KR20230149976A - Composition for prevention and treatment of inflammation containing 8-epiasterolid extracted from atractylodes macrocephala as active ingredient - Google Patents
Composition for prevention and treatment of inflammation containing 8-epiasterolid extracted from atractylodes macrocephala as active ingredient Download PDFInfo
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- KR20230149976A KR20230149976A KR1020220049348A KR20220049348A KR20230149976A KR 20230149976 A KR20230149976 A KR 20230149976A KR 1020220049348 A KR1020220049348 A KR 1020220049348A KR 20220049348 A KR20220049348 A KR 20220049348A KR 20230149976 A KR20230149976 A KR 20230149976A
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- inflammatory reactions
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Abstract
본 발명은 염증반응 예방 및 치료용 조성물에 관한 것으로, 보다 구체적으로는 백출에서 추출한 8-에피아스테롤리드를 유효성분으로 함유하는 염증반응 예방 및 치료용 조성물에 관한 것이다. 본 발명의 유효성분인 8-에피아스테롤리드는 염증반응의 완화, 개선 및 치료에 효과가 있음에 따라, 본 발명은 과도한 염증반응으로 인한 염증성 질환의 발병 위험성을 감소시키고, 다양한 염증반응의 예방, 개선 및 치료용 의약, 식품, 의약외품 등으로 활용될 수 있다.The present invention relates to a composition for preventing and treating inflammatory reactions, and more specifically, to a composition for preventing and treating inflammatory reactions containing 8-epiasterolide extracted from Baekchul as an active ingredient. As 8-epiasterolide, the active ingredient of the present invention, is effective in alleviating, improving and treating inflammatory reactions, the present invention reduces the risk of developing inflammatory diseases due to excessive inflammatory reactions and prevents various inflammatory reactions. , It can be used as medicine, food, and quasi-drugs for improvement and treatment.
Description
본 발명은 염증반응 예방 및 치료용 조성물에 관한 것으로, 보다 구체적으로는 백출에서 추출한 8-에피아스테롤리드를 유효성분으로 함유하는 염증반응 예방 및 치료용 조성물에 관한 것이다.The present invention relates to a composition for preventing and treating inflammatory reactions, and more specifically, to a composition for preventing and treating inflammatory reactions containing 8-epiasterolide extracted from Baekchul as an active ingredient.
염증은 국소적으로 손상을 최소화하고 원상 복구를 하고자 하는 일련의 생체 반응이라고 할 수 있다. 이러한 염증반응은 주로 혈관과 혈구를 중심으로 일어난다. 염증반응은 크게 급성과 만성으로 나누어질 수 있으며, 급성인 경우는 즉각적이고 비특이적이고 다형핵 백혈구의 침윤이 특징으로 전신 증상으로 발열, 피로, 식욕 감퇴, 쇠약 등이 있으며, 국소 증상으로 발적, 국소적 발열, 종창, 농(pus), 통증을 들 수 있다. 만성 염증으로는 단핵구(대식 세포, 림프구, 형질 세포)가 모이며 섬유 모세포와 모세 혈관의 증식이 있고 섬유 모세포에서 생성한 교원 섬유가 침착되어 섬유화 된다. 이때 조직의 파괴가 급성 염증일 때 보다 더 심하게 나타난다. 염증의 형태적 분류를 보면 자극의 종류 및 크기, 염증 반응의 정도, 손상된 조직의 종류 등에 따라 다르며 주로 장액성 염증, 섬유소성 염증, 화농성 염증, 궤양 등으로 나타난다. 최근 현대인들에게 급성염증, 류마티스 관절염과 같은 만성염증 등 다양한 염증질환이 증가하는 추세에 있다. 염증 치료를 위해서, 항생제 및 소염제와 같은 약제가 사용되고 있으나 부작용이 점차 문제화 되고 있다.Inflammation can be said to be a series of biological reactions that seek to minimize local damage and restore the original state. This inflammatory reaction mainly occurs around blood vessels and blood cells. Inflammatory reactions can be largely divided into acute and chronic. The acute case is immediate and non-specific and is characterized by infiltration of polymorphonuclear leukocytes. Systemic symptoms include fever, fatigue, loss of appetite, and weakness, and local symptoms include redness and localized symptoms. Examples include fever, swelling, pus, and pain. In chronic inflammation, monocytes (macrophages, lymphocytes, and plasma cells) gather, fibroblasts and capillaries proliferate, and collagen fibers produced by fibroblasts are deposited, leading to fibrosis. At this time, tissue destruction appears more severe than in acute inflammation. The morphological classification of inflammation varies depending on the type and size of the stimulus, the degree of inflammatory reaction, and the type of damaged tissue, and mainly appears as serous inflammation, fibrinous inflammation, purulent inflammation, and ulcers. Recently, various inflammatory diseases such as acute inflammation and chronic inflammation such as rheumatoid arthritis are on the rise among modern people. To treat inflammation, drugs such as antibiotics and anti-inflammatory drugs are used, but side effects are increasingly becoming a problem.
염증반응의 특징은 혈액내 염증성 혈구세포(백혈구, 호중구, 대식세포 등)와 그 전구세포 및 HSC 들이 많이 분포하게 되고, 염증성 사이토카인(TNF-alpha, IL2, IL4, IL6 등)의 증가와 항염증성 사이토카인(IL10 등) 감소가 특징적이다(Eva Mezey et al, Nature Medicine 2009 vol15, 42-49). 또한 손상조직에 많은 염증세포가 쌓이게 된다.The characteristics of the inflammatory response are a large distribution of inflammatory blood cells (leukocytes, neutrophils, macrophages, etc.), their progenitor cells, and HSCs in the blood, an increase in inflammatory cytokines (TNF-alpha, IL2, IL4, IL6, etc.), and an increase in anti-inflammatory cytokines. It is characterized by a decrease in inflammatory cytokines (IL10, etc.) (Eva Mezey et al, Nature Medicine 2009 vol15, 42-49). Additionally, many inflammatory cells accumulate in the damaged tissue.
일반적으로 염증반응은 선천적 면역반응의 생체 방어적 반응 중의 하나이지만, 염증세포 특히 호중구 세포들이 분비하는 활성산소와 단백질 분해효소 등은 주변조직의 심각한 손상을 초래하게 된다. 그러므로 염증반응이 길어지면 만성 혹은 난치성 궤양 등으로 발전하게 되고, 치유 후에도 섬유상 조직(fibrosis)으로 변화되어 조직의 경화(sclerosis)를 초래하여 조직의 기능을 현저히 감소시킨다.In general, the inflammatory response is one of the biological defense responses of the innate immune response, but reactive oxygen species and proteolytic enzymes secreted by inflammatory cells, especially neutrophil cells, cause serious damage to surrounding tissues. Therefore, if the inflammatory reaction is prolonged, it develops into a chronic or intractable ulcer, and even after healing, it changes into fibrosis, causing sclerosis of the tissue and significantly reducing the function of the tissue.
