KR101756020B1 - Composition for Prevention, Improvement, or Treatment of Atopic Dermatitis Comprising Fermented Extract of Alnus sibirica Fitch. ex Turcz. - Google Patents
Composition for Prevention, Improvement, or Treatment of Atopic Dermatitis Comprising Fermented Extract of Alnus sibirica Fitch. ex Turcz. Download PDFInfo
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- KR101756020B1 KR101756020B1 KR1020160060534A KR20160060534A KR101756020B1 KR 101756020 B1 KR101756020 B1 KR 101756020B1 KR 1020160060534 A KR1020160060534 A KR 1020160060534A KR 20160060534 A KR20160060534 A KR 20160060534A KR 101756020 B1 KR101756020 B1 KR 101756020B1
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- extract
- atopic dermatitis
- fermented
- composition
- fermented extract
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- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
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Abstract
본 발명은 물오리나무 발효추출물을 유효성분으로 포함하는 아토피피부염의 예방, 개선, 또는 치료용 조성물에 관한 것이다.
본 발명에 따른 물오리나무 발효추출물은 항산화, 항염증 효과를 비롯하여 아토피피부염 마우스 모델에서 아토피피부염 증상 개선, Th1/Th2 사이토카인 분비 억제, 및 IgE 생성 억제 효과가 있으며, 이러한 효과는 발효시키지 않은 물오리나무 추출물에 비하여 현저히 향상된 것을 확인하였다. 따라서 부작용이 거의 없는 천연물인 물오리나무의 발효추출물은 아토피피부염의 예방, 개선, 또는 치료를 위한 의약품, 건강기능성 식품, 및 화장품 등의 개발에 유용하게 이용될 수 있을 것으로 기대된다. The present invention relates to a composition for preventing, ameliorating, or treating atopic dermatitis, which comprises a fermented extract of Staphylococcus aureus as an active ingredient.
The fermented extract of Staphylococcus aureus according to the present invention has an antioxidant, anti-inflammatory effect, atopic dermatitis symptom improvement, suppression of Th1 / Th2 cytokine secretion and IgE generation inhibition in a mouse model of atopic dermatitis, Which was significantly improved compared with the extract. Therefore, it is expected that the fermented extract of the watery wood, which is a natural product with little side effects, can be usefully used for the development of medicines, health functional foods and cosmetics for prevention, improvement or treatment of atopic dermatitis.
Description
본 발명은 물오리나무 발효추출물을 유효성분으로 포함하는 아토피피부염의 예방, 개선, 또는 치료용 조성물에 관한 것이다. The present invention relates to a composition for preventing, ameliorating, or treating atopic dermatitis, which comprises a fermented extract of Staphylococcus aureus as an active ingredient.
알레르기(Allergy)는 면역시스템의 오작동으로 보통 사람에게는 별 영향이 없는 물질이 특정 사람에게만 두드러기, 가려움, 콧물, 기침 등의 과민반응을 유발하는 질환으로서, 환경오염, 식생활과 생활습관의 서구화, 및 스트레스와 같은 환경인자, 유전, 및 다양한 알레르겐에 의해 유발될 수 있다. 전 세계적으로 유병률이 증가하고 있는 추세이며, 전 국민의 20~25%가 비염, 천식, 아토피피부염, 및 식품알레르기 등의 알레르기 질환으로 고통 받고 있다.Allergy is a disease caused by a malfunction of the immune system that causes irritation such as urticaria, itching, runny nose, and cough in a specific person. It is a disease caused by environmental pollution, westernization of diet and lifestyle, Environmental factors such as stress, genetics, and various allergens. The prevalence rate is increasing worldwide, and 20 to 25% of all people suffer from allergic diseases such as rhinitis, asthma, atopic dermatitis, and food allergy.
이러한 알레르기 질환 중 최근 전 세계적으로 유병률이 증가하고 있는 아토피피부염은 가려움증을 주된 증상으로 하는 만성적인 염증성 피부질환으로 주로 유아기 또는 소아기에 시작되며 유병률이 전 세계 인구의 20%를 차지한다고 보고되어 있다.Atopic dermatitis is a chronic inflammatory skin disease that mainly causes itching. It is reported to occur in early childhood or early childhood, and its prevalence accounts for 20% of the world's population.
아토피피부염은 림프구, 대식세포와 과립화된 비만세포가 병변부위에 침투되어 있으며, 혈액 내에서 호산구 비율이 높아지고 IgE(Immunoglobulin E)의 양이 증가하는 특징을 갖는다. 아토피피부염의 발병 기전은 유전적 요인, 환경적 요인, 약리학적 작용, 피부장벽 이상 및 면역학적 요인 등이 복잡하게 작용하며, 특히 Th2 세포에 의해 분비되는 인터루킨-4(IL-4), IL-5는 아토피피부염 발병에 중요한 역할을 한다고 알려져 있다. IL-4 매개 IgE는 B 세포에 의해서 유도되고, IL-5는 IL-4에 의해서 유도된 IgE 합성을 촉진시킨다.Atopic dermatitis is characterized by lymphocytes, macrophages and granular mast cells infiltrating lesions, increasing the eosinophil ratio in the blood and increasing the amount of IgE (Immunoglobulin E). The pathogenesis of atopic dermatitis is complicated by genetic factors, environmental factors, pharmacological effects, skin barrier abnormalities, and immunological factors. In particular, interleukin-4 (IL-4) 5 is known to play an important role in the development of atopic dermatitis. IL-4 mediated IgE is induced by B cells, and IL-5 promotes IL-4 induced IgE synthesis.
현재 아토피피부염을 비롯한 알레르기 치료용 약물들은 대부분 히스타민의 분비를 억제하거나, 증상을 치료하는데 치중되어 있으며, 확실한 효과를 보이는 치료제가 거의 없다. 대부분 아토피피부염에 탁월한 치료효과를 보이는 약물들은 스테로이드제로 많이 사용되고 있으나, 장기간 사용은 심각한 부작용을 초래할 수 있다. 더욱이, 아토피피부염은 소아, 청소년 환자들이 대부분이므로 독성과 부작용이 없는 안전성이 확보된 치료제 개발이 매우 중요하며, 이러한 한계점을 극복하기 위한 연구들이 이루어지고 있으나, 치료제 개발이 쉽지 않은 실정이다. Currently, drugs for allergy treatment, including atopic dermatitis, are mostly focused on suppressing the secretion of histamine or treating symptoms, and there are few treatments that have definite effects. Most of the drugs with excellent therapeutic effects for atopic dermatitis are used as steroids, but long-term use can cause serious side effects. In addition, since atopic dermatitis is the most common in children and adolescents, it is very important to develop a safe treatment without toxicity and side effects. To overcome these limitations, it is difficult to develop therapeutic agents.
발효(fermentation)는 미생물이 자신이 가지고 있는 효소로 유기물을 분해 또는 변화시켜 유익한 최종산물을 만들어내는 현상으로, 인간은 다양한 음식에 발효를 활용하여 왔으며, 인간이 먹는 음식의 1/3이 발효된 음식으로 알려져 있다. 이 중 요구르트, 치즈, 된장 등의 발효식품에 풍부한 세균은 아토피피부염을 포함하는 알레르기 질환을 예방한다고 알려져 있다. 이처럼 맛뿐만 아니라 발효의 유익한 효과가 널리 알려지면서 발효식품 뿐만 아니라 발효를 이용하여 질병을 개선하거나 치료하기 위한 용도로써 연구가 활발히 진행되고 있다.Fermentation is a phenomenon in which microorganisms decompose or change organic matter with their own enzymes and produce beneficial end products. Humans have utilized fermentation for various foods, and one third of human food is fermented It is known as food. Among them, bacteria rich in fermented foods such as yogurt, cheese, miso, etc. are known to prevent allergic diseases including atopic dermatitis. As well as taste, the beneficial effects of fermentation are widely known, and studies have been actively conducted to improve or treat diseases using fermented foods as well as fermented foods.
한편, 물오리나무(Alnus sibirica Fitch. ex Turcz.)는 자작나무과 오리나무속에 속하는 식물로 15종 이상이 우리나라에 자생하는 것으로 알려져 있으며, 한국 경기 이북지역과 중국, 일본에 분포하고 있다. 민간 및 한방에서는 물오리나무 수피를 색적양(赤楊)이라 부르며, 청열(淸熱), 강화(降火)하는 작용이 있어 비출혈(鼻出血), 설사, 외상출혈의 목적에 쓰여 왔으며, 그 외 민간적으로 숙취해소 등의 목적에도 응용한 것으로 나타나 있다(국내등록특허 제10-0345798호). 이외에 기구재(器具材), 토목용재(土木用材), 마루로 사용하고 수피와 열매는 염료로 쓰며, 사방조림용으로 많이 식재되고 있다. 그러나 물오리나무 추출물의 아토피피부염 치료효과에 대해서는 아직 알려진 바가 없으며, 더욱이 물오리나무 추출물을 발효시킴으로써 항아토피 효과를 향상시킨 연구결과는 보고된 바가 없다.On the other hand, Alnus sibirica Fitch. Ex Turcz. Is a plant belonging to birch and ducklings. It is known that more than 15 species are native to Korea, and it is distributed in North Korea, China, and Japan. In civilian and oriental medicine, the bark of the water tree is called "red 楊". It has been used for the purpose of non bleeding, diarrhea, trauma bleeding due to the action of cleansing and strengthening. It is also shown that it is applied to the purpose of hanging out hangover in the private (Korean Patent No. 10-0345798). In addition, it is used as instrument material, civil engineering material, and floor, and bark and fruit are used as dyestuff, and it is planted widely for planting everywhere. However, there is no known effect on the treatment of atopic dermatitis of the extracts of Staphylococcus aureus, and furthermore, no research has been reported to improve the anti-atopic effect by fermenting Strawberry Extract.
