KR102182554B1 - A composition for preventing or improving dermatitis comprising caulophyllogenin and use thereof - Google Patents
A composition for preventing or improving dermatitis comprising caulophyllogenin and use thereof Download PDFInfo
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- KR102182554B1 KR102182554B1 KR1020180133143A KR20180133143A KR102182554B1 KR 102182554 B1 KR102182554 B1 KR 102182554B1 KR 1020180133143 A KR1020180133143 A KR 1020180133143A KR 20180133143 A KR20180133143 A KR 20180133143A KR 102182554 B1 KR102182554 B1 KR 102182554B1
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- KR
- South Korea
- Prior art keywords
- composition
- cowlophyllogenin
- dermatitis
- cells
- skin
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- A61K31/19—Carboxylic acids, e.g. valproic acid
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- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
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- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
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- A—HUMAN NECESSITIES
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Abstract
카울로필로게닌을 포함하는 피부염을 예방 또는 개선하기 위한 조성물 및 그의 용도를 제공한다.It provides a composition for preventing or ameliorating dermatitis comprising cowlophyllogenin and a use thereof.
Description
카울로필로게닌을 포함하는 피부염을 예방 또는 개선하기 위한 조성물 및 그의 용도에 관한 것이다.It relates to a composition for preventing or ameliorating dermatitis comprising cowlophyllogenin and a use thereof.
아토피 피부염(Atopic dermatitis)은 가려움증을 동반하는 만성 재발성 피부질환이며, 천식이나 알레르기 비염을 동반하는 경우가 많다. 임상증상은 유아의 경우 안면과 사지 신측부에 습진 양상, 소양증, 피부건조증, 어린선, 피부감염의 증가와 모공각화증 등을 보인다. 환경적인 영향을 받아서 다인성으로 유전되며 혈청 immunoglobulin E (IgE)가 과도하게 생성되는 것으로 알려져 있다. Atopic dermatitis is a chronic recurrent skin disease accompanied by itching, and is often accompanied by asthma or allergic rhinitis. Clinical symptoms include eczema, pruritus, dry skin, young glands, increased skin infections, and keratosis of the skin in infants on the renal side of the face and limbs. It is known to be multifactorial due to environmental influences and to produce excessive serum immunoglobulin E (IgE).
아토피 피부염 병변 내 림프구는 CD4:CD8의 비가 7:1 정도로 증가되어 있고 interleukin-4(IL-4)에 강한 반응성을 보여 T helper2(Th2) 세포에 의한 면역반응이 우세하다. 조직학적으로 과각화증, 이상각화증, 극세포증과 세포간 부종 및 소혈관의 확장 현상과 진피 상부에 호산구, 임파구, 조직구 등의 혈관주위 세포 침윤이 나타난다. 최근에는 면역학적 이상 외에 피부장벽기능 손상이 중요한 요인 중의 하나로 생각되고 있다. 장벽기능의 손상은 각질층 지질 중 세라마이드의 감소에서 기인하며 피부의 수분유지기능과 피부장벽기능이 저하되어 알레르겐이나 자극성 물질의 피부 투과성을 높여 피부 염증반응을 유발 또는 악화시키며, 피부건조, 소양증 등이 발생하고, 역으로 면역학적 이상에 의해 발생한 피부염은 피부장벽기능을 손상시킬 수 있어 이와 같은 악순환의 고리를 차단하는 것이 치료의 중요한 과제 중 하나가 된다. Lymphocytes in atopic dermatitis lesions have an increased CD4:CD8 ratio of 7:1 and a strong reactivity to interleukin-4 (IL-4), leading to an immune response by T helper2 (Th2) cells. Histologically, hyperkeratosis, dyskeratosis, hypercytosis, intercellular edema and small blood vessel dilation, and perivascular cell infiltration such as eosinophils, lymphocytes, and histocytes appear in the upper dermis. Recently, in addition to immunological abnormalities, damage to the skin barrier function is considered as one of the important factors. The impairment of the barrier function is caused by the decrease of ceramide in the stratum corneum, and the skin's moisture retention function and the skin barrier function are deteriorated, increasing the skin permeability of allergens or irritants, causing or worsening the skin inflammatory reaction, skin dryness, itching, etc. It occurs, and conversely, dermatitis caused by immunological abnormalities can impair skin barrier function, and thus blocking such a vicious cycle becomes one of the important tasks of treatment.
아토피 질환은 아토피에 의해 임상적 증상으로 발현되는 경우를 의미하며, 여기에는 아토피 피부염, 천식, 알레르기 비염, 알레르기 결막염 등의 질환들이 모두 포함된다. '아토피 피부염'이라는 용어가 길어서 짧게 '아토피'라고 하지만 두 용어의 정의는 의학적으로 분명히 다르다. 아토피 질환은 상호작용하면서 동시에 또는 시간차를 두고 발현되는 경향을 보이기 때문에 '알레르기 행진'이라는 특성으로 설명하기도 한다. 알레르기 행진은 어린 영아가 성장하면서 아토피 피부염, 식품 알레르기, 천식 및 알레르기 비염의 순서로 알레르기 질환을 앓게 되는 현상을 말하며, 알레르기 유발원에 대한 감작의 진행과 관련이 있다. 국내 연구에 의하면, 유전적 요인에 의한 아토피 피부염 발생률은 부모 모두 아토피 질환이 있는 경우 41.7%, 부모 모두 알레르기 병력이 없을 경우 14.7%로 나타나 아토피 피부염 발생과 부모의 알레르기 질환력 사이의 연관성을 보여주고 있다. Atopic disease refers to a case that is expressed as a clinical symptom by atopy, and includes all diseases such as atopic dermatitis, asthma, allergic rhinitis, and allergic conjunctivitis. The term'atopic dermatitis' is long and is called'atopic' for short, but the definitions of the two terms are clearly different medically. Atopic disease is sometimes described as a characteristic of'allergic streak' because it tends to develop simultaneously or at a time difference while interacting. Allergic streak refers to a phenomenon in which young infants develop allergic diseases in the order of atopic dermatitis, food allergy, asthma and allergic rhinitis, and is related to the progression of sensitization to allergens. According to a domestic study, the incidence of atopic dermatitis caused by genetic factors was 41.7% when both parents had atopic disease and 14.7% when both parents had no history of allergies, showing a correlation between the occurrence of atopic dermatitis and the history of allergic diseases of the parents. have.
아토피 피부염은 알레르기 행진이 일어나는 첫 번째 질환으로 인식되고 있고, 아토피성 질환이 발생할 것을 예측할 수 있는 지표로 이용되고 있다. 아토피 피부염 시기에 면역반응을 조절하지 않을 경우 알레르기 행진이 가속화되는 것으로 추정되므로 천식, 비염 등을 예방하기 위해서라도 아토피 피부염 조절이 필요하다. 아토피 피부염의 병인은 크게 피부장벽과 연관된 병인(outside-in model)과 비정상적인 면역반응과 연관된 병인(inside-out model)으로 나누고 있으며, 유전과 환경적인 요인에 대한 통합적인 고려가 필요하다. Atopic dermatitis is recognized as the first disease in which an allergic streak occurs, and is used as an index to predict the occurrence of atopic disease. If the immune response is not controlled during atopic dermatitis, it is estimated that the allergic march will accelerate. Therefore, it is necessary to control atopic dermatitis to prevent asthma and rhinitis. The etiology of atopic dermatitis is largely divided into the etiology associated with the skin barrier (outside-in model) and the etiology associated with an abnormal immune response (inside-out model), and an integrated consideration of genetic and environmental factors is required.
현재 사용 중인 아토피 질환 치료제는 알레르기 반응의 최종산물인 히스타민 분비를 억제하거나 알레르기 증상의 하나인 염증반응을 억제하는 효과를 가진 스테로이드제 및 항히스타민제에 치중되며, 일부 면역조절제와 광선치료법이 사용되고 있다. 기존 치료제의 경우 알레르기 증상 완화에 효과가 있으나 근본적인 치료방법이 아니며 장기적인 사용시 약물의 효능 감소 및 다양한 부작용 발생의 위험이 있다. 스테로이드제의 부작용은 비만, 당뇨, 고혈압, 우울증 등이 있으며, 항히스타민제의 부작용은 우울증, 집중력 장애, 무기력증, 졸림, 성기능 장애 등이 있으며, 면역억제제의 부작용은 국소자극, 고혈압, 신장독성 등이 있다. 이러한 점에서 스테로이드제, 항히스타민제, 면역억제제를 대체할 수 있는 혹은 기존 치료제의 사용을 낮출 수 있어 장기간 사용시 부작용이 적은 신개념 치료 소재의 개발 필요성이 대두되고 있다. The currently used atopic disease treatments are focused on steroids and antihistamines that have the effect of suppressing the secretion of histamine, which is the final product of allergic reactions, or suppressing the inflammatory reaction, which is one of the symptoms of allergies, and some immunomodulators and phototherapy are used. Existing treatments are effective in relieving allergy symptoms, but they are not fundamental treatment methods, and there is a risk of reducing the efficacy of the drug and causing various side effects when used for a long time. Side effects of steroids include obesity, diabetes, high blood pressure, and depression. Side effects of antihistamines include depression, concentration disorder, lethargy, sleepiness, and sexual dysfunction. Side effects of immunosuppressants include local irritation, high blood pressure, and kidney toxicity. have. In this regard, there is a need to develop a new concept therapeutic material that can replace steroids, antihistamines, and immunosuppressants or reduce the use of existing treatments, which have less side effects when used for a long time.