이와 같은 염증반응에 관한 질환 및 이의 기전 등에 대한 연구가 활발히 진행되고 있으나 기존 약물 치료의 한계점들이 지적되고 있다. 따라서, 염증반응을 효과적으로 치료, 개선하면서도 장기 손상이나 독성을 나타내지 않는 천연물 또는 천연물 유래 약물에 대한 필요성이 있다.Although research is being actively conducted on diseases related to inflammatory reactions and their mechanisms, limitations of existing drug treatments are being pointed out. Therefore, there is a need for natural products or drugs derived from natural products that effectively treat and improve inflammatory responses but do not cause organ damage or toxicity.
한편, 백출은 국화과에서 속하는 여러해살이 풀이며 삽주 뿌리를 손질해서 말린 것으로서, 산개, 천개라고도 한다. 백출은 매우 쓰며 약간의 단맛이 있으며, 속이 희고 알이 찬 것이 좋고 특히 가을에 채취한 것이 효능이 좋다고 알려져 있다.Meanwhile, Baekchul is a perennial herb belonging to the Asteraceae family. It is made by trimming and drying the root of the spatula, and is also called Sangae or Cheongae. Baekchul is very bitter and has a slightly sweet taste. The ones with white insides and cold eggs are good, and those collected in the fall are known to be especially effective.
비위(脾胃)의 기능이 허약해서 소식하거나 권태감이 생기고 얼굴빛이 황색이며 대변을 묽게 보거나 설사를 하는 사람에게 좋으며 수분이 정체되어 전신이 붓고 소화가 안 될 때 수분 배설을 돕는다. 비(脾)에 수(水)와 습(濕)이 쌓여 담음(痰飮)을 인한 가슴 뜀, 기침, 맑은 가래 등에도 쓰며, 비기(脾氣) 허약으로 피부에 땀이 저절로 날 때, 임신 구토에도 사용한다. 위장 장애가 있는 감기, 사지동통에도 쓴다. 약리적으로 생쥐의 체중 증가와 지구력 증가, 탐식 능력을 증가, 세포 면역 기능 촉진이 보고되었다. 또한 장관(腸管) 억제 작용과 흥분 작용을 조절, 항궤양 및 간 기능 보호 작용, 면역 기능 항진작용, 혈관 확장 작용, 이뇨 작용 및 혈당 강하 작용, 항암 작용 등이 보고되었다. It is good for people who have weak nasogastric function, feel tired, have a yellow complexion, have watery stools, or have diarrhea. It helps excrete moisture when the entire body swells and digestion is difficult due to stagnant moisture. It is also used for heartbeat, coughing, and clear phlegm caused by water and moisture accumulating in the spleen, and for vomiting during pregnancy and when sweating occurs naturally on the skin due to weakness in the spleen. Also used. It is also used for colds with gastrointestinal disorders and pain in the extremities. Pharmacologically, it has been reported to increase body weight and endurance in mice, increase phagocytosis ability, and promote cellular immune function. In addition, it has been reported to regulate intestinal suppression and excitability, anti-ulcer and liver function protection, immune function enhancement, vasodilation, diuretic and blood sugar lowering effects, and anticancer activity.
이에 본 발명자들은 백출을 증류수로 열수 추출함으로써, 다량의 수용성 활성성분을 추출하였고, 이러한 백출 추출물이 염증반응을 개선,완화 및 치료할 수 있음을 확인하여 본 발명을 완성하였다.Accordingly, the present inventors extracted a large amount of water-soluble active ingredients by thermally extracting the white extract with distilled water, and completed the present invention by confirming that the extract of the white extract can improve, alleviate, and treat inflammatory reactions.
본 발명은 백출에서 추출한 8-에피아스테롤리드를 유효성분으로 함유하는 염증반응 예방 및 치료용 조성물을 제공하는 것을 목적으로 한다.The purpose of the present invention is to provide a composition for preventing and treating inflammatory reactions containing 8-epiasterolide extracted from Baekchul as an active ingredient.
상기 목적을 달성하기 위하여, 본 발명은 백출 추출물을 유효성분으로 함유하는, 염증반응 예방 및 치료용 약학적 조성물을 개시한다.In order to achieve the above object, the present invention discloses a pharmaceutical composition for preventing and treating inflammatory reactions, which contains an extract of Chrysanthemum chinensis as an active ingredient.
여기서, 상기 백출 추출물은 하기 화학식 1로 표시되는 8-에피아스테롤리드(8-epiasterolid)일 수 있다.Here, the Baekchul extract may be 8-epiasterolid represented by the following formula (1).
[화학식 1][Formula 1]
여기서, 상기 백출 추출물은 백출을 물, 탄소수 1 내지 4의 저급 알코올 또는 이들의 혼합 용매로 추출한 추출물일 수 있다.Here, the white extract may be an extract obtained by extracting white extract with water, a lower alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof.
여기서, 상기 약학적 조성물은 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽 및 에어로졸로 이루어진 군으로부터 선택된 1종의 경구형 제형, 외용제, 좌제 및 멸균된 수용액의 형태로 제형화하여 사용되는 것일 수 있다.Here, the pharmaceutical composition is used in the form of an oral dosage form selected from the group consisting of powders, granules, tablets, capsules, suspensions, emulsions, syrups, and aerosols, external preparations, suppositories, and sterilized aqueous solutions. It may be.
한편, 상기 목적을 달성하기 위하여 본 발명은 백출 추출물을 포함하는, 염증반응 예방 및 개선용 식품 조성물을 추가로 개시한다.Meanwhile, in order to achieve the above object, the present invention further discloses a food composition for preventing and alleviating inflammatory reactions, comprising an extract of Chrysanthemum chinensis.
여기서, 상기 백출 추출물은 하기 화학식 1로 표시되는 8-에피아스테롤리드(8-epiasterolid)일 수 있다.Here, the Baekchul extract may be 8-epiasterolid represented by the following formula (1).
[화학식 1][Formula 1]
여기서, 상기 백출 추출물은 백출을 물, 탄소수 1 내지 4의 저급 알코올 또는 이들의 혼합 용매로 추출한 추출물일 수 있다.Here, the white extract may be an extract obtained by extracting white extract with water, a lower alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof.
한편, 상기 목적을 달성하기 위하여 본 발명은 백출 추출물을 포함하는, 염증반응 예방 및 개선용 의약외품 조성물을 추가로 개시한다.Meanwhile, in order to achieve the above object, the present invention further discloses a quasi-drug composition for preventing and improving inflammatory reactions, comprising an extract of Chrysanthemum Chrysanthemum.
여기서, 상기 백출 추출물은 하기 화학식 1로 표시되는 8-에피아스테롤리드(8-epiasterolid)일 수 있다.Here, the Baekchul extract may be 8-epiasterolid represented by the following formula (1).
[화학식 1][Formula 1]
한편, 상기 목적을 달성하기 위하여 본 발명은 백출을 물, 탄소수 1 내지 4의 저급 알코올 또는 이들의 혼합 용매로 추출하여 백출 추출물을 제조하는 단계;를 포함하는, 염증반응 예방 및 치료용 약학적 조성물의 제조방법을 추가로 개시한다.Meanwhile, in order to achieve the above object, the present invention provides a pharmaceutical composition for preventing and treating inflammatory reactions, comprising the step of preparing a white extract by extracting the white extract with water, a lower alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof. The manufacturing method is further disclosed.
