KR102144566B1 - A composition for preventing or terating atopic dermatitis comprising lycopi herba extract as an active ingredient - Google Patents
A composition for preventing or terating atopic dermatitis comprising lycopi herba extract as an active ingredient Download PDFInfo
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- KR102144566B1 KR102144566B1 KR1020180120220A KR20180120220A KR102144566B1 KR 102144566 B1 KR102144566 B1 KR 102144566B1 KR 1020180120220 A KR1020180120220 A KR 1020180120220A KR 20180120220 A KR20180120220 A KR 20180120220A KR 102144566 B1 KR102144566 B1 KR 102144566B1
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- South Korea
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- atopic dermatitis
- extract
- taekran
- composition
- active ingredient
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- A61P17/00—Drugs for dermatological disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/318—Foods, ingredients or supplements having a functional effect on health having an effect on skin health and hair or coat
Abstract
본 발명은 택란(Lycopus lucidus) 추출물을 유효성분으로 포함하는 아토피 피부염의 예방, 개선 및 치료용 조성물을 제공한다.The present invention provides a composition for the prevention, improvement and treatment of atopic dermatitis comprising the extract of Taekran (Lycopus lucidus ) as an active ingredient.
Description
본 발명은 택란(Lycopi Herba) 추출물을 포함하는 아토피 피부염의 예방, 개선 또는 치료용 조성물에 관한 것이다.The present invention relates to a composition for the prevention, improvement or treatment of atopic dermatitis comprising a takran ( Licopi Herba ) extract.
아토피 피부염은 심한 소양성, 재발성을 지니는 급성 습진과 만성 피부염으로 주로 영유아에서 발생한다. Atopic dermatitis is acute eczema and chronic dermatitis with severe itching and recurrence. It occurs mainly in infants and young children.
연령의 증가에 따라 대부분 자연치유의 경과를 보이지만 사춘기 성인에서 지속되거나 초발하기도 하고, 소아에서 10-20 %, 성인에서 1-3 %의 이환율을 보이며, 최근 심한 성인형 아토피 피부염 환자가 증가하고 있다고 보고된 바 있다.Most of them show the progress of natural healing according to the increase of age, but it persists or initiates in adolescent adults, with a morbidity rate of 10-20% in children and 1-3% in adults, and recently, patients with severe adult atopic dermatitis are increasing. Have been reported.
또한 최근 보고에 따르면 선진국에서는 아토피 피부염 증가 추세가 둔화되거나 정점에 이르렀다고 하지만, 한국의 경우 대기오염, 주거환경의 변화, 식품 유해인자에 의한 항원노출의 증가 등으로 인해 아토피 피부염이 증가 추세인 것으로 추정된다고 보고되고 있다. In addition, according to a recent report, the trend of atopic dermatitis increase has slowed or peaked in developed countries, but in Korea, atopic dermatitis is on the rise due to air pollution, changes in residential environment, and increase in antigen exposure due to food harmful factors. It is reported to be estimated.
아토피 피부염은 유전적 소인, 피부장벽 기능의 이상, 면역학적 이상 및 환경적인 요인이 복합적으로 관여하여 발생하는 것으로 추정된다. 아토피 피부염의 발생 기전은 아직 명확하게 밝혀지지 않았으나, 피부 안의 염증반응(INSIDE)과 피부 바깥의 장벽 기능 이상(OUTSIDE)이 중요한 두 축을 이루면서 상호작용을 하는 것으로 보인다. Atopic dermatitis is presumed to be caused by a combination of genetic predisposition, abnormal skin barrier function, immunological abnormalities, and environmental factors. The mechanism of occurrence of atopic dermatitis has not yet been clearly identified, but it seems that the inflammatory reaction inside the skin (INSIDE) and the abnormal barrier function outside the skin (OUTSIDE) form two important axes and interact.
즉, 알레르겐 등의 외부항원이 아토피 피부염 환자의 손상된 피부장벽을 통해 피부에 도달하게 되고 이로 인한 알레르기 염증 반응이 일어나게 된다. 아토피 피부염의 발생과 관련하여 피부 안팎의 작용이 그 선후에 관해 논란을 빚어 왔으며, 최근에는 피부장벽의 필라그린(fillagrin)에 대한 연구가 두드러지면서 피부장벽 기능 이상이 먼저(OUTSIDE/INSIDE)라는 주장과 함께 피부장벽에 대한 중요성이 대두되고 있다. In other words, external antigens such as allergens reach the skin through the damaged skin barrier of atopic dermatitis patients, resulting in an allergic inflammatory reaction. In relation to the occurrence of atopic dermatitis, the effects of inside and outside the skin have been controversial, and recently, research on fillagrin of the skin barrier has been remarkable, claiming that skin barrier function abnormalities are first (OUTSIDE/INSIDE). Along with this, the importance of the skin barrier is emerging.
그러나 아토피 피부염의 치료에 대한 평가지표로서의 접근을 위해서는 염증반응으로 나타나는 면역학적 이상(INSIDE)에 대한 이해가 동반되어야 한다.However, for an approach as an evaluation index for the treatment of atopic dermatitis, an understanding of the immunological abnormalities (INSIDE) manifested by the inflammatory reaction must be accompanied.
본 발명자들은 아토피 피부염을 야기하는 비만세포의 알레르기 유발 물질 분비를 효과적으로 차단하는 물질을 개발하고자 노력한 결과, 택란(Lycopi Herba) 추출물의 항-아토피 효과를 규명하고 본 발명을 완성하였다.As a result of trying to develop a substance that effectively blocks the secretion of allergens from mast cells causing atopic dermatitis, the present inventors have investigated the anti-atopic effect of the extract of Lycopi Herba and completed the present invention.
본 발명은 택란 추출물을 유효성분으로 포함함으로써 아토피 피부염에 대한 예방, 개선 및 치료 효능이 우수한 조성물을 제공하는 것을 목적으로 한다.An object of the present invention is to provide a composition having excellent preventive, improved, and therapeutic efficacy for atopic dermatitis by including the Taekran extract as an active ingredient.
본 발명의 일 측면에 따르면, 택란(Lycopi Herba) 추출물을 유효성분으로 포함하는 아토피 피부염의 예방 또는 치료용 약학적 조성물이 제공된다.According to an aspect of the present invention, there is provided a pharmaceutical composition for the prevention or treatment of atopic dermatitis, comprising an extract of Lycopi Herba as an active ingredient.
일 실시예에 있어서, 상기 조성물은 표피 및 진피의 두께를 감소시킬 수 있다.In one embodiment, the composition may reduce the thickness of the epidermis and the dermis.
일 실시예에 있어서, 상기 조성물은 피부조직 내 호산구 및 비만세포의 침윤을 감소시킬 수 있다.In one embodiment, the composition may reduce the infiltration of eosinophils and mast cells in skin tissue.
일 실시예에 있어서, 상기 조성물은 MAPK 인산화(MAPK phosphorylation)를 억제할 수 있다.In one embodiment, the composition may inhibit MAPK phosphorylation.
일 실시예에 있어서, 상기 조성물은 NF-kB 신호 전달 경로(NF-kB signal pathway)를 억제할 수 있다.In one embodiment, the composition may inhibit the NF-kB signal pathway.
본 발명의 다른 측면에 따르면, 택란 추출물을 유효성분으로 포함하는 아토피 피부염의 예방 또는 개선용 화장료 조성물이 제공된다.According to another aspect of the present invention, there is provided a cosmetic composition for preventing or improving atopic dermatitis, comprising a takran extract as an active ingredient.
본 발명의 다른 측면에 따르면, 택란 추출물을 유효성분으로 포함하는 아토피 피부염의 예방 또는 개선용 식품 조성물이 제공된다.According to another aspect of the present invention, there is provided a food composition for preventing or improving atopic dermatitis, comprising an extract of taekran as an active ingredient.
본 발명에 따르면, 상기 택란 추출물을 함유하는 조성물은 비만세포의 매개되는 알레르기성 염증 반응을 효과적으로 억제하므로 아토피 피부염의 예방, 개선 및 치료 효과가 우수하다.According to the present invention, the composition containing the taekran extract is excellent in preventing, improving and treating atopic dermatitis because it effectively suppresses the mediated allergic inflammatory response of mast cells.
본 발명의 효과는 상기한 효과로 한정되는 것은 아니며, 본 발명의 상세한 설명 또는 청구범위에 기재된 발명의 구성으로부터 추론 가능한 모든 효과를 포함하는 것으로 이해되어야 한다.The effects of the present invention are not limited to the above effects, and should be understood to include all effects that can be deduced from the configuration of the invention described in the detailed description or claims of the present invention.
도 1은 설치류의 대식세포(RAW 264.7)에서 택란 추출물의 세포독성을 평가한 것이다.