본 발명자들은 종래의 문제점을 극복하기 위하여 예의 연구한 결과, 물오리나무 추출물에 미생물을 접종하여 발효시켜 얻은 물오리나무 발효추출물이 항산화, 항염증 효과와 더불어 현저히 향상된 항아토피 효과를 나타냄을 확인하였는바, 이에 기초하여 본 발명을 완성하였다. As a result of extensive studies to overcome the conventional problems, the inventors of the present invention have found that fermented extracts of P. vivax obtained by fermenting microorganisms in the extracts of P. vivax have remarkably improved anti-atopic effect in addition to antioxidant and anti- On this basis, the present invention has been completed.
이에, 본 발명은 물오리나무 발효추출물을 유효성분으로 포함하는, 아토피피부염 예방, 개선, 또는 치료용 조성물을 제공하는 것을 목적으로 한다. Accordingly, it is an object of the present invention to provide a composition for prevention, improvement, or treatment of atopic dermatitis, comprising a fermented extract of Staphylococcus aureus as an active ingredient.
그러나 본 발명이 이루고자 하는 기술적 과제는 이상에서 언급한 과제에 제한되지 않으며, 언급되지 않은 또 다른 과제들은 아래의 기재로부터 당업자에게 명확하게 이해될 수 있을 것이다.However, the technical problem to be solved by the present invention is not limited to the above-mentioned problems, and other matters not mentioned can be clearly understood by those skilled in the art from the following description.
상기와 같은 본 발명의 목적을 달성하기 위하여, 본 발명은 물오리나무(Alnus sibirica Fitch. ex Turcz.) 발효추출물을 유효성분으로 포함하는, 아토피피부염 예방 또는 치료용 약학적 조성물을 제공한다. In order to accomplish the object of the present invention, the present invention provides a pharmaceutical composition for prevention or treatment of atopic dermatitis, comprising the fermented extract of Alnus sibirica Fitch. Ex Turcz. As an active ingredient.
또한, 본 발명은 물오리나무(Alnus sibirica Fitch. ex Turcz.) 발효추출물을 유효성분으로 포함하는, 아토피피부염 개선용 건강기능성 식품 조성물을 제공한다. In addition, the present invention provides a health functional food composition for improving atopic dermatitis, which comprises a fermented extract of Alnus sibirica Fitch. Ex Turcz. As an active ingredient.
또한, 본 발명은 물오리나무(Alnus sibirica Fitch. ex Turcz.) 발효추출물을 유효성분으로 포함하는, 아토피피부염 개선용 화장료 조성물을 제공한다.In addition, the present invention provides a cosmetic composition for improving atopic dermatitis, comprising a fermented extract of Alnus sibirica Fitch. Ex Turcz. As an active ingredient.
본 발명의 일 구현예로, 상기 발효추출물은 물오리나무 추출물에 미생물을 접종하고 5일 내지 9일 동안 발효시킴으로써 수득된 것일 수 있다.In one embodiment of the present invention, the fermentation extract may be one obtained by inoculating microorganisms into the extract of the woody line and fermenting the mixture for 5 to 9 days.
본 발명의 다른 구현예로, 상기 미생물은 락토바실러스 플란타럼(Lactobacillus plantarum)일 수 있다. In another embodiment of the present invention, the microorganism may be Lactobacillus plantarum .
본 발명의 또 다른 구현예로, 상기 물오리나무 추출물은 물, C1내지 C4의 저급알코올, n-헥산, 에틸아세테이트, 아세톤, 부틸아세테이트, 1,3-부틸렌 글리콜, 메틸렌클로라이드, 및 이들의 혼합용매로 구성된 군으로부터 선택된 용매로 추출된 것일 수 있다. In another embodiment of the present invention, the watery extract comprises water, a C 1 to C 4 lower alcohol, n-hexane, ethyl acetate, acetone, butyl acetate, 1,3-butylene glycol, methylene chloride, ≪ / RTI > in a solvent selected from the group consisting of < RTI ID = 0.0 >
본 발명의 또 다른 구현예로, 상기 조성물은 항산화능을 갖는 것일 수 있다. In another embodiment of the present invention, the composition may be one having antioxidant ability.
본 발명의 또 다른 구현예로, 상기 조성물은 일산화질소(Nitric oxide) 생성 억제능을 갖는 것일 수 있다. In another embodiment of the present invention, the composition may be one having ability to inhibit nitric oxide production.
본 발명의 또 다른 구현예로, 상기 조성물은 Th1 사이토카인 또는 Th2 사이토카인 생성을 억제하는 것일 수 있다. In another embodiment of the present invention, the composition may inhibit Th1 cytokine or Th2 cytokine production.
본 발명의 또 다른 구현예로, 상기 조성물은 IgE 생성을 억제하는 것일 수 있다.In another embodiment of the present invention, the composition may be one that inhibits IgE production.
또한, 본 발명은 상기 조성물을 개체에 투여하는 단계를 포함하는, 아토피피부염 예방 또는 치료방법을 제공한다. The present invention also provides a method of preventing or treating atopic dermatitis comprising administering the composition to a subject.
또한, 본 발명은 상기 조성물의 아토피피부염 예방 또는 치료용도를 제공한다.The present invention also provides the use of the composition for the prevention or treatment of atopic dermatitis.
본 발명에 따른 물오리나무 발효추출물은 항산화, 항염증 효과를 비롯하여 아토피피부염 마우스 모델에서 아토피피부염 증상 개선, Th1/Th2 사이토카인 분비 억제, 및 IgE 생성 억제 효과가 있으며, 이러한 효과는 발효시키지 않은 물오리나무 추출물에 비하여 현저히 향상된 것을 확인하였다. 따라서 부작용이 거의 없는 천연물인 물오리나무의 발효추출물은 아토피피부염의 예방, 개선, 또는 치료를 위한 의약품, 건강기능성 식품, 및 화장품 등의 개발에 유용하게 이용될 수 있을 것으로 기대된다. The fermented extract of Staphylococcus aureus according to the present invention has an antioxidant, anti-inflammatory effect, atopic dermatitis symptom improvement, suppression of Th1 / Th2 cytokine secretion and IgE generation inhibition in a mouse model of atopic dermatitis, Which was significantly improved compared with the extract. Therefore, it is expected that the fermented extract of the watery wood, which is a natural product with little side effects, can be usefully used for the development of medicines, health functional foods and cosmetics for prevention, improvement or treatment of atopic dermatitis.
도 1은 마우스 대식세포주 Raw 264.7에 LPS와 물오리나무 발효추출물을 처리한 후 ELISA를 통해 Th1/Th2 사이토카인인 인터페론-감마(IFN-γ) 및 인터루킨-4(IL-4)의 농도를 측정한 결과이다(Control: LPS 단독 처리, Normal: 아무것도 처리하지 않은 군, Ex: LPS+물오리나무 추출물 처리군, 발효: LPS+물오리나무 발효추출물 처리군).
도 2는 아토피피부염을 유발시킨 마우스에 물오리나무 발효추출물을 100 mg/kg의 양으로 2주일 동안 주 4회 경구 투여한 후 육안으로 시간에 따른 아토피피부염 개선 정도를 관찰한 결과이다(B: 정상대조군, Ex: 물오리나무 추출물 투여군, 발효: 물오리나무 발효추출물 투여군, DNCB: 아토피피부염 유발 후 아무것도 처리하지 않은 군).
도 3a 및 도 3b는 상기 도 2와 동일한 실험군에서 시간에 따른 귀 두께 변화(도 3a) 및 마우스의 체중변화(도 3b)를 측정하여 나타낸 것이다.
도 4는 상기 도 2 및 도 3의 실험 종료 후 각 그룹의 마우스로부터 혈액을 채취한 후 ELISA를 통해 혈청 내 IgE의 농도를 측정한 결과이다.
도 5는 상기 도 2 및 도 3의 실험 종료 후 각 그룹의 마우스로부터 비장을 적출하여 real-time PCR을 통해 비장 면역세포 내 IFN-γ 및 IL-4의 양을 측정한 결과이다.FIG. 1 shows the results of ELISA after treatment of LPS and L. fermented extract with mouse macrophage cell line Raw 264.7 and measuring the concentration of interferon-gamma (IFN-γ) and interleukin-4 (IL-4) which are Th1 / Th2 cytokines (Control: LPS alone treatment, Normal: Nothing treated, Ex: LPS + strawberry extract treated group, Fermentation: LPS + fermented fruit extract extract group).
FIG. 2 shows the results of observing the improvement of atopic dermatitis over time in the eyes after oral administration of the extract of Fusarium oxysporum (Fusarium oxysporum) at a dose of 100 mg / kg for 4 weeks for 2 weeks (B: normal Control group, Ex: group treated with water extract, fermentation: group treated with fermented water extract, and DNCB: treated without any treatment after induction of atopic dermatitis).