본 발명의 유효성분인 8-에피아스테롤리드는 염증반응의 완화, 개선 및 치료에 효과가 있음에 따라, 본 발명은 과도한 염증반응으로 인한 염증성 질환의 발병 위험성을 감소시키고, 다양한 염증반응의 예방, 개선 및 치료용 의약, 식품, 의약외품 등으로 활용될 수 있다.As 8-epiasterolide, the active ingredient of the present invention, is effective in alleviating, improving and treating inflammatory reactions, the present invention reduces the risk of developing inflammatory diseases due to excessive inflammatory reactions and prevents various inflammatory reactions. , It can be used as medicine, food, and quasi-drugs for improvement and treatment.
도 1은 정상군, 리포폴리사카라이드 처리에 따른 염증 유발군, 8-에피아스테롤리드 처리군의 세포독성 평가를 그래프로 도시한 것이다.
도 2는 정상군, 리포폴리사카라이드 처리에 따른 염증 유발군, 8-에피아스테롤리드 처리군의 프로스타글란딘의 생성 평가를 그래프로 도시한 것이다.
도 3은 정상군, 리포폴리사카라이드 처리에 따른 염증 유발군, 8-에피아스테롤리드 처리군의 염증성 싸이토카인의 생성 평가를 그래프로 도시한 것이다.
도 4는 정상군, 리포폴리사카라이드 처리에 따른 염증 유발군, 8-에피아스테롤리드 처리군의 염증인자 효소 발현 평가를 그래프로 도시한 것이다.
도 5는 정상군, 리포폴리사카라이드 처리에 따른 염증 유발군, 8-에피아스테롤리드 처리군의 , nuclear factor kappa B 경로 활성 평가를 그래프로 도시한 것이다.Figure 1 graphically shows the cytotoxicity evaluation of the normal group, the inflammation-induced group following lipopolysaccharide treatment, and the 8-epiasterolide treatment group.
Figure 2 graphically shows the evaluation of prostaglandin production in the normal group, the inflammation-induced group following lipopolysaccharide treatment, and the 8-epiasterolide treatment group.
Figure 3 graphically shows the evaluation of the production of inflammatory cytokines in the normal group, the inflammation-induced group following lipopolysaccharide treatment, and the 8-epiasterolide treatment group.
Figure 4 graphically shows the evaluation of inflammatory factor enzyme expression in the normal group, the inflammation-induced group following lipopolysaccharide treatment, and the 8-epiasterolide treatment group.
Figure 5 is a graph showing the evaluation of nuclear factor kappa B pathway activity in the normal group, the inflammation-induced group following lipopolysaccharide treatment, and the 8-epiasterolide treatment group.
본 출원에서 사용하는 용어는 단지 특정한 예시를 설명하기 위하여 사용되는 것이다. 때문에 가령 단수의 표현은 문맥상 명백하게 단수여야만 하는 것이 아닌 한, 복수의 표현을 포함한다. 덧붙여, 본 출원에서 사용되는 "포함하다" 또는 "구비하다"등의 용어는 명세서 상에 기재된 특징, 단계, 기능, 구성요소 또는 이들을 조합한 것이 존재함을 명확히 지칭하기 위하여 사용되는 것이지, 다른 특징들이나 단계, 기능, 구성요소 또는 이들을 조합한 것의 존재를 예비적으로 배제하고자 사용되는 것이 아님에 유의해야 한다.The terms used in this application are only used to describe specific examples. Therefore, for example, a singular expression includes a plural expression, unless the context clearly requires it to be singular. In addition, terms such as “comprise” or “comprise” used in the present application are used to clearly indicate the presence of features, steps, functions, components, or combinations thereof described in the specification, and are used to clearly indicate the presence of other features. It should be noted that it is not used to preliminarily rule out the existence of any elements, steps, functions, components, or combinations thereof.
한편, 다르게 정의되지 않는 한, 본 명세서에서 사용되는 모든 용어들은 본 발명이 속하는 기술 분야에서 통상의 지식을 가진 자에 의해 일반적으로 이해되는 것과 동일한 의미를 가진 것으로 보아야 한다. 따라서, 본 명세서에서 명확하게 정의하지 않는 한, 특정 용어가 과도하게 이상적이거나 형식적인 의미로 해석되어서는 안 된다.Meanwhile, unless otherwise defined, all terms used in this specification should be viewed as having the same meaning as generally understood by those skilled in the art to which the present invention pertains. Therefore, unless clearly defined in this specification, specific terms should not be interpreted in an overly idealistic or formal sense.
본 발명에서 사용되는 용어, "염증반응"은 병원체, 손상된 세포 혹은 자극물에 의한 신체 조직 손상에 반응하는 복합적인 생물학적 반응을 의미하며, 화학물, 화상, 동상, 외상 등과 같은 물리/화학적 요소와 병원체에 의한 감염, 과민증에 의한 면역 반응, 스트레스 등과 같은 생물학적 요소에 의한 것을 모두 포함한다. 또한, 급성 염증반응과 만성 염증반응을 모두 포함하는 것으로 한다.The term "inflammatory response" used in the present invention refers to a complex biological reaction in response to body tissue damage caused by pathogens, damaged cells, or irritants, and includes physical/chemical factors such as chemicals, burns, frostbite, trauma, and pathogens. It includes all those caused by biological factors such as infection, immune response due to hypersensitivity, and stress. In addition, it is assumed to include both acute and chronic inflammatory responses.
본 발명에서 사용되는 용어, "예방"은 본 발명에 따른 약학적 조성물 또는 식품 조성물의 투여에 의해 염증반응을 억제시키거나 발명을 지연시키는 모든 행위를 의미한다.The term “prevention” used in the present invention refers to all actions that suppress or delay the inflammatory response by administering the pharmaceutical composition or food composition according to the present invention.
본 발명에서 사용되는 용어, "치료"는 본 발명에 따른 약학적 조성물의 투여에 의해 염증반응에 관한 증세가 호전되거나 이롭게 변경되는 모든 행위를 의미한다.The term “treatment” used in the present invention refers to any action in which symptoms related to an inflammatory response are improved or beneficially changed by administration of the pharmaceutical composition according to the present invention.
본 발명에서 사용되는 용어, "개선"은 치료되는 상태와 관련된 파라미터, 예를 들면 증상의 정도를 적어도 감소시키는 모든 행위를 의미한다. 본 발명에 따른 식품 조성물은 염증반응의 예방 또는 개선을 위하여 해당 질환의 발병 단계 이전 또는 발병 후, 치료를 위한 약제와 동시에 또는 별개로서 사용될 수 있다.As used herein, the term "improvement" means any action that results in at least a reduction in the severity of a parameter, such as a symptom, associated with the condition being treated. The food composition according to the present invention can be used simultaneously or separately with a drug for treatment before or after the onset of the disease in order to prevent or improve inflammatory reactions.
본 발명은 백출 추출물을 유효성분으로 함유하는, 염증반응 예방 및 치료용 약학적 조성물을 개시한다.The present invention discloses a pharmaceutical composition for preventing and treating inflammatory reactions, which contains an extract of Chrysanthemum chinensis as an active ingredient.
