KR102450143B1 - Composition for improving, preventing or treating skin disease comprising Thymus plant extract - Google Patents
Composition for improving, preventing or treating skin disease comprising Thymus plant extract Download PDFInfo
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- KR102450143B1 KR102450143B1 KR1020200044572A KR20200044572A KR102450143B1 KR 102450143 B1 KR102450143 B1 KR 102450143B1 KR 1020200044572 A KR1020200044572 A KR 1020200044572A KR 20200044572 A KR20200044572 A KR 20200044572A KR 102450143 B1 KR102450143 B1 KR 102450143B1
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- South Korea
- Prior art keywords
- extract
- thyme
- group
- allergic
- inflammatory skin
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- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 229940011671 vitamin b6 Drugs 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
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Abstract
본 발명은 알레르기성 또는 염증성 피부질환 개선, 치료 또는 예방용 조성물에 관한 것으로, 보다 상세하게는 타임 추출물, 또는 타임 추출물 및 자주천인국 착즙액을 유효성분으로 포함하여 염증성 피부질환 동물 모델의 귀의 부종을 감소시키고, 혈액 검사에서 전체 백혈구, 호중구, 호산구, 혈중 IgE 등의 수준을 감소시키고, 조직병리학적으로 표피 내 염증세포 침윤 수준 및 비만세포 침윤 수준을 감소시키므로 알레르기성 또는 염증성 피부질환 치료 또는 예방용 약학 조성물, 알레르기성 또는 염증성 피부질환 치료 또는 예방용 동물용 약학 조성물, 알레르기성 또는 염증성 피부질환 개선용 식품 조성물, 또는 알레르기성 또는 염증성 피부질환 개선용 사료 조성물로 활용될 수 있다.The present invention relates to a composition for improving, treating, or preventing allergic or inflammatory skin disease, and more particularly, it contains thyme extract, or thyme extract and purple cheoninguk extract as an active ingredient to treat edema of the ear of an animal model of inflammatory skin disease. It reduces the level of total leukocytes, neutrophils, eosinophils, blood IgE, etc. in blood tests, and histopathologically reduces the level of inflammatory cell infiltration and mast cell infiltration in the epidermis, so it is used for the treatment or prevention of allergic or inflammatory skin diseases It can be used as a pharmaceutical composition, an animal pharmaceutical composition for treating or preventing allergic or inflammatory skin disease, a food composition for improving allergic or inflammatory skin disease, or a feed composition for improving allergic or inflammatory skin disease.
Description
본 발명은 피부질환, 특히 알레르기성 또는 염증성 피부질환 개선, 치료 또는 예방용 조성물에 관한 것으로, 보다 상세하게는 타임 추출물, 또는 타임 추출물 및 자주천인국 착즙액을 유효성분으로 포함하는 알레르기성 또는 염증성 피부질환 치료 또는 예방용 약학 조성물, 알레르기성 또는 염증성 피부질환 치료 또는 예방용 동물용 약학 조성물, 알레르기성 또는 염증성 피부질환 개선용 식품 조성물, 또는 알레르기성 또는 염증성 피부질환 개선용 사료 조성물에 관한 것이다. The present invention relates to a composition for improving, treating, or preventing skin diseases, particularly allergic or inflammatory skin diseases, and more particularly, allergic or inflammatory skin comprising thyme extract, or thyme extract and extract of thyme extract and extract of purple cheonguk as an active ingredient. It relates to a pharmaceutical composition for treating or preventing a disease, a pharmaceutical composition for an animal for treating or preventing allergic or inflammatory skin disease, a food composition for improving allergic or inflammatory skin disease, or a feed composition for improving allergic or inflammatory skin disease.
사람의 피부는 진피와 표피로 구성되어 있다. 특히, 피부의 최외각에 위치하고 있는 표피는 외부로부터의 다양한 자극, 예를 들면 화학 물질, 대기 오염 물질, 건조한 환경, 자외선 등의 물리화학적 자극인자에 대한 방어와 피부를 통한 체내 수분의 과도한 발산을 막는 보호 기능을 수행하고 있다. Human skin consists of the dermis and epidermis. In particular, the epidermis, which is located at the outermost part of the skin, protects against various external stimuli, for example, physical and chemical irritants such as chemicals, air pollutants, dry environment, and ultraviolet rays, as well as excessive dissipation of body moisture through the skin. It is performing a protective function.