FIGS. 3A and 3B show changes in ear thickness (FIG. 3A) and weight change (FIG. 3B) of mice in the same experimental group as FIG.
FIG. 4 shows the results of measurement of IgE concentration in serum by ELISA after collecting blood from each group of mice after completion of the experiments shown in FIGS. 2 and 3. FIG.
FIG. 5 shows the result of measuring the amount of IFN-γ and IL-4 in spleen immunocytes by real-time PCR after spleen was extracted from each group of mice after completion of the experiments of FIGS. 2 and 3.
본 발명자들은 높은 안전성 및 항아토피 효과를 가지는 아토피피부염 치료제 개발을 위해 예의 연구한 결과, 물오리나무 발효추출물의 뛰어난 항아토피 효과를 확인함으로써 본 발명을 완성하였다. The inventors of the present invention have conducted intensive studies for the development of a therapeutic agent for atopic dermatitis which has high safety and anti-atopic effect. As a result, the present inventors have completed the present invention by confirming the excellent anti-atopic effect of the fermented extract of Liliaceae.
이에, 본 발명은 물오리나무(Alnus sibirica Fitch. ex Turcz.) 발효추출물을 유효성분으로 포함하는 아토피피부염 예방 또는 치료용 약학적 조성물을 제공한다.Accordingly, the present invention provides a pharmaceutical composition for preventing or treating atopic dermatitis, which comprises a fermented extract of Alnus sibirica Fitch. Ex Turcz. As an active ingredient.
본 발명에서 사용되는 용어, “예방”이란 본 발명에 따른 약학적 조성물의 투여에 의해 아토피피부염을 억제시키거나 발병을 지연시키는 모든 행위를 의미한다.As used herein, the term " prevention " means any action which inhibits or delays the onset of atopic dermatitis by administration of the pharmaceutical composition according to the present invention.
본 발명에서 사용되는 용어, “치료”란 본 발명에 따른 약학적 조성물의 투여에 의해 아토피피부염에 대한 증세가 호전되거나 이롭게 변경되는 모든 행위를 의미한다. As used herein, the term " treatment " means any action that alleviates or alleviates symptoms of atopic dermatitis by administration of the pharmaceutical composition according to the present invention.
본 발명에 있어서, 물오리나무는 사용부위에 특별한 제한은 없으나, 보다 바람직하게는 물오리나무 줄기를 이용하여 추출물을 제조할 수 있다.In the present invention, no particular limitation is imposed on the site of use of the dwarf tree, but more preferably, the dwarf tree can be used to produce the extract.
본 발명에서 사용되는 용어, “발효”란, 유기물이 미생물작용에 의해 분해 및 변화하여 유용한 물질이 생산되는 것을 의미한다. 발효는 환경에 따라 다양하게 일어날 수 있는데, 전형적으로는 효모의 알코올발효, 글리세롤발효, 젖산균의 젖산발효, 헤테로젖산발효, 메탄세균의 메탄발효, 및 대장균 등에 의한 혼합유기산발효가 있다. 산화발효는 기질의 불완전산화에 의한 중간대사물의 축적을 이용하는 것으로 아세트산균에 의한 아세트산발효, 글루콘산발효, 소르보오스발효나 사상균에 의한 시트르산, 글루콘산, 푸마르산, 옥살산 등의 유기산발효가 있다. 본 발명에 있어서 발효는 물오리나무 추출물에 물을 첨가하고 살균 과정 후 미생물, 보다 바람직하게는 락토바실러스 플란타럼(Lactobacillus plantarum)을 접종하고 실온에서 5일 내지 9일, 보다 바람직하게는 7일 동안 배양하는 과정을 통해 수득될 수 있다. As used herein, the term " fermentation " means that an organic material is decomposed and changed by microbial action to produce a useful substance. The fermentation may be various depending on the environment. Typically, there are fermentation of alcohol by yeast, fermentation of glycerol, fermentation of lactic acid bacteria with lactic acid, fermentation with lactic acid, methane fermentation with methane bacteria, and mixed organic acid fermentation with Escherichia coli. Oxidative fermentation utilizes the accumulation of intermediate metabolites by incomplete oxidation of the substrate, such as fermentation of acetic acid by acetic acid bacteria, fermentation of gluconic acid, fermentation of sorbose or organic acids such as citric acid, gluconic acid, fumaric acid and oxalic acid by fungi. According to the present invention, the fermentation is carried out by adding water to the extract of Liliaceae and inoculating the microorganism, more preferably Lactobacillus plantarum , after the sterilization process, for 5 days to 9 days at room temperature, more preferably for 7 days And culturing the cells.
본 발명의 발효 대상인 상기 물오리나무 추출물은 천연물로부터 추출물을 추출하는 당업계에 공지된 통상적인 방법에 따라, 즉, 통상적인 온도, 압력의 조건 하에서 통상적인 용매를 사용하여 추출할 수 있다. 예컨대, 본 발명에서 물오리나무 추출물은 물오리나무에 물, 탄소 수 1 내지 4의 알코올, 에틸아세테이트, 아세톤, 부틸아세테이트, 1,3-부틸렌 글리콜, 메틸렌클로라이드, 및 이들의 혼합 용매로 이루어진 군으로부터 선택된 1종 이상의 용매를 사용하여 추출할 수 있고, 바람직하게는 에탄올, 더욱 바람직하게는 프레타놀 A(prethanol A)을 사용하여 추출할 수 있다. 또한, 물오리나무 추출물을 추출하는 방법은 상온 추출, 열수 추출, 냉침 추출, 환류 추출, 마이크로웨이브 추출, 및 초음파 추출 등의 다양한 방법을 통하여 추출할 수 있다. The extract of Strawberry, which is the subject of fermentation of the present invention, can be extracted using conventional solvents known in the art for extracting the extract from natural products, that is, under ordinary temperature and pressure conditions. For example, in the present invention, the watery tree extract is prepared from the group consisting of water, a carbonic acid having 1 to 4 carbon atoms, ethyl acetate, acetone, butyl acetate, 1,3-butylene glycol, methylene chloride, Can be extracted using one or more selected solvents, and can be extracted preferably using ethanol, more preferably using prethanol A (prethanol A). In addition, the method of extracting the watery tree extract can be extracted by various methods such as room temperature extraction, hot water extraction, cold extraction, reflux extraction, microwave extraction, and ultrasonic extraction.
상기 제조된 추출물은 이후 여과하거나 농축 또는 건조과정을 수행하여 용매를 제거할 수 있으며, 여과, 농축 및 건조를 모두 수행할 수 있다. 예컨대, 여과는 여과지를 이용하거나 감압여과기를 이용할 수 있으며, 농축은 감압 농축기, 건조는 동결건조법 등을 수행할 수 있으나, 이것으로 제한되는 것은 아니다.The extract thus prepared may be filtered, concentrated or dried to remove the solvent, and may be subjected to both filtration, concentration and drying. For example, the filtration can be performed using a filter paper or a vacuum filter, the concentration can be carried out using a vacuum concentrator, and the lyophilization can be carried out, but the present invention is not limited thereto.
또한, 상기 용매로 추출한 추출물은 이후 부탄올, 헥산, 메틸렌클로라이드, 아세톤, 에틸아세테이트, 에틸에테르, 클로로포름, 물, 및 이들의 혼합용매로 이루어진 군으로부터 선택된 용매로 분획과정을 더욱 실시할 수도 있다. 상기 분획 시 온도는 4℃ 내지 120℃일 수 있으나, 이에 제한되지는 않는다.Further, the extract extracted with the solvent may be further fractionated with a solvent selected from the group consisting of butanol, hexane, methylene chloride, acetone, ethyl acetate, ethyl ether, chloroform, water, and a mixed solvent thereof. The fractionation temperature may be 4 캜 to 120 캜, but is not limited thereto.
본 발명에서는 상기 방법에 따라 수득한 물오리나무 발효추출물의 항아토피 효과를 검증하기 위하여 다양한 실험을 수행하였으며, 이때 발효시키지 않은 물오리나무 추출물과 함께 실험하여 그 효과를 비교하였다. In the present invention, various experiments were carried out to verify the anti-atopic effect of the fermented extract of P. vivax obtained according to the above method.
본 발명의 일실시예에서는, 물오리나무 발효추출물의 항산화 효과를 평가하기 위해 DPPH 라디칼 소거활성 및 NBT/superoxide 소거활성을 측정한 결과, 물오리나무 발효추출물이 높은 항산화능을 나타냄을 확인하였으며, 물오리나무 추출물에 비하여 우수한 효과를 나타내는 것을 알 수 있었다(실시예 2 참고). In one embodiment of the present invention, the DPPH radical scavenging activity and the NBT / superoxide scavenging activity were measured to evaluate the antioxidative effect of the fermented extract of P. vivax, (See Example 2). ≪ tb > < TABLE >
본 발명의 다른 실시예에서는, 일산화질소(NO) 생성 억제 활성을 측정함으로써 물오리나무 발효추출물의 항염증 효과를 평가하였다. 그 결과, 물오리나무 발효추출물은 발효시키지 않은 물오리나무 추출물에 비하여 LPS에 의해 유도되는 NO 생성을 억제하는 효과가 뛰어남을 확인하였다(실시예 3 참고). In another embodiment of the present invention, the anti-inflammatory effect of the fermented extract of Staphylococcus aureus was evaluated by measuring the inhibitory activity of nitrogen monoxide (NO) production. As a result, it was confirmed that the fermented extract of Staphylococcus aureus had an excellent effect of inhibiting the production of NO induced by LPS as compared with the fermented Staphylococcus aureus extract (see Example 3).