본 발명의 백출 추출물은 하기 화학식 1로 표시되는 8-에피아스테롤리드(8-epiasterolid)일 수 있다.The Baekchul extract of the present invention may be 8-epiasterolid represented by the following formula (1).
상기 백출은 재배한 것 또는 시판되는 것 등 제한없이 사용할 수 있으며, 상기 백출은 통상적인 추출 방법에 의해 얻을 수 있고, 시판되는 것을 구입하여 사용할 수 있다. 상기 추출물은 추출 처리에 의해 얻어지는 추출액, 추출액의 희석액 또는 농축액, 추출액을 건조하여 얻어지는 건조물, 또는 이들 조정제물 또는 정제물 중 어느 하나를 포함하는 것으로 한다. The white extract can be used without restrictions, such as cultivated or commercially available. The white extract can be obtained by a conventional extraction method, and can be purchased and used commercially. The extract shall include any of the following: an extract obtained by extraction treatment, a diluted or concentrated liquid of the extract, a dried product obtained by drying the extract, or a crude or purified product thereof.
상기 추출물을 제조하는 방법은 특별히 제한되지 아니하며, 당해 기술 분야에서 통상적으로 사용하는 방법에 따라 추출할 수 있다. 상기 추출물을 제조하는 방법의 비제한적인 예로는, 열수 추출법, 초음파 추출법, 여과법, 환류 추출법, 침지 추출법, 고온 및 고압 증기 추출법 등을 들 수 있으며, 이들은 단독으로 수행되거나 2 종 이상의 방법을 병용하여 수행될 수 있다.The method for preparing the extract is not particularly limited, and it can be extracted according to a method commonly used in the art. Non-limiting examples of methods for producing the extract include hot water extraction, ultrasonic extraction, filtration, reflux extraction, immersion extraction, high temperature and high pressure steam extraction, etc., which can be performed alone or by combining two or more methods. It can be done.
또한, 본 발명의 백출 추출물은 친수성 용매(hydrophilic solvent)로 하여 추출된 것일 수 있다. 상기 친수성 용매는 물, C1 내지 C10의 알코올 또는 이들의 혼합물일 수 있다. 상기 알코올은 C1 내지 C10, C1 내지 C6 또는 C1 내지 C4의 하나 이상의 -OH기를 갖는 화합물일 수 있다. 상기 알코올은 메탄올, 에탄올, n-프로판올, 이소프로판올, n-부탄올, sec-부탄올, 이소부탄올, tert-부탄올 또는 이들의 혼합물일 수 있다. 나아가, 상기 백출 추출물은 물, 탄소수 1 내지 4의 저급 알코올 또는 이들의 혼합물로 추출된 추출물인 것이 바람직하나, 이에 한정되는 것은 아니다.Additionally, the white extract of the present invention may be extracted using a hydrophilic solvent. The hydrophilic solvent may be water, C1 to C10 alcohol, or a mixture thereof. The alcohol may be a compound having one or more -OH groups of C1 to C10, C1 to C6, or C1 to C4. The alcohol may be methanol, ethanol, n-propanol, isopropanol, n-butanol, sec-butanol, isobutanol, tert-butanol, or mixtures thereof. Furthermore, the white extract is preferably an extract extracted with water, a lower alcohol having 1 to 4 carbon atoms, or a mixture thereof, but is not limited thereto.
나아가, 본 발명의 백출 추출물은 80 내지 120 ℃의 온도 범위에서 약 1 내지 3 시간동안 열수 추출하여 얻어지는 추출액인 것이 보다 바람직하다.Furthermore, it is more preferable that the white extract of the present invention is an extract obtained by hot water extraction at a temperature range of 80 to 120° C. for about 1 to 3 hours.
또한, 본 발명의 백출 추출물은 상기 추출물을 다시 한번 분획한 분획물을 포함하는 것이며, 상기 분획물을 추출물을 클로로포름, 에틸아세테이트, 부탄올, 메탄올 및 물로부터 이루어진 군으로부터 선택된 1종 이상의 용매를 사용하여 제조한 분획물일 수 있다.In addition, the white extract of the present invention includes a fraction obtained by fractionating the extract again, and the fraction is prepared by using one or more solvents selected from the group consisting of chloroform, ethyl acetate, butanol, methanol and water. It may be a fraction.
본 발명의 약학적 조성물은 상기 유효성분 외에 약학적 조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형제 및 희석제를 더 포함할 수 있다. 본 발명의 약학적 조성물은 이밖에 다른 약학적 활성 성분이나 활성 혼합물을 더 포함할 수 있다.In addition to the above active ingredients, the pharmaceutical composition of the present invention may further include appropriate carriers, excipients, and diluents commonly used in the preparation of pharmaceutical compositions. The pharmaceutical composition of the present invention may further include other pharmaceutically active ingredients or active mixtures.
본 발명의 약학적 조성물은, 각각 통상의 방법에 따라 패치제, 피복제, 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있다. 보다 구체적으로, 상기 약학적 조성물은 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽 및 에어로졸로 이루어진 군으로부터 선택된 1종의 경구형 제형, 외용제, 좌제 및 멸균된 수용액의 형태로 제형화하여 사용될 수 있다. The pharmaceutical composition of the present invention can be prepared in oral dosage forms such as patches, coatings, powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories, and sterile injectable solutions according to conventional methods. It can be formulated and used in a form. More specifically, the pharmaceutical composition is formulated in the form of an oral dosage form selected from the group consisting of powders, granules, tablets, capsules, suspensions, emulsions, syrups, and aerosols, external preparations, suppositories, and sterilized aqueous solutions. can be used
조성물에 포함 될 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. 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 상기 조성물에 적어도 하나 이상의 부형제, 예를 들면, 전분, 칼슘카보네이트 (Calcium carbonate), 수크로스 (Sucrose) 또는 락토오스 (Lactose), 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크 같은 윤활제들도 사용된다. 경구를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜 (Propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔 (Witepsol), 마크로골, 트윈 (Tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다. Carriers, excipients and diluents that may be included in the composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, Examples include methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. When formulated, it is prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc. These solid preparations contain at least one excipient, such as starch, calcium carbonate, sucrose ( It is prepared by mixing sucrose, lactose, and gelatin. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral use include suspensions, oral solutions, emulsions, syrups, etc. In addition to the commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included. . Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solvents and suspensions include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate. As a base for suppositories, Witepsol, Macrogol, Tween 61, cacao, laurin, glycerogenatin, etc. can be used.
본 발명의 약학적 조성물의 바람직한 투여량은 환자의 상태 및 체중, 질병의 정도, 약물형태, 투여경로 및 기간에 따라 다르지만, 당업자에 의해 적절하게 선택될 수 있다. 투여는 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수도 있다. 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다.The preferred dosage of the pharmaceutical composition of the present invention varies depending on the patient's condition and weight, degree of disease, drug form, administration route and period, but can be appropriately selected by a person skilled in the art. Administration may be administered once a day, or may be administered several times. The above dosage does not limit the scope of the present invention in any way.