표피 중에서도 가장 바깥에 존재하는 각질층은 각질 형성세포로부터 형성되며, 분화가 완결된 각질세포와 그를 둘러싼 지질층으로 구성되어 있다. 각질세포는 일정 기간이 경과하면 피부에서 탈락되고, 표피 최하층으로부터 올라온 새로운 각질형성세포가 그 기능을 대신하게 되는데, 이러한 반복적인 일련의 변화 과정을 표피 분화(epidermis differentiation) 또는 각화(keratinization)라 한다. 이러한 각화 과정에서 각질형성세포는 천연보습인자(Natural Moisturizing Factor; NMF)와 세포 간 지질을 생성하면서 각질층을 형성하여, 각질층이 견고함과 유연성을 갖도록 하여 외부와의 차단층 역할을 하는 피부장벽으로서의 기능을 보유하게 된다.Among the epidermis, the outermost stratum corneum is formed from keratinocytes and consists of keratinocytes that have completed differentiation and a lipid layer surrounding them. Keratinocytes fall off from the skin after a certain period of time, and new keratinocytes from the lowermost layer of the epidermis take over their functions. This repeated series of changes is called epidermis differentiation or keratinization. . In this keratinization process, keratinocytes form the stratum corneum while generating Natural Moisturizing Factor (NMF) and intercellular lipids. function will be retained.
이러한 각질층은 과도한 세안이나, 목욕 등의 생활 습관적 요소나, 건조한 대기 오염 물질 등의 환경적인 요인, 및 아토피성 피부나 노인성 피부 같은 내인성 질환 등으로 인해 쉽게 그 기능이 손실될 수 있다. 실제로 현대에 들어서 피부에 대한 위해 요인이 점점 증가되고 있으며, 식생활 양상의 변화로 각질층의 생성 및 탈락 속도가 늦어지고, 각질형성세포의 기능 저하로 각질층의 보습인자와 지질의 양이 감소됨에 따라, 각질층이 정상적인 피부 장벽 기능을 발휘하지 못하는 피부를 가진 사람들이 증가하고 있는 추세이다.The stratum corneum may easily lose its function due to lifestyle factors such as excessive washing or bathing, environmental factors such as dry air pollutants, and intrinsic diseases such as atopic skin or senile skin. In fact, in modern times, harmful factors to the skin are gradually increasing, and the generation and exfoliation rate of the stratum corneum is slowed due to changes in dietary patterns, and the amount of moisturizing factors and lipids in the stratum corneum is decreased due to the deterioration of the function of keratinocytes. The number of people with skin in which the stratum corneum does not exert a normal skin barrier function is increasing.
특히 아토피 피부염은 최근 들어, 유병률이 급격히 증가함에 따라 그 위험성이 크게 부각되고 있는 알레르기성 또는 염증성 피부질환으로 유전적인 요인과 면역계 결핍에 관련 있는 것으로 추정될 뿐 아직 정확한 원인은 밝혀진 바 없고, 환경 및 식생활 개선을 통해 다소 완화되는 것으로 기대될 뿐 근본적인 치료방법이 전무한 실정이다.In particular, atopic dermatitis is an allergic or inflammatory skin disease whose risk has been greatly highlighted as the prevalence has rapidly increased in recent years. It is expected that it will be alleviated to some extent through dietary improvement, but there is no fundamental treatment method.
현재까지 밝혀진 바에 따르면 아토피 피부염은 인체에 접촉하거나 들어온 알레르기 유발물질을 제거하는 과정에서 비만세포에 IgE가 생기게 되고, 추후 동일한 알레르기 유발물질과 접촉하거나 들어오게 되면 인체가 알레르기 유발물질에 대해 과민반응을 일으켜서, 히스타민을 발생하게 됨으로써 아토피성 피부염이 발병하게 된다. According to what has been revealed so far, in atopic dermatitis, IgE is generated in mast cells in the process of removing allergens that have come into contact with or entered the human body. This causes atopic dermatitis by generating histamine.