아토피 피부염의 병인 중 유전적인 요소가 매우 중요한 역할을 하는데, T세포 과다 활성화를 유발하는 인터루킨-4(IL-4), 인터루킨-5(IL-5), 및 인터루킨-13(IL-13)은 Th2 헬퍼 세포에 의해 분비되며 면역글로불린E(IgE)의 합성을 조절하여 아토피 피부염의 시작에 매우 중요한 역할을 하는 것으로 알려져 있다.Among the etiologies of atopic dermatitis, genetic factors play a very important role. Interleukin-4 (IL-4), interleukin-5 (IL-5), and interleukin-13 (IL-13), which induce excessive T cell activation, It is secreted by Th2 helper cells and is known to play a very important role in the onset of atopic dermatitis by regulating the synthesis of immunoglobulin E (IgE).
미국특허 공개 2007/0014739는 카울로필로게닌(Caulophyllogenin)이 항-미생물 활성을 갖는 것을 개시하고 있다.US Patent Publication 2007/0014739 discloses that Caulophyllogenin has anti-microbial activity.
상기한 종래 기술에도 불구하고, 피부염을 예방 또는 개선하는데 효과적인 물질에 대한 요구가 있다.In spite of the above-described prior art, there is a need for a material effective in preventing or improving dermatitis.
일 양상은 카울로필로게닌을 유효성분으로 포함하는 피부염을 예방 또는 치료하기 위한 약학적 조성물을 제공한다.One aspect provides a pharmaceutical composition for preventing or treating dermatitis comprising cowlophyllogenin as an active ingredient.
일 양상은 카울로필로게닌을 유효성분으로 포함하는 피부염을 예방 또는 개선하기 위한 식품학적 조성물을 제공한다.One aspect provides a food composition for preventing or improving dermatitis comprising cowlophyllogenin as an active ingredient.
일 양상은 카울로필로게닌을 유효성분으로 포함하는 피부염을 예방 또는 개선하거나 피부 수분을 유지하는데 사용하기 위한 화장품학적 조성물을 제공한다.One aspect provides a cosmetic composition for use in preventing or improving dermatitis or maintaining skin moisture, including kaolophyloggenin as an active ingredient.
또 다른 양상은 상기 조성물을 피부염을 예방 또는 치료시키기에 유효한 양으로 개체에게 투여하는 단계를 포함하는 개체의 피부염을 예방 또는 치료하는 방법을 제공한다.Another aspect provides a method of preventing or treating dermatitis in a subject comprising administering to the subject the composition in an amount effective to prevent or treat dermatitis.
또 다른 양상은 상기한 조성물을 피부염을 예방 또는 개선하거나, 피부 수분을 유지하는데 유효한 양으로 개체의 피부에 적용하는 단계를 포함하는 개체의 패부염을 예방 또는 치료하거나 피부 수분을 유지기 위하여 화장하는 방법을 제공한다.Another aspect is to prevent or improve dermatitis, or to prevent or treat rustitis of an individual, comprising applying the composition to the skin of the individual in an amount effective to maintain skin moisture, or applying makeup to maintain skin moisture. Provides a way.
제1 양상은 카울로필로게닌 또는 그의 약학적으로 허용가능한 염을 유효성분으로 포함하는 피부염을 예방 또는 치료하는데 사용하기 위한 약학적 조성물을 제공한다. A first aspect provides a pharmaceutical composition for use in preventing or treating dermatitis comprising cowlophyllogenin or a pharmaceutically acceptable salt thereof as an active ingredient.
제2 양상은 카울로필로게닌 또는 그의 식품학적으로 허용가능한 염을 유효성분으로 포함하는 피부염을 예방 또는 개선하는데 사용하기 위한 식품 조성물을 제공한다.A second aspect provides a food composition for use in preventing or improving dermatitis comprising cowlophyllogenin or a food pharmaceutically acceptable salt thereof as an active ingredient.
제3 양상은 카울로필로게닌 또는 그의 화장품학적으로 허용가능한 염을 유효성분으로 포함하는 화장료 조성물을 제공한다. A third aspect provides a cosmetic composition comprising cowlophyllogenin or a cosmetically acceptable salt thereof as an active ingredient.
제1-3 양상에 있어서, 상기 카울로필로게닌은 Th0 세포의 Th2 헬퍼 세포로의 분화를 억제시켜서 피부염을 예방, 개선 또는 치료하는 것일 수 있다.In aspect 1-3, the kaolophyllogenin may prevent, ameliorate, or treat dermatitis by inhibiting differentiation of Th0 cells into Th2 helper cells.
상기 카울로필로게닌은 면역세포의 과활성화를 억제시켜 면역기능을 안정화 또는 회복시키거나, 인터루킨-4(Interleukin-4, IL-4)의 발현을 저해함으로써 피부염을 예방, 개선 또는 치료하는 것일 수 있다.The cowlophyllogenin can be used to stabilize or restore immune function by inhibiting overactivation of immune cells, or to prevent, improve or treat dermatitis by inhibiting the expression of interleukin-4 (IL-4). have.
상기 피부염은 피부 소양증, 지루성 피부염, 접촉성 피부염, 아토피성 피부염, 당뇨병성 피부염, 모낭염, 여드름, 알레르기성 피부염 및 신경성 피부염으로 이루어진 군으로부터 선택된 것일 수 있다.The dermatitis may be selected from the group consisting of skin pruritus, seborrheic dermatitis, contact dermatitis, atopic dermatitis, diabetic dermatitis, folliculitis, acne, allergic dermatitis, and neurodermatitis.
따라서 상기 조성물 중에 상기 카울로필로게닌 또는 그의 염은 세포에서 IL-4의 발현을 억제시키거나, 피부염을 개선시키거나, 특히 아토피성 피부염을 개선시키기에 유효한 양으로 포함될 수 있다. 상기 유효한 양은 당업자가 선택되는 세포 또는 개체에 따라 적절하게 선택할 수 있다. 상기 유효한 양은 상기 조성물 당 0.1 mg 내지 1,000 mg, 예를 들면, 0.1 mg 내지 500 mg, 0.1 mg 내지 100 mg, 0.1 mg 내지 50 mg, 0.1 mg 내지 25 mg, 1 mg 내지 1,000 mg, 1 mg 내지 500 mg, 1 mg 내지 100 mg, 1 mg 내지 50 mg, 1 mg 내지 25 mg, 5mg 내지 1,000 mg, 5 mg 내지 500 mg, 5 mg 내지 100 mg, 5 mg 내지 50 mg, 5 mg 내지 25 mg, 10mg 내지 1,000 mg, 10 mg 내지 500 mg, 10 mg 내지 100 mg, 10 mg 내지 50 mg, 또는 10 mg 내지 25 mg일 수 있다. Accordingly, the cowlophyllogenin or a salt thereof in the composition may be included in an amount effective to inhibit the expression of IL-4 in cells, improve dermatitis, or particularly improve atopic dermatitis. The effective amount can be appropriately selected by a person skilled in the art depending on the cells or individuals selected. The effective amount is 0.1 mg to 1,000 mg per composition, for example, 0.1 mg to 500 mg, 0.1 mg to 100 mg, 0.1 mg to 50 mg, 0.1 mg to 25 mg, 1 mg to 1,000 mg, 1 mg to 500 mg, 1 mg to 100 mg, 1 mg to 50 mg, 1 mg to 25 mg, 5 mg to 1,000 mg, 5 mg to 500 mg, 5 mg to 100 mg, 5 mg to 50 mg, 5 mg to 25 mg, 10 mg To 1,000 mg, 10 mg to 500 mg, 10 mg to 100 mg, 10 mg to 50 mg, or 10 mg to 25 mg.
상기 조성물은 인 비트로 또는 개체 중의 세포에서 Th2 세포로의 분화를 억제시키거나, IL-4의 발현을 억제시키기 위한 것일 수 있다. 개체 중의 세포는 예를 들면 IL-4 발현 증가에 의하여 피부염이 진행되고 있는 부위, 또는 IL-4의 침적에 의하여 염증이 과도하게 진행되어 외부적으로 피부염 증상을 보이는 부위에 위치하는 것일 수 있다. 상기 피부염은 아토피성 피부염일 수 있다. 또한, 상기 피부염은 아토피성 피부염 환자에서 피부장벽 기능 약화로 인한 피부 감염증일 수 있다.The composition may be for inhibiting the differentiation of cells in vitro or from cells in an individual to Th2 cells, or for inhibiting the expression of IL-4. The cells in the individual may be located at a site where dermatitis is progressing due to, for example, an increase in IL-4 expression, or a site where inflammation is excessively progressed due to deposition of IL-4 and externally exhibits dermatitis symptoms. The dermatitis may be atopic dermatitis. In addition, the dermatitis may be a skin infection caused by a weakened skin barrier function in atopic dermatitis patients.
상기 조성물은 화장품학적으로, 약학적으로, 또는 식품적으로 허용가능한 부형제 또는 담체를 더 포함하는 것일 수 있다. 상기 조성물은 약학, 식품 또는 화장료 조성물일 수 있다.The composition may further include a cosmetically, pharmaceutically, or food-acceptable excipient or carrier. The composition may be a pharmaceutical, food or cosmetic composition.