본 발명의 약학적 조성물은 쥐, 생쥐, 가축, 인간 등의 포유동물에 다양한 경로로 투여될 수 있다. 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 경구, 경피, 직장 또는 정맥, 근육, 피하, 주사에 의해 투여될 수 있다. The pharmaceutical composition of the present invention can be administered to mammals such as rats, mice, livestock, and humans through various routes. All modes of administration are contemplated, for example, oral, transdermal, rectal or intravenous, intramuscular, subcutaneous, by injection.
본 발명의 상기 부형제, 결합제, 붕해제, 활택제, 교미제, 착향료 등에 대한 용어 정의는 당업계에 공지된 문헌에 기재된 것으로 그 기능 등이 동일 내지 유사한 것들을 포함한다.Definitions of the excipients, binders, disintegrants, lubricants, flavoring agents, etc. of the present invention are those described in literature known in the art and include those with the same or similar functions.
한편, 본 발명은 백출 추출물을 포함하는, 염증반응 예방 및 개선용 식품 조성물을 추가로 개시한다. 나아가, 본 발명은 백출 추출물을 포함하는, 염증반응 예방 및 개선용 의약외품 조성물, 건강기능식품 등을 추가로 개시한다.Meanwhile, the present invention further discloses a food composition for preventing and alleviating inflammatory reactions, comprising an extract of Chrysanthemum Chrysanthemum. Furthermore, the present invention further discloses a quasi-drug composition for preventing and improving inflammatory reactions, a health functional food, etc., containing an extract of White Chrysanthemum.
본 발명의 백출 추출물은 하기 화학식 1로 표시되는 8-에피아스테롤리드(8-epiasterolid)일 수 있다.The Baekchul extract of the present invention may be 8-epiasterolid represented by the following formula (1).
[화학식 1][Formula 1]
본 발명의 백출 추출물은 백출을 물, 탄소수 1 내지 4의 저급 알코올 또는 이들의 혼합 용매로 추출한 추출물일 수 있다.The white extract of the present invention may be an extract obtained by extracting white extract with water, a lower alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof.
본 발명의 백출 추출물은 전체 식품 조성물에 대해 0.01 내지 99.99% 중량비로 포함될 수 있다.The Baekchul extract of the present invention may be included in a weight ratio of 0.01 to 99.99% based on the total food composition.
본 발명의 백출 추출물은 전체 의약외품 조성물에 대해 0.01 내지 99.99% 중량비로 포함될 수 있다.The Baekchul extract of the present invention may be included in a weight ratio of 0.01 to 99.99% based on the total quasi-drug composition.
상기 건강기능식품 또는 식품 조성물은 백출 추출물을 단독 또는 다른 식품 또는 식품 성분과 함께 포함할 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 유효 성분의 혼합양은 사용 목적 (예방, 건강 또는 치료적 처치)에 따라 적합하게 결정될 수 있다. 일반적으로, 식품 또는 음료의 제조시에 본 발명의 조성물은 총 중량에 대하여 15 중량부 이하, 10 중량부 이하, 1중량 내지 15중량부, 1중량 내지 10중량부, 1중량 내지 5중량부, 또는 0.1중량 내지 15중량부의 양으로 첨가될 수 있다. 그러나 건강 및 위생을 목적으로 하거나 또는 건강 조절을 목적으로 하는 장기간의 섭취의 경우에는 상기 양은 상기 범위 이하일 수 있으며, 안전성 면에서 아무런 문제가 없기 때문에 유효성분은 상기 범위 이상의 양으로도 사용될 수 있다. The health functional food or food composition may contain Baekchul extract alone or together with other foods or food ingredients, and may be used appropriately according to conventional methods. The mixing amount of the active ingredient can be appropriately determined depending on the purpose of use (prevention, health, or therapeutic treatment). Generally, when producing a food or beverage, the composition of the present invention is used in an amount of 15 parts by weight or less, 10 parts by weight or less, 1 to 15 parts by weight, 1 to 10 parts by weight, 1 to 5 parts by weight, based on the total weight. Alternatively, it may be added in an amount of 0.1 to 15 parts by weight. However, in the case of long-term intake for the purpose of health and hygiene or health control, the amount may be below the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount above the above range.
상기 식품의 종류에는 특별한 제한은 없다. 상기 물질을 첨가할 수 있는 식품의 예로는 육류, 소세지, 빵, 쵸코렛, 캔디류, 스넥류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 차, 드링크제, 알콜 음료 및 비타민 복합제 등이 있으며, 통상적인 의미에서의 식품을 모두 포함한다. 상기 식품 조성물은 예를 들어, 우유, 요플레 등의 식품 소재, 식음료, 기능성 식품으로 이용될 수 있다. 상기 식품 조성물은 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물은 포도당, 과당과 같은 모노사카라이드, 말토스, 슈크로스와 같은 디사카라이드, 및 덱스트린, 사이클로덱스트린과 같은 폴리사카라이드, 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 감미제로서는 타우마틴, 스테비아 추출물과 같은 천연 감미제나, 사카린, 아스파르탐과 같은 합성 감미제 등을 사용할 수 있다. There are no special restrictions on the types of foods above. Examples of foods to which the above substances can be added include meat, sausages, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, drinks, These include alcoholic beverages and vitamin complexes, and include all foods in the conventional sense. The food composition can be used, for example, as food ingredients such as milk and yogurt, food and beverages, and functional foods. The food composition may contain various flavoring agents or natural carbohydrates as additional ingredients. The above-mentioned natural carbohydrates include monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As a sweetener, natural sweeteners such as thaumatin and stevia extract or synthetic sweeteners such as saccharin and aspartame can be used.
본 발명의 식품 조성물은 또한 영양제, 비타민, 전해질, 풍미제, 착색제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산 음료에 사용되는 탄산화제, 또는 그 조합을 함유할 수 있다. 본 발명의 식품 조성물은 또한, 천연 과일쥬스, 과일쥬스 음료, 야채 음료의 제조를 위한 과육, 또는 그 조합을 함유할 수 있다. 이러한 첨가제는 조성물 100 중량부당 0.01 내지 0.1 중량부의 범위에서 선택될 수 있다.The food composition of the present invention also contains nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonated drinks. It may contain a carbonating agent used for, or a combination thereof. The food composition of the present invention may also contain pulp for the production of natural fruit juice, fruit juice beverage, vegetable beverage, or a combination thereof. These additives may be selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition.
본 발명의 의약외품 조성물은 질병에 대한 치료, 경감, 처치 또는 예방의 효과를 나타내나 의약품보다 인체에 미치는 작용이 경미한 물품을 의미한다. 약사법에 따른 의약품의 용도로 사용되는 물품을 제외하며, 보건복지부가 따로 정한 분류 기준에 의한 물품을 포함한다. 구체적으로 피부 외용제 또는 개인 위생용품일 수 있으나, 이에 제한되지 않는다.The quasi-drug composition of the present invention refers to a product that exhibits the effect of treating, alleviating, treating, or preventing a disease, but has a milder effect on the human body than a pharmaceutical. Excludes products used for pharmaceutical purposes under the Pharmaceutical Affairs Act, and includes products according to classification standards separately set by the Ministry of Health and Welfare. Specifically, it may be an external skin preparation or a personal hygiene product, but is not limited thereto.