아토피 피부염의 치료제로는 주로 스테로이드 외용제, 항히스타민제, 칼시뉴린 저해제, 항생제, 자외선 요법 등이 사용되어 왔으나, 스테로이드의 경우 피부층을 지나 혈관까지 흡수됨에 따라 장기 사용할 경우, 피부위축, 모세혈관 확장 등 이상반응이 발생하였으며, 부신 억제 유발 위험이 있는 등 각종 부작용 때문에 제한이 있으므로, 상대적으로 부작용이 적으며 아토피를 치료할 수 있는 새로운 치료제에 대한 관심이 증대되고 있다.As a treatment for atopic dermatitis, external steroids, antihistamines, calcineurin inhibitors, antibiotics, and ultraviolet therapy have been used. A reaction has occurred, and there are limitations due to various side effects such as the risk of inducing adrenal suppression, and therefore, interest in new therapeutic agents that have relatively few side effects and can treat atopy is increasing.
한편 타임(Thymus vulgaris)은 꿀풀과의 키가 작은 목본 식물로서 유럽과 아프리카에 분포하며, 민간 요법으로 항염증제, 거담제, 항균제, 구취제, 진정 및 발한 효과가 있는 것으로 알려져 있다.Meanwhile, thyme ( Thymus vulgaris ) is a small woody plant of the Lamiaceae family, distributed in Europe and Africa, and is known to have anti-inflammatory, expectorant, antibacterial, deodorant, soothing and sweating effects as folk remedies.
타임(Thymus vulgaris)과 관련하여 라시드 이스마일리 등의 2016년 논문은 타임의 정유를 피부에 도포함으로써 접촉성 피부염 치료 효과가 있는 것으로 개시되어 있고, 일본공개특허 2015-107953호에는 진피 추출물, 타임 추출물 및 루이보스티 추출물이 혼합된 욕실제품이 보습 및 피부장벽 보호작용을 하는 것으로 개시되어 있으나, 타임 추출물의 경구 투여에 따른 아토피 치료 효과에 대해서는 전혀 개시되어 있지 않다.In relation to thyme ( Thymus vulgaris ), a 2016 paper by Rashid Ismaili et al. discloses that there is an effect of treating contact dermatitis by applying essential oil of thyme to the skin. And bath products mixed with rooibos tea extract have been disclosed to have moisturizing and skin barrier protection, but the therapeutic effect of atopy according to oral administration of thyme extract is not disclosed at all.
또한 자주천인국(Echinacea purpurea)은 국화과의 여러해살이 식물로서 북미가 원산이며, 꽃이 화려해서 전 세계적으로 관상용으로 널리 재배되고 있으며, 면역력을 증강시켜 감기나 각종 바이러스 감염의 치료제로도 사용되고 있다.In addition , Echinacea purpurea is a perennial plant of the Asteraceae family, native to North America, and is widely cultivated for ornamental purposes around the world because of its gorgeous flowers.
자주천인국(Echinacea purpurea)과 관련하여 한국공개특허 제2010-0074688호에는 조직 배양한 에키네시아 부정근 추출물이 피부 자극을 유발하지 않으면서 피부 보습 효과를 가지므로 화장료 조성물로 사용될 수 있음이 개시되어 있으나, 자주천인국 착즙액의 경구 투여에 따른 아토피 치료 효과에 대해서는 전혀 개시되어 있지 않다.Korean Patent Publication No. 2010-0074688 in relation to self-reliance cheonin-guk (Echinacea purpurea ) discloses that tissue-cultured Echinacea root extract has a skin moisturizing effect without causing skin irritation, so it can be used as a cosmetic composition. There is no disclosure on the therapeutic effect of atopic dermatitis following oral administration of the juice of Jajucheonin Guk.
본 발명이 해결하고자 하는 과제는 타임 추출물, 또는 타임 추출물 및 자주천인국 착즙액을 유효성분으로 포함하는 알레르기성 또는 염증성 피부질환 치료 또는 예방용 약학 조성물을 제공하는 것이다.The problem to be solved by the present invention is to provide a pharmaceutical composition for treating or preventing allergic or inflammatory skin diseases comprising a thyme extract, or a thyme extract, and a juice extract of thyme extract as an active ingredient.
본 발명이 해결하고자 하는 다른 과제는 타임 추출물, 또는 타임 추출물 및 자주천인국 착즙액을 유효성분으로 포함하는 알레르기성 또는 염증성 피부질환 치료 또는 예방용 동물용 약학 조성물을 제공하는 것이다.Another object to be solved by the present invention is to provide a pharmaceutical composition for animals for the treatment or prevention of allergic or inflammatory skin diseases, comprising a thyme extract, or a thyme extract, and the extract of thyme and purple cheoninguk juice as active ingredients.