본 발명의 또 다른 실시예에서는, 상기 결과들을 바탕으로 물오리나무 발효추출물의 항아토피 효과를 평가하였다. 먼저, 물오리나무 발효추출물은 Th1/Th2 사이토카인인 IFN-γ 및 IL-4의 분비를 억제시킴을 확인하였으며(실시예 4 참고), 나아가 아토피피부염을 유발시킨 마우스 모델에 물오리나무 발효추출물을 2주간 주 4회 경구 투여한 후 육안관찰을 통한 아토피피부염 개선, 혈청 내 IgE 분비 감소, 및 Th1/Th2 사이토카인 생성 감소 효과를 확인함으로써 물오리나무 추출물보다 우수한 항아토피 효능을 확인하였다(실시예 5 참고).In another embodiment of the present invention, the anti-atopic effect of the fermented water extract of Staphylococcus aureus was evaluated based on the above results. First, it was confirmed that the fermented extract of Staphylococcus aureus inhibited the secretion of IFN-γ and IL-4, which are Th1 / Th2 cytokines (see Example 4) After oral administration four times a week, it was confirmed that the atopic dermatitis was improved by visual observation, the decrease of serum IgE secretion and the reduction of Th1 / Th2 cytokine production, ).
따라서 본 발명의 물오리나무 발효추출물은 발효과정을 통한 현저히 증진된 항아토피 효과를 나타내며, 아토피피부염 예방, 개선, 또는 치료를 위한 용도로 유용하게 이용될 수 있다.Therefore, the fermented extract of Staphylococcus aureus according to the present invention exhibits remarkably enhanced anti-atopic effect through the fermentation process and can be usefully used for prevention, improvement, or treatment of atopic dermatitis.
본 발명에 따른 약학적 조성물은 물오리나무 발효추출물을 유효성분으로 포함하며, 약학적으로 허용 가능한 담체를 더 포함할 수 있다. 상기 약학적으로 허용 가능한 담체는 제제시에 통상적으로 이용되는 것으로서, 식염수, 멸균수, 링거액, 완충 식염수, 사이클로덱스트린, 덱스트로즈 용액, 말토덱스트린 용액, 글리세롤, 에탄올, 리포좀 등을 포함하지만 이에 한정되지 않으며, 필요에 따라 항산화제, 완충액 등 다른 통상의 첨가제를 더 포함할 수 있다. 또한 희석제, 분산제, 계면활성제, 결합제, 윤활제 등을 부가적으로 첨가하여 수용액, 현탁액, 유탁액 등과 같은 주사용 제형, 환약, 캡슐, 과립, 또는 정제로 제제화할 수 있다. 적합한 약학적으로 허용되는 담체 및 제제화에 관해서는 레밍턴의 문헌에 개시되어 있는 방법을 이용하여 각 성분에 따라 바람직하게 제제화할 수 있다. 본 발명의 약학적 조성물은 제형에 특별한 제한은 없으나 주사제, 흡입제, 피부 외용제 등으로 제제화할 수 있다. The pharmaceutical composition according to the present invention may further comprise a pharmaceutically acceptable carrier, which comprises a fermented extract of Staphylococcus aureus as an active ingredient. Such pharmaceutically acceptable carriers are those conventionally used in the field of application and include, but are not limited to, saline, sterile water, Ringer's solution, buffered saline, cyclodextrin, dextrose solution, maltodextrin solution, glycerol, ethanol, And may further contain other conventional additives such as antioxidants and buffers as needed. It may also be formulated into injectable formulations, pills, capsules, granules, or tablets such as aqueous solutions, suspensions, emulsions and the like by additionally adding diluents, dispersants, surfactants, binders, lubricants and the like. Suitable pharmaceutically acceptable carriers and formulations can be suitably formulated according to the respective ingredients using the methods disclosed in Remington's reference. The pharmaceutical composition of the present invention is not particularly limited to a formulation, but may be formulated into injections, inhalants, external skin preparations, and the like.
본 발명의 약학적 조성물은 목적하는 방법에 따라 경구 투여하거나 비경구투여(예를 들어, 정맥 내, 피하, 복강 내 또는 국소에 적용)할 수 있으며, 투여량은 환자의 상태 및 체중, 질병의 정도, 약물형태, 투여경로 및 시간에 따라 다르지만, 당업자에 의해 적절하게 선택될 수 있다.The pharmaceutical composition of the present invention may be administered orally or parenterally (for example, intravenously, subcutaneously, intraperitoneally or topically) depending on the intended method, and the dose may vary depending on the condition and the weight of the patient, The mode of administration, the route of administration, and the time, but may be appropriately selected by those skilled in the art.
본 발명의 약학적 조성물은 약학적으로 유효한 양으로 투여한다. 본 발명에 있어서 “약학적으로 유효한 양”은 의학적 치료에 적용 가능한 합리적인 수혜/위험 비율로 질환을 치료하기에 충분한 양을 의미하며, 유효용량 수준은 환자의 질환 종류, 중증도, 약물의 활성, 약물에 대한 민감도, 투여 시간, 투여 경로 및 배출비율, 치료기간, 동시 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 결정될 수 있다. 본 발명에 다른 약학적 조성물은 개별 치료제로 투여하거나 다른 치료제와 병용하여 투여될 수 있고 종래 의 치료제와는 순차적 또는 동시에 투여될 수 있으며, 단일 또는 다중 투여될 수 있다. 상기한 요소들을 모두 고려하여 부작용 없이 최소한의 양으로 최대 효과를 얻을 수 있는 양을 투여하는 것이 중요하며, 이는 당업자에 의해 용이하게 결정될 수 있다.The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. In the present invention, " pharmaceutically effective amount " means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment. The effective dose level is determined depending on the type of disease, severity, The time of administration, the route of administration and the rate of excretion, the duration of the treatment, factors including co-administered drugs, and other factors well known in the medical arts. The pharmaceutical composition according to the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, sequentially or concurrently with conventional therapeutic agents, and may be administered singly or in multiple doses. It is important to take into account all of the above factors and to administer the amount in which the maximum effect can be obtained in a minimal amount without side effects, which can be easily determined by those skilled in the art.
구체적으로 본 발명의 약학적 조성물의 유효량은 환자의 연령, 성별, 상태, 체중, 체내에 활성 성분의 흡수도, 불활성률 및 배설속도, 질병종류, 병용되는 약물에 따라 달라질 수 있으며, 일반적으로는 체중 1 ㎏ 당 0.001 내지 150 ㎎, 바람직하게는 0.01 내지 100 ㎎을 매일 또는 격일 투여하거나, 1일 1 내지 3회로 나누어 투여할 수 있다. 그러나 투여 경로, 비만의 중증도, 성별, 체중, 연령 등에 따라서 증감 될 수 있으므로 상기 투여량이 어떠한 방법으로도 본 발명의 범위를 한정하는 것은 아니다.Specifically, the effective amount of the pharmaceutical composition of the present invention may vary depending on the age, sex, condition, body weight, the degree of absorption of the active ingredient in the body, the rate of inactivation and the excretion rate, the type of disease, 0.001 to 150 mg, preferably 0.01 to 100 mg per kg of body weight, may be administered daily or every other day, or one to three divided doses per day. However, the dosage may be varied depending on the route of administration, the severity of obesity, sex, weight, age, etc. Therefore, the dosage is not limited to the scope of the present invention by any means.
본 발명의 다른 양태로서, 본 발명은 물오리나무 발효추출물을 유효성분으로 포함하는 아토피피부염 개선용 건강기능성 식품 조성물을 제공한다. According to another aspect of the present invention, there is provided a health functional food composition for improving atopic dermatitis comprising a fermented extract of Staphylococcus aureus as an active ingredient.
본 발명에서 사용되는 용어, “개선”이란, 치료되는 상태와 관련된 파라미터, 예를 들면 증상의 정도를 적어도 감소시키는 모든 행위를 의미한다. 이때 상기 건강기능성 식품 조성물은 아토피피부염의 예방 또는 개선을 위하여 해당 질환의 발병 단계 이전 또는 발병 후, 치료를 위한 약제와 동시에 또는 별개로서 사용될 수 있다.The term " improvement " as used in the present invention means all actions that at least reduce the degree of symptom associated with the condition being treated. At this time, the health functional food composition may be used simultaneously or separately with the medicament for treatment before or after onset of the disease for the prevention or improvement of atopic dermatitis.