도 2는 LPS에 의해 자극된 설치류의 대식세포에서 택란 추출물의 처리에 따른 염증성 사이토카인(IFN-g 및 TNF-a)의 mRNA 발현 수준을 측정한 것이다.
도 3은 DNCB(2,4-dinitrochlorobenzene)에 의해 아토피 피부염이 유도된 마우스 모델에서 택란 추출물 처리에 따른 진피 및 표피의 두께를 측정한 것이다. (A) H&E 염색법으로 표피 및 진피의 두께를 측정하였다. (B) 표피의 두께를 측정한 것이다. (C) 진피의 두께를 측정한 것이다.
도 4는 DNCB에 의해 아토피 피부염이 유도된 마우스 모델에서 택란 추출물 처리에 따른 호산구의 침윤 정도를 측정한 것이다. (A) H&E 염색법으로 피부 병변에서 호산구의 침윤을 측정하였다. (B) 호산구 세포의 숫자를 정량한 것이다.
도 5는 DNCB에 의해 아토피 피부염이 유도된 마우스 모델에서 택란 추출물 처리에 따른 비만세포의 침윤 정도를 측정한 것이다. (A) 톨루이딘블루 염색법으로 피부 병변에서 비만세포의 침윤을 측정하였다. (B) 비만세포의 숫자를 정량한 것이다.
도 6은 DNCB에 의해 아토피 피부염이 유도된 마우스 모델에서 혈청 내 IgE의 수준을 측정한 것이다.
도 7은 DNCB에 의해 아토피 피부염이 유도된 마우스 모델에서 NF-κB 단백질의 발현을 측정한 것이다.
도 8은 DNCB에 의해 아토피 피부염이 유도된 마우스 모델에서 MAPK 단백질의 발현을 측정한 것이다.Figure 1 is an evaluation of the cytotoxicity of taekran extract in rodent macrophage (RAW 264.7).
Figure 2 is a measure of the mRNA expression level of inflammatory cytokines (IFN-g and TNF-a) according to the treatment of taekran extract in rodent macrophages stimulated by LPS.
Figure 3 is a measurement of the thickness of the dermis and epidermis according to the treatment of the taekran extract in a mouse model in which atopic dermatitis is induced by DNCB (2,4-dinitrochlorobenzene). (A) The thickness of the epidermis and the dermis was measured by the H&E staining method. (B) The thickness of the epidermis was measured. (C) The thickness of the dermis was measured.
Figure 4 is a measure of the degree of infiltration of eosinophils according to the treatment of atopic dermatitis in a mouse model induced by DNCB. (A) Eosinophil infiltration was measured in skin lesions by H&E staining. (B) The number of eosinophil cells was quantified.
Figure 5 is a measure of the degree of infiltration of mast cells according to the treatment of taekran extract in a mouse model in which atopic dermatitis is induced by DNCB. (A) Toluidine blue staining was used to measure mast cell infiltration in skin lesions. (B) The number of mast cells was quantified.
6 is a measurement of the level of IgE in serum in a mouse model in which atopic dermatitis was induced by DNCB.
7 is a measurement of the expression of NF-κB protein in a mouse model in which atopic dermatitis was induced by DNCB.
8 is a measurement of the expression of MAPK protein in a mouse model in which atopic dermatitis was induced by DNCB.
본 명세서에서 사용되는 용어는 본 발명에서의 기능을 고려하면서 가능한 현재 널리 사용되는 일반적인 용어들을 선택하였으나, 이는 당 분야에 종사하는 기술자의 의도 또는 판례, 새로운 기술의 출현 등에 따라 달라질 수 있다. 또한, 특정한 경우는 출원인이 임의로 선정한 용어도 있으며, 이 경우 해당되는 발명의 설명 부분에서 상세히 그 의미를 기재할 것이다. 따라서 본 발명에서 사용되는 용어는 단순한 용어의 명칭이 아닌, 그 용어가 가지는 의미와 본 발명의 전반에 걸친 내용을 토대로 정의되어야 한다.Terms used in the present specification have selected general terms that are currently widely used as possible while considering functions in the present invention, but this may vary depending on the intention or precedent of a technician working in the art, the emergence of new technologies, and the like. In addition, in certain cases, there are terms arbitrarily selected by the applicant, and in this case, the meaning of the terms will be described in detail in the description of the corresponding invention. Therefore, the terms used in the present invention should be defined based on the meaning of the term and the overall contents of the present invention, not a simple name of the term.
다르게 정의되지 않는 한, 기술적이거나 과학적인 용어를 포함해서 여기서 사용되는 모든 용어들은 본 발명이 속하는 기술 분야에서 통상의 지식을 가진 자에 의해 일반적으로 이해되는 것과 동일한 의미를 가지고 있다. 일반적으로 사용되는 사전에 정의되어 있는 것과 같은 용어들은 관련 기술의 문맥상 가지는 의미와 일치하는 의미를 가지는 것으로 해석되어야 하며, 본 출원에서 명백하게 정의하지 않는 한, 이상적이거나 과도하게 형식적인 의미로 해석되지 않는다. Unless otherwise defined, all terms used herein, including technical or scientific terms, have the same meaning as commonly understood by one of ordinary skill in the art to which the present invention belongs. Terms such as those defined in a commonly used dictionary should be interpreted as having a meaning consistent with the meaning of the related technology, and should not be interpreted as an ideal or excessively formal meaning unless explicitly defined in this application. Does not.
수치 범위는 상기 범위에 정의된 수치를 포함한다. 본 명세서에 걸쳐 주어진 모든 최대의 수치 제한은 낮은 수치 제한이 명확히 쓰여져 있는 것처럼 모든 더 낮은 수치 제한을 포함한다. 본 명세서에 걸쳐 주어진 모든 최소의 수치 제한은 더 높은 수치 제한이 명확히 쓰여져 있는 것처럼 모든 더 높은 수치 제한을 포함한다. 본 명세서에 걸쳐 주어진 모든 수치 제한은 더 좁은 수치 제한이 명확히 쓰여져 있는 것처럼, 더 넓은 수치 범위 내의 더 좋은 모든 수치 범위를 포함할 것이다.Numeric ranges are inclusive of the numerical values defined in the above range. All maximum numerical limits given throughout this specification include all lower numerical limits as if the lower numerical limits were expressly written. All minimum numerical limits given throughout this specification include all higher numerical limits as higher numerical limits are clearly written. All numerical limits given throughout this specification will include all better numerical ranges within a broader numerical range, as narrower numerical limits are clearly written.
이하, 본 발명의 실시예를 상세히 기술하나, 하기 실시예에 의해 본 발명이 한정되지 아니함은 자명하다.Hereinafter, examples of the present invention will be described in detail, but it is obvious that the present invention is not limited by the following examples.
본 발명의 일 측면에 따르면, 택란(Lycopi Herba) 추출물을 유효성분으로 포함하는 아토피 피부염의 예방 또는 치료용 약학적 조성물이 제공된다.According to an aspect of the present invention, there is provided a pharmaceutical composition for the prevention or treatment of atopic dermatitis, comprising an extract of Lycopi Herba as an active ingredient.
상기 “택란(Lycopi Herba)”은 꿀풀과(Labiatae) 식물인 쉽싸리(Lycopus lucidus)의 꽃이 피기 전의 지상부로서, “호란, 용조 또는 호포”로도 호칭된다.The "Taekran ( Licopi Herba )" is the above-ground part before flowering of the Lamiaceae (Labiatae) plant, Lycopus lucidus , and is also referred to as "Horan, Longjo or Hopo".
상기 택란은 주로 산과 들의 습한 곳에서 서식하며, 여름철 꽃이 피는 시기에 전초를 베어 햇볕에서 말려 사용한다. 상기 택란은 냄새가 없고 맛은 쓰고 매우며 성질은 약간 따뜻하며, 산후 복통과 부종, 월경 장애, 상처, 타박상, 부스럼 등의 치료에 사용되어 왔다.The above taekran mainly lives in humid places in the mountains and fields, and is used after cutting the outposts and drying them in the sun during the flowering period in summer. The taekran has no odor, has a very bitter taste, has a slightly warm nature, and has been used for the treatment of postpartum abdominal pain and swelling, menstrual disorders, wounds, bruises, and swelling.
그러나, 상기 택란이 아토피 피부염의 개선 효과 또는 관련한 작용 기전이나 효능은 현재까지 알려진 바 없으며, 본 발명자들은 상기 택란 추출물의 알레르기 유발 물질 분비 차단 효과를 규명하고자 하였다.However, the effect of improving atopic dermatitis or the mechanism of action or effect related to it has not been known until now, and the present inventors sought to investigate the effect of blocking the secretion of allergens inducing substance of the taekran extract.