본 발명이 해결하고자 하는 다른 과제는 타임 추출물, 또는 타임 추출물 및 자주천인국 착즙액을 유효성분으로 포함하는 알레르기성 또는 염증성 피부질환 개선용 식품 조성물을 제공하는 것이다.Another object to be solved by the present invention is to provide a food composition for alleviating allergic or inflammatory skin diseases comprising a thyme extract, or a thyme extract, and a juice extract of purple cheoninguk as an active ingredient.
본 발명이 해결하고자 하는 또 다른 과제는 타임 추출물, 또는 타임 추출물 및 자주천인국 착즙액을 유효성분으로 포함하는 알레르기성 또는 염증성 피부질환 개선용 사료 조성물을 제공하는 것이다.Another object to be solved by the present invention is to provide a feed composition for alleviating allergic or inflammatory skin diseases comprising a thyme extract, or a thyme extract, and a juice extract of purple chrysanthemum as an active ingredient.
본 발명은 상기 과제를 달성하기 위하여, 타임 추출물을 유효성분으로 포함하는 알레르기성 또는 염증성 피부질환 치료 또는 예방용 약학 조성물을 제공한다.The present invention provides a pharmaceutical composition for treating or preventing allergic or inflammatory skin disease comprising a thyme extract as an active ingredient in order to achieve the above object.
본 발명의 일 실시예에 의하면, 상기 알레르기성 또는 염증성 피부질환은 피부 염증, 습진, 접촉성 피부염, 아토피 피부염, 지루성 피부염, 만성단순태선, 간찰진, 박탈 피부염, 구진상 두드러기, 건선, 건선관절염, 일광 피부염, 일광화상 및 여드름 중에서 선택되는 어느 하나의 피부질환일 수 있다.According to an embodiment of the present invention, the allergic or inflammatory skin disease is skin inflammation, eczema, contact dermatitis, atopic dermatitis, seborrheic dermatitis, chronic lichen simplex, hepatic dermatitis, exfoliative dermatitis, papular urticaria, psoriasis, psoriatic arthritis , may be any one skin disease selected from sun dermatitis, sunburn, and acne.
본 발명의 일 실시예에 의하면, 상기 타임은 타임의 줄기, 잎 또는 지상부 전초일 수 있다.According to an embodiment of the present invention, the thyme may be a stem, a leaf or an above-ground part of the thyme.
본 발명의 일 실시예에 의하면, 상기 추출물은 물, 탄소수 1 내지 4의 알코올 또는 그들의 혼합 용매에 의한 추출물일 수 있다.According to an embodiment of the present invention, the extract may be an extract using water, an alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof.
본 발명의 일 실시예에 의하면, 상기 약학 조성물은 자주천인국 착즙액을 추가로 포함할 수 있다.According to an embodiment of the present invention, the pharmaceutical composition may further comprise a juice of cheonin-guk.
본 발명의 일 실시예에 의하면, 타임 추출물 및 자주천인국 착즙액의 혼합비율은 고형분 기준 혼합 비율은 1 : 99 내지 99 : 1 중량비일 수 있다. According to an embodiment of the present invention, the mixing ratio of the thyme extract and the juice of purple cheonin-guk may be 1:99 to 99: 1 by weight based on the solid content.
본 발명의 일 실시예에 의하면, 상기 자주천인국은 자주천인국의 줄기, 잎 또는 지상부 전초일 수 있다.According to an embodiment of the present invention, the self-propelled cheonin-guk may be a stem, a leaf, or an above-ground part of the self-propelled cheonin-guk.
본 발명의 일 실시예에 의하면, 상기 약학 조성물은 경구용 제제일 수 있다.According to an embodiment of the present invention, the pharmaceutical composition may be an oral preparation.
본 발명의 일 실시예에 의하면, 상기 경구용 제제는 산제, 과립제, 정제, 캡슐제, 트로키제, 현탁액, 에멀젼, 시럽 또는 에어로졸일 수 있다.According to an embodiment of the present invention, the oral preparation may be a powder, granule, tablet, capsule, troche, suspension, emulsion, syrup or aerosol.
또한 본 발명은 타임 추출물을 유효성분으로 포함하는 알레르기성 또는 염증성 피부질환 치료 또는 예방용 동물용 약학 조성물을 제공한다.In addition, the present invention provides a pharmaceutical composition for animals for the treatment or prevention of allergic or inflammatory skin disease comprising a thyme extract as an active ingredient.
