도제인 콜라겐과 에피네프린 혼합용액(1.4ug/mouse+ 85ug/mouse) 50 ㎕를 마우스 꼬리정맥에 주사하였다. 약물 시료의 항혈전 효과를 알아보기 위해 혈소판 응집 유도제를 주사하기 90분 전에 약물 시료를 체중에 비례하여 1회 경구투여하였다. 실험동물은 각 군 당 10마리이며 약물 시료는 증류수에 현탁하여 투여하였다. 이후, 혈소판 응집 유도제 주사로 인하여 발생하는 마우스 뒷다리의 마비나 사망으로부터 보호된 실험동물 수의 백분율, 즉 보호율(Protection, %)을 계산하여 약물의 항혈전 효능을 평가하였다. 혈소판 응집 유도제 주사 후 15분 이상 마비의 지속, 사망 또는 마비로부터의 회복 여부를 관찰하고 약물 시료의 항혈전 효과를 판정하였다. 각 실험군의 보호율(Protection, %)은 아래의 수학식 2를 이용하여 산출하였다.Five week old male ICR-based mice (around 25-30 g) were purchased from Raon Bio. It was used for experiment after purifying and breeding for one week while supplying enough feed and water to the purchased mouse. As a breeding environment condition, 23±2℃ temperature, 55±15% relative humidity, 10 to 20 ventilations per hour, 12 hr lighting time (08:00 on, 20:00 off), and 150 to 300 Lux illumination conditions are used. Did. The thrombosis-induced animal model experiment was performed based on an experimental method such as Diminno. Specifically, 50 µl of a collagen and epinephrine mixed solution (1.4 ug/mouse+ 85 ug/mouse), which is a platelet aggregation inducer, was injected into the mouse tail vein. To investigate the antithrombotic effect of the drug sample, the drug sample was orally administered once in proportion to body weight 90 minutes before the injection of the platelet aggregation inducer. The experimental animals were 10 animals per group, and the drug samples were suspended in distilled water and administered. Subsequently, the antithrombotic efficacy of the drug was evaluated by calculating the percentage of the number of experimental animals protected from paralysis or death of the mouse hind limb caused by injection of a platelet aggregation inducer, that is, protection (%). After injection of the platelet aggregation inducer, the persistence of paralysis for 15 minutes or longer, recovery from death or paralysis was observed, and the antithrombotic effect of the drug sample was determined. The protection rate (Protection, %) of each experimental group was calculated using Equation 2 below.
[수학식 2] [Equation 2]
C : 실험군 전체 개체수C: Total population of the experimental group
D : 실험군 전체 개체수 중 죽거나 마비된 개체수D: dead or paralyzed population among the total population of the experimental group
도 2는 혈전증 유도 동물 모델을 이용한 복합 추출물의 항혈전 효능 평가 실험 결과를 보호율(Protection, %) 값으로 나타낸 것이다. 도 2에서 X축의 'Control'은 대조군으로서 약물 시료로 비히클(Vehicle)인 증류수만을 투여한 군이고, 'ASA 100'은 양성 대조군으로서 약물 시료로 아세틸살리실산(Acetylsalicylic acid, 또는 아스피린)을 100 ㎎/㎏(weight)의 용량으로 투여한 군이며, ''ACG-1 extract'는 약물 시료로 제조예 4에서 제조한 복합 추출물을 해당 용량으로 투여한 군이다. 또한, 하기 표 3에 실험군에 따른 사망 또는 마비된 마우스의 수와 보호율을 나타내었다.Figure 2 shows the results of the anti-thrombotic efficacy evaluation of the complex extract using a thrombosis-induced animal model as a protection (%) value. In FIG. 2,'Control' of the X-axis is a group in which only vehicle (distilled water) as a drug sample is administered as a control group, and'ASA 100' is a positive control drug containing acetylsalicylic acid (Acetylsalicylic acid, or aspirin) as 100 mg/ It is a group administered in a dose of ㎏ (weight), and''ACG-1 extract' is a group in which the complex extract prepared in Preparation Example 4 is administered as a drug sample in a corresponding dose. In addition, Table 3 below shows the number and protection rates of the dead or paralyzed mice according to the experimental groups.
상기 표 3에서 보이는 바와 같이 제조예 4에서 제조한 복합 추출물은 상업적인 항혈전제인 아세틸살리실산(Acetylsalicylic acid, 또는 아스피린)에 근접하는 효과를 나타내었다.As shown in Table 3, the composite extract prepared in Preparation Example 4 showed an effect close to that of a commercial antithrombotic agent, acetylsalicylic acid (or aspirin).