상기 “추출물”은 용매와 추출재료를 특정 조건하에서 접촉시킴으로써 추출재료에 함유된 유효성분을 분리해낸 것으로, 상기 추출물은 택란에 대한 추출 공정에 의해 원료 내의 유효성분을 포함할 수 있다.The "extract" is obtained by separating the active ingredient contained in the extract material by contacting the solvent and the extract material under specific conditions, and the extract may contain the active ingredient in the raw material by the extraction process for taekran.
상기 택란 추출물은 천연물로부터 추출물을 추출하는 당업계에 공지된 통상적인 방법에 따라, 즉, 통상적인 온도, 압력의 조건 하에서 통상적인 용매를 사용하여 추출할 수 있다. 예컨대, 상기 택란 추출물은 물, 알코올, 에틸아세테이트, 아세톤, 핵산, 디클로로메탄 또는 이들의 혼합 용매를 사용하여 추출할 수 있으며, 바람직하게는 물을 사용할 수 있다. The taekran extract may be extracted according to a conventional method known in the art for extracting an extract from a natural product, that is, using a conventional solvent under conditions of a normal temperature and pressure. For example, the taekran extract may be extracted using water, alcohol, ethyl acetate, acetone, nucleic acid, dichloromethane, or a mixed solvent thereof, and water may be preferably used.
또한, 상기 추출 방법은 열수 추출, 냉침 추출, 환류 추출, 초음파 추출 등의 다양한 방법을 사용할 수 있으며, 바람직하게는 환류 추출을 사용할 수 있으나 이에 제한되는 것은 아니다.In addition, the extraction method may use various methods such as hot water extraction, cold needle extraction, reflux extraction, ultrasonic extraction, etc., preferably reflux extraction, but is not limited thereto.
상기 “유효성분으로 포함하는”은 투여하고자 하는 개체에 대한 치료적 또는 예방적 효과를 제공하기에 충분한 택란 추출물을 포함하는 것을 의미하며, 택란 추출물은 인체에 대한 독성이 없으므로 당업자가 다양한 변수를 고려하여 양적 상한을 적절히 조정할 수 있다.The term "contained as an active ingredient" means containing a taekran extract sufficient to provide a therapeutic or prophylactic effect to the individual to be administered, and the taekran extract is not toxic to the human body, so a person skilled in the art considers various variables. Thus, the upper limit of quantity can be appropriately adjusted.
상기 “예방”은 동물의 병리학적 현상의 발생 빈도 또는 정도를 억제시키거나 발명을 지연시키는 모든 행위를 의미한다. 예방은 완전할 수 있으며 또는 부분적일 수도 있다. The "prevention" means any action that suppresses the frequency or degree of occurrence of pathological phenomena in animals or delays the invention. Prevention can be complete or partial.
상기 “개선”은 조성물의 투여에 의해 증상의 정도를 적어도 감소시키는 모든 행위를 의미한다. The "improvement" means any action of at least reducing the severity of symptoms by administering the composition.
상기 “치료”는 치료하고자 하는 대상 또는 세포의 천연 과정을 변경시키기 위하여 임상적으로 개입하는 모든 행위를 의미하며, 임상 병리 상태가 진행되는 동안 또는 이를 예방하기 위하여 수행될 수 있다. 목적하는 치료 효과는 질병의 발생 또는 재발을 예방하거나, 증상을 완화시키거나, 질병에 따른 모든 직접 또는 간접적인 병리학적 결과를 저하시키거나, 전이를 예방하거나, 질병 진행 속도를 감소시키거나, 질병 상태를 경감 또는 일시적 완화시키거나, 예후를 개선시키는 것을 포함할 수 있다.The “treatment” refers to any action that clinically intervenes in order to change the natural process of a target or cell to be treated, and may be performed during or to prevent a clinical pathology condition. The desired therapeutic effect is to prevent the occurrence or recurrence of the disease, alleviate symptoms, reduce all direct or indirect pathological consequences of the disease, prevent metastasis, reduce the rate of disease progression, or It may include alleviating or temporarily alleviating the condition, or improving the prognosis.
상기 조성물은 비만세포(mast cell)가 매개하는 알레르기성 염증 반응을 억제할 수 있다. The composition may suppress an allergic inflammatory reaction mediated by mast cells.
상기 비만세포는 모든 포유 동물 조직에 있으며, 염증 및 자가 면역 질환의 발병 기전에 중요한 역할을 한다(Heger et al., 2014). 상기 비만세포는 생명을 위협하는 아나필락시스, 알레르기성 비염, 아토피성 피부염과 같은 알레르기성 반응의 초기 단계 또는 후기 단계 염증 반응 중에 효과기 세포(effector cells)로서 기능할 수 있다(El-Agamy, 2012).The mast cells are in all mammalian tissues and play an important role in the pathogenesis of inflammatory and autoimmune diseases (Heger et al., 2014). The mast cells may function as effector cells during an early or late stage inflammatory reaction of an allergic reaction such as life-threatening anaphylaxis, allergic rhinitis, and atopic dermatitis (El-Agamy, 2012).
활성화되어 탈과립(degranulation)된 비만세포는 사이토카인(cytokines) 및 케모카인(chemokines)을 생성할 수 있다. 상기 비만세포에 의해 방출되는 사이토카인은 상주 세포(resident cells)에 의한 염증유발 사이토카인(proinflammatory cytokine)의 생성을 증대시킬 수 있다.Activated and degranulated mast cells can produce cytokines and chemokines. Cytokines released by mast cells can increase the production of proinflammatory cytokines by resident cells.
특히, 방출된 히스타민은 혈관(vessel) 투과성(permeabilization)을 증대시켜 염증 조직으로 호산구(eosinophils), 호중구(neutrophils), 및 대식세포의 이동을 촉진할 수 있다. 따라서, 비만세포의 활성화 및 탈과립은 상기 염증 반응을 증대 및 지속시킬 수 있다(Galli and Tsai, 2012).In particular, the released histamine can promote the movement of eosinophils, neutrophils, and macrophages to inflamed tissue by increasing vessel permeabilization. Therefore, activation and degranulation of mast cells can increase and sustain the inflammatory response (Galli and Tsai, 2012).
따라서 상기 조성물은 상기 비만세포의 활성화 및 탈과립화를 저해하므로 상기 비만세포에 의해 매개되는 알레르기성 염증 반응을 효과적으로 억제할 수 있다. Therefore, since the composition inhibits activation and degranulation of the mast cells, it can effectively suppress the allergic inflammatory reaction mediated by the mast cells.
구체적으로 상기 조성물은 비만세포의 MAPK 인산화(MAPKs phosphorylation) 및 NF-kB 신호 전달 경로(NF-kB signal pathway)를 억제할 수 있고, 상기 비만세포의 히스타민 방출을 억제하여 알레르기성 염증 반응을 완화 또는 제거할 수 있다. Specifically, the composition can inhibit MAPK phosphorylation and NF-kB signal pathway of mast cells, and suppress the release of histamine from mast cells to alleviate or reduce allergic inflammatory reactions. Can be removed.
염증성 사이토카인의 발현은 NF-kB 및 MAPKs의 신호 전달(transductions)에 의존한다. 상기 비만세포는 DNCB의 자극에 의해 MAPKs 및 NF-kB 신호가 활성화되고, 이로 인해 다량의 사이토카인 및 케모카인, 부착분자(adhesion molecule), 염증 매개물질(inflammatory mediator), 매트릭스 분해 효소(matrix degrading enzyme)의 과량 발현 및 방출을 야기할 수 있다. The expression of inflammatory cytokines depends on the transductions of NF-kB and MAPKs. In the mast cells, MAPKs and NF-kB signals are activated by stimulation of DNCB, and thereby a large amount of cytokines and chemokines, adhesion molecules, inflammatory mediators, matrix degrading enzymes ) Overexpression and release.
MAPKs는 중요한 NF-kB 활성화 인자이다. 상기 NF-kB는 세포 외 신호-조절 키나아제(ERK), P38, 및 c-Jun N-말단 키나아제(JNK)와 같은 MAPK 패밀리 멤버에 의해 활성화될 수 있다(Han et al., 2013).MAPKs are important NF-kB activating factors. The NF-kB can be activated by members of the MAPK family such as extracellular signal-regulated kinase (ERK), P38, and c-Jun N-terminal kinase (JNK) (Han et al., 2013).
신호전달 반응에 의해서 비만세포가 활성화되면 세포질 내 칼슘 농도가 상승하고 비만세포의 탈과립이 유도되어 과립 내의 히스타민, 프로스타글란딘, 류코트리엔, TNF-α, IL-1β, IL-4, IL-5, IL-6, IL-13 등의 사이토카인을 분비하며, 분비된 염증성 사이토카인은 혈관 확장이나 투과성의 항진, 신경종말의 자극, 점액 분비의 항진, 평활근의 수축 등 조기 알레르기 반응을 촉진할 수 있다(Meltzer, E. O. et al, 2000).When mast cells are activated by signaling reaction, calcium concentration in the cytoplasm rises and degranulation of mast cells is induced, resulting in histamine, prostaglandin, leukotriene, TNF-α, IL-1β, IL-4, IL-5, IL- in granules. It secretes cytokines such as 6, IL-13, and the secreted inflammatory cytokines can promote early allergic reactions such as vasodilation or hyperpermeability, stimulation of nerve endings, promotion of mucus secretion, and contraction of smooth muscles (Meltzer , EO et al, 2000).