본 발명의 일 실시예에 의하면, 상기 동물용 약학 조성물은 자주천인국 착즙액을 추가로 포함할 수 있다.According to an embodiment of the present invention, the pharmaceutical composition for animals may additionally contain a juice extract of cheonin-guk.
또한 본 발명은 타임 추출물을 유효성분으로 포함하는 알레르기성 또는 염증성 피부질환 개선용 식품 조성물을 제공한다.In addition, the present invention provides a food composition for improving allergic or inflammatory skin diseases comprising a thyme extract as an active ingredient.
본 발명의 일 실시예에 의하면, 상기 식품 조성물은 자주천인국 착즙액을 추가로 포함할 수 있다.According to an embodiment of the present invention, the food composition may further include a juice extract of cheonin-guk.
본 발명의 일 실시예에 의하면, 상기 식품 조성물은 산제, 과립제, 정제, 캡슐제, 환제, 엑스제, 젤리 제형, 티백 제형 또는 음료 제형일 수 있다.According to an embodiment of the present invention, the food composition may be a powder, granules, tablets, capsules, pills, extracts, jelly formulations, tea bag formulations or beverage formulations.
본 발명의 일 실시예에 의하면, 상기 식품 조성물은 알레르기성 또는 염증성 피부질환 개선용 건강기능식품일 수 있다.According to an embodiment of the present invention, the food composition may be a health functional food for improving allergic or inflammatory skin disease.
또한 본 발명은 타임 추출물을 유효성분으로 포함하는 알레르기성 또는 염증성 피부질환 개선용 사료 조성물을 제공한다.In addition, the present invention provides a feed composition for improving allergic or inflammatory skin disease comprising a thyme extract as an active ingredient.
본 발명의 일 실시예에 의하면, 상기 사료 조성물은 자주천인국 착즙액을 추가로 포함할 수 있다.According to an embodiment of the present invention, the feed composition may further include a juice extract of cheonin-guk.
또한 본 발명은 인간, 또는 인간을 제외한 동물에게 상기 조성물을 경구 투여하는 알레르기성 또는 염증성 피부질환의 치료방법을 제공한다.In addition, the present invention provides a method for treating allergic or inflammatory skin diseases by orally administering the composition to humans or non-human animals.
또한 본 발명은 알레르기성 또는 염증성 피부질환 치료용 의약, 또는 동물용 의약 제조를 위한 타임 추출물, 또는 타임 추출물 및 자주천인국 착즙액의 신규 용도를 제공한다.In addition, the present invention provides a novel use of a thyme extract, or a thyme extract, and a juice extract of thyme for the treatment of an allergic or inflammatory skin disease, or an animal medicine.
본 발명의 타임 추출물, 또는 타임 추출물 및 자주천인국 착즙액을 유효성분으로 포함하는 알레르기성 또는 염증성 피부질환 개선, 치료 또는 예방용 조성물은 염증성 피부질환 동물 모델의 귀의 부종을 감소시키고, 혈액 검사에서 전체 백혈구, 호중구, 호산구며, 혈중 IgE 수준을 감소시키고, 조직병리학적으로 표피 내 염증세포 침윤 수준 및 비만세포 침윤 수준을 감소시키므로 알레르기성 또는 염증성 피부질환 치료 또는 예방용 약학 조성물, 알레르기성 또는 염증성 피부질환 치료 또는 예방용 동물용 약학 조성물, 알레르기성 또는 염증성 피부질환 개선용 식품 조성물, 또는 알레르기성 또는 염증성 피부질환 개선용 사료 조성물로 활용될 수 있다.The composition for improving, treating, or preventing allergic or inflammatory skin diseases, comprising the thyme extract or thyme extract and the extract of thyme of the present invention as an active ingredient, reduces ear edema in an animal model of inflammatory skin disease, and reduces the total Leukocytes, neutrophils, eosinophils, and pharmaceutical compositions for the treatment or prevention of allergic or inflammatory skin diseases, as it reduces the level of IgE in the blood, and histopathologically reduces the level of inflammatory cell infiltration and mast cell infiltration in the epidermis, allergic or inflammatory skin It can be used as a pharmaceutical composition for animals for treating or preventing disease, a food composition for improving allergic or inflammatory skin disease, or a feed composition for improving allergic or inflammatory skin disease.