5. 비만 유도 동물 모델을 이용한 복합 추출물의 콜레스테롤 저하, 중성지질 저하 효능 평가5. Evaluation of cholesterol-lowering and neutral lipid-lowering efficacy of complex extracts using obesity-induced animal models
(1) 동물실험 방법(1) Animal test method
5주령 수컷 ICR계 마우스(25-30 g 내외)를 라온바이오로부터 구입하였다. 구입한 마우스에 사료와 물을 충분히 공급하면서 1주일 동안 순화사육을 거쳐 실험에 사용하였다. 사육 환경 조건으로 23±2℃ 온도, 55±15% 상대습도, 시간당 10 내지 20회의 환기, 12 hr의 조명시간(08:00 점등, 20:00 소등), 150 내지 300 Lux의 조도 조건을 사용하였다. Five week old male ICR-based mice (around 25-30 g) were purchased from Raon Bio. It was used for experiments after purifying and breeding for one week while supplying enough feed and water to the purchased mice. As a breeding environment, 23±2℃ temperature, 55±15% relative humidity, 10 to 20 ventilations per hour, 12 hr lighting time (08:00 lighting, 20:00 off), and 150 to 300 Lux lighting conditions are used. Did.
실험동물용 일반식이 사료(6%의 지방이 함유된 사료) 및 고지방 사료(60%의 지방이 함유된 사료)는 라온바이오에서 공급받아 사용하였다. 실험동물은 각 군 당 10마리이며, 사육기간 중 실험동물의 체중은 주 1회 측정하였다. 일반 식이군(n=10)에 일반식이 사료를 급여함과 동시에 증류수를 12주 동안 1일 1회 경구투여하였다. 또한, 고지방 식이군(n=40)을 10마리씩 4개의 그룹으로 나누고, 각 실험군에 고지방 사료를 급여함과 동시에 약물 시료를 증류수에 현탁하여 12주 동안 1일 1회 경구투여하였다. 하기 표 4에 각 실험군에 대한 실험 조건을 정리하였다.General dietary feed for laboratory animals (feed containing 6% fat) and high fat feed (feed containing 60% fat) were supplied from Raon Bio and used. There are 10 experimental animals per group, and the weight of the experimental animals during the breeding period was measured once a week. The normal diet group (n=10) was fed with a normal dietary feed, and distilled water was orally administered once a day for 12 weeks. In addition, the high-fat diet group (n=40) was divided into four groups of 10 animals, and the high-fat diet was fed to each experimental group and the drug sample was suspended in distilled water and orally administered once a day for 12 weeks. Table 4 below summarizes the experimental conditions for each experimental group.
* 비히클(Vehicel) : 증류수* Vehicle: Distilled water
(2) 체중 증가량(2) Weight gain
전 실험기간 동안 매일 일정한 시각에 실험동물의 체중을 측정하였고, 이를 바탕으로 12주 동안의 체중 증가량을 계산하였다. 도 3은 비만 유도 동물 모델을 이용한 실험 결과 중 체중 증가량을 나타낸 것이다. 또한, 비만 유도 동물 모델 실험 결과 중 체중 증가량을 하기 표 5에 나타내었다.During the entire experimental period, the weight of the experimental animals was measured at regular times every day, and the weight gain for 12 weeks was calculated based on this. Figure 3 shows the weight gain in the experimental results using the obese-inducing animal model. In addition, the weight gain of the obesity-induced animal model experiment results are shown in Table 5 below.
상기 표 5에서 보이는 바와 같이 제조예 4에서 제조한 복합 추출물은 우수한 항비만 효과를 나타내었다.As shown in Table 5, the composite extract prepared in Preparation Example 4 exhibited an excellent anti-obesity effect.