본 발명의 조성물을 의약외품 조성물에 첨가할 경우, 상기 조성물을 그대로 첨가하거나 다른 의약외품 성분과 함께 사용할 수 있고, 통상적인 방법에 따라 적절하게 사용할 수 있다. 유효 성분의 혼합량은 사용 목적에 따라 적합하게 결정할 수 있다.When adding the composition of the present invention to a quasi-drug composition, the composition can be added as is or used together with other quasi-drug ingredients, and can be used appropriately according to conventional methods. The mixing amount of the active ingredient can be appropriately determined depending on the purpose of use.
한편, 본 발명은 백출을 물, 탄소수 1 내지 4의 저급 알코올 또는 이들의 혼합 용매로 추출하여 백출 추출물을 제조하는 단계;를 포함하는, 염증반응 예방 및 치료용 약학적 조성물의 제조방법을 추가로 개시한다.Meanwhile, the present invention further provides a method for producing a pharmaceutical composition for preventing and treating inflammatory reactions, comprising the step of preparing a white extract by extracting the white extract with water, a lower alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof. Begin.
본 발명의 백출 추출물은 하기 화학식 1로 표시되는 8-에피아스테롤리드(8-epiasterolid)일 수 있다.The Baekchul extract of the present invention may be 8-epiasterolid represented by the following formula (1).
[화학식 1][Formula 1]
상기 조성물은 약학적, 건강기능식품, 식품 또는 의약외품 조성물일 수 있다.The composition may be a pharmaceutical, health functional food, food, or quasi-drug composition.
중복되는 내용은 본 명세서의 복잡성을 고려하여 생략하며, 본 명세서에서 달리 정의되지 않은 용어들은 본 발명이 속하는 기술분야에서 통상적으로 사용되는 의미를 갖는 것이다.Redundant content is omitted in consideration of the complexity of the present specification, and terms not otherwise defined in this specification have meanings commonly used in the technical field to which the present invention pertains.
이하, 첨부한 도면 및 실시예들을 참조하여 본 명세서가 청구하는 바에 대하여 더욱 자세히 설명한다. 다만, 본 명세서에서 제시하고 있는 도면 내지 실시예 등은 통상의 기술자에게 의하여 다양한 방식으로 변형되어 여러 가지 형태를 가질 수 있는 바, 본 명세서의 기재사항은 본 발명을 특정 개시 형태에 한정되는 것이 아니고 본 발명의 사상 및 기술 범위에 포함되는 모든 균등물 내지 대체물을 포함하고 있는 것으로 보아야 한다. 또한, 첨부된 도면은 본 발명을 통상의 기술자로 하여금 더욱 정확하게 이해할 수 있도록 돕기 위하여 제시되는 것으로서 실제보다 과장되거나 축소되어 도시될 수 있다.Hereinafter, what the present specification claims will be described in more detail with reference to the accompanying drawings and examples. However, the drawings, examples, etc. presented in this specification can be modified in various ways by those skilled in the art to have various forms, and the description in this specification does not limit the present invention to a specific disclosed form. It should be viewed as including all equivalents or substitutes included in the spirit and technical scope of the present invention. In addition, the attached drawings are presented to help those skilled in the art understand the present invention more accurately, and may be shown exaggerated or reduced compared to reality.
{실시예 및 평가}{Examples and Evaluation}
1. 연구배경1. Research background
백출에서 추출한 8-에피아스테롤리드(8-epiasterolid)을 유효성분으로 함유하는 염증반응 예방 및 치료용 약학적 조성물을 이용하여, 염증 유발된 동물모델에 있어 염증반응 예방, 치료, 개선, 완화 등의 효과가 있는지 확인하였다. 마우스 유래 대식세포 및 미세아교세포에서의 뛰어난 항염증 효과를 확인하고자 하였으며, 리포폴리사카라이드(LPS)는 염증반응을 일으키는 물질로 알려져 있음에 따라 리포폴리사카라이드(LPS)를 처리하여 염증 유발군을 형성하였다.Using a pharmaceutical composition for preventing and treating inflammatory reactions containing 8-epiasterolid extracted from Baekchul as an active ingredient, prevention, treatment, improvement, relief, etc. of inflammatory reactions in animal models with inflammation. It was confirmed whether it was effective. We aimed to confirm the excellent anti-inflammatory effect on mouse-derived macrophages and microglial cells, and since lipopolysaccharide (LPS) is known to be a substance that causes inflammatory reactions, lipopolysaccharide (LPS) was treated to induce inflammation. was formed.
2. 실험예 (염증반응 유발 세포 모델실험)2. Experimental example (cell model experiment inducing inflammatory response)
2.1. 실험디자인2.1. Experimental design
본 실험에서는 마우스 유래 대식세포인 RAW264.7 세포주와 마우스 유래 미세아교세포인 BV2 세포주에 리포폴리사카라이드(LPS)를 처리하여 염증반응 유발 세포 모델을 제작하였다. 실험군은 다음과 같이 나누었다. In this experiment, a cell model inducing an inflammatory response was created by treating the RAW264.7 cell line, a mouse-derived macrophage cell line, and the BV2 cell line, a mouse-derived microglial cell line, with lipopolysaccharide (LPS). The experimental group was divided as follows.
① 비교예 1. control group① Comparative example 1. control group
② 비교예 2. LPS group (1 ㎍/mL)② Comparative example 2. LPS group (1 ㎍/mL)
③ 실시예 1. LPS + 8-epiasterolid group (20 μM)③ Example 1. LPS + 8-epiasterolid group (20 μM)
④ 실시예 2. LPS + 8-epiasterolid group (40 μM)④ Example 2. LPS + 8-epiasterolid group (40 μM)
⑤ 실시예 3. LPS + 8-epiasterolid group (80 μM)⑤ Example 3. LPS + 8-epiasterolid group (80 μM)
2.3. 실험방법2.3. Experiment method
정상군, 비교군(염증 유발군), 및 실험군(8-에피아스테롤리드 처리군)을 대상으로 세포독성 평가, 프로스타글란딘의 생성 평가, 염증성 싸이토카인의 생성 평가, 염증인자 효소 발현 평가, nuclear factor kappa B 경로 활성 평가 등을 수행하였다.Cytotoxicity evaluation, prostaglandin production evaluation, inflammatory cytokine production evaluation, inflammatory factor enzyme expression evaluation, nuclear factor kappa for normal group, comparison group (inflammatory group), and experimental group (8-epiasterolide treated group). B pathway activity evaluation, etc. were performed.
3. 평가3. Evaluation
3.1. 8-에피아스테롤리드의 투여에 의한 세포독성 평가3.1. Evaluation of cytotoxicity by administration of 8-epiasterolide
도 1은 정상군, 리포폴리사카라이드 처리에 따른 염증 유발군, 8-에피아스테롤리드 처리군의 세포독성 평가를 그래프로 도시한 것이다.Figure 1 graphically shows the cytotoxicity evaluation of the normal group, the inflammation-induced group following lipopolysaccharide treatment, and the 8-epiasterolide treatment group.