택란 추출물은 IFN-g 및 TNF-a 등 알레르기 염증 반응에 관여하는 사이토카인의 생성을 억제하며, 사이토카인의 전사인자인 NF-kB 및 상기 NF-kB의 활성화에 관여하는 MAPK(ERK 및 JNK)를 효과적으로 저해하므로 아토피 피부염의 예방 및 치료 효과가 우수하다.Taekran extract inhibits the production of cytokines involved in allergic inflammatory reactions such as IFN-g and TNF-a, and NF-kB, a transcription factor of cytokines, and MAPK (ERK and JNK) involved in the activation of the NF-kB. Since it effectively inhibits atopic dermatitis, the prevention and treatment effect is excellent.
한편, 상기 조성물은 약학 조성물의 제조에 사용되는 담체, 부형제 및 희석제를 더 포함할 수 있다. Meanwhile, the composition may further include a carrier, an excipient, and a diluent used to prepare a pharmaceutical composition.
상기 담체, 부형제 및 희석제로는 락토오스, 덱스트로오스, 수크로오스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로오스, 메틸 셀룰로오스, 미정질 셀룰로오스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 또는 광물유를 들 수 있으나, 이에 한정되는 것은 아니다. Examples of the carrier, excipient and diluent include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, Polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, or mineral oil, but are not limited thereto.
또한, 상기 조성물은 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제제화 하여 사용할 수 있다. In addition, the composition may be formulated and used in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, and aerosols, external preparations, suppositories, and sterile injectable solutions.
상기 경구 투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 상기 페이미닌과 적어도 하나 이상의 부형제, 예컨대, 전분, 칼슘카보네이트, 수크로오스, 락토오스, 또는 젤라틴 등을 혼합하여 조제할 수 있다. 상기 부형제 이외에 마그네슘 스티레이트, 탈크 같은 윤활제가 사용될 수도 있다. The solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and these solid preparations include the faiminin and at least one excipient such as starch, calcium carbonate, sucrose, lactose, or gelatin. It can be prepared by mixing and the like. In addition to the above excipients, lubricants such as magnesium stearate and talc may be used.
상기 경구 투여를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 사용될 수 있으며, 단순희석제인 물, 리퀴드 파라핀 외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. Liquid preparations for oral administration may include suspensions, liquid solutions, emulsions, syrups, etc., and various excipients, such as wetting agents, sweeteners, fragrances, preservatives, etc., in addition to water and liquid paraffin, which are simple diluents, may be used. have.
상기 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제제, 좌제가 사용될 수 있다. 상기 비수성용제, 현탁제로는 프로필렌글리콜(propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르가 사용될 수 있다. 상기 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로제라틴이 사용될 수 있다.In the formulation for parenteral administration, a sterilized aqueous solution, a non-aqueous solvent, a suspension, an emulsion, a freeze-dried formulation, and a suppository may be used. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate may be used. As a base for the suppository, witepsol, macrogol, tween 61, cacao butter, laurin paper, and glycerogelatin may be used.
상기 택란 추출물을 유효성분으로 포함하는 약학적 조성물은 약제학적으로 유효한 양이 대상체에 투여될 수 있다. 상기 “유효한 양”은 의학적 치료에 적용 가능한 합리적인 수혜 또는 위험 비율로 질환을 치료하기에 충분한 양을 의미한다. 상기 유효 용량 수준은 환자의 질환의 종류, 중증도, 약물의 활성, 약물에 대한 민감도, 투여 시간, 투여 경로 및 배출 비율, 치료 기간, 동시 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 결정될 수 있다. The pharmaceutical composition containing the taekran extract as an active ingredient may be administered to a subject in a pharmaceutically effective amount. The above "effective amount" means an amount sufficient to treat a disease with a reasonable benefit or risk ratio applicable to medical treatment. The effective dose level depends on the type of disease, the severity, the activity of the drug, the sensitivity to the drug, the time of administration, the route of administration and the rate of excretion, the duration of treatment, factors including concurrent drugs, and other factors well known in the medical field. Can be determined accordingly.
상기 약학적 조성물은 개별 치료제로 투여하거나 다른 치료제와 병용하여 투여될 수 있고, 종래의 치료제와 순차적으로 또는 동시에 투여될 수 있으며 단일 또는 다중 투여될 수 있다. 상기 요소들을 모두 고려하여 부작용 없이 최소한의 양으로 최대 효과를 얻을 수 있는 양을 투여하는 것이 바람직하며, 이는 당업자에 의해 용이하게 결정될 수 있다.The pharmaceutical composition may be administered as an individual therapeutic agent or administered in combination with other therapeutic agents, may be administered sequentially or simultaneously with a conventional therapeutic agent, and may be administered single or multiple. It is preferable to administer an amount capable of obtaining the maximum effect in a minimum amount without side effects in consideration of all the above factors, and this can be easily determined by a person skilled in the art.
본 발명의 다른 측면은 택란 추출물을 유효성분으로 포함하는 아토피 피부염의 예방 또는 개선용 화장료 조성물을 제공한다.Another aspect of the present invention provides a cosmetic composition for the prevention or improvement of atopic dermatitis, comprising a takran extract as an active ingredient.
상기 “화장료 조성물”은 통상의 방법에 의해 제형화될 수 있다. 피부 외용제의 제형화에 있어서 Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA에 개시되어 있는 내용을 참조할 수 있고, 화장료 조성물의 제형화에 있어서 International cosmetic ingredient dictionary, 6th ed(The cosmetic, Toiletry and Fragrance Association, Inc., Washington, 1995)에 개시되어 있는 내용을 참조할 수 있다.The “cosmetic composition” may be formulated by a conventional method. Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA can refer to the contents disclosed in the formulation of external preparations for skin, and the International cosmetic ingredient dictionary, 6th ed (The cosmetic, Toiletry and Fragrance Association) in the formulation of cosmetic compositions. , Inc., Washington, 1995).
구체적으로, 상기 화장료 조성물은 일반적인 유화 제형 및 가용화 제형으로 제조할 수 있다. 예컨대, 유연 화장수 또는 영양 화장수 등의 화장수; 훼이셜 로션, 바디로션 등의 유액; 영양 크림, 수분 크림, 아이 크림 등의 크림; 에센스; 화장연고; 스프레이; 젤; 팩; 선 스크린; 메이크업 베이스; 액체 타입, 고체 타입 또는 스프레이 타입 등의 파운데이션; 파우더; 클렌징 크림, 클렌징 로션, 클렌징 오일 등의 메이크업 제거제; 또는 클렌징 폼, 비누, 바디워시 등의 세정제로 제형화될 수 있으나 이에 한정되는 것은 아니다. 또한 상기 피부 외용제는, 연고, 패취, 겔, 크림 또는 분무제로 제형화될 수 있으나 이에 한정되는 것은 아니다.Specifically, the cosmetic composition can be prepared in a general emulsion formulation and solubilization formulation. For example, a lotion such as a flexible lotion or a nutritional lotion; Emulsions such as facial lotion and body lotion; Creams such as nourishing cream, moisture cream, and eye cream; essence; Cosmetic ointment; spray; Gel; pack; Sunscreen; Makeup base; Foundations such as liquid type, solid type or spray type; powder; Makeup removers such as cleansing cream, cleansing lotion, and cleansing oil; Alternatively, it may be formulated with a detergent such as cleansing foam, soap, and body wash, but is not limited thereto. In addition, the external preparation for skin may be formulated as an ointment, patch, gel, cream, or spray, but is not limited thereto.
상기 화장료 조성물은 각각의 제형에 있어서 상기 필수성분 외에 제형의 종류 또는 사용 목적 등에 따라 본 발명에 따른 목적을 저해하지 않는 범위 내에서 다른 성분들이 적절히 배합될 수 있다.In the cosmetic composition, in addition to the essential ingredients in each formulation, other ingredients may be appropriately blended within a range that does not impair the object according to the present invention depending on the type of formulation or purpose of use.
상기 화장료 조성물은 통상적으로 허용 가능한 담체를 포함할 수 있으며, 예컨대 유분, 물, 계면활성제, 보습제, 저급 알코올, 증점제, 킬레이트제, 색소, 방부제, 향료 등을 적절히 배합할 수 있으나, 이에 한정되는 것은 아니다.The cosmetic composition may include a generally acceptable carrier, for example, oil, water, surfactant, moisturizer, lower alcohol, thickener, chelating agent, colorant, preservative, fragrance, etc. may be appropriately blended, but are limited thereto. no.