제2 양상에 있어서, 상기 식품 조성물은 카울로필로게닌을 단독 또는 다른 식품 또는 식품 성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 유효 성분의 혼합 양은 사용 목적 예를 들면, 예방, 건강 또는 치료적 처치에 따라 적합하게 결정될 수 있다. 일반적으로, 식품 또는 음료의 제조시에 본 발명의 약학적 조성물은 원료에 대하여 15 중량부 이하, 바람직하게는 10 중량부 이하의 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.In the second aspect, the food composition may be used alone or in combination with other foods or food ingredients, and may be appropriately used according to a conventional method. The mixing amount of the active ingredient may be appropriately determined according to the purpose of use, for example, prophylactic, health or therapeutic treatment. In general, when preparing food or beverage, the pharmaceutical composition of the present invention may be added in an amount of 15 parts by weight or less, preferably 10 parts by weight or less based on the raw material. However, in the case of long-term intake for the purpose of health and hygiene or for the purpose of health control, the amount may be less than 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.
제2 양상에 있어서, 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.In the second aspect, there is no particular limitation on the type of food. Examples of foods to which the above substances can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, various soups, beverages, tea, drinks, Alcoholic beverages and vitamin complexes, and all foods in the usual sense are included.
상기 음료수는 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물은 포도당, 과당과 같은 모노사카리드, 말토스, 슈크로스와 같은 디사카리드, 및 덱스트린, 사이클로덱스트린과 같은 폴리사카리드, 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 감미제로서는 타우마틴, 스테비아 추출물과 같은 천연 감미제나, 사카린, 아스파르탐과 같은 합성 감미제 등을 사용할 수 있다.The beverage may contain various flavoring agents or natural carbohydrates as an additional component, like ordinary beverages. The natural carbohydrates described above are monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, and polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol and erythritol. As the sweetener, natural sweeteners such as taumatin and stevia extract, and synthetic sweeteners such as saccharin and aspartame can be used.
상기 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. 상기 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 is also used in nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonated beverages Carbonation agent, or a combination thereof. The food composition may also contain natural fruit juice, fruit juice beverage, pulp for the production of vegetable beverages, or a combination thereof. These additives may be selected from 0.01 to 0.1 parts by weight per 100 parts by weight of the composition.
제1-3 양상에 있어서, 상기 조성물은 경구 또는 비경구 투여 제형으로 제형화될 수 있다. 경구 투여 제형은 과립제, 산제, 액제, 정제, 캅셀제, 건조시럽제, 또는 그 조합일 수 있다. 비경구 투여 제형은 주사제, 또는 피부 외용제일 수 있다. 피부 외용제는 크림, 겔, 연고, 피부 유화제, 피부 현탁액, 경피전달성 패치, 약물 함유 붕대, 로션, 스프레이, 또는 그 조합일 수 있다.In the 1-3 aspect, the composition may be formulated as an oral or parenteral dosage form. The oral dosage form may be a granule, powder, liquid, tablet, capsule, dry syrup, or a combination thereof. The parenteral dosage form may be an injection or an external preparation for the skin. The external preparation for skin may be a cream, gel, ointment, skin emulsifier, skin suspension, transdermal patch, drug-containing bandage, lotion, spray, or a combination thereof.
상기 피부 외용제는 통상 화장품이나 의약품 등의 피부 외용제에 사용되는 성분, 예컨대 수성성분, 유성성분, 분말성분, 알코올류, 보습제, 증점제, 자외선흡수제, 미백제, 방부제, 산화방지제, 계면활성제, 향료, 색제, 각종 피부 영양제 등을 필요에 따라서 적절하게 배합할 수 있다.The external preparations for skin are ingredients commonly used in external preparations for skin such as cosmetics or pharmaceuticals, such as aqueous ingredients, oily ingredients, powder ingredients, alcohols, moisturizers, thickeners, ultraviolet absorbers, whitening agents, preservatives, antioxidants, surfactants, fragrances, colorants. , Various skin nutrients, etc. can be appropriately blended as needed.
상기 피부 외용제는, 에데트산이나트륨, 에데트산삼나트륨, 시트르산나트륨, 폴리인산나트륨, 메타인산나트륨, 글루콘산 등의 금속봉쇄제, 카페인, 탄닌, 벨라파밀, 감초추출물, 글라블리딘, 칼린의 과실의 열수추출물, 각종생약, 아세트산토코페롤, 글리틸리틴산, 트라넥삼산 및 그 유도체 또는 그 염등의 약제, 비타민 C, 아스코르브산인산마그네슘, 아스코르브산글루코시드, 알부틴, 코지산, 글루코스, 프룩토스, 트레할로스 등의 당류 등도 적절하게 배합할 수 있다.The external preparations for skin include metal sequestering agents such as disodium edetate, trisodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, and gluconic acid, caffeine, tannin, bellapamil, licorice extract, glavidine, and caline. Hot water extract of fruit, various herbal medicines, drugs such as tocopherol acetate, glytilithic acid, tranexamic acid and derivatives or salts thereof, vitamin C, ascorbic acid magnesium phosphate, ascorbic acid glucoside, arbutin, kojic acid, glucose, fructose, Sugars such as trehalose can also be appropriately blended.
제1 양상에 있어서, 상기 조성물은 약제학적으로 허용가능한 희석제 또는 담체를 포함할 수 있다. 상기 담체는 부형제, 붕해제, 결합제, 활택제, 또는 그 조합일 수 있다. 상기 부형제는 미결정 셀룰로오즈, 유당, 저치환도 히드록시셀룰로오즈, 또는 그 조합일 수 있다. 상기 붕해제는 전분글리콜산 나트륨, 무수인산일수소 칼슘, 또는 그 조합일 수 있다. 상기 결합제는 폴리비닐피롤리돈, 저치환도 히드록시프로필셀룰로오즈, 히드록시프로필셀룰로오즈, 또는 그 조합일 수 있다. 상기 활택제는 스테아린산 마그네슘, 이산화규소, 탈크, 또는 그 조합일 수 있다.In the first aspect, the composition may include a pharmaceutically acceptable diluent or carrier. The carrier may be an excipient, a disintegrant, a binder, a lubricant, or a combination thereof. The excipient may be microcrystalline cellulose, lactose, low-substituted hydroxycellulose, or a combination thereof. The disintegrant may be sodium starch glycolate, anhydrous calcium monohydrogen phosphate, or a combination thereof. The binder may be polyvinylpyrrolidone, low-substituted hydroxypropylcellulose, hydroxypropylcellulose, or a combination thereof. The lubricant may be magnesium stearate, silicon dioxide, talc, or a combination thereof.
제3 양상에 있어서, 상기 조성물은 피부염을 예방 또는 개선하기 위한 화장용 조성물일 수 있다. 상기 화장용 조성물은 피부 보습용일 수 있다. 상기 화장용 조성물은 피부 염증이 없는 영역에 국소적으로 적용하는 것일 수 있다. 상기 화장용 조성물은 피부염 치료용 약학 조성물과는 별개로 사용될 수 있다. In a third aspect, the composition may be a cosmetic composition for preventing or improving dermatitis. The cosmetic composition may be for skin moisturizing. The cosmetic composition may be topically applied to an area without skin inflammation. The cosmetic composition may be used separately from the pharmaceutical composition for treating dermatitis.
제4 양상은 제1 양상의 조성물을 개체에게 투여하는 단계를 포함하는 개체의 피부염을 예방 또는 치료하는 방법을 제공한다.A fourth aspect provides a method of preventing or treating dermatitis in a subject comprising administering to the subject a composition of the first aspect.
투여는 당업계에 알려진 방법에 의하여 투여될 수 있다. 투여는 예를 들면, 정맥내, 근육내, 경구, 경피 (transdermal), 점막, 코안 (intranasal), 기관내 (intratracheal) 또는 피하 투여와 같은 경로로, 임의의 수단에 의하여 개체로 직접적으로 투여될 수 있다. 상기 투여는 전신적으로 또는 국부적으로 투여될 수 있다. 상기 투여는 피부염이 존재하는 부위 또는 피부 건조가 있거나 건조하여 지기 쉬운 부위에 국소적으로 투여하는 것일 수 있다. 국부 투여의 일 예는 피부에 적용하는 것일 수 있다.Administration may be administered by a method known in the art. Administration can be administered directly to a subject by any means, for example by routes such as intravenous, intramuscular, oral, transdermal, mucosal, intranasal, intratracheal or subcutaneous administration. I can. The administration can be administered systemically or locally. The administration may be topically administered to a region where dermatitis is present or to a region where there is dryness or prone to dryness. An example of topical administration may be application to the skin.
상기 조성물은 개체의 피부염을 효율적으로 개선시키기 위해 스테로이드, 항염증제, 항히스타민제, 항생제, 및 항진균제와 같은 다른 약물과 함께 투여될 수 있다. 상기 투여는 순차적, 동시적, 또는 개별적으로 개체에 투여되는 것일 수 있다.The composition may be administered together with other drugs such as steroids, anti-inflammatory agents, antihistamines, antibiotics, and antifungal agents in order to effectively improve dermatitis in a subject. The administration may be sequential, simultaneous, or individually administered to the individual.
상기 개체는 포유동물, 예를 들면, 사람, 소, 말, 돼지, 개, 양, 염소, 또는 고양이일 수 있다. 상기 개체는 아토피 피부염과 같은 피부염의 개선을 필요로 하는 개체일 수 있다.The subject may be a mammal, for example a human, cow, horse, pig, dog, sheep, goat, or cat. The individual may be an individual in need of improvement of dermatitis such as atopic dermatitis.