본 발명에 따른 건강기능성 식품 조성물은 담체, 희석제, 부형제, 및 첨가제 중 하나 이상을 포함하여 정제, 환제, 산제, 과립제, 분말제, 캡슐제, 및 액제 제형으로 이루어진 군에서 선택된 하나로 제형된 것을 특징으로 한다. 본 발명의 추출물에 첨가 할 수 있는 식품으로는, 각종 식품류, 분말, 과립, 정제, 캡슐, 시럽제, 음료, 껌, 차, 비타민 복합제, 건강기능성 식품류 등이 있다. 상기 본 발명에 더 포함될 수 있는 첨가제로는, 천연 탄수화물, 향미제, 영양제, 비타민, 광물(전해질), 풍미제(합성 풍미제, 천연 풍미제 등), 착색제, 충진제, 팩트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH조절제, 안정화제, 방부제, 산화 방지제, 글리세린, 알코올, 탄산화제 및 과육으로 이루어진 구으로부터 선택된 1종 이상의 성분을 사용할 수 있다. 상술한 천연 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토오스, 수크로오스 등; 및 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린 등과 같은 통상적인 당, 및 자일리톨, 소르비톨, 에리트리톨 등의 당알코올이다. 상기 향미제로서 천연 향미제(타우마틴, 스테비아추출물 (예를 들어 레바우디오시드 A, 글리시르히진 등) 및 합성 향미제(사카린, 아스파르탐 등)를 유리하게 사용할 수 있다. 상기 외에 본 발명에 따른 조성물은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제, 팩트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 그밖에 본 발명에 다른 조성물은 천연 과일 주스 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 상기 담체, 부형제, 희석제, 및 첨가제의 구체적인 예로는 이에 한정하는 것은 아니나, 락토오스, 덱스트로즈, 수크로오스, 솔비톨, 만니톨, 에리스리톨, 전분, 아카시아 고무, 인산칼슘, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 미세결정성 셀룰로즈, 폴리비닐키롤리돈, 셀룰로즈, 폴리비닐피로리돈, 메틸셀룰로즈, 물, 설탕시럽, 메틸 하이드록시 벤조에이트, 프로필하이드록시 벤조에이트, 활석, 스테아르산 마그네슘 및 미네랄 오일로 이루어진 그룹으로부터 선택된 1종 이상이 사용되는 것이 바람직하다.The health functional food composition according to the present invention is formulated into one selected from the group consisting of tablets, pills, powders, granules, powders, capsules, and liquid formulations including at least one of carrier, diluent, excipient, . Examples of foods that can be added to the extract of the present invention include various foods, powders, granules, tablets, capsules, syrups, drinks, gums, tea, vitamin complexes, and health functional foods. Examples of the additive that can be further included in the present invention include natural carbohydrates, flavors, nutrients, vitamins, minerals (electrolytes), flavors (synthetic flavors, natural flavors and the like), colorants, fillers, At least one component selected from alginic acid and its salts, organic acids, protective colloid thickening agents, pH adjusting agents, stabilizers, preservatives, antioxidants, glycerin, alcohols, carbonating agents and fats can be used. Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And polysaccharides such as dextrin, cyclodextrin and the like, and sugar alcohols such as xylitol, sorbitol and erythritol. As the above-mentioned flavors, natural flavors (tautatin, stevia extract (for example, rebaudioside A and glycyrrhizin) and synthetic flavors (saccharin, aspartame, etc.) can be advantageously used. The composition according to the present invention can be used in various forms such as flavorings such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, colorants and heavies, factic acid and its salts, alginic acid and its salts, , pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated beverages, etc. Other compositions according to the present invention may contain flesh for the production of natural fruit juices and vegetable drinks . These components may be used independently or in combination. Specific examples of the carrier, excipient, diluent, and additive include, but are not limited to, lactose, dextrose But are not limited to, sucrose, sorbitol, mannitol, erythritol, starch, acacia gum, calcium phosphate, alginate, gelatin, calcium phosphate, calcium silicate, microcrystalline cellulose, polyvinylquilolidone, cellulose, polyvinylpyrrolidone, methylcellulose, water , At least one selected from the group consisting of sugar syrup, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil is preferably used.
본 발명의 또 다른 양태로서, 본 발명은 물오리나무 발효추출물을 유효성분으로 포함하는 아토피피부염 개선용 화장료 조성물을 제공한다.As another embodiment of the present invention, the present invention provides a cosmetic composition for improving atopic dermatitis, which comprises an extract of fermented black tea tree as an active ingredient.
본 발명의 상기 화장료 조성물은 물오리나무 발효추출물뿐만 아니라, 화장료 조성물에 통상적으로 이용되는 성분들을 포함할 수 있으며, 예컨대 항산화제, 안정화제, 용해화제, 비타민, 안료, 및 향료와 같은 통상적인 보조제, 그리고 담체를 포함할 수 있다. The cosmetic composition of the present invention may contain components commonly used in cosmetic compositions as well as fermented extracts of the woody plants and may contain conventional additives such as antioxidants, stabilizers, solubilizers, vitamins, pigments, and perfumes, And may include a carrier.
또한, 본 발명의 조성물은 물오리나무 발효추출물 이외에, 물오리나무 발효추출물과 반응하여 피부보호 효과를 손상시키지 않는 한도에서 종래부터 사용되어오던 유기 자외선 차단제를 혼합하여 사용할 수도 있다. 상기 유기 자외선 차단제로는 글리세릴파바, 드로메트리졸트리실록산, 드로메트리졸, 디갈로일트리올리에이트, 디소듐페닐디벤즈이미다졸테트라설포네이트, 디에틸헥실부타미도트리아존, 디에틸아미노하이드록시벤조일헥실벤조에이트, 디이에이-메톡시신나메이트, 로우손과 디하이드록시아세톤의 혼합물, 메틸렌비스-벤조트리아졸릴테트라메칠부틸페놀, 4-메틸벤질리덴캠퍼, 멘틸안트라닐레이트, 벤조페논-3(옥시벤존),벤조페논-4, 벤조페논-8(디옥시페벤존), 부틸메톡시디벤조일메탄, 비스에틸헥실옥시페놀메톡시페닐트리아진, 시녹세이트, 에틸디하이드록시프로필파바, 옥토크릴렌, 에틸헥실디메틸파바, 에틸헥실메톡시신나메이트, 에틸헥실살리실레이트, 에틸헥실트리아존, 이소아밀-p-메톡시신나메이트, 폴리실리콘-15(디메치코디에틸벤잘말로네이트), 테레프탈릴리덴디캠퍼설포닉애씨드 및 그 염류, 티이에이-살리실레이트 및 아미노벤조산(파바)으로 이루어진 군으로부터 선택된 1종 이상을 사용할 수 있다. In addition, the composition of the present invention may be used in combination with an organic UV blocking agent which has been used in the past so long as it does not deteriorate the skin protecting effect by reacting with the fermented extract of P. vivax, in addition to the fermented extract of P. falciparum. Examples of the organic UV blocking agent include glyceryl paraben, drometrizol trisiloxane, drometrizol, dipaloyyl triolate, disodium phenyldibenzimidazole tetrasulfonate, diethylhexylbutamidotriazone, diethylamino Hydroxybenzoylhexyl benzoate, di-methoxycinnamate, a mixture of Rawson and dihydroxyacetone, methylene bis-benzotriazolyltetramethylbutylphenol, 4-methylbenzylidene camphor, menthyl anthranylate, benzophenone (Benzophenone-4), benzophenone-8 (dioxyphenylbenzone), butylmethoxydibenzoylmethane, bisethylhexyloxyphenol methoxyphenyltriazine, synoxate, ethyl dihydroxypropylparaben, Ethylhexyldimethylpivalate, ethylhexylmethoxycinnamate, ethylhexylsalicylate, ethylhexyltriazone, isoamyl-p-methoxy cinnamate, polysilicon-15 (dimethicodimethylbenzalmate, At least one selected from the group consisting of terephthalylidene dicam peresophilic acid and its salts, thiai-salicylate and aminobenzoic acid (parabe) can be used.
본 발명의 화장료 조성물을 첨가할 수 있는 제품으로는, 예를 들어, 수렴화장수, 유연화장수, 영양화장수, 각종 크림, 에센스, 팩, 파운데이션 등과 같은 화장품류와 클렌징, 세안제, 비누, 트리트먼트, 미용액 등이 있다. 본 발명의 화장료 조성물의 구체적인 제형으로서는 스킨로션, 스킨 소프너, 스킨토너, 아스트린젠트, 로션, 밀크로션, 모이스쳐 로션, 영양로션, 마사지크림, 영양크림, 모이스쳐 크림, 핸드크림, 에센스, 영양에센스, 팩, 비누, 샴푸, 클렌징폼, 클렌징로션, 클렌징크림, 바디로션, 바디클렌저, 유액, 립스틱, 메이크업 베이스, 파운데이션, 프레스파우더, 루스파우더, 아이섀도 등의 제형을 포함한다. Examples of products to which the cosmetic composition of the present invention can be added include cosmetics such as astringent lotion, softening longevity lotion, nutrition lotion, various creams, essences, packs, foundation and the like, cleansing, cleanser, soap, . Specific formulations of the cosmetic composition of the present invention include skin lotions, skin softeners, skin toners, astringents, lotions, milk lotions, moisturizing lotions, nutritional lotions, massage creams, nutritional creams, moisturizing creams, hand creams, essences, It includes formulations such as soap, shampoo, cleansing foam, cleansing lotion, cleansing cream, body lotion, body cleanser, latex, lipstick, makeup base, foundation, press powder, loose powder, eye shadow and the like.