도 1을 참조하면, 백출로부터 유래된 8-에피아스테롤리드는 80 μM 농도까지 세포독성을 나타내지 않았으며(실시예 1 내지 3), 정상군(비교예 1)과 비교하여 리포폴리사카라이드 처리에 따른 염증 유발군(비교예 2)에서는 산화질소의 생성이 증가하였으며, 8-에피아스테롤리드 처리군에서는 산화질소의 생성이 억제되는 것을 확인할 수 있다. 리포폴리사카라이드 처리에 따른 염증 유발군(비교예 2) 대비 8-에피아스테롤리드 처리군(실시예 1 내지 3)은 95%로 검정하였을 때 유의적인 차이를 나타내었다(***p < 0.001).Referring to Figure 1, 8-epiasterolide derived from Baekchul did not show cytotoxicity up to a concentration of 80 μM (Examples 1 to 3), and compared to the normal group (Comparative Example 1), lipopolysaccharide treatment It can be seen that the production of nitric oxide increased in the inflammation-inducing group (Comparative Example 2), and the production of nitric oxide was suppressed in the 8-epiasterolide-treated group. The 8-epiasterolide-treated group (Examples 1 to 3) showed a significant difference compared to the inflammation-induced group (Comparative Example 2) due to lipopolysaccharide treatment when tested at 95% (***p < 0.001).
3.2. 8-에피아스테롤리드의 투여에 의한 프로스타글란딘의 생성 평가3.2. Evaluation of prostaglandin production by administration of 8-epiasterolide
도 2는 정상군, 리포폴리사카라이드 처리에 따른 염증 유발군, 8-에피아스테롤리드 처리군의 프로스타글란딘의 생성 평가를 그래프로 도시한 것이다.Figure 2 graphically shows the evaluation of prostaglandin production in the normal group, the inflammation-induced group following lipopolysaccharide treatment, and the 8-epiasterolide treatment group.
도 2를 참조하면, 정상군(비교예 1)과 비교하여 리포폴리사카라이드 처리에 따른 염증 유발군(비교예 2)에서는 프로스타글란딘의 생성이 증가하였으며, 8-에피아스테롤리드 처리군(실시예 2 및 3)에서는 프로스타글란딘의 생성이 억제되는 것을 확인할 수 있다. 리포폴리사카라이드 처리에 따른 염증 유발군(비교예 2) 대비 8-에피아스테롤리드 처리군(실시예 3)에서 95%로 검정하였을 때 유의적인 차이를 나타내었다 (**p < 0.01, ***p < 0.001). Referring to Figure 2, compared to the normal group (Comparative Example 1), the production of prostaglandins increased in the inflammation-induced group (Comparative Example 2) following lipopolysaccharide treatment, and the 8-epiasterolide treated group (Example In 2 and 3), it can be seen that the production of prostaglandin is suppressed. There was a significant difference when tested at 95% in the 8-epiasterolide-treated group (Example 3) compared to the inflammation-induced group due to lipopolysaccharide treatment (Comparative Example 2) (**p < 0.01, * **p < 0.001).
3.3. 8-에피아스테롤리드의 투여에 의한 염증성 싸이토카인의 생성 평가3.3. Evaluation of inflammatory cytokine production by administration of 8-epiasterolide
도 3은 정상군, 리포폴리사카라이드 처리에 따른 염증 유발군, 8-에피아스테롤리드 처리군의 염증성 싸이토카인의 생성 평가를 그래프로 도시한 것이다.Figure 3 graphically shows the evaluation of the production of inflammatory cytokines in the normal group, the inflammation-induced group following lipopolysaccharide treatment, and the 8-epiasterolide treatment group.
도 3을 참조하면, 정상군(비교예 1)과 비교하여 리포폴리사카라이드 처리에 따른 염증 유발군(비교예 2)에서는 염증성 싸이토카인의 생성이 증가하였으며, 8-에피아스테롤리드 처리군(실시예 2 및 3)에서는 염증성 싸이토카인의 생성이 억제되는 것을 확인할 수 있다. 리포폴리사카라이드 처리에 따른 염증 유발군(비교예 2) 대비 8-에피아스테롤리드 처리군(실시예 3)에서 95%로 검정하였을 때 유의적인 차이를 나타내었다 (**p < 0.01, ***p < 0.001). Referring to Figure 3, compared to the normal group (Comparative Example 1), the production of inflammatory cytokines increased in the inflammation-induced group (Comparative Example 2) following lipopolysaccharide treatment, and the 8-epiasterolide treated group (Example In Examples 2 and 3), it can be confirmed that the production of inflammatory cytokines is suppressed. There was a significant difference when tested at 95% in the 8-epiasterolide-treated group (Example 3) compared to the inflammation-induced group due to lipopolysaccharide treatment (Comparative Example 2) (**p < 0.01, * **p < 0.001).
3.4. 8-에피아스테롤리드의 투여에 의한 염증인자 효소 발현 평가3.4. Evaluation of inflammatory factor enzyme expression by administration of 8-epiasterolide
도 4는 정상군, 리포폴리사카라이드 처리에 따른 염증 유발군, 8-에피아스테롤리드 처리군의 염증인자 효소 발현 평가를 그래프로 도시한 것이다.Figure 4 graphically shows the evaluation of inflammatory factor enzyme expression in the normal group, the inflammation-induced group following lipopolysaccharide treatment, and the 8-epiasterolide treatment group.
도 4를 참조하면, 정상군(비교예 1)과 비교하여 리포폴리사카라이드 처리에 따른 염증 유발군(비교예 2)에서는 염증인자 효소의 발현이 증가하였으며, 8-에피아스테롤리드 처리군(실시예 2 및 3)에서는 염증인자 효소인 iNOS와 COX-2 단백질의 발현이 억제되는 것을 확인할 수 있다.Referring to Figure 4, compared to the normal group (Comparative Example 1), the expression of inflammatory factor enzymes increased in the inflammation-induced group (Comparative Example 2) following lipopolysaccharide treatment, and the 8-epiasterolide treated group ( In Examples 2 and 3), it can be confirmed that the expression of iNOS and COX-2 proteins, which are inflammatory factor enzymes, is suppressed.
3.5. 8-에피아스테롤리드의 투여에 의한 nuclear factor kappa B 경로 활성 평가3.5. Evaluation of nuclear factor kappa B pathway activity by administration of 8-epiasterolide
도 5는 정상군, 리포폴리사카라이드 처리에 따른 염증 유발군, 8-에피아스테롤리드 처리군의 , nuclear factor kappa B 경로 활성 평가를 그래프로 도시한 것이다.Figure 5 is a graph showing the evaluation of nuclear factor kappa B pathway activity in the normal group, the inflammation-induced group following lipopolysaccharide treatment, and the 8-epiasterolide treatment group.