(3) 혈장 중성지질 및 콜레스테롤(3) plasma neutral lipid and cholesterol
비만 유도 동물 모델을 이용한 실험 종료 후 자동혈청 분석기(Komelab 20XT, Thermo Electron, Louisville, CO, USA)를 이용하여 마우스의 혈장 내 트리글리세리드(triglyceride), 총 콜레스테롤 및 LDL 콜레스테롤 함량을 측정하였다. 도 4는 비만 유도 동물 모델을 이용한 실험 결과 중 혈장 내 트리글리세리드(triglyceride) 함량을 나타낸 것이고, 도 5는 비만 유도 동물 모델을 이용한 실험 결과 중 혈장 내 총 콜레스테롤 함량을 나타낸 것이고, 도 6은 비만 유도 동물 모델을 이용한 실험 결과 중 혈장 내 LDL 콜레스테롤 함량을 나타낸 것이다. 도 4 내지 도 6에서 보이는 바와 같이 제조예 4에서 제조한 복합 추출물은 우수한 중성지질 저하 효과, 총 콜레스테롤 저하 효과 및 LDL 콜레스테롤 저하 효과를 보였다.After completion of the experiment using an obese-derived animal model, triglyceride, total cholesterol and LDL cholesterol content in plasma of mice were measured using an automatic serum analyzer (Komelab 20XT, Thermo Electron, Louisville, CO, USA). FIG. 4 shows the triglyceride content in plasma among the experimental results using the obese-inducing animal model, FIG. 5 shows the total cholesterol content in plasma among the experimental results using the obese-inducing animal model, and FIG. 6 shows the obese-inducing animal Among the experimental results using the model, it shows the LDL cholesterol content in plasma. 4 to 6, the composite extract prepared in Preparation Example 4 showed excellent neutral lipid lowering effect, total cholesterol lowering effect and LDL cholesterol lowering effect.
총 콜레스테롤의 증가는 고혈압과 같은 심혈관 질환을 일으키는 중요한 요소로 알려져 있다. 또한, HDL 콜레스테롤은 말초 조직이나 혈액 중에 축적된 콜레스테롤을 콜레스테롤 에스테르로 만들어 간으로 수송하여 혈액 중 콜레스테롤 함량을 저하시켜 동맥경화증의 개선 및 예방에 효과가 있다고 알려져 있으나, LDL 콜레스테롤 함량은 상기 HDL 콜레스테롤과 역상관 관계를 나타낸다. 따라서, 본 발명의 제조예 4에서 제조한 복합 추출물을 유효성분으로 포함하는 조성물은 비만을 예방, 개선 또는 치료할 수 있을 뿐 아니라 고지혈증, 동맥경화증 등을 예방, 개선 및 치료할 수 있다는 것을 실험을 통하여 확인할 수 있었다.Increased total cholesterol is known to be an important factor causing cardiovascular disease, such as hypertension. In addition, HDL cholesterol is known to be effective in improving and preventing arteriosclerosis by lowering cholesterol content in the blood by making cholesterol accumulated in peripheral tissues or blood into cholesterol esters and transporting it to the liver, but the LDL cholesterol content is It represents an inverse correlation. Therefore, the composition comprising the composite extract prepared in Preparation Example 4 of the present invention as an active ingredient can prevent, improve or treat obesity as well as prevent, improve and treat hyperlipidemia, arteriosclerosis, etc. through experiments. Could.
6. 약학 조성물의 제조6. Preparation of pharmaceutical compositions
<6-1> 산제의 제조<6-1> Preparation of powder
제조예 4의 복합 추출물 2 g2 g of the complex extract of Preparation Example 4
유당 1 g1 g of lactose
상기의 성분을 혼합하고 기밀포에 충진하여 산제를 제조하였다.A powder was prepared by mixing the above components and filling the gas-tight fabric.
<6-2> 정제의 제조<6-2> Preparation of tablet
제조예 4의 복합 추출물 100 ㎎100 mg composite extract of Preparation Example 4
옥수수전분 100 ㎎
유 당 100 ㎎Lactose 100mg
스테아린산 마그네 2 ㎎Stearic acid magnet 2mg
상기의 성분을 혼합한 후, 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조하였다.After mixing the above components, tablets were prepared by tableting according to a conventional tablet manufacturing method.
<6-3> 캡슐제의 제조<6-3> Preparation of capsules
제조예 4의 복합 추출물 100 ㎎100 mg composite extract of Preparation Example 4
옥수수전분 100 ㎎
유 당 100 ㎎Lactose 100mg
스테아린산 마그네슘 2 ㎎Magnesium stearate 2mg
상기의 성분을 혼합한 후, 통상의 캡슐제의 제조방법에 따라서 젤라틴 캡슐에 충전하여 캡슐제를 제조하였다.After mixing the above components, the capsules were prepared by filling the gelatin capsules according to a conventional capsule preparation method.
<6-4> 환의 제조<6-4> Preparation of ring
제조예 4의 복합 추출물 1 g1 g composite extract of Preparation Example 4
유당 1.5 g1.5 g lactose
글리세린 1 gGlycerin 1 g
자일리톨 0.5 gXylitol 0.5 g
상기의 성분을 혼합한 후, 통상의 방법에 따라 1환 당 4 g이 되도록 제조하였다.After mixing the above components, it was prepared to be 4 g per ring according to a conventional method.