본 발명의 바람직한 구현예에 따르면, 본 발명의 물오리나무 발효추출물의 함량은 조성물 총 중량에 대하여 0.00001-30 중량%이며, 바람직하게는 0.5-20 중량%이며, 보다 바람직하게는 1.0-10 중량%이다. 상기 물오리나무 발효추출물의 함량이 0.00001 중량% 미만이면 자외선 흡수 효과가 크게 감소되고, 30 중량%를 초과하는 경우에는 피부 자극을 초래할 수 있으며, 제형상의 문제점이 발생할 수 있다.According to a preferred embodiment of the present invention, the content of the fermented extract of Staphylococcus aureus according to the present invention is 0.00001-30% by weight, preferably 0.5-20% by weight, more preferably 1.0-10% by weight, to be. If the content of the fermented extract is less than 0.00001% by weight, the effect of absorbing ultraviolet light is greatly reduced. If the content is more than 30% by weight, skin irritation may be caused.
이하, 본 발명의 이해를 돕기 위하여 바람직한 실시예를 제시한다. 그러나 하기의 실시예는 본 발명을 보다 쉽게 이해하기 위하여 제공되는 것일 뿐, 하기 실시예에 의해 본 발명의 내용이 한정되는 것은 아니다.Hereinafter, preferred embodiments of the present invention will be described in order to facilitate understanding of the present invention. However, the following examples are provided only for the purpose of easier understanding of the present invention, and the present invention is not limited by the following examples.
[실시예][Example]
실시예 1. 실험 준비 및 방법Example 1. Experimental preparation and method
1-1. 물오리나무 발효추출물의 제조1-1. Preparation of Fermented Extracts of Watery Wood
물오리나무 발효추출물은 청계산 국사봉에서 수집한 물오리나무 줄기를 이용하여 제조하였다. 물오리나무 추출물 발효는 한국농업미생물자원센터(Korean Agricultural Culture Collection; KACC)에서 구입한 락토바실러스 플란타럼 아종 아젠토라텐시스(Lactobacillus plantarum subsp. argentoratensis)를 이용하였다. 상기 균주는 락토바실리 MRS 배지((6.4% Dextrose, 18.2% Proteose peptone No.3, 18.2% Beef extract, 9.1% Yeast extract, 9.1% Sodium acetate, 1.8% Polysorbate 80, 3.6% Amonium Citrate, 3.6% Dipotassium phosphate, 0.9% Magnesium sulfate, 0.5% Manganese sulfate)에 보관하고, 발효 시 액체배지에 접종하고 37℃에서 48시간 동안 배양한 후 실험에 이용하였다.The fermented extracts of Staphylococcus aureus were prepared by using the stem of Staphylococcus aureus collected from. Lactobacillus plantarum subsp. Argentoratensis was purchased from the Korean Agricultural Culture Collection (KACC). The strain was cultured on Lactobacillus MRS medium (6.4% Dextrose, 18.2% Proteose peptone No. 3, 18.2% Beef extract, 9.1% Yeast extract, 9.1% sodium acetate, 1.8
물오리나무 발효추출물을 제조하기 위해, 물오리나무 줄기 0.9 ㎏에 80% 프레타놀 A(prethanol A) 10 L를 첨가하고 실온에서 3회 반복 추출하였다. 이후 진공상태에서 추출물로부터 prethanol A를 제거하여 농축된 물오리나무 추출물을 얻었다. 다음으로 상기 방법으로 수득한 물오리나무 추출물 100 g에 9 L의 물을 첨가하고 121℃에서 20분 동안 살균시킨 후 상기 균주를 접종하고 30℃에서 혼합한 후 7일 동안 발효시켰다. 발효과정 후 건조시켜 물오리나무 발효추출물을 수득하였다. In order to prepare fermented extracts of P. vivax, 10 L of 80% predanol A (prethanol A) was added to 0.9 kg of the tree trunk and repeatedly extracted three times at room temperature. After that, prethanol A was removed from the extract in a vacuum state to obtain concentrated juvenile extract. Then, 9 L of water was added to 100 g of the extract of Streptococcus sp. Obtained by the above method, sterilized at 121 ° C for 20 minutes, inoculated with the strain, mixed at 30 ° C, and fermented for 7 days. After the fermentation process, the fermented extract was dried to obtain a fermented extract.
1-2. DPPH 자유 라디칼 소거활성 측정1-2. Measurement of DPPH free radical scavenging activity
항산화 활성을 검증하기 위한 방법으로써 1,1-디페닐-2-피크릴-히드라질(1,1-diphenyl-2-picryl-hydrazyl; DPPH) 자유 라디칼(Sigma, St. Louis, USA)의 소거활성을 측정하였다. 각 샘플 즉, 물오리나무 발효추출물(Fermented extract), 물오리나무 추출물(extract), 및 양성대조군인 아스코르브산(Ascorbic acid) 20 ㎕를 180 ㎕의 DPPH 용액(0.2mM, in absolute ethanol)에 첨가하고 잘 섞어 30분 동안 놓아둔 후 ELISA reader(TECAN, Salzburg, Austria)로 518 nm에서 흡광도를 측정하였다. (DPPH) free radical (Sigma, St. Louis, USA) as a method for verifying the antioxidant activity of 1,1-diphenyl-2-picryl- hydrazyl Activity was measured. 20 μl of each sample, ie, fermented extract, watery extract, and positive control group, ascorbic acid, was added to 180 μl of DPPH solution (0.2 mM, in absolute ethanol) After incubation for 30 minutes, the absorbance was measured at 518 nm with an ELISA reader (TECAN, Salzburg, Austria).
자유라디칼 소거활성은 하기에 나타낸 수식에 따라 흡광도 측정값을 대입하여 구하였다. The free radical scavenging activity was determined by substituting absorbance measurement values according to the following formula.
Inhibition rate (%) = 100-(sample O.D. / control O.D.) × 100. Inhibition rate (%) = 100- (sample O.D./control O.D.) x100.
1-3. NBT/superoxide 소거활성 측정 1-3. Measurement of NBT / superoxide scavenging activity
항산화 활성을 검증하기 위한 또 다른 방법으로써 니트로테트라졸리움 블루 클로라이드(Nitrotetrazolium Blue chloride; NBT) superoxide 소거활성을 측정하였다. 이를 위해, 샘플 20 ㎕, 1mM의 NBT 용액을 포함한 혼합액 160 ㎕, EDTA(0.05 mM)를 포함하는 50 mM 인산 완충액(phosphate buffer, pH 7.5)에 녹인 크잔틴 산화효소(xantine oxidase, 1.2 U/㎕)(Sigma, St. Louis, MO) 20 ㎕를 섞고 37℃에서 10분 동안 반응시킨 후 분광광도계(spectrophotometer)를 이용하여 590 nm에서 흡광도를 측정하였다. 양성대조군으로는 L-아스코르브산을 이용하였다. Nitrotetrazolium blue chloride (NBT) superoxide scavenging activity was measured as another method for verifying antioxidant activity. To this end, 20 μl of a sample, 160 μl of a mixed solution containing 1 mM of NBT solution, 1.2 μl / μl of xantine oxidase dissolved in 50 mM phosphate buffer (pH 7.5) containing EDTA (0.05 mM) ) (Sigma, St. Louis, Mo.) was reacted at 37 ° C for 10 minutes, and the absorbance was measured at 590 nm using a spectrophotometer. As a positive control, L-ascorbic acid was used.
NBT superoxide 소거활성은 하기에 나타낸 수식에 따라 흡광도 측정값을 대입하여 구하였다. The NBT superoxide scavenging activity was determined by substituting absorbance measurements according to the following formula.
NBT superoxide 소거활성 = 100-(sample O.D. - blank O.D.) / (control O.D. - blank O.D.) × 100. NBT superoxide scavenging activity = 100- (sample O.D. - blank O.D.) / (control O.D. - blank O.D.) 100.
1-4. NO 생성 억제활성 측정1-4. NO production inhibitory activity measurement
Raw 264.7 마우스 대식세포주를 96 well plate에 분주하고 5% CO2, 37℃ 조건하에서 3시간 동안 배양한 후 0.1 ㎍/㎖ LPS(Sigma, St. Louis, MO, USA)와 샘플 즉, 물오리나무 발효추출물 또는 물오리나무 추출물을 포함하는 배지에서 배양하였다. 배양 24시간 후 Griess 시약(0.1 % naphthylethylenediamine 및 1 % sulfanilamide in 5 % H3PO4 solution)(Sigma,St.Louis,MO,USA)을 상기 LPS와 샘플을 처리한 세포 배양액과 섞어 30분 동안 반응시킨 후 540 nm에서 흡광도를 측정하였다. 양성대조군으로는 샘플로 NO 합성효소(NO synthase; NOS) 억제제인 L-NMMA를 사용하였다. Raw 264.7 mouse macrophages were inoculated into 96-well plates and cultured for 3 hours at 37 ° C in 5% CO 2. After incubation with 0.1 μg / ml LPS (Sigma, St. Louis, Mo., USA) The extracts were cultivated in a medium containing the extracts of Streptomyces sp. After incubation for 24 hours, the cells were incubated with the Griess reagent (0.1% naphthylethylenediamine and 1% sulfanilamide in 5% H 3 PO 4 solution) (Sigma, St. Louis, Mo., USA) And the absorbance was measured at 540 nm. As a positive control, L-NMMA, a NO synthase (NOS) inhibitor, was used as a sample.