상기 투여는 카울로필로게닌을 개체당 일당 0.1 mg 내지 1,000 mg, 예를 들면, 0.1 mg 내지 500 mg, 0.1 mg 내지 100 mg, 0.1 mg 내지 50 mg, 0.1 mg 내지 25 mg, 1 mg 내지 1,000 mg, 1 mg 내지 500 mg, 1 mg 내지 100 mg, 1 mg 내지 50 mg, 1 mg 내지 25 mg, 5mg 내지 1,000 mg, 5 mg 내지 500 mg, 5 mg 내지 100 mg, 5 mg 내지 50 mg, 5 mg 내지 25 mg, 10mg 내지 1,000 mg, 10 mg 내지 500 mg, 10 mg 내지 100 mg, 10 mg 내지 50 mg, 또는 10 mg 내지 25 mg을 투여하는 것일 수 있다.The administration is 0.1 mg to 1,000 mg of cowlophyllogenin per individual per day, for example, 0.1 mg to 500 mg, 0.1 mg to 100 mg, 0.1 mg to 50 mg, 0.1 mg to 25 mg, 1 mg to 1,000 mg , 1 mg to 500 mg, 1 mg to 100 mg, 1 mg to 50 mg, 1 mg to 25 mg, 5 mg to 1,000 mg, 5 mg to 500 mg, 5 mg to 100 mg, 5 mg to 50 mg, 5 mg To 25 mg, 10 mg to 1,000 mg, 10 mg to 500 mg, 10 mg to 100 mg, 10 mg to 50 mg, or 10 mg to 25 mg may be administered.
제5 양상은 제3 양상의 조성물을 피부염을 개선하기에 유효한 양으로 개체의 피부에 적용하는 단계를 포함하는 개체의 피부염을 예방 또는 개선하거나, 피부 수분을 유지하기 화장하는 방법을 제공한다.A fifth aspect provides a method of preventing or ameliorating dermatitis in a subject, comprising applying the composition of the third aspect to the skin of the subject in an amount effective to ameliorate dermatitis, or applying make-up to maintain skin moisture.
상기 개체는 포유동물일 수 있다. 피부에 적용하는 단계는 피부에 바르거나, 뿌리거나 패치 형태로 붙이는 것일 수 있다. The subject may be a mammal. The step of applying to the skin may be applied to the skin, sprayed or applied in the form of a patch.
일 양상에 따른 개체에서 피부염을 예방 또는 치료하기 위한 약학적 조성물에 의하면, 아토피 피부염과 같은 피부염을 예방 또는 치료하는데 사용될 수 있다.According to the pharmaceutical composition for preventing or treating dermatitis in an individual according to an aspect, it may be used to prevent or treat dermatitis such as atopic dermatitis.
다른 양상에 따른 개체에서 피부염을 예방 또는 개선하기 위한 식품학적 조성물에 의하면, 아토피 피부염과 같은 피부염을 예방 또는 개선하는데 사용될 수 있다.According to the food composition for preventing or improving dermatitis in an individual according to another aspect, it may be used to prevent or ameliorate dermatitis such as atopic dermatitis.
다른 양상에 따른 개체에서 피부염을 예방 또는 개선하거나, 피부 수분을 유지하는데 사용하기 위한 화장품학적 조성물에 의하면, 아토피 피부염과 같은 피부염을 예방 또는 개선하거나, 피부 수분을 유지하는데 사용될 수 있다.According to a cosmetic composition for use in preventing or improving dermatitis or maintaining skin moisture in an individual according to another aspect, it may be used to prevent or improve dermatitis such as atopic dermatitis, or to maintain skin moisture.
또 다른 양상에 따른 개체의 피부염을 예방 또는 치료하는 방법에 의하면, 개체의 상기 질환을 효율적으로 예방 또는 치료할 수 있다.According to the method for preventing or treating dermatitis in an individual according to another aspect, the disease in the individual can be efficiently prevented or treated.
또 다른 양상에 따른 개체의 피부염을 예상 또는 개선하거나, 또는 피부 수분을 유지하기 위하여 화장하는 방법에 의하면, 피부염을 예상 또는 개선하거나, 또는 피부 수분을 효율적으로 유지할 수 있다.According to the method of predicting or improving the dermatitis of an individual according to another aspect, or applying makeup to maintain skin moisture, it is possible to predict or improve dermatitis, or to efficiently maintain skin moisture.
도 1은 EL4 세포에서 카울로필로게닌 처리 후 Th0 세포에서 Th2 헬퍼 세포로의 분화 억제를 그 마커인 IL-4의 발현 변화로 나타낸 것이다.
도 2는 RBL-2H3 세포에서 카울로필로게닌 처리 후 IL-4 발현변화를 나타낸 것이다.
도 3은 RBL-2H3 세포에서 카울로필로게닌 처리 후 탈과립 정도를 나타낸 것이다.
도 4는 RBL-2H3 세포에서 카울로필로게닌 처리 후 히스타민 분비 정도를 나타낸 것이다.
도 5는 무모 마우스에서 카울로필로게닌 처리 후 시간 경과에 따른 경피 수분 손실량(TEWL)을 측정한 결과를 나타낸 것이다.
도 6은 무모 마우스에서 카울로필로게닌을 처리한 후 수분 함유량(hydration)을 측정한 결과를 나타낸 것이다.
도 7 및 8은 무모 마우스에서 카울로필로게닌을 처리한 후 혈청내 IgE 및 IL-4 의 단백질 양을 측정한 결과를 나타낸 것이다.
도 9는 무모 마우스에서 카울로필로게닌을 처리한 후 표피변화를 확인하기 위해 헤마톡실린과 에오신으로 조직염색한 것이다.
도 10은 무모 마우스에서 카울로필로게닌을 처리한 후 표피 두께를 측정한 결과를 나타낸 것이다.
도 11은 무모 마우스에서 카울로필로게닌을 처리한 후 비만세포를 확인하기위해 톨루이딘 블루로 조직 염색한 것이다.
도 12는 무모 마우스에서 카울로필로게닌을 처리한 후 비만세포의 수를 나타낸 것이다.FIG. 1 shows the inhibition of differentiation from Th0 cells to Th2 helper cells after cowlophyllogenin treatment in EL4 cells as a change in the expression of IL-4, a marker thereof.
2 shows changes in IL-4 expression after cowlophyllogenin treatment in RBL-2H3 cells.
Figure 3 shows the degree of degranulation after cowlophyllogenin treatment in RBL-2H3 cells.
Figure 4 shows the degree of histamine secretion after cowlophyllogenin treatment in RBL-2H3 cells.
Figure 5 shows the results of measuring the transdermal water loss (TEWL) over time after cowlophyllogenin treatment in hairless mice.
6 shows the result of measuring moisture content (hydration) after treatment with cowlophyllogenin in hairless mice.
7 and 8 show the results of measuring the protein amounts of IgE and IL-4 in serum after cowlophyllogenin treatment in hairless mice.
9 is a tissue staining with hematoxylin and eosin in order to confirm epidermal changes after cowlophyllogenin treatment in hairless mice.
10 shows the results of measuring epidermal thickness after treatment with cowlophyllogenin in hairless mice.
11 is a tissue staining with toluidine blue in order to identify mast cells after kaulophylogenin treatment in hairless mice.
12 shows the number of mast cells after treatment with cowlophyllogenin in hairless mice.
이하 본 발명을 실시예를 통하여 보다 상세하게 설명한다. 그러나, 이들 실시예는 본 발명을 예시적으로 설명하기 위한 것으로 본 발명의 범위가 이들 실시예에 한정되는 것은 아니다.Hereinafter, the present invention will be described in more detail through examples. However, these examples are for illustrative purposes only, and the scope of the present invention is not limited to these examples.
실시예 1: 카울로필로게닌의 효과 확인Example 1: Confirmation of the effect of cowlophyllogenin
본 실시예에서는 카울로필로게닌이 아토피 피부염 개선에 미치는 효과를 확인하였다.In this example, the effect of cowlophyllogenin on improving atopic dermatitis was confirmed.
1. 카울로필로게닌 1. Cowlophyllogenin
본 실시예에서 사용된 카울로필로게닌은 하기 식 1의 Extrasynthese 사 (프랑스, #0005S, =98.5%)에서 판매하는 것을 구매하여 사용하였다. The cowlophyllogenin used in this example was purchased and used by Extrasynthese (France, #0005S, =98.5%) of the following
카울로필로게닌 (Caulophyllogenin, CAS No. 52936-64-8, 조성식 C30H48O5, 분자량 488.7)Caulophyllogenin (CAS No. 52936-64-8, composition formula C30H48O5, molecular weight 488.7)
2. 카울로필로게닌이 Th2 헬퍼 세포로의 분화에 미치는 영향2. Effect of cowlophyllogenin on Th2 helper cell differentiation
본 실험에서 사용한 마우스 T 세포주인 EL4 세포는 한국세포주은행 (Korea Cell Line Bank; Seoul, Korea)에서 분양받아 사용하였다. EL4 세포는 마우스 유래 림프종 세포로 Th0에서 Th2 헬퍼 세포로의 분화를 조절하는 연구를 하는데 사용된다. 분화 마커는 IL-4이다. EL4 cells, a mouse T cell line used in this experiment, were sold and used by Korea Cell Line Bank (Seoul, Korea). EL4 cells are mouse-derived lymphoma cells and are used to study the regulation of differentiation from Th0 to Th2 helper cells. The differentiation marker is IL-4.