<6-5> 과립의 제조<6-5> Preparation of granules
제조예 4의 복합 추출물 150 ㎎150 mg of the complex extract of Preparation Example 4
대두추출물 50 ㎎Soybean extract 50 mg
포도당 200 ㎎
전분 600 ㎎Starch 600 mg
상기의 성분을 혼합한 후, 30% 에탄올 100 ㎎을 첨가하여 섭씨 60 ℃에서 건조하여 과립을 형성한 후 포에 충진하였다.After mixing the above components, 100 mg of 30% ethanol was added, dried at 60° C. to form granules, and then filled into the fabric.
<6-6> 주사제의 제조<6-6> Preparation of Injection
제조예 4의 복합 추출물 100 ㎎100 mg composite extract of Preparation Example 4
소디움 메타비설파이트 3.0 ㎎Sodium metabisulfite 3.0 mg
메틸파라벤 0.8 ㎎Methylparaben 0.8 mg
프로필파라벤 0.1 ㎎Propylparaben 0.1 mg
주사용 멸균증류수 적량Suitable amount of sterile distilled water for injection
상기의 성분을 혼합한 후, 이중 2㎖를 앰플에 충전하고 멸균하여 주사제를 제조하였다.After mixing the above ingredients, 2 ml of these were filled in an ampoule and sterilized to prepare an injection.
7. 식품 조성물의 제조7. Preparation of food composition
<7-1> 밀가루 식품의 제조<7-1> Preparation of flour food
제조예 4의 복합 추출물 0.5~5.0 중량부를 밀가루 100 중량부에 첨가하고, 이 혼합물을 이용하여 빵, 케이크, 쿠키, 크래커 및 면류를 제조하였다.0.5 to 5.0 parts by weight of the composite extract of Preparation Example 4 was added to 100 parts by weight of flour, and bread, cake, cookies, crackers and noodles were prepared using this mixture.
<7-2> 스프 및 육즙(gravies)의 제조<7-2> Preparation of soup and gravy
제조예 4의 복합 추출물 0.1~5.0 중량부를 스프 및 육즙에 첨가하여 건강 증진용 육가공 제품, 면류의 수프 및 육즙을 제조하였다.0.1 to 5.0 parts by weight of the composite extract of Preparation Example 4 was added to soup and gravy to prepare a health-enhancing meat processing product, noodles soup and gravy.
<7-3> 그라운드 비프(ground beef)의 제조<7-3> Preparation of ground beef
제조예 4의 복합 추출물 10 중량부를 그라운드 비프 100 중량부에 첨가하여 건강 증진용 그라운드 비프를 제조하였다.10 parts by weight of the composite extract of Preparation Example 4 was added to 100 parts by weight of ground beef to prepare a ground beef for health promotion.
<7-4> 유제품(dairy products)의 제조<7-4> Manufacturing Dairy Products
제조예 4의 복합 추출물 5~10 중량부를 우유 100 중량부에 첨가하고, 상기 우유를 이용하여 버터 및 아이스크림과 같은 다양한 유제품을 제조하였다.5-10 parts by weight of the complex extract of Preparation Example 4 was added to 100 parts by weight of milk, and various dairy products such as butter and ice cream were prepared using the milk.
<7-5> 선식의 제조<7-5> Preparation of wire
현미, 보리, 찹쌀, 율무를 공지의 방법으로 알파화시켜 건조시킨 것을 배전한 후 분쇄기로 입도 60 메쉬의 분말로 제조하였다.The brown rice, barley, glutinous rice, and yulmu were alpha-polished by a known method to distribute the dried one, and then prepared with a powder having a particle size of 60 mesh with a grinder.
검정콩, 검정깨, 들깨도 공지의 방법으로 쪄서 건조시킨 것을 배전한 후 분쇄기로 입도 60 메쉬의 분말로 제조하였다.Black soybeans, black sesame seeds, and perilla seeds were also steamed and dried by a known method, and then distributed into a powder having a particle size of 60 mesh with a grinder.
상기에서 제조한 곡물류, 종실류 및 제조예 4의 복합 추출물을 다음의 비율로 배합하여 제조하였다.It was prepared by mixing the above-prepared grains, seeds and complex extracts of Preparation Example 4 in the following proportions.