상기 허용 가능한 담체는 제형에 따라 달리할 수 있다. 예컨대, 연고, 페이스트, 크림 또는 젤로 제형화될 때 담체 성분으로서 동물성 유, 식물성 유, 왁스, 파라핀, 전분, 트라칸트, 셀룰로오스 유도체, 폴리에틸렌 글리콜, 실리콘, 벤토나이트, 실리카, 탈크, 산화아연 또는 이들의 혼합물이 사용될 수 있다The acceptable carrier may vary depending on the formulation. For example, when formulated as an ointment, paste, cream or gel, as a carrier component, animal oil, vegetable oil, wax, paraffin, starch, tracanth, cellulose derivatives, polyethylene glycol, silicone, bentonite, silica, talc, zinc oxide or these Mixtures can be used
상기 화장료 조성물은 파우더 또는 스프레이로 제형화될 때, 담체 성분으로서 락토스, 탈크, 실리카, 알루미늄 히드록사이드, 칼슘 실케이트, 폴리아미드 파우더 또는 이들의 혼합물이 사용될 수 있고, 스프레이의 경우 클로로플루오로히드로카본, 프로판, 부탄 또는 디메틸 에테르와 같은 추진제를 더 포함할 수 있다.When the cosmetic composition is formulated as a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, polyamide powder, or a mixture thereof may be used as a carrier component, and in the case of spray, chlorofluorohydrogen Propellants such as carbon, propane, butane or dimethyl ether may be further included.
상기 화장료 조성물은 용액 또는 유탁액으로 제형화될 때, 담체 성분으로서 용매, 용해화제, 또는 유탁화제가 사용될 수 있고, 예컨대 물, 에탄올, 이소프로판올, 에틸 카보네이트, 에틸 아세테이트, 벤질 벤조에이트, 프로필렌 글리콜, 1,3-브틸글리콜 오일이 사용될 수 있고, 특히, 목화씨 오일, 땅콩 오일, 옥수수 배종 오일, 올리브 오일, 피마자 오일 및 참깨 오일, 글리세롤 지방족 에스테르, 폴리에틸렌 글리콜 또는 소르비탄의 지방산 에스테르가 사용될 수 있다. When the cosmetic composition is formulated as a solution or emulsion, a solvent, a solubilizing agent, or an emulsifying agent may be used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl benzoate, propylene glycol, 1,3-Butylglycol oil may be used, and in particular cottonseed oil, peanut oil, corn germ oil, olive oil, castor oil and sesame oil, glycerol aliphatic ester, polyethylene glycol or fatty acid ester of sorbitan may be used.
상기 화장료 조성물은 현탁액으로 제형화될 때, 담체 성분으로서 물, 에탄올 또는 프로필렌 글리콜과 같은 액상의 희석제, 에톡실화 이소스테아릴 알코올, 폴리옥시에틸렌 소르비톨 에스테르 및 폴리 옥시에틸렌 소르비탄 에스테르와 같은 현탁제, 미소결정성 셀룰로오스, 알루미늄 메타히드록시드, 벤토나이트, 아가 또는 트라칸트 등이 사용될 수 있다.When the cosmetic composition is formulated as a suspension, as a carrier component, a liquid diluent such as water, ethanol or propylene glycol, an ethoxylated isostearyl alcohol, a suspending agent such as polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, Microcrystalline cellulose, aluminum metahydroxide, bentonite, agar or tracant, and the like can be used.
상기 화장료 조성물이 비누로 제형화될 때, 담체 성분으로서 지방산의 알칼리 금속 염, 지방산 헤미에스테르 염, 지방산 단백질 히드롤리제이트, 이세티오네이트, 라놀린 유도체, 지방족 알코올, 식물성 유, 글리세롤, 당 등이 사용될 수 있다.When the cosmetic composition is formulated with soap, as a carrier component, alkali metal salts of fatty acids, fatty acid hemiester salts, fatty acid protein hydrolyzate, isethionate, lanolin derivatives, aliphatic alcohols, vegetable oils, glycerol, sugars, etc. Can be used.
상기 화장료 조성물은 최종 제품의 품질이나 기능에 따라 업계에서 통상적으로 사용되는 지방 물질, 유기용매, 용해제, 농축제, 겔화제, 연화제, 항산화제, 현탁화제, 안정화제, 발포제(foaming agent), 방향제, 계면활성제, 물, 이온형 또는 비이온형 유화제, 충전제, 금속이온봉 쇄제, 킬레이트화제, 보존제, 차단제, 습윤화제, 필수 오일, 염료, 안료, 친수성 또는 친유성 활성제, 화장품에 통상적으로 사용되는 임의의 다른 성분과 같은 화장품학 또는 피부과학 분야에서 통상적으로 사용되는 보조제를 추가적으로 함유할 수 있다.The cosmetic composition is a fatty substance, an organic solvent, a solubilizer, a thickener, a gelling agent, an emollient, an antioxidant, a suspending agent, a stabilizer, a foaming agent, and a fragrance, which are commonly used in the industry depending on the quality or function of the final product. , Surfactants, water, ionic or nonionic emulsifiers, fillers, sequestering agents, chelating agents, preservatives, blocking agents, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic activators, commonly used in cosmetics It may additionally contain adjuvants commonly used in the field of cosmetology or dermatology, such as any other ingredients.
다만, 상기 보조제 및 그 혼합 비율은 본 발명에 따른 화장료 조성물의 바람직한 성질에 영향을 미치지 않도록 적절히 선택할 수 있다.However, the adjuvant and its mixing ratio can be appropriately selected so as not to affect the desirable properties of the cosmetic composition according to the present invention.
본 발명의 다른 측면은 택란 추출물을 유효성분으로 포함하는 아토피 피부염의 예방 또는 개선용 식품 조성물을 제공한다.Another aspect of the present invention provides a food composition for the prevention or improvement of atopic dermatitis, comprising a taekran extract as an active ingredient.
상기 “식품 조성물”은 통상적인 기능성 식품 또는 건강기능식품을 모두 포함하는 개념으로 이용될 수 있다.The "food composition" may be used as a concept including all of a general functional food or a health functional food.
상기 기능성 식품은 통상의 식품 첨가물을 포함할 수 있으며, 상기 식품 첨가물은 다른 규정이 없는 한 식품의약품안전처에 승인된 식품 첨가물 공전의 총칙 및 일반시험법 등에 따라 해당 품목에 관한 규격 및 기준에 의하여 적합성 여부를 판단할 수 있다.The functional food may contain ordinary food additives, and unless otherwise specified, the food additives shall comply with the standards and standards for the relevant item according to the general rules and general test methods of food additives approved by the Ministry of Food and Drug Safety. Whether it is appropriate or not can be judged.
상기 식품 첨가물 공전에 기재된 품목은 예컨대 케톤류, 글리신, 구연산칼륨, 니코틴산, 계피산 등의 화학적 합성물, 감색소, 감초추출물, 결정셀룰로오스, 고량색소, 구아검 등의 천연첨가물, L-글루타민산나트륨 제제, 면류첨가알칼리제, 보존료제제, 타르색소제제 등의 혼합제제류를 들 수 있다.The items described in the food additive code include, for example, ketones, glycine, potassium citrate, nicotinic acid, cinnamic acid, and other chemical compounds, dyestuffs, licorice extract, crystalline cellulose, high-volume pigments, natural additives such as guar gum, sodium L-glutamate preparations, and noodles. Mixed preparations, such as an added alkali agent, a preservative preparation, and a tar color preparation, are mentioned.
상기 기능성 식품은 아토피 피부염, 피부 보습 및 피부 진정 등의 개선을 위한 식품 및 음료 등에 다양하게 이용될 수 있으며, 예컨대, 각종 식품류, 음료, 껌, 차, 비타민 복합제, 건강기능성 보조 식품, 식품 첨가제 등에 사용될 수 있다.The functional food may be variously used in foods and beverages for improvement of atopic dermatitis, skin moisturizing and skin soothing, for example, various foods, beverages, gum, tea, vitamin complexes, health functional supplements, food additives, etc. Can be used.
상기 기능성 식품은 아토피 피부염, 피부 보습 및 피부 진정 등의 개선을 위한 목적으로, 전체 중량 대비 1.0 내지 10.0 중량%의 상기 조성물을 포함할 수 있다. 상기 조성물이 1.0 중량% 미만이면 항산화 및 항염증 효과가 충분히 구현되지 않을 수 있고 10.0 중량% 초과이면 제품 본연의 품질이 구현되지 않거나 비용 효율이 저하될 수 있다.The functional food may contain 1.0 to 10.0% by weight of the composition based on the total weight for the purpose of improving atopic dermatitis, skin moisturizing, and skin soothing. If the composition is less than 1.0% by weight, antioxidant and anti-inflammatory effects may not be sufficiently implemented, and if it is more than 10.0% by weight, the original product quality may not be implemented or cost efficiency may be lowered.