EL4 세포를 10% 우태아혈청(Fetal Bovine Serum: FBS)과 1% 페니실린/스트렙토미신이 첨가된 DMEM 배지 중에서 5% CO2, 37℃에서 배양하였다. EL4 세포(KCLB No. 40039, 마우스 T 세포 림포마(lymphoma), 한국세포주은행)를 Th2 헬퍼 세포로의 분화를 확인하기 위하여 6-웰 플레이트의 웰에 5x105 cells/well 밀도로 분주하여 16시간 배양하여 웰에 부착시켰다. 다음으로, 양성대조군으로 면역억제제로 사용되는 1uM의 시클로스포린(Cyclosporine A: CyA)과 시료를 농도대로 첨가하고 1시간 뒤 세포를 면역학적으로 활성화시키기 위해 1ng/ml의 포르볼-12-미리스테이트-13-아세테이트(phorbol-12-myristate-13-acetate: PMA)(Sigma, #P8139)와 5uM/ml의 4-tert-옥틸페놀(4-tert-Octylphenol: OP)(Sigma, #442858)를 첨가하고 5% CO2, 37℃에서 24시간 배양하였다. EL4 cells were cultured in DMEM medium supplemented with 10% Fetal Bovine Serum (FBS) and 1% penicillin/streptomycin at 5% CO 2 , 37°C. To confirm the differentiation of EL4 cells (KCLB No. 40039, mouse T cell lymphoma, Korea Cell Line Bank) into Th2 helper cells, the cells were dispensed at a density of 5x10 5 cells/well into the wells of a 6-well plate for 16 hours. Incubated and attached to the wells. Next, 1uM of Cyclosporine A (CyA) used as an immunosuppressive agent as a positive control and 1 ng/ml of phorbol-12-myristate were added to the concentration and 1 hour later to activate cells immunologically. -13-acetate (phorbol-12-myristate-13-acetate: PMA) (Sigma, #P8139) and 5 uM/ml of 4-tert-Octylphenol (OP) (Sigma, #442858) It was added and incubated for 24 hours at 5% CO 2 and 37°C.
RNA는 QIAQube (Qiagen)를 이용하여 초고속으로 분리하여 total RNA를 추출하였다. 추출한 RNA는 Agilent 2100 BioAnalyzer (Agilent Technologies, SantaClara, CA, USA)를 사용하여 견고성(integrity)을 확인하였다. cDNA는 ImProm-II Reverse Transcription System (Promega, Madison, WI, USA)을 이용하여 1 ㎍의 RNA를 cDNA로 합성하였다. PCR은 GeneAmp PCR System 9700 (Applied Biosystems, Foster City, CA, USA)을 사용하여 수행하였다. RNA was separated at high speed using QIAQube (Qiagen) to extract total RNA. The extracted RNA was confirmed to be robust (integrity) using an Agilent 2100 BioAnalyzer (Agilent Technologies, SantaClara, CA, USA). For cDNA, 1 μg of RNA was synthesized as cDNA using the ImProm-II Reverse Transcription System (Promega, Madison, WI, USA). PCR was performed using GeneAmp PCR System 9700 (Applied Biosystems, Foster City, CA, USA).
PCR 반응은 0.02 ㎕ Ex taq 폴리머라제(TAKARA, Otsu, Shiga, Japan), 2 ㎕ Ex taq 폴리머라제 버퍼, 1.6 ㎕ dNTP (10 mM), 2 ㎕ 포워드 프라이머 (20 μM), 2 ㎕ 리버스 프라이머 (20 uM), 11.38 ㎕ 물과 1 ㎕의 합성한 제1 가닥 cDNA를 잘 섞어 총 20 ㎕ 용량의 반응 혼합물에 대하여 PCR을 수행하였다. 사용된 프라이머는 IL4 및 베타-actin 유전자 증폭을 위하여 각각 서열번호 1 및 2; 서열번호 3 및 4의 폴리뉴클레오티드를 사용하였다. PCR reactions were 0.02 μl Ex taq polymerase (TAKARA, Otsu, Shiga, Japan), 2 μl Ex taq polymerase buffer, 1.6 μl dNTP (10 mM), 2 μl forward primer (20 μM), 2 μl reverse primer (20 uM), 11.38 µl of water and 1 µl of the synthesized first-stranded cDNA were well mixed, and PCR was performed on a reaction mixture having a total volume of 20 µl. The primers used were SEQ ID NOs: 1 and 2, respectively, for amplifying IL4 and beta-actin genes; Polynucleotides of SEQ ID NOs: 3 and 4 were used.
IL-4의 PCR 조건은 94 ℃에서 4분 (1 회), 94 ℃에서 30 초, 60 ℃에서 30 초 그리고 72 ℃에서 30 초 (25 회), 72 ℃에서 5 분 (1 회)이었고, 베타-액틴 조건은 94 ℃에서 4 분 (1 회), 94 ℃에서 30 초, 55 ℃에서 30 초 그리고 72 ℃에서 30 초 (20 회), 72 ℃에서 5 분 (1 회)이었다. RT-PCR 결과는 QIAxcel advanced (Qiagen) 기기를 사용하여 밴드의 강도를 측정하였다. 효능에 대한 분석은 [PMA + OP](PO) 처리군의 비율을 100으로 하여 이와 비교하여 결정하였다. The PCR conditions of IL-4 were 94°C for 4 minutes (1 time), 94°C for 30 seconds, 60°C for 30 seconds and 72°C for 30 seconds (25 times), and 72°C for 5 minutes (1 time), Beta-actin conditions were 4 minutes (1 time) at 94 ℃, 30 seconds at 94 ℃, 30 seconds at 55 ℃, 30 seconds at 72 ℃ (20 times), 5 minutes (1 time) at 72 ℃. For RT-PCR results, the strength of the band was measured using a QIAxcel advanced (Qiagen) instrument. Analysis of the efficacy was determined by comparing the ratio of the [PMA + OP] (PO) treatment group as 100.
표 1 및 도 1은 카울로필로게닌이 IL-4 발현에 미치는 영향을 PO 처리군을 100으로 하여 그에 대한 비율로 IL-4가 저해되는 정도를 나타낸 것이다. Table 1 and FIG. 1 show the degree of inhibition of IL-4 at a ratio of the PO-treated group to 100 for the effect of cowlophyllogenin on IL-4 expression.
표 1에서, CsA는 시클로스포린 A를 나타낸다. 표 1과 도 1에 나타낸 바와 같이, 카울로필로게닌은 EL4 세포에서 IL-4의 발현을 저해시켰으며 이는 아토피 증상 완화에 도움이 될 수 있음을 보여주는 결과이다. In Table 1, CsA represents cyclosporin A. As shown in Table 1 and FIG. 1, cowlophyllogenin inhibited the expression of IL-4 in EL4 cells, which is a result showing that it may help relieve atopic symptoms.
3. 카울로필로게닌이 IL-4 발현에 미치는 영향3. Effect of cowlophyllogenin on IL-4 expression
본 실험에서 사용한 랫트 호염기성 백혈병 세포(rat basophilic leukemia cell)인 RBL-2H3 세포는 한국세포주은행 (Korea Cell Line Bank; Seoul, Korea)에서 분양받아 사용하였다. RBL-2H3 cells, rat basophilic leukemia cells used in this experiment, were pre-sold and used by Korea Cell Line Bank (Seoul, Korea).
RBL-2H3 세포를 웰당 5x105개 농도로 6-웰 플레이트의 각 웰에 접종하여 10% 우태아혈청 (fetal bovine serum: FBS)과 1% 페니실린/스트렙토마이신이 함유된 DMEM (Dulecco' Modified Eagle Medium) 배지 중에서 37 ℃, 5 % CO2 조건의 인큐베이터에서 배양하고, 16 시간 후에 1 μM의 시클로스포린 A와 카울로필로게닌을 10 μM의 농도로 각각 첨가하고 1 시간 동안 배양하여 전처리하였다. 다음으로, PMA 50 ng/ml와 이오노미신(ionomycin) 1 μM을 첨가하고 동일한 조건에서 9 시간 동안 배양하였다. PMA와 이오노미신은 인터페론, 페르포린, IL-2, 및 IL-4와 같은 시토킨의 세포내 생산을 자극하기 위하여 사용된다. 대조군으로서, 시클로스포린 A, 카울로필로게닌, PMA 및 이오노미신을 첨가하지 않은 무처리군, 및 PMA 및 이오노미신를 첨가하지 않은 것(이하 "PI 군"이라 함)을 사용하였다.DMEM (Dulecco' Modified Eagle Medium) containing 10% fetal bovine serum (FBS) and 1% penicillin/streptomycin by inoculating RBL-2H3 cells into each well of a 6-well plate at a concentration of 5x10 5 per well. ) Cultured in an incubator under conditions of 37° C. and 5% CO 2 in a medium, and after 16 hours, 1 μM of cyclosporin A and cowlophyllogenin were added at a concentration of 10 μM, respectively, and cultured for 1 hour to pretreat. Next, 50 ng/ml of PMA and 1 μM of ionomycin were added and incubated for 9 hours under the same conditions. PMA and ionomycin are used to stimulate the intracellular production of cytokines such as interferon, perforin, IL-2, and IL-4. As a control group, cyclosporine A, kaolophyllogenin, PMA and ionomycin were not added, and PMA and ionomycin were not added (hereinafter referred to as “PI group”).