도 5를 참조하면, 정상군(비교예 1)과 비교하여 리포폴리사카라이드 처리에 따른 염증 유발군(비교예 2)에서는 nuclear factor kappa B 경로가 활성화되었으며, 8-에피아스테롤리드 처리군(실시예 2 및 3)에서는 경로의 활성이 억제되는 것을 확인할 수 있다. 8-에피아스테롤리드 처리군(실시예 2 및 3)에서는 IκB-α의 인산화 및 소멸 반응과 p65의 인산화 반응이 억제되었다. Referring to Figure 5, compared to the normal group (Comparative Example 1), the nuclear factor kappa B pathway was activated in the inflammation-induced group (Comparative Example 2) following lipopolysaccharide treatment, and the 8-epiasterolide treated group ( In Examples 2 and 3), it can be confirmed that the activity of the pathway is suppressed. In the 8-epiasterolide treated group (Examples 2 and 3), the phosphorylation and extinction reactions of IκB-α and the phosphorylation reactions of p65 were inhibited.
상술한 실험예들로부터, 리포폴리사카라이드(LPS)로 염증 반응을 유도한 대식세포 및 미세아교세포 모델에서 염증 인자의 생성 및 발현, 염증 반응 기전 활성화 억제 효능을 검증하였다.From the above-mentioned experimental examples, the production and expression of inflammatory factors and the efficacy of suppressing the activation of inflammatory response mechanisms were verified in macrophage and microglial cell models in which inflammatory responses were induced with lipopolysaccharide (LPS).
실시예 및 평가의 내용을 종합해 볼 때, 본 발명의 유효성분인 8-에피아스테롤리드는 염증반응의 완화, 개선 및 치료에 효과가 있음에 따라, 본 발명은 과도한 염증반응으로 인한 염증성 질환의 발병 위험성을 감소시키고, 다양한 염증반응의 예방, 개선 및 치료용 의약, 식품, 의약외품 등으로 활용될 수 있음을 확인할 수 있다.Considering the details of the examples and evaluations, 8-epiasterolide, the active ingredient of the present invention, is effective in alleviating, improving, and treating inflammatory reactions, and thus, the present invention is effective in treating inflammatory diseases caused by excessive inflammatory reactions. It can be confirmed that it reduces the risk of developing , and can be used as medicine, food, and quasi-drugs for the prevention, improvement, and treatment of various inflammatory reactions.
이상의 설명은 본 발명의 기술 사상을 예시적으로 설명한 것에 불과한 것으로서, 본 발명이 속하는 기술 분야에서 통상의 지식을 가진 자라면 본 발명의 본질적인 특성에서 벗어나지 않는 범위에서 다양한 수정 및 변형이 가능할 것이다.The above description is merely an illustrative explanation of the technical idea of the present invention, and various modifications and variations will be possible to those skilled in the art without departing from the essential characteristics of the present invention.
따라서, 본 발명에 개시된 실시예들은 본 발명의 기술 사상을 한정하기 위한 것이 아니라 설명하기 위한 것이고, 이러한 실시예에 의하여 본 발명의 기술 사상의 범위가 한정되는 것은 아니다. 본 발명의 보호 범위는 아래의 청구범위에 의하여 해석되어야 하며, 그와 동등한 범위 내에 있는 모든 기술 사상은 본 발명의 권리범위에 포함되는 것으로 해석되어야 할 것이다.Accordingly, the embodiments disclosed in the present invention are not intended to limit the technical idea of the present invention, but are for illustrative purposes, and the scope of the technical idea of the present invention is not limited by these embodiments. The scope of protection of the present invention should be interpreted in accordance with the claims below, and all technical ideas within the equivalent scope should be construed as being included in the scope of rights of the present invention.
Claims (10)
A pharmaceutical composition for preventing and treating inflammatory reactions, containing extract of Chrysanthemum Chrysanthemum as an active ingredient.
상기 백출 추출물은 하기 화학식 1로 표시되는 8-에피아스테롤리드(8-epiasterolid)인, 염증반응 예방 및 치료용 약학적 조성물.
[화학식 1]
According to paragraph 1,
A pharmaceutical composition for preventing and treating inflammatory reactions, wherein the Baekchul extract is 8-epiasterolid represented by the following formula (1).
[Formula 1]
상기 백출 추출물은 백출을 물, 탄소수 1 내지 4의 저급 알코올 또는 이들의 혼합 용매로 추출한 추출물인, 염증반응 예방 및 치료용 약학적 조성물.
According to paragraph 1,
The pharmaceutical composition for preventing and treating inflammatory reactions, wherein the white extract is an extract obtained by extracting white extract with water, a lower alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof.
상기 약학적 조성물은 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽 및 에어로졸로 이루어진 군으로부터 선택된 1종의 경구형 제형, 외용제, 좌제 및 멸균된 수용액의 형태로 제형화하여 사용되는 것을 특징으로 하는, 염증반응 예방 및 치료용 약학적 조성물.
According to paragraph 1,
The pharmaceutical composition is characterized in that it is formulated and used in the form of an oral dosage form selected from the group consisting of powders, granules, tablets, capsules, suspensions, emulsions, syrups and aerosols, external preparations, suppositories and sterilized aqueous solutions. A pharmaceutical composition for preventing and treating inflammatory reactions.
A food composition for preventing and improving inflammatory reactions, comprising an extract of Chrysanthemum chinensis.
상기 백출 추출물은 하기 화학식 1로 표시되는 8-에피아스테롤리드(8-epiasterolid)인, 염증반응 예방 및 개선용 식품 조성물.
[화학식 1]
According to clause 5,
A food composition for preventing and improving inflammatory reactions, wherein the Baekchul extract is 8-epiasterolid represented by the following formula (1).
[Formula 1]
상기 백출 추출물은 백출을 물, 탄소수 1 내지 4의 저급 알코올 또는 이들의 혼합 용매로 추출한 추출물인, 염증반응 예방 및 개선용 식품 조성물.
According to clause 5,
The food composition for preventing and improving inflammatory reactions, wherein the white extract is an extract obtained by extracting white extract with water, a lower alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof.
A quasi-drug composition for preventing and improving inflammatory reactions, comprising an extract of Chrysanthemum Chrysanthemum.
상기 백출 추출물은 하기 화학식 1로 표시되는 8-에피아스테롤리드(8-epiasterolid)인, 염증반응 예방 및 개선용 의약외품 조성물.
[화학식 1]
According to clause 8,
A quasi-drug composition for preventing and improving inflammatory reactions, wherein the Baekchul extract is 8-epiasterolid represented by the following formula (1).
[Formula 1]
A method for producing a pharmaceutical composition for preventing and treating inflammatory reactions, comprising: preparing a white extract by extracting the white extract with water, a lower alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof.
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Citations (1)
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KR100543075B1 (en) | 2003-11-28 | 2006-01-20 | 학교법인 건국대학교 | An Extract of Atractylodis Rhizoma Alba Having an Anti-allergic Effect |
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KR100543075B1 (en) | 2003-11-28 | 2006-01-20 | 학교법인 건국대학교 | An Extract of Atractylodis Rhizoma Alba Having an Anti-allergic Effect |
Non-Patent Citations (1)
Title |
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Eva Mezey et al, Nature Medicine 2009 vol15, 42-49 |
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