상기 기능성 식품은 아토피 피부염, 피부 보습 및 피부 진정 등의 개선을 목적으로 정제, 과립, 분말, 캅셀, 액상의 용액 및 환으로 이루어진 군에서 선택된 어느 하나의 제형으로 제조 및 가공될 수 있다.The functional food may be prepared and processed into any one formulation selected from the group consisting of tablets, granules, powders, capsules, liquid solutions, and pills for the purpose of improving atopic dermatitis, skin moisturizing, and skin soothing.
구체적으로 상기 정제 형태의 기능성 식품은 식물 추출물 또는 이의 분획물, 부형제, 결합제, 붕해제 및 다른 첨가제와의 혼합물을 통상의 방법으로 과립화한 다음, 활택제 등을 넣어 압축 성형하거나, 상기 혼합물을 직접 압축 성형하여 제조할 수 있다. 또한, 상기 정제 형태의 기능성 식품은 필요에 따라 교미제 등을 함유할 수 있으며, 필요에 따라 적당한 제피제로 제피할 수도 있다.Specifically, the functional food in the form of a tablet is a plant extract or a fraction thereof, an excipient, a binder, a mixture of a disintegrant and other additives are granulated by a conventional method, and then compression molded by putting a lubricant or the like, or the mixture is directly It can be manufactured by compression molding. In addition, the functional food in the form of a tablet may contain a flavoring agent or the like as necessary, and may be coated with a suitable coating agent if necessary.
상기 캅셀 형태의 기능성 식품 중 경질캅셀제는 통상의 경질캅셀에 가지 추출물 및 부형제 등의 첨가제와의 혼합물 또는 그의 입상물 또는 제피한 입상물을 충진하여 제조할 수 있으며, 연질캅셀제는 식물 추출물 또는 이의 분획물, 및 부형제 등의 첨가제와의 혼합물을 젤라틴 등 캅셀기제에 충진하여 제조할 수 있다. 상기 연질캅셀제는 필요에 따라 글리세린 또는 솔비톨 등의 가소제, 착색제, 보존제 등을 함유할 수 있다.Among the functional foods in the form of capsules, hard capsules can be prepared by filling a conventional hard capsule with a mixture of additives such as eggplant extracts and excipients, or granules or skinned granules thereof, and soft capsules are plant extracts or fractions thereof. , And a mixture of additives such as excipients can be prepared by filling a capsule base such as gelatin. The soft capsules may contain a plasticizer such as glycerin or sorbitol, a colorant, a preservative, and the like, if necessary.
상기 환 형태의 기능성 식품은 식물 추출물 또는 이의 분획물, 부형제, 결합제, 붕해제 등의 혼합물을 적당한 방법으로 성형하여 조제할 수 있으며, 필요에 따라 백당이나 다른 적당한 제피제로 제피를, 또는 전분, 탈크 또는 적당한 물질로 환의를 입힐 수도 있다.The ring-shaped functional food may be prepared by molding a mixture of plant extracts or fractions thereof, excipients, binders, disintegrants, and the like in an appropriate method, and if necessary, the coating may be coated with a white sugar or other suitable coating agent, or starch, talc, or You can also create a ring with a suitable substance.
상기 과립형태의 기능성 식품은 식물 추출물 또는 이의 분획물, 부형제, 결합제, 붕해제 등의 혼합물을 적당한 방법으로 입상으로 제조할 수 있으며, 필요에 따라 착향제, 교미제 등을 함유할 수 있다The granular functional food may be prepared in granular form by a suitable method of a mixture of plant extracts or fractions thereof, excipients, binders, disintegrants, etc., and may contain flavoring agents, flavoring agents, etc., if necessary.
또한, 상기 부형제, 결합제, 붕해제, 활택제, 교미제, 착향제 등에 대한 용어 정의는 당업계에 공지된 문헌에 기재된 것으로 그 기능 등이 동일 내지 유사한 것들을 포함할 수 있다.In addition, the definitions of terms for the excipients, binders, disintegrants, lubricants, flavoring agents, flavoring agents, and the like are described in documents known in the art, and may include those having the same or similar functions.
상기 건강기능식품은 건강기능식품에 관한 법률 제6727호에 따른 인체에 유용한 기능성을 가진 원료나 성분을 사용하여 제조 및 가공한 식품을 말하며, 인체의 구조 및 기능에 대하여 영양소를 조절하거나 생리학적 작용 등과 같은 보건 용도에 유용한 효과를 얻을 목적으로 섭취하는 것을 말한다. 본 발명의 건강기능식품은 통상의 식품 첨가물을 포함할 수 있으며, 식품 첨가물로서의 적합 여부는 다른 규정이 없는 한, 식품의약품안전처에 승인된 식품 첨가물 공전의 총칙 및 일반시험법 등에 따라 해당 품목에 관한 규격 및 기준에 의하여 판정한다.The health functional food refers to a food manufactured and processed using raw materials or ingredients having useful functions for the human body according to the Health Functional Food Act No.6727, and controls nutrients or physiological effects on the structure and function of the human body. It refers to ingestion for the purpose of obtaining useful effects for health uses such as. The health functional food of the present invention may contain ordinary food additives, and the appropriateness as a food additive is determined by the general rules and general test methods of food additives approved by the Ministry of Food and Drug Safety, unless otherwise specified. It is judged according to the relevant standards and standards.
상기 건강기능식품은 담체, 희석제, 부형제 및 첨가제 중 하나 이상을 포함하여 정제, 환제, 산제, 과립제, 분말제, 켑슐제 및 액제 제형으로 이루어진 군에서 선택된 하나로 제형된 것을 특징으로 한다.The health functional food is characterized in that it is formulated as one selected from the group consisting of tablets, pills, powders, granules, powders, capsules, and liquid formulations, including at least one of carriers, diluents, excipients and additives.
상기 건강기능식품에 첨가할 수 있는 식품으로는, 각종 식품류, 분말, 과립, 정제, 캡슐, 시럽제, 음료, 껌, 차, 비타민 복합제, 건강기능성식품류 등이 있다.Foods that can be added to the health functional food include various foods, powders, granules, tablets, capsules, syrups, beverages, gums, teas, vitamin complexes, and health functional foods.
상기 건강기능식품에 더 포함될 수 있는 첨가제로는, 천연 탄수 화물, 향미제, 영양제, 비타민, 광물(전해질), 풍미제(합성 풍미제, 천연 풍미제 등), 착색제, 충진제, 팩트산 및 그의 염, 일간산 및 그의 염, 유기산, 보호성 콜로이드 증점제, PH조절제, 안정화제, 방부제, 산화 방지제, 글리세린, 알콜, 탄산화제 및 과육으로 이루어진 군으로부터 선택된 1종 이상의 성분을 사용할 수 있다.Additives that may be further included in the health functional food include natural carbohydrates, flavoring agents, nutrients, vitamins, minerals (electrolytes), flavoring agents (synthetic flavoring agents, natural flavoring agents, etc.), coloring agents, fillers, lactic acids and their Salts, daily acids and salts thereof, organic acids, protective colloidal thickeners, PH regulators, stabilizers, preservatives, antioxidants, glycerin, alcohols, carbonation agents, and one or more components selected from the group consisting of pulp may be used.
상기 천연 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스 등; 및 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린 등과 같은 통상적인 당, 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다.Examples of the natural carbohydrate include monosaccharides such as glucose, fructose, and the like; Disaccharides such as maltose, sucrose, and the like; And polysaccharides, for example, common sugars such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol.
상기 향미제로서 천연 향미제(타우마틴, 스테비아추출물(예를 들어 레바우디오시드 A, 글리시르히진 등) 및 합성 향미제(사카린, 아스파르탐 등)를 유리하게 사용할 수 있다.As the flavoring agent, natural flavoring agents (taumatine, stevia extract (for example, rebaudioside A, glycyrrhizine, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used.
또한, 상기 건강기능식품은 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, 알콜, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있다.In addition, the health functional foods are various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic flavoring agents and natural flavoring agents, coloring agents and thickeners, lactic acid and salts thereof, alginic acid and salts thereof, organic acids, protective properties. Colloidal thickeners, PH regulators, stabilizers, preservatives, glycerin, alcohols, carbonates used in carbonated beverages, etc. may be contained.