세포는 RNeasy mini kit (Qiagen)을 사용하여 QIAsymphony 또는 QIAQube (Qiagen) 기기에 장착하여 RNA를 추출하였다. 추출한 RNA는 Agilent 2100 BioAnalyzer (Agilent Technologies, SantaClara, CA, USA)를 사용하여 견고성(integrity)을 확인하였다. cDNA는 ImProm-II Reverse Transcription System (Promega, Madison, WI, USA)을 이용하여 1 ㎍의 RNA를 cDNA로 합성하였다. PCR은 GeneAmp PCR System 9700 (Applied Biosystems, Foster City, CA, USA)을 사용하여 수행하였다. The cells were mounted on a QIAsymphony or QIAQube (Qiagen) instrument using an RNeasy mini kit (Qiagen) to extract RNA. The extracted RNA was confirmed to be robust (integrity) using an Agilent 2100 BioAnalyzer (Agilent Technologies, SantaClara, CA, USA). For cDNA, 1 μg of RNA was synthesized as cDNA using the ImProm-II Reverse Transcription System (Promega, Madison, WI, USA). PCR was performed using GeneAmp PCR System 9700 (Applied Biosystems, Foster City, CA, USA).
PCR 반응은 0.02 ㎕ Ex taq 폴리머라제(TAKARA, Otsu, Shiga, Japan), 2 ㎕ Ex taq 폴리머라제 버퍼, 1.6 ㎕ dNTP (10 mM), 2 ㎕ 포워드 프라이머 (20 uM), 2 ㎕ 리버스 프라이머 (20 uM), 11.38 ㎕ 물과 1 ㎕의 합성한 제1 가닥 cDNA를 잘 섞어 총 20 ㎕ 용량의 반응 혼합물에 대하여 PCR을 수행하였다. PCR reactions were 0.02 μl Ex taq polymerase (TAKARA, Otsu, Shiga, Japan), 2 μl Ex taq polymerase buffer, 1.6 μl dNTP (10 mM), 2 μl forward primer (20 uM), 2 μl reverse primer (20 uM), 11.38 µl of water and 1 µl of the synthesized first-stranded cDNA were well mixed, and PCR was performed on a reaction mixture having a total volume of 20 µl.
IL-4의 PCR 조건은 94 ℃에서 4분 (1 회), 94 ℃에서 30 초, 60 ℃에서 30 초 그리고 72 ℃에서 30 초 (25 회), 72 ℃에서 5 분 (1 회)이었고, 베타-액틴 조건은 94 ℃에서 4 분 (1 회), 94 ℃에서 30 초, 55 ℃에서 30 초 그리고 72 ℃에서 30 초 (20 회), 72 ℃에서 5 분 (1 회)이었다. RT-PCR 결과는 QIAxcel advanced (Qiagen) 기기를 사용하여 밴드의 강도를 측정하였다. 효능에 대한 분석은 [PMA + 이오노미신](PI) 처리군의 비율을 100으로 하여 이와 비교하여 결정하였다. The PCR conditions of IL-4 were 94°C for 4 minutes (1 time), 94°C for 30 seconds, 60°C for 30 seconds and 72°C for 30 seconds (25 times), and 72°C for 5 minutes (1 time), Beta-actin conditions were 4 minutes (1 time) at 94 ℃, 30 seconds at 94 ℃, 30 seconds at 55 ℃, 30 seconds at 72 ℃ (20 times), 5 minutes (1 time) at 72 ℃. For RT-PCR results, the strength of the band was measured using a QIAxcel advanced (Qiagen) instrument. Analysis of the efficacy was determined by comparing the ratio of the [PMA + ionomycin] (PI) treatment group to 100.
표 2 및 도 2는 카울로필로게닌이 IL-4 발현에 미치는 영향을 PI 처리군을 100으로 하여 그에 대한 비율로 IL-4가 저해되는 정도를 나타낸 것이다. Table 2 and FIG. 2 show the extent to which IL-4 is inhibited in proportion to the effect of cowlophyllogenin on IL-4 expression in the PI treatment group as 100.
표 2 및 도 2에서, CsA는 시클로스포린 A를 나타낸다. 표 2와 도 2에 나타낸 바와 같이, 카울로필로게닌은 RBL-2H3 세포에서 IL-4의 발현을 저해시켰으며 이는 아토피 증상 완화에 도움이 될 수 있음을 보여주는 결과이다. In Table 2 and Figure 2, CsA represents cyclosporin A. As shown in Table 2 and FIG. 2, cowlophyllogenin inhibited the expression of IL-4 in RBL-2H3 cells, which is a result showing that it may help relieve atopic symptoms.
4. 카울로필로게닌이 탈과립에 미치는 영향4. Effect of cowlophyllogenin on degranulation
카울로필로게닌 존재하에서 면역세포의 탈과립화 정도를 측정하였다. 탈과립화는 면역 세포가 염증물질을 방출하는 과정이다, 탈과립화는 탈과립화에 의하여 방출되는 β-헥소스아미니다제의 활성을 측정하여 확인하였다.The degree of degranulation of immune cells in the presence of cowlophyllogenin was measured. Degranulation is a process by which immune cells release inflammatory substances, and degranulation was confirmed by measuring the activity of β-hexosaminidase released by degranulation.
구체적으로, RBL-2H3 세포를 10% FBS가 포함된 DMEM (HYCLONE,#sh30284.01)에 현탁시킨 후 24-웰 플레이트에 5x105 cells/well 밀도로 분주하여 37℃, 5% CO2의 조건에서 배양하였다. 배양 16시간 후 항-DNP-IgE 항체(Sigma, #D8406)를 100 ng/ml 농도로 웰에 첨가한 후 37℃, 5% CO2의 조건에서 4시간 세포를 배양하였다. Specifically, RBL-2H3 cells were suspended in DMEM (HYCLONE, #sh30284.01) containing 10% FBS, and then dispensed in a 24-well plate at a density of 5x10 5 cells/well at 37°C and 5% CO2. Cultured. After 16 hours of culture, an anti-DNP-IgE antibody (Sigma, #D8406) was added to the wells at a concentration of 100 ng/ml, and the cells were cultured for 4 hours at 37° C. and 5% CO 2 .
4시간 후 siraganian buffer (119 mM NaCl, 5 mM KCl, 0.4 mM MgCl2, 25 mM PIPES, 40 mM NaOH)로 2회 세포를 세척하고, 표 3에 지정된 농도의 케토티펜 30 μM 또는 카울로필로게닌을 함유하는 siraganian buffer (119 mM NaCl, 5 mM KCl, 0.4 mM MgCl2, 25 mM PIPES, 40 mM NaOH, 5.6 mM glucose, 1 mM CaCl2, 및 0.1% BSA) 200 μl를 첨가하고 1시간 동안 37℃, 5% CO2의 조건에서 배양하였다. PIPES는 piperazine-N,N′-bis(2-ethanesulfonic acid)를 나타낸다. 1시간 배양 후 항원으로서 DNP-BSA를 100ng/ml의 농도로 첨가하여 1시간 반응시키고 얼음조(ice bath)에서 10분간 방치하여 반응을 종결시켰다.After 4 hours, the cells were washed twice with siraganian buffer (119 mM NaCl, 5 mM KCl, 0.4 mM MgCl 2 , 25 mM PIPES, 40 mM NaOH), and 30 μM of ketotifen or cowlophile at the concentration specified in Table 3 200 μl of a siraganian buffer containing genin (119 mM NaCl, 5 mM KCl, 0.4 mM MgCl 2 , 25 mM PIPES, 40 mM NaOH, 5.6 mM glucose, 1 mM CaCl 2 , and 0.1% BSA) was added and then for 1 hour. Incubated under conditions of 37°C and 5% CO2. PIPES stands for piperazine-N,N'-bis(2-ethanesulfonic acid). After 1 hour incubation, DNP-BSA was added as an antigen at a concentration of 100 ng/ml, reacted for 1 hour, and left in an ice bath for 10 minutes to terminate the reaction.
이후 반응액 즉, siraganian buffer를 채취하고 2,000 RPM에서 원심분리하여 상등액을 취하고, 여기에 β-헥소스아미니다제의 기질 즉, 1 mM 4-니트로페닐 N-아세틸-β-D-글루코사미디드(4-Nitrophenyl N-acetyl-β-D-glucosaminide)(sigma, #N9376)와 37℃에서 1시간 반응시킨 후 0.1M NaCO3/NaHCO3 용액을 넣어 반응을 정지시켰다. microplate spectrophotometer (biotek)로 405nm 파장에서 흡광도를 측정하였다.After that, the reaction solution, that is, the siraganian buffer, is collected and centrifuged at 2,000 RPM to take the supernatant, and the substrate of β-hexosaminidase, that is, 1 mM 4-nitrophenyl N-acetyl-β-D-glucosamide After reacting with (4-Nitrophenyl N-acetyl-β-D-glucosaminide)(sigma, #N9376) for 1 hour at 37°C, 0.1M NaCO 3 /NaHCO 3 solution was added to stop the reaction. Absorbance was measured at a wavelength of 405 nm with a microplate spectrophotometer (biotek).
표 3 및 도 3은 카울로필로게닌이 탈과립에 미치는 영향을 무처리군에 대한 비율로 탈과립이 저해되는 정도를 나타낸 것이다. Table 3 and FIG. 3 show the extent to which degranulation is inhibited as a ratio of the untreated group to the effect of cowlophyllogenin on degranulation.