NO 생성 억제활성은 하기에 나타낸 수식에 따라 흡광도 측정값을 대입하여 구하였다.The NO production inhibitory activity was determined by substituting absorbance measurement values according to the following formula.
Inhibition rate (%) = 100-(sample O.D.- blank O.D.) / (control O.D. - blank O.D.) × 100.Inhibition rate (%) = 100- (sample O.D.- blank O.D.) / (control O.D. - blank O.D.) 100.
실시예 2. 물오리나무 발효추출물의 항산화 효과 검증Example 2: Antioxidative effects of fermented extracts of Staphylococcus aureus
2-1. DPPH 라디칼 소거활성 분석2-1. Analysis of DPPH radical scavenging activity
상기 실시예 1-1의 방법에 따라 제조한 물오리나무 발효추출물에 대한 항아토피 효과를 평가하고자 이와 관련된 항산화 능력을 검증하기 위해 실시예 1-2의 방법에 따라 DPPH 라디칼 소거활성을 측정하였으며, 대조군으로는 발효시키지 않은 물오리나무 추출물을 이용하여 동일한 조건에서 실험을 진행하였다. The DPPH radical scavenging activity was measured according to the method of Example 1-2 in order to evaluate the antioxidative ability of the fermented extract of P. vivax prepared according to the method of Example 1-1, The experiment was carried out under the same conditions using the extracts of non - fermented watery plants.
그 결과, 하기 표 1에 나타낸 바와 같이, 물오리나무 발효추출물(Fermented extract)의 경우 물오리나무 추출물(Extract)에 비하여 DPPH 라디칼 소거활성이 더 우수함을 확인하였다.As a result, it was confirmed that DPPH radical scavenging activity of Fermented extract was better than that of Extract of Strawberry, as shown in Table 1 below.
2-2. NBT/superoxide 소거활성 분석2-2. NBT / superoxide scavenging activity assay
상기 실시예 2-1의 결과에 더하여 물오리나무 발효추출물의 항산화효과를 검증하기 위해 실시예 1-3의 방법에 따라 NBT/superoxide 소거활성을 측정하였다. In addition to the results of Example 2-1, NBT / superoxide scavenging activity was measured according to the method of Examples 1-3 in order to verify the antioxidative effect of the fermented extract of Staphylococcus aureus.
그 결과, 하기 표 2에 나타낸 바와 같이, 물오리나무 발효추출물(Fermented extract)의 경우 물오리나무 추출물(Extract)에 비하여 NBT/superoxide 소거활성이 현저히 우수함을 확인하였다.As a result, as shown in the following Table 2, it was confirmed that the fermented extract of Fermented Extract was significantly superior in NBT / superoxide scavenging activity than Extract of Strawberry.
상기 결과들을 통해 물오리나무 발효추출물이 발효시키지 않은 물오리나무 추출물에 비하여 항산화 효과가 현저히 뛰어남을 알 수 있으며, 이는 발효 과정을 통해 물오리나무 추출물의 항산화능이 증진되었음을 의미한다. The above results indicate that the antioxidative effect is remarkably superior to that of the watery tree extract which is not fermented by the fermented extract of the watery wood. This means that the antioxidant ability of the watery extract is enhanced by the fermentation process.
실시예 3. 물오리나무 발효추출물의 항염증 효과 검증Example 3: Anti-inflammatory effects of fermented extracts of Staphylococcus aureus
상기 실시예를 통해 물오리나무 발효추출물이 항아토피 효능과 관련 있는 항산화 효과가 우수함을 확인하였는바, 이에 더하여 항염증 효과가 있는지 평가하고자 하였다. 이를 위해, 물오리나무 발효추출물 및 발효시키지 않은 물오리나무 추출물을 대상으로 상기 실시예 1-4의 방법에 따라 일산화질소(Nitric oxide; NO) 생성 억제능을 측정하여 비교하였다. Through the above examples, it was confirmed that the fermented extract of Staphylococcus aureus had excellent antioxidative effects related to the anti-atopic effect, and in addition, the anti-inflammatory effect was evaluated. For this purpose, inhibition of nitric oxide (NO) production was measured and compared according to the method of Example 1-4 with respect to the extracts of fermented watery fermented and fermented watery plants.
그 결과, 하기 표 3에 나타낸 바와 같이, 물오리나무 발효추출물(Fermented extract)이 발효시키지 않은 물오리나무 추출물(Extract)에 비하여 LPS에 의해 유도되는 NO 생성을 억제하는 효과가 더 뛰어남을 확인하였다.As a result, as shown in the following Table 3, it was confirmed that the effect of inhibiting the production of NO induced by LPS was superior to that of the extract of Strawberry without fermented fermented extract (Fermented extract).
실시예 4. 물오리나무 발효추출물의 Th1/Th2 사이토카인 생성 억제효과 검증Example 4: Inhibition of Th1 / Th2 cytokine production inhibition of fermented extract of Staphylococcus aureus
상기 실시예 결과들을 통해 물오리나무 발효추출물이 항산화 및 항염증 효과가 있음을 확인하였는바, 나아가 항아토피 효과가 있는지 검증하기 위하여, 먼저 세포수준에서 물오리나무 발효추출물이 Th1/Th2 사이토카인(cytokine) 생성에 미치는 영향을 알아보고자 하였다. 이를 위해, Raw 264.7 마우스 대식세포주에 LPS와 물오리나무 발효추출물 또는 발효시키지 않은 물오리나무 추출물을 처리한 후 ELISA를 실시하여 배양배지 내 인터페론-감마(IFN-γ) 및 인터루킨-4(IL-4)의 농도를 측정하였다.Thulium fermentation extracts showed antioxidative and antiinflammatory effects through the results of the above examples, and furthermore, in order to examine whether they have anti-atopic effect, And to investigate its effect on the production of. For this purpose, interferon-gamma (IFN-γ) and interleukin-4 (IL-4) in the culture medium were treated with LPS, fermented water extract of Strawberry tree, Was measured.
그 결과, 도 1에 나타낸 바와 같이, 물오리나무 발효추출물을 처리한 경우 발효시키지 않은 물오리나무 추출물에 비해 IFN-γ 및 IL-4의 농도가 더 낮은 것을 확인하였다. 상기 결과를 통해 물오리나무 발효추출물이 Th1/Th2 사이토카인 생성 억제효과 즉, 항알레르기 효과가 더 우수함을 알 수 있었다.As a result, as shown in Fig. 1, it was confirmed that the concentration of IFN-y and IL-4 was lower when the fermented extract of Staphylococcus aureus was treated than the fermented Staphylococcus aureus extract. From the above results, it was found that the fermented extract of Staphylococcus aureus had a better inhibitory effect on Th1 / Th2 cytokine production, that is, an antiallergic effect.
실시예 5. Example 5. in vivoin vivo 실험을 통한 물오리나무 발효추출물의 항아토피 효능 검증 Experimental Study of Antioxidant Effectiveness of Fermented Extracts from Woody Wood
상기 실시예 4를 통해 세포수준에서 물오리나무 발효추출물의 항알레르기 효과가 우수함을 확인하였으므로, 아토피피부염 마우스 모델을 이용한 in vivo 실험을 통해 직접적으로 물오리나무 발효추출물의 항아토피 효능을 검증해보고자 하였다. In Example 4, it was confirmed that the antiallergic effect of the fermented extract of Staphylococcus aureus at the cell level was excellent. Therefore, in vivo experiment using the atopic dermatitis mouse model was conducted to directly examine the anti-atopic effect of the fermented extract of Staphylococcus aureus.
보다 구체적으로, 9주령의 Balb/c 마우스 귀에 1% DNCB(2,4-dintrochlorobenzene)를 하루에 한 번 총 1주일 동안 20 ㎕씩 도포하여 아토피피부염을 유발시켰다. 이후 물오리나무 발효추출물을 100 mg/kg의 양으로 2주일 동안 주 4회 경구 투여한 후 육안으로 아토피피부염 개선 정도를 관찰하고, 매일 체중을 측정하여 비교하였다. 이때, 실험군은 아토피피부염을 유발시키지 않은 정상대조군(B), 발효시키지 않은 물오리나무 추출물을 투여한 군(Ex), 물오리나무 발효추출물을 투여한 군(발효), 및 아토피피부염을 유발시키고 아무것도 처리하지 않은 군(DNCB)로 분류하여 실험을 진행하였다. More specifically, 20 μl of 1% DNCB (2,4-dintrochlorobenzene) was applied once a day to Balb / c mouse ears at 9 weeks of age to induce atopic dermatitis. The extracts were then administered orally four times a week for two weeks at a dose of 100 mg / kg, and the degree of improvement of atopic dermatitis was observed with the naked eye, and the body weight was measured and compared daily. At this time, the experimental group was treated with a normal control group (B) that did not induce atopic dermatitis, a group administered with an unfermented juvenile extract (Ex), a group administered with a fermented extract of aquatic tree (fermentation), and atopic dermatitis (DNCB), respectively.