상기 담체, 부형제, 희석제 및 첨가제의 구체적인 예로는 이에 한정하는 것은 아니나, 락토스, 덱스트로즈, 슈크로즈, 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, 스테아트산 마그네슘 및 미네랄 오일로 이루어진 그룹으로부터 선택된 1종 이상이 사용되는 것이 바람직하나, 이에 제한되는 것은 아니다.Specific examples of the carrier, excipient, diluent and additive are, but are not limited to, lactose, dextrose, sucrose, sorbitol, mannitol, erythritol, starch, gum acacia, calcium phosphate, alginate, gelatin, calcium phosphate, calcium silicate. , Microcrystalline cellulose, polyvinylpyrrolidone, cellulose, polyvinylpyrrolidone, methylcellulose, water, sugar syrup, methyl hydroxy benzoate, propyl hydroxy benzoate, talc, magnesium stearate, and mineral oil. At least one selected from the group is preferably used, but is not limited thereto.
이하, 첨부된 도면을 참고하여 본 발명의 실시예에 관하여 상세히 서술하나, 하기 실시예에 의해 본 발명이 제한되지 아니함은 자명하다.Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings, but it is obvious that the present invention is not limited by the following examples.
제조예 1 : 택란 추출물의 제조Preparation Example 1: Preparation of Taekran extract
택란(경북, 영천, 대한민국) 500g을 증류수 5000mL에 첨가하여 환류냉각장치 하에서 2시간 진탕한 후 실온에서 식혀 여과하였다. 그 후 감압농축기를 이용하여 농축하였으며, 동결건조하여 57.1 g의 택란 추출물(LCL)을 수득하였으며, 수득률은 11.04 %이다.500 g of Taekran (Gyeongbuk, Yeongcheon, Korea) was added to 5000 mL of distilled water, shaken for 2 hours under a reflux cooling device, cooled at room temperature, and filtered. After that, it was concentrated using a vacuum concentrator, and lyophilized to obtain 57.1 g of Taekran extract (LCL), and the yield was 11.04%.
세포 배양시 사용한 택란 추출물은 0.22㎛ 멸균 필터로 여과하여 사용하였다.The taekran extract used for cell culture was filtered through a 0.22 μm sterile filter and used.
제조예 2 : 세포 배양Preparation Example 2: Cell culture
마우스의 대식세포주인 RAW264.7 세포는 한국세포주은행(Korean Cell line bank, NO. 40071)에서 분양 받아 사용하였다.RAW264.7 cells, a macrophage cell line of mice, were pre-sale and used from Korean Cell line bank (NO. 40071).
10 % FBS(Fetal Bovine Serum) 및 1 %의 P/S(페니실린 및 스트렙토마이신)를 포함하는 DMEM(Dulbecco's Modified Eagle Medium) 배지에 상기 세포를 분주하여 95 %의 습도, 37 ℃, 5% CO2의 조건에서 배양하였다.The cells were dispensed in DMEM (Dulbecco's Modified Eagle Medium) medium containing 10% Fetal Bovine Serum (FBS) and 1% P/S (penicillin and streptomycin), and 95% humidity, 37° C., 5% CO 2 It was cultured under the conditions of.
실시예 1 : 세포독성 분석Example 1: Cytotoxicity analysis
택란 추출물의 세포독성을 알아보기 위해 상기 제조예 1의 택란 추출물을 상기 제조예 2의 세포에 처리한 후 MTT assay를 이용하여 세포 증식을 측정하였다.In order to determine the cytotoxicity of the taekran extract, after treating the cells of Preparation Example 2 with the taekran extract of Preparation Example 1, cell proliferation was measured using MTT assay.
구체적으로, 상기 세포를 24시간 동안 안정화 후 배양액에 택란 추출물 1, 10, 100 μg/mL을 각각 처리한 후 동일한 조건의 배양기에서 24시간 동안 배양하였다.Specifically, the cells were stabilized for 24 hours and then treated with 1, 10, and 100 μg/mL of taekran extract in the culture solution, respectively, and then cultured for 24 hours in an incubator under the same conditions.
배양된 세포들은 MTT assay solution 처리 후 570nm에서 흡광도를 측정하였다.The cultured cells were treated with MTT assay solution and the absorbance was measured at 570 nm.
세포 독성 측정 결과는 시료의 흡광도를 대조군(택란 추출물 0 μg/mL, Normal)의 흡광도에 대한 백분율로 표시하였다.As for the cytotoxicity measurement results, the absorbance of the sample was expressed as a percentage with respect to the absorbance of the control group (0 μg/mL, Normal).
측정 결과, 택란 추출물 1, 10, 100 μg/mL을 처리하였을 때 세포 독성이 나타나지 않았다(도 1).As a result of the measurement, cytotoxicity was not observed when treated with 1, 10, and 100 μg/mL of Taekran extract (Fig. 1).
실험예 2 : 사이토카인 mRNA 발현량 측정 시험Experimental Example 2: Cytokine mRNA expression level measurement test
택란 추출물의 투여로 염증성 세포인 RAW264.7 세포에 미치는 영향을 확인하고자 mRNA 활성을 평가하였다.The mRNA activity was evaluated to confirm the effect on RAW264.7 cells, which are inflammatory cells, by administration of the Taekran extract.
구체적으로, 상기 제조예 2에서 제조한 RAW264.7 세포에 LPS를 처리하고, 택란 추출물 0, 1, 10, 100 μg/mL를 각각 처리한 후 6시간 동안 배양 후 RNA를 추출하여 cDNA를 합성하였다.Specifically, the RAW264.7 cells prepared in Preparation Example 2 were treated with LPS, treated with 0, 1, 10, and 100 μg/mL of taekran extract, respectively, and cultured for 6 hours, and then RNA was extracted to synthesize cDNA. .
GAPDH(Glyceraldehyde 3-phosphate dehydrogenase)를 이용하여 mRNA 농도를 표준화(normalization) 하였고, Image J software(Ver. 1.46, National Institutes of Health)를 사용하여 각 band density의 데이터를 분석하였다(도 2).The mRNA concentration was normalized using GAPDH (Glyceraldehyde 3-phosphate dehydrogenase), and data of each band density was analyzed using Image J software (Ver. 1.46, National Institutes of Health) (FIG. 2).
실험에 사용된 프라이머 서열은 하기 표 1과 같다.The primer sequences used in the experiment are shown in Table 1 below.
도 2를 참조하면, 택란 추출물이 LPS로 유도된 염증성 사이토카인인 IFN-g 및 TNF-a의 발현을 유의하게 감소시켰다(p<0.01).Referring to FIG. 2, the Taekran extract significantly reduced the expression of IFN-g and TNF-a, inflammatory cytokines induced by LPS (p<0.01).
실험예 3 : 아토피 피부염 억제 효과 시험Experimental Example 3: Atopic dermatitis inhibition effect test
In vivo에서 택란 추출물의 아토피 피부염에 대한 억제 효과를 분석하고자, 생후 6주령된 BALB/c 마우스를 대상으로 아토피 피부염 모델을 구축하였다. In order to analyze the inhibitory effect on atopic dermatitis of atopic dermatitis in vivo , an atopic dermatitis model was constructed in 6-week-old BALB/c mice.
DNCB(2,4-dinitrochlorobenzene)를 일정 조건에 따라 마우스에 처리하여 아토피 피부염을 유발하였다.DNCB (2,4-dinitrochlorobenzene) was treated to mice according to certain conditions to induce atopic dermatitis.
적응 기간이 끝난 마우스는 아토피성 피부염을 유발하지 않은 양성 대조군, 아토피성 피부염을 유발시킨 음성 대조군, 아토피성 피부염을 유발시킨 후 1mg/kg의 택란 추출물을 도포한 실험군(LCL-L) 및 5mg/kg의 택란 추출물을 도포한 실험군(LCL-H)으로 분류하였다.The mice after the adaptation period were the positive control group that did not induce atopic dermatitis, the negative control group that caused atopic dermatitis, and the experimental group (LCL-L) and 5 mg/kg to which 1 mg/kg of Taekran extract was applied after inducing atopic dermatitis. It was classified into the experimental group (LCL-H) to which kg of taekran extract was applied.
상기 대조군 및 실험군을 대상으로 피부조직에 호산구(eosinophil) 세포 및 부종을 식별하는 H&E(hematoxyline and eosin) 염색과 비만세포를 식별하는 톨루이딘블루(toluidine blue) 염색을 하고 조직 내 비만세포의 침윤을 관찰하였다.The control and experimental groups were subjected to H&E (hematoxyline and eosin) staining to identify eosinophil cells and edema and toluidine blue staining to identify mast cells to observe the infiltration of mast cells in the tissue. I did.
H&E 염색을 한 대조군의 피부 조직은 표피 및 진피의 두께가 부종으로 인해 유의하게 증가하였으나, 택란 추출물을 도포한 실험군은 대조군과 비교하여 표피 및 진피의 두께가 유의적으로 감소하였다(도 3).In the skin tissue of the control group subjected to H&E staining, the thickness of the epidermis and the dermis significantly increased due to edema, but the thickness of the epidermis and the dermis significantly decreased in the experimental group to which the taekran extract was applied compared to the control group (Fig. 3).