표 3 및 도 3에서, CsA는 시클로스포린 A를 나타낸다. 표 3와 도 3에 나타낸 바와 같이, 카울로필로게닌은 RBL-2H3 세포에서 탈과립을 저해시켰으며 이는 탈과립에 의한 급격한 알레르기 반응이나 가려움증 등의 아토피 증상 완화에 도움이 될 수 있음을 보여주는 결과이다. In Table 3 and Figure 3, CsA represents cyclosporin A. As shown in Table 3 and FIG. 3, cowlophyllogenin inhibited degranulation in RBL-2H3 cells, which is a result showing that it can help relieve atopic symptoms such as sudden allergic reaction or itching caused by degranulation.
5. 카울로필로게닌이 히스타민 분비에 미치는 영향5. The effect of cowlophyllogenin on histamine secretion
카울로필로게닌의 존재하에서 면역세포가 히스타민을 분비하는 정도를 측정하였다. 히스타민을 염증을 야기하는 물질이다.The degree of secretion of histamine by immune cells in the presence of cowlophyllogenin was measured. Histamine is a substance that causes inflammation.
구체적으로, 면역 세포인 RBL-2H3 세포를 10% FBS가 포함된 DMEM(HYCLONE,#)에 현탁시킨 후 24-웰 플레이트에 5x105 cells/well 밀도로 분주한 후 항-DNP-IgE (Sigma, #D8406)를 50 ng/ml 농도로 첨가한 후 37℃, 5% CO2의 조건에서 24시간 배양하였다. 24시간 후 siraganian buffer (119 mM NaCl, 5 mM KCl, 0.4 mM MgCl2, 25mM PIPES, 40mM NaOH)로 세포를 2회 세척하고, Specifically, the immune cells, RBL-2H3 cells, were suspended in DMEM (HYCLONE,#) containing 10% FBS, and then dispensed in a 24-well plate at a density of 5x10 5 cells/well, and then anti-DNP-IgE (Sigma, #D8406) was added at a concentration of 50 ng/ml and incubated for 24 hours at 37°C and 5% CO 2 . After 24 hours, the cells were washed twice with siraganian buffer (119 mM NaCl, 5 mM KCl, 0.4 mM MgCl 2 , 25 mM PIPES, 40 mM NaOH),
표 4에 지정된 농도의 케토티펜 또는 카울로필로게닌을 함유하는 siraganian buffer (119 mM NaCl, 5 mM KCl, 0.4 mM MgCl2, 25mM PIPES, 40mM NaOH, 5.6 mM glucose, 1 mM CaCl2, and 0.1% BSA) 200 μl를 첨가하고 1시간 동안 37℃ 5% CO2의 조건에서 배양한다. 1시간 배양 후 항원으로서 DNP-BSA을 200ng/ml 농도로 첨가하고 1시간 반응시킨 후 얼음조에서 10분간 방치하여 반응을 종결시켰다. 이후 반응액 즉, 버퍼를 채취해 2000 RPM에서 원심분리하여 Histamine ELISA kit (abcam, #ab213975)를 이용해 microplate spectrophotometer (biotek)로 450nm에서 흡광도를 측정하였다.Siraganian buffer (119 mM NaCl, 5 mM KCl, 0.4 mM MgCl 2 , 25 mM PIPES, 40 mM NaOH, 5.6 mM glucose, 1 mM CaCl 2 , and 0.1) containing ketotifen or cowlophyllogenin at the concentrations specified in Table 4. % BSA) 200 μl is added and incubated for 1 hour at 37°C and 5% CO2. After 1 hour incubation, DNP-BSA as an antigen was added at a concentration of 200 ng/ml, reacted for 1 hour, and left in an ice bath for 10 minutes to terminate the reaction. After that, the reaction solution, that is, the buffer was collected and centrifuged at 2000 RPM, and the absorbance was measured at 450 nm using a microplate spectrophotometer (biotek) using a Histamine ELISA kit (abcam, #ab213975).
표 4 및 도 4는 카울로필로게닌이 히스타민 분비에 미치는 영향을 나타낸 것이다. Table 4 and Figure 4 show the effect of cowlophyllogenin on histamine secretion.
도 4에서, keto는 Ketotifen을 나타낸다. 표 4와 도 4에 나타낸 바와 같이, 카울로필로게닌은 RBL-2H3 세포에서 히스타민 분비를 저해시켰으며 이는 히스타민에 의한 급격한 알레르기 반응이나 가려움증 등의 아토피 증상 완화에 도움이 될 수 있음을 보여주는 결과이다. In Figure 4, keto represents Ketotifen. As shown in Table 4 and Figure 4, cowlophyllogenin inhibited histamine secretion in RBL-2H3 cells, which is a result showing that it can help relieve atopic symptoms such as acute allergic reaction or itching caused by histamine. .
6. 카울로필로게닌이 DNCB에 의하여 아토피 피부염 유도된 무모 마우스(hairless mouse)에서 피부 장벽기능에 미치는 영향6. The effect of cowlophyllogenin on the skin barrier function in hairless mice induced atopic dermatitis by DNCB
아토피 피부염 유도-무모 마우스(hairless mouse)에 카울로필로게닌을 처리하는 경우 질병 마우스의 피부 수분 함유량을 증진시켜 피부장벽 기능을 개선시킬 수 있는지 여부를 확인하기 위한 실험을 수행하였다. Induction of atopic dermatitis-in case of treatment of cowlophyllogenin in hairless mice, an experiment was conducted to determine whether it is possible to improve skin barrier function by increasing the skin moisture content of diseased mice.
구체적으로, 6 주령(암컷, 23-27g) 무모 마우스(hairless mouse, 오리엔트바이오에서 구입)를 3개의 군으로 분리하였다: 무처리군, 2,4-디니트로클로로벤젠(2,4-dinitrochlorobenzene: DNCB) 유도 후 비히클 처리군, DNCB 유도 후 카울로필로게닌 처리군(0.5 %). DNCB는 물 중 99 % 아세톤과 올리브 오일을 부피 기준으로 3:1로 섞은 용액을 용매로 사용하였다. 비히클은 프로필렌 글리콜과 에탄올을 부피 기준으로 7:3으로 섞은 것을 사용하였다. 군 분리 후 7일 동안 1일 1회 1 (w/v/)% DNCB 용액을 마우스 등에 200 ㎕ 씩 도포하였다. 마지막 도포 후 일주일 간 처리하지 않고 일주일 후 2일 간격으로 총 7번 0.1(w/v)% DNCB 용액을 위와 같은 방법으로 도포하였다. 0.1(w/v)% DNCB 용액을 도포하며 14일 동안 비히클을 용매로 한 카울로필로게닌 0.5 (w/v)% 용액과 비히클을 오전 및 오후로 나누어 1일 2회로 마우스 등에 200 ㎕ 씩 각각 도포하였다. Specifically, 6-week-old (female, 23-27g) hairless mice (purchased from Orient Bio) were separated into three groups: untreated group, 2,4-dinitrochlorobenzene: DNCB) induction followed by vehicle treatment group, DNCB induction followed by cowlophyllogenin treatment group (0.5%). DNCB used a solution of 99% acetone and olive oil in water at a volume of 3:1 as a solvent. As a vehicle, propylene glycol and ethanol were mixed at a volume of 7:3. After group separation, 200 µl of a 1 (w/v/)% DNCB solution was applied to mice once a day for 7 days. After the last application, a 0.1(w/v)% DNCB solution was applied in the same manner as above seven times without treatment for one week and at intervals of two days after a week. 0.1(w/v)% DNCB solution was applied, and a 0.5 (w/v)% solution of cowlophyllogenin with vehicle as a solvent and vehicle was divided into morning and afternoon for 14 days, and 200 µl each of mice twice a day Applied.
시료가 도포된 마우스 피부에 대하여, 경피수분손실량 (TEWL, Trans Epidermal Water Loss)은 AquaFlux (Biox, London, UK)를 이용해서 측정하였고, 피부 수분 함유량(hydration)은 Skin-O-Mat (COSMOMEP, Berlin, Germany)를 이용하여 측정하였다. 처음 DNCB에 의하여 아토피 피부염을 유도하기 전, 유도 후 7일 후, 14일 후 및 21일 후 측정하였다. For the mouse skin to which the sample was applied, the amount of transdermal water loss (TEWL, Trans Epidermal Water Loss) was measured using AquaFlux (Biox, London, UK), and the skin moisture content (hydration) was Skin-O-Mat (COSMOMEP, Berlin, Germany). Measurements were made before induction of atopic dermatitis by the first DNCB, 7 days, 14 days, and 21 days after induction.
표 5 및 도 5는 무모 마우스에서 카울로필로게닌 처리 후 시간 경과에 따른 경피 수분 손실량(TEWL)(g/m2/h)을 측정한 결과를 나타낸 것이다.Tables 5 and 5 show the results of measuring transdermal water loss (TEWL) (g/m 2 /h) over time after cowlophyllogenin treatment in hairless mice.
표 6 및 도 6은 무모 마우스에서 카울로필로게닌을 처리한 후 수분 함유량(hydration) (%)을 측정한 결과를 나타낸 것이다.Table 6 and FIG. 6 show the results of measuring the moisture content (hydration) (%) after treatment with cowlophyllogenin in hairless mice.