곡물류(현미 30 중량부, 율무 15 중량부, 보리 20 중량부),Grains (30 parts by weight of brown rice, 15 parts by weight of barley, 20 parts by weight of barley),
종실류(들깨 7 중량부, 검정콩 8 중량부, 검정깨 7 중량부),Seeds (7 parts by weight of perilla, 8 parts by weight of black beans, 7 parts by weight of black sesame seeds),
제조예 13의 복합 추출물(3 중량부),Composite extract of Preparation Example 13 (3 parts by weight),
영지(0.5 중량부),Territory (0.5 parts by weight),
지황(0.5 중량부)Ground sulfur (0.5 parts by weight)
<7-6> 건강음료의 제조<7-6> Preparation of health drinks
액상과당(0.5g), 올리고당(2g), 설탕(2g), 식염(0.5g), 물(75g)과 같은 부재료와 제조예 4의 복합 추출물 5 g을 균질하게 배합하여 순간 살균을 한 후 이를 유리병, 패트병 등 소포장 용기에 포장하여 제조하였다.Liquid ingredients (0.5g), oligosaccharides (2g), sugar (2g), salt (0.5g), water (75g) and 5 g of the complex extract of Preparation Example 4 are homogeneously blended and then sterilized. It was manufactured by packaging in small packaging containers such as glass bottles and plastic bottles.
<7-7> 야채 주스의 제조<7-7> Preparation of vegetable juice
제조예 4의 복합 추출물 5 g을 토마토 또는 당근 주스 1,000 ㎖에 가하여 야채 주스를 제조하였다.Vegetable juice was prepared by adding 5 g of the complex extract of Preparation Example 4 to 1,000 ml of tomato or carrot juice.
<7-8> 과일 주스의 제조<7-8> Preparation of fruit juice
제조예 4의 복합 추출물 1 g을 사과 또는 포도 주스 1,000 ㎖ 에 가하여 과일 주스를 제조하였다.Fruit juice was prepared by adding 1 g of the complex extract of Preparation Example 4 to 1,000 ml of apple or grape juice.
이상에서와 같이 본 발명을 상기의 실시예를 통해 설명하였지만 본 발명이 반드시 여기에만 한정되는 것은 아니며 본 발명의 범주와 사상을 벗어나지 않는 범위 내에서 다양한 변형실시가 가능함은 물론이다. 따라서, 본 발명의 보호범위는 본 발명에 첨부된 특허청구의 범위에 속하는 모든 실시 형태를 포함하는 것으로 해석되어야 한다.As described above, the present invention has been described through the above embodiments, but the present invention is not necessarily limited thereto, and various modifications can be made without departing from the scope and spirit of the present invention. Accordingly, the protection scope of the present invention should be construed to include all embodiments falling within the scope of the claims appended to the present invention.
Claims (4)
A pharmaceutical composition for preventing or treating dyslipidemia, comprising a complex extract consisting of a true Angelica extract, a white sallow extract and a ginkgo leaf extract as an active ingredient.
The pharmaceutical composition for preventing or treating dyslipidemia according to claim 1, wherein the dyslipidemia is at least one selected from the group consisting of hyperlipidemia, hypercholesterolemia and hypertriglyceridemia.
A food composition for preventing or improving dyslipidemia, comprising a complex extract consisting of a true Angelica extract, a white sorghum extract and a ginkgo leaf extract as an active ingredient.
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Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
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KR20110125958A (en) * | 2010-05-14 | 2011-11-22 | 한국식품연구원 | Composition for lowering cholesterol in blood containing the ethanol extract of cynanchum wilfordii as effective component |
KR20170069462A (en) * | 2015-12-11 | 2017-06-21 | (주) 머니키 | Health care food of composition comprising the extract material in Ginkgo biloba and Plantago ovata |
KR20180042035A (en) * | 2016-10-17 | 2018-04-25 | (주)웰니스업리서치 | Composition containing extract of Angelica gigas for preventing and treating dyslipidemia |
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Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
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KR20110125958A (en) * | 2010-05-14 | 2011-11-22 | 한국식품연구원 | Composition for lowering cholesterol in blood containing the ethanol extract of cynanchum wilfordii as effective component |
KR20170069462A (en) * | 2015-12-11 | 2017-06-21 | (주) 머니키 | Health care food of composition comprising the extract material in Ginkgo biloba and Plantago ovata |
KR20180042035A (en) * | 2016-10-17 | 2018-04-25 | (주)웰니스업리서치 | Composition containing extract of Angelica gigas for preventing and treating dyslipidemia |
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