또한, 대조군의 피부 조직은 호산구의 침윤이 확인되었으나, 택란 추출물을 도포한 실험군은 대조군과 비교하여 호산구의 침윤이 유의적으로 감소하였다(도 4).In addition, in the skin tissue of the control group, eosinophil infiltration was confirmed, but in the experimental group to which the taekran extract was applied, the infiltration of eosinophils was significantly reduced compared to the control group (FIG. 4).
더불어, 톨루이딘블루로 염색된 대조군의 피부 조직은 비만세포의 침윤이 관찰되었으나, 택란 추출물을 도포한 실험군은 대조군과 비교하여 비만세포의 침윤이 유의적으로 감소하였다(도 5).In addition, the infiltration of mast cells was observed in the skin tissue of the control group stained with toluidine blue, but the invasion of mast cells was significantly reduced in the experimental group to which the taekran extract was applied compared to the control group (Fig. 5).
실험예 4 : 아토피 피부염 모델의 혈청 내 사이토카인 측정 시험Experimental Example 4: Cytokine measurement test in serum of atopic dermatitis model
실험예 3의 아토피 피부염 모델에서 택란 추출물의 투여에 따른 사이토카인의 생성량의 변화를 확인하기 위해 ELISA assay를 수행하여 대표적 면역학 지표인 IgE 값을 분석하였다(도 6).In the atopic dermatitis model of Experimental Example 3, ELISA assay was performed to confirm the change in the amount of cytokine production according to the administration of the Taekran extract, and the IgE value, a representative immunological index, was analyzed (FIG. 6).
도 6을 참조하면, 택란 추출물을 도포함 실험군은 음성 대조군과 비교하여 IgE 발현이 현저하게 감소하였으며, 상기 결과는 택란 추출물이 IgE 활성을 효과적으로 조절함으로써 항-알레르기 효과를 구현할 수 있음을 시사한다.Referring to Figure 6, the experimental group applying the taekran extract significantly decreased IgE expression compared to the negative control, and the results suggest that the taekran extract can implement an anti-allergic effect by effectively regulating IgE activity.
실험예 5 : 아토피 피부염 모델의 NF-κ의 활성 시험Experimental Example 5: NF-κ activity test of atopic dermatitis model
실험예 3의 아토피 피부염 모델에서 택란 추출물의 투여가 염증 유발 유전자를 조절하는 핵 내 NF-κ의 단백질 발현에 미치는 영향을 확인하고자 western blot을 수행하였다(도 7).In the atopic dermatitis model of Experimental Example 3, western blot was performed to confirm the effect of administration of the Taekran extract on the protein expression of NF-κ in the nucleus that regulates inflammation-causing genes (FIG. 7).
도 7을 참조하면, DNCB 유도된 대조군에서 NF-κ발현 농도는 정상군에 비해 증가하였으며, 실험군(LCL-L 및 LCL-H 군)에서는 대조군에 비해 유의적으로 감소하였다.Referring to FIG. 7, the NF-κ expression concentration in the DNCB-induced control group was increased compared to the normal group, and the experimental group (LCL-L and LCL-H groups) significantly decreased compared to the control group.
실험예 6 : 아토피 피부염 모델의 MAPK 활성 시험Experimental Example 6: MAPK activity test of atopic dermatitis model
실험예 3의 아토피 피부염 모델에서 NF-κ의 활성화 과정에 관계되는 MAP kinase 인산화를 추가로 확인하였다(도 8).In the atopic dermatitis model of Experimental Example 3, MAP kinase phosphorylation related to the activation process of NF-κ was further confirmed (FIG. 8).
도 8을 참조하면, 정상군에 비해 DNCB 유도된 대조군에서 phosphor-ERK1/2 및 -JNK의 활성이 증가하였으며, 실험군에서는 DNCB 유도된 대조군에 비해 P-ERK는 LCL-L, LCL-H 순으로 억제하였으며, P-JNK는 LCL-H에서만 억제하였다.Referring to FIG. 8, the activity of phosphor-ERK1/2 and -JNK was increased in the DNCB-induced control group compared to the normal group, and in the experimental group, P-ERK was in the order of LCL-L and LCL-H compared to the DNCB-induced control group. Inhibited, and P-JNK was inhibited only in LCL-H.
실험예 7 : 아토피 피부염 개선 효과 평가Experimental Example 7: Evaluation of atopic dermatitis improvement effect
상기 제조예 1에서 수득된 택란 추출물을 포함하는 피부 외용제의 아토피 개선 효과를 평가하기 위해 다른 조성은 모두 동일하고 택란 추출물(실시예)과 정제수(비교예)의 시료만 달리한 크림을 제형화하였다.In order to evaluate the atopy improvement effect of the external preparation for skin containing the taekran extract obtained in Preparation Example 1, a cream was formulated in which all the other compositions were the same and only samples of taekran extract (Example) and purified water (Comparative Example) were different. .
30 내지 50세 여성 중 선정된 80명에 대하여 제형화한 실시예 및 비교예의 크림을 적용하고 아토피 피부염 개선 정도를 평가하였다.The creams of Examples and Comparative Examples formulated for 80 selected women aged 30 to 50 were applied and the degree of improvement of atopic dermatitis was evaluated.
유사한 피부염 증상을 나타내는 여성 80명에 대하여, 10명씩 8개의 조로 나누고 상기 제형화한 크림을 온도 24 내지 26 ℃, 습도 75 % 조건에서 매일 2 회씩 12 주간 안면에 전체에 도포시켰다.For 80 women with similar dermatitis symptoms, each of 10 was divided into 8 groups, and the formulated cream was applied to the entire face twice daily for 12 weeks at a temperature of 24 to 26°C and a humidity of 75%.
시험을 종료한 시점에 시험 대상자들로 하여금 설문지를 작성하게 하여 주관적인 효능 평가를 실시하였다. At the end of the test, subjects were asked to fill out a questionnaire to conduct a subjective efficacy evaluation.
설문에서는 아토피 피부염의 증상을 "소양감", "건조함", "각질 발생", "비듬", "홍반", "부어오름", "피부균열", "진물과 습진", 및 "태선화본"으로 나누고, 상기 증상이 있는 경우 각각의 증상에 대하여 개선 정도를 평가한 후 이를 평균하여 아토피 피부염 증상 개선 효과를 개인별로 평가하였다(표 2).In the questionnaire, the symptoms of atopic dermatitis were "pruritus", "dry", "keratin development", "dandruff", "erythema", "swelling", "skin cracks", "sickness and eczema", and "lichenflower". In the case of the above symptoms, the degree of improvement was evaluated for each symptom and then averaged to evaluate the effect of improving symptoms of atopic dermatitis for each individual (Table 2).
표 2를 참조하면, 실시예는 비교예와 비교하여 아토피 피부염 개선 효과가 우수한 것으로 평가되었다.전술한 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. 예를 들어, 단일형으로 설명되어 있는 각 구성 요소는 분산되어 실시될 수도 있으며, 마찬가지로 분산된 것으로 설명되어 있는 구성 요소들도 결합된 형태로 실시될 수 있다.Referring to Table 2, the Example was evaluated to have an excellent atopic dermatitis improvement effect compared to the Comparative Example. The foregoing description of the present invention is for illustration purposes only, and those of ordinary skill in the art to which the present invention belongs It will be understood that it is possible to easily transform into other specific forms without changing the technical idea or essential features of the invention. Therefore, it should be understood that the embodiments described above are illustrative and non-limiting in all respects. For example, each component described as a single type may be implemented in a distributed manner, and similarly, components described as being distributed may also be implemented in a combined form.
본 발명의 범위는 후술하는 청구범위에 의하여 나타내어지며, 청구범위의 의미 및 범위 그리고 그 균등 개념으로부터 도출되는 모든 변경 또는 변형된 형태가 본 발명의 범위에 포함되는 것으로 해석되어야 한다.The scope of the present invention is indicated by the claims to be described later, and all changes or modified forms derived from the meaning and scope of the claims and the concept of equivalents thereof should be interpreted as being included in the scope of the present invention.
Claims (7)
표피 및 진피의 두께를 감소시키는 약학적 조성물.The method of claim 1,
Pharmaceutical composition for reducing the thickness of the epidermis and dermis.
피부조직 내 호산구 및 비만세포의 침윤을 감소시키는 약학적 조성물.The method of claim 1,
A pharmaceutical composition for reducing the infiltration of eosinophils and mast cells in skin tissue.
MAPK 인산화(MAPK phosphorylation)를 억제하는 약학적 조성물.The method of claim 1,
A pharmaceutical composition that inhibits MAPK phosphorylation.
NF-kB 신호 전달 경로(NF-kB signal pathway)를 억제하는 약학적 조성물.The method of claim 1,
A pharmaceutical composition that inhibits the NF-kB signal pathway.
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