그 결과, 도 2 및 도 3a에 나타낸 바와 같이, 육안으로 아토피피부염 정도를 관찰하였을 때 정상대조군을 제외한 실험군에서는 모두 시간이 지남에 따라 귀가 붉어지고 두께가 증가하는 것을 관찰 할 수 있었다. 그러나 물오리나무 발효추출물을 투여한 군에서는 실험 8일째부터 귀의 발적(redness) 및 귀 두께가 DNCB군에 비하여 점차 개선되는 것을 뚜렷하게 관찰하였다. 반면에 도 3b와 같이 체중은 실험기간 동안 큰 변화가 없는 것을 확인하였다.As a result, when the degree of atopic dermatitis was visually observed, as shown in Fig. 2 and Fig. 3A, all of the experimental groups except for the normal control group showed irregular ear thickness and increased thickness over time. However, in the group treated with the fermented extract of P. falciparum, the redness and ear thickness gradually improved from the 8th day of experiment to the DNCB group. On the other hand, as shown in FIG. 3B, the body weight was not significantly changed during the experiment.
나아가, 실험 종료 후 각 그룹의 상기 마우스들을 희생시키고 혈액을 채취하여 혈청 내 IgE의 농도를 ELISA를 통해 측정하였다. 그 결과, 도 4에 나타낸 바와 같이, 아토피피부염을 유발시키고 아무것도 투여하지 않은 군(D)의 경우 정상대조군에 비하여 혈청 내 IgE의 농도가 현저히 증가한 반면, 물오리나무 추출물을 투여한 군(Ex)의 경우 유의하게 IgE 농도가 감소하였으며, 물오리나무 발효추출물을 투여한 군(발효)에서는 IgE 농도가 더욱 감소되어 있는 것을 확인하였다. 상기 결과를 통해 물오리나무 발효추출물이 발효시키지 않은 물오리나무 추출물에 비하여 더욱 효과적으로 IgE 생성을 억제하는 것을 알 수 있었다.After completion of the experiment, the mice in each group were sacrificed and blood was collected, and the concentration of IgE in the serum was measured by ELISA. As a result, as shown in FIG. 4, the concentration of IgE in the serum was significantly increased in the group (D) in which atopic dermatitis was induced and nothing was administered, while the concentration of IgE in the group (Ex) The IgE concentration was significantly decreased and the IgE concentration was further decreased in the group treated with the fermented extract of St. From the above results, it can be seen that the fermented extract of P. thunbergii inhibits the production of IgE more effectively than the extract of P. falciparum not fermented.
이에 더하여, 상기 실험종료 후 희생시킨 각 그룹의 마우스들의 비장을 적출하여 비장에 있는 면역세포들로부터 mRNA를 추출한 후 real-time PCR을 수행하여 IFN-gamma 및 IL-4의 양을 측정하였다. 그 결과, 도 5에 나타낸 바와 같이, 상기 도 4의 결과와 마찬가지로 아토피피부염을 유발시키고 아무것도 투여하지 않은 군(D)의 경우 상기 사이토카인의 함량이 현저히 증가한 반면, 물오리나무 발효추출물을 투여한 군(발효)의 경우 발효시키지 않은 물오리나무 추출물 투여군(E)보다 상기 사이토카인의 함량이 더욱 감소되어 있는 것을 확인하였다. 상기 결과를 통해 in vivo 실험에서도 in vitro 실험결과와 마찬가지로 물오리나무 발효추출물이 우수한 Th1/Th2 사이토카인 생성 억제 효과를 나타내는 것을 알 수 있었다. In addition, the spleen of each group of mice sacrificed after completion of the experiment was extracted to extract mRNA from the spleen immunized cells, and real-time PCR was performed to measure the amounts of IFN-gamma and IL-4. As a result, as shown in Fig. 5, in the case of the group (D) in which atopic dermatitis was induced and nothing was administered, the content of the cytokine was remarkably increased, It was confirmed that the content of the above cytokine was further reduced in the case of the fermentation (fermentation) than in the group of the fermentation without extract (E). As a result of in vivo experiments, it was found that the fermented extracts of P. thunbergii showed an excellent inhibitory effect on Th1 / Th2 cytokine production similarly to the in vitro test results.
상기 in vitro 및 in vivo 실험결과를 종합하여 물오리나무 발효추출물 및 물오리나무 추출물의 효과를 하기 표 4에 정리하여 나타내었다. 하기 표에서 볼 수 있듯이 물오리나무 발효추출물이 발효시키지 않은 물오리나무 추출물에 비하여 항산화, 항염 및 아토피피부염 개선 효과가 모두 뛰어남을 알 수 있다.The results of the in vitro and in vivo experiments are summarized in Table 4 below. As can be seen from the table below, the antioxidant, antiinflammatory and atopic dermatitis improvement effects are superior to those of the watery wood extracts which have not been fermented by the fermented extract.
상기 진술한 본 발명의 설명은 예시를 위한 것이며, 본 발명이 속하는 기술분야의 통상의 지식을 가진 자는 본 발명의 기술적 사상이나 필수적인 특징을 변경하지 않고서 다른 구체적인 형태로 쉽게 변형이 가능하다는 것을 이해할 수 있을 것이다. 그러므로 이상에서 기술한 실시예들은 모든 면에서 예시적인 것이며 한정적이 아닌 것으로 이해해야만 한다. It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the spirit or scope of the invention. There will be. It is therefore to be understood that the above-described embodiments are illustrative in all aspects and not restrictive.
Claims (10)
Th1 사이토카인의 생성을 억제하는 것을 특징으로 하는, 아토피피부염 예방 또는 치료용 약학적 조성물.
(Alnus sibirica Fitch. Ex Turcz.) Fermented extract as an active ingredient,
A composition for preventing or treating atopic dermatitis, which inhibits the production of Th1 cytokine.
상기 발효추출물은 물오리나무 추출물에 미생물을 접종하고 5일 내지 9일 동안 발효시킴으로써 수득된 것을 특징으로 하는, 조성물.
The method according to claim 1,
Characterized in that the fermentation extract is obtained by inoculating the microorganism to the dwarf extract and fermenting for 5 to 9 days.
상기 미생물은 락토바실러스 플란타럼(Lactobacillus plantarum)인 것을 특징으로 하는, 조성물.
3. The method of claim 2,
Wherein the microorganism is Lactobacillus plantarum .
상기 물오리나무 추출물은 물, C1내지 C4의 저급알코올, n-헥산, 에틸아세테이트, 아세톤, 부틸아세테이트, 1,3-부틸렌 글리콜, 메틸렌클로라이드, 및 이들의 혼합용매로 구성된 군으로부터 선택된 용매로 추출된 것을 특징으로 하는, 조성물.
3. The method of claim 2,
Wherein the watery extract is selected from the group consisting of water, C 1 to C 4 lower alcohols, n-hexane, ethyl acetate, acetone, butyl acetate, 1,3-butylene glycol, methylene chloride, . ≪ / RTI >
상기 조성물은 항산화능을 갖는 것을 특징으로 하는, 조성물.
The method according to claim 1,
Wherein the composition has an antioxidant ability.
상기 조성물은 일산화질소(Nitric oxide) 생성 억제능을 갖는 것을 특징으로 하는, 조성물.
The method according to claim 1,
Wherein the composition has the ability to inhibit nitric oxide production.
상기 조성물은 Th2 사이토카인의 생성을 억제하는 것을 특징으로 하는, 조성물.
The method according to claim 1,
Wherein said composition inhibits the production of Th2 cytokines.
상기 조성물은 IgE 생성을 억제하는 것을 특징으로 하는, 조성물.
The method according to claim 1,
Wherein said composition inhibits IgE production.
Th1 사이토카인의 생성을 억제하는 것을 특징으로 하는, 아토피피부염 개선용 건강기능성 식품 조성물.
(Alnus sibirica Fitch. Ex Turcz.) Fermented extract as an active ingredient,
Lt; RTI ID = 0.0 > Th1 < / RTI > cytokine.
Th1 사이토카인의 생성을 억제하는 것을 특징으로 하는, 아토피피부염 개선용 화장료 조성물.(Alnus sibirica Fitch. Ex Turcz.) Fermented extract as an active ingredient,
A composition for improving atopic dermatitis characterized by inhibiting the production of Th1 cytokine.
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KR20190046096A (en) | 2017-10-25 | 2019-05-07 | (주)예스킨 | Composition for treating atopic dermatitis |
KR20190123167A (en) | 2018-04-23 | 2019-10-31 | 경북대학교 산학협력단 | Composition comprising Platyphyllone for Preventing or Treating Atopic Dermatitis |
KR102217551B1 (en) | 2019-08-14 | 2021-02-19 | 광주여자대학교 산학협력단 | Method of Preparing Extract Containing High Content of Oregonin From Plant of Alnus spp. |
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KR20190046096A (en) | 2017-10-25 | 2019-05-07 | (주)예스킨 | Composition for treating atopic dermatitis |
KR20190123167A (en) | 2018-04-23 | 2019-10-31 | 경북대학교 산학협력단 | Composition comprising Platyphyllone for Preventing or Treating Atopic Dermatitis |
KR102217551B1 (en) | 2019-08-14 | 2021-02-19 | 광주여자대학교 산학협력단 | Method of Preparing Extract Containing High Content of Oregonin From Plant of Alnus spp. |
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