도 5에 나타낸 바와 같이, 카울로필로게닌은 무모 마우스에서 대조군인 비히클에 비해 경피 수분 손실량이 50% 이상 낮아진 것을 확인할 수 있다. 따라서, 카울로필로게닌이 무모 마우스에서 비히클에 비해 확연하게 피부장벽 기능이 강화시키는 것을 알 수 있다.As shown in Figure 5, it can be seen that the amount of transdermal water loss of cowlophyllogenin was lowered by 50% or more compared to the vehicle, which is a control, in hairless mice. Therefore, it can be seen that cowlophyllogenin remarkably strengthens the skin barrier function compared to the vehicle in hairless mice.
또한, 도 6에 나타낸 바와 같이, 파울로필로게닌이 무모 마우스에서 대조군인 비히클에 비해 수분함유량(hydration)을 높이는 것을 확인하였다. In addition, as shown in FIG. 6, it was confirmed that paulophyllogenin increased the moisture content (hydration) in hairless mice compared to the vehicle, which is a control group.
또한, 상기 마우스의 혈액 중 혈장에서 아토피 피부염의 마커로 쓰이며 아토피 피부염에서 가장 중요한 요인 중 하나인 면역글로불린E(IgE)와 면역세포의 시토킨 중 하나인 인터루킨-4(IL-4)의 단백질 양을 ELISA 실험법을 이용하여 측정하였다.In addition, the amount of protein of immunoglobulin E (IgE), one of the most important factors in atopic dermatitis, and interleukin-4 (IL-4), which is one of the cytokines of immune cells, used as a marker of atopic dermatitis in the blood plasma of the mouse. Was measured using the ELISA test method.
구체적으로, 마우스 마취시킨 후에 0.18 M EDTA 30 ul가 들어있는 주사기를 이용하여 복부대동맥에서 혈액을 채취하였다. 원심분리기를 이용하여 4℃ 8,000 rpm에서 15 분간 원심분리한 후 혈장과 혈구를 분리하였다. 이중 혈장에 대하여 마우스 IgE ELISA quantitation kit (Bethy Laboratories, Montgomery, TX, USA)와 마우스 IL-4 ELISA quantitation kit (Bethy Laboratories, Montgomery, TX, USA)를 사용하였다. Specifically, after the mouse was anesthetized, blood was collected from the abdominal aorta using a syringe containing 30 ul of 0.18 M EDTA. Plasma and blood cells were separated after centrifuging for 15 minutes at 8,000 rpm at 4°C using a centrifuge. For double plasma, a mouse IgE ELISA quantitation kit (Bethy Laboratories, Montgomery, TX, USA) and a mouse IL-4 ELISA quantitation kit (Bethy Laboratories, Montgomery, TX, USA) were used.
표 7 및 도 7; 및 표 8 및 도 8은 무모 마우스에서 카울로필로게닌을 처리한 후 혈청 내 IgE 및 IL-4의 단백질 양을 측정한 결과를 나타낸 것이다. Table 7 and Figure 7; And Tables 8 and 8 show the results of measuring the amount of proteins of IgE and IL-4 in serum after cowlophyllogenin treatment in hairless mice.
도 7과 8에 나타낸 바와 같이 카울로필로게닌은 무모 마우스에서 대조군인 비히클에 비해 혈장 내 IgE 단백질 양과 IL-4 단백질 양을 감소시키는 경향을 확인하였다. As shown in Figs. 7 and 8, it was confirmed that cowlophylogenin tends to decrease the amount of IgE protein and the amount of IL-4 protein in plasma compared to the vehicle, which is a control, in hairless mice.
마우스의 표피두께와 조직학적 변화를 확인하기 위하여 마우스 조직을 10% 포르말린으로 고정한 후 헤마톡실린과 에오신으로 염색하였다. 염색한 조직을 도립현미경(TE-2000U, Nikon)을 이용하여 촬영하였고, Leica application suite 프로그램을 이용하여 표피층의 두께를 측정하였다.Mouse tissues were fixed with 10% formalin and stained with hematoxylin and eosin in order to check the epidermal thickness and histological changes of the mouse. The stained tissue was photographed using an inverted microscope (TE-2000U, Nikon), and the thickness of the epidermal layer was measured using the Leica application suite program.
도 9는 무모 마우스에서 카울로필로게닌을 처리한 후 표피변화를 확인하기 위해 헤마톡실린과 에오신으로 조직염색한 것이다. 9 is a tissue staining with hematoxylin and eosin in order to confirm epidermal changes after cowlophyllogenin treatment in hairless mice.
표 10 및 도 10은 무모 마우스에서 카울로필로게닌을 처리한 후 표피 두께(Epidermal thicknes)를 측정한 결과를 나타낸 것이다. Table 10 and FIG. 10 show the results of measuring epidermal thicknes after treatment with cowlophyllogenin in hairless mice.
그 결과 도 9와 10에 나타낸 바와 같이 카울로필로게닌은 무모 마우스에서 대조군인 비히클에 비해 피부 두께와 표피층의 두께도 감소하였으며, 병변부위의 면역 세포수도 감소하였다. As a result, as shown in Figs. 9 and 10, cowlophyllogenin decreased skin thickness and epidermal layer thickness in hairless mice compared to the control vehicle, and the number of immune cells at the lesion site decreased.
마우스 병변 부위의 비만세포가 침윤된 정도를 확인하기 위하여 마우스 조직을 10% 포르말린으로 고정한 후 톨루이딘 블루로 염색하였다. 염색한 조직을 도립현미경(TE-2000U, Nikon)을 이용하여 촬영하였고, Image J 프로그램을 이용하여 비만세포의 수를 측정하였다.In order to confirm the degree of invasion of the mast cells in the mouse lesion, the mouse tissue was fixed with 10% formalin and stained with toluidine blue. The stained tissue was photographed using an inverted microscope (TE-2000U, Nikon), and the number of mast cells was measured using the Image J program.
도 11은 무모 마우스에서 카울로필로게닌을 처리한 후 비만세포를 확인하기위해 톨루이딘 블루로 조직 염색한 것이다. FIG. 11 shows tissue staining with toluidine blue in order to identify mast cells after cowlophyllogenin treatment in hairless mice.
표 10 및 도 12는 무모 마우스에서 카울로필로게닌을 처리한 후 비만세포의 수를 나타낸 것이다.Table 10 and FIG. 12 show the number of mast cells after treatment with cowlophyllogenin in hairless mice.
도 11과 12에 나타낸 바와 같이, 카울로필로게닌은 무모 마우스에서 대조군인 비히클에 비해 병변부위로 침윤된 비만세포의 수가 감소하였다. As shown in Figs. 11 and 12, cowlophyllogenin decreased the number of mast cells infiltrating the lesion site in hairless mice compared to the vehicle, which is a control group.
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<120> A composition for preventing or improving dermatitis comprising
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<110> Korea Institute of Science and Technology
<120> A composition for preventing or improving dermatitis comprising
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Claims (13)
상기 조성물은 Th2 헬퍼 세포로의 분화억제, 면역기능을 안정화시키는 것, 또는 IL-4의 발현을 저해하는 것인 조성물.As a pharmaceutical composition for use in preventing or treating atopic dermatitis induced by dinitrochlorobenzene (DNCB) comprising only cowlophyllogenin or a pharmaceutically acceptable salt thereof as an active ingredient,
The composition inhibits differentiation into Th2 helper cells, stabilizes immune function, or inhibits the expression of IL-4.
상기 상기 조성물은 Th2 헬퍼 세포로의 분화억제, 면역기능을 안정화시키는 것, 또는 IL-4의 발현을 저해하는 것인 조성물.As a food composition for use in preventing or improving atopic dermatitis induced by dinitrochlorobenzene (DNCB) comprising only cowlophyllogenin or a food acceptable salt thereof as an active ingredient,
The composition inhibits differentiation into Th2 helper cells, stabilizes immune function, or inhibits the expression of IL-4.
상기 조성물은 Th2 헬퍼 세포로의 분화억제, 면역기능을 안정화시키는 것, 또는 IL-4의 발현을 저해하는 것인 조성물.As a cosmetic composition for improving atopic dermatitis induced by dinitrochlorobenzene (DNCB) comprising only cowlophyllogenin or a cosmetically acceptable salt thereof as an active ingredient,
The composition inhibits differentiation into Th2 helper cells, stabilizes immune function, or inhibits the expression of IL-4.
상기 조성물은 Th2 헬퍼 세포로의 분화억제, 면역기능을 안정화시키는 것, 또는 IL-4의 발현을 저해하는 것인 방법.
A method for treating atopic dermatitis induced by dinitrochlorobenzene (DNCB) in an individual comprising administering to the individual the composition of any one of claims 1 and 4 to 5 in an amount effective to treat dermatitis, The method wherein the subject is a mammal, not a human,
The composition inhibits differentiation into Th2 helper cells, stabilizes immune function, or inhibits the expression of IL-4.
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| KR1020180133143A KR102182554B1 (en) | 2018-11-01 | 2018-11-01 | A composition for preventing or improving dermatitis comprising caulophyllogenin and use thereof |
| PCT/KR2019/014655 WO2020091485A1 (en) | 2018-11-01 | 2019-11-01 | Composition to be used for preventing or alleviating dermatitis, comprising caulophyllogenin, and use thereof |
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| Maité Rodríguez-Díaz et al. Journal of Pharmacy and Pharmacology. 2011, 63, 718-724* |
| Navneet Kumar Yadav 등, Oxidative Medicine and Cellular Longevity Volume 2017, Article ID 9094641* |
| Tran Hong Quang 등. Arch. Pharm. Res. (2013) 36, 327-334* |
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