이하, 본 발명을 상세하게 설명한다.Hereinafter, the present invention will be described in detail.
본 발명의 발명자들은 알레르기성 또는 염증성 피부질환 동물 모델에서 타임 추출물, 또는 타임 추출물 및 자주천인국 착즙액을 경구 투여하여, 귀의 부종, 혈액 검사에서 전체 백혈구, 호중구, 호산구, 혈중 IgE 등의 수준 및 조직병리학적으로 표피 내 염증세포 침윤 수준 및 비만세포 침윤 수준을 평가하였다. 그 결과, 타임 추출물, 또는 타임 추출물 및 자주천인국 착즙액의 경구 투여에 의한 알레르기성 또는 염증성 피부질환에 현저한 치료 효능이 있음을 확인하였다.The inventors of the present invention orally administer thyme extract, or thyme extract, and extract of thyme in an animal model of allergic or inflammatory skin disease, and the level and tissue of total leukocytes, neutrophils, eosinophils, blood IgE, etc. in ear edema and blood tests Pathologically, the level of infiltration of inflammatory cells in the epidermis and the level of infiltration of mast cells were evaluated. As a result, it was confirmed that there is a significant therapeutic effect on allergic or inflammatory skin diseases by oral administration of thyme extract, or thyme extract and extract of jasmine cheoninguk.
본 발명은 타임 추출물을 유효성분으로 포함하는 알레르기성 또는 염증성 피부질환 치료 또는 예방용 약학 조성물에 관한 것이다.The present invention relates to a pharmaceutical composition for treating or preventing allergic or inflammatory skin disease comprising a thyme extract as an active ingredient.
또한 본 발명은 타임 추출물을 유효성분으로 포함하는 알레르기성 또는 염증성 피부질환 치료 또는 예방용 동물용 약학 조성물에 관한 것이다.In addition, the present invention relates to a pharmaceutical composition for animals for the treatment or prevention of allergic or inflammatory skin disease comprising a thyme extract as an active ingredient.
상기 타임(Thyme)은 선백리향으로 알려져 있는 티무스 불가리스(Thymus vulgaris), 티무스 지기스(Thymus zygis) 또는 이들의 혼합물로서, 백리향(Thymus quinquecostatus)과 구별된다. 타임(Thyme)은 백리향에 비해 항염증 활성이 현저히 뛰어나므로 백리향 보다 알레르기성 또는 염증성 피부질환의 치료 효과가 현저히 우수하다.The thyme ( Thyme ) is a thyme vulgaris ( Thymus vulgaris ), Thymus zygis ), or a mixture thereof, which is known as thyme, and is distinguished from thyme ( Thymus quinquecostatus ). Thyme has significantly superior anti-inflammatory activity compared to thyme, so it is significantly more effective in treating allergic or inflammatory skin diseases than thyme.
상기 타임은 타임의 잎, 줄기 또는 이를 포함하는 지상부 전초의 추출물일 수 있으나, 경구 투여에 의한 알레르기성 또는 염증성 피부질환 치료 효능은 지상부 전초의 추출물이 뛰어나다.The thyme may be an extract of leaves, stems, or an above-ground part of the thyme, but the extract of the thyme has superior efficacy in treating allergic or inflammatory skin diseases by oral administration.
상기 타임 추출물은 물, 탄소수 1 내지 4의 알코올 또는 그들의 혼합 용매에 의한 추출물일 수 있다. The thyme extract may be an extract using water, an alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof.
상기 물은 식품 제조에 적합할 경우 특별히 한정할 필요는 없으나 예를 들어 지하수, 정제수, 증류수, 탈이온수 등이 이용될 수 있다. The water does not need to be particularly limited when suitable for food production, but for example, groundwater, purified water, distilled water, deionized water, etc. may be used.
상기 탄소수 1 내지 4의 알코올은 특별히 한정할 필요는 없으나 예를 들어 메탄올, 에탄올, 프로판올, 부탄올, 노말-프로판올, 이소-프로판올 또는 노말-부탄올 등이 이용될 수 있고, 바람직하게는 에탄올이다. The alcohol having 1 to 4 carbon atoms is not particularly limited, but for example, methanol, ethanol, propanol, butanol, normal-propanol, iso-propanol or normal-butanol may be used, and preferably ethanol.
상기 혼합 용매는 특별히 한정할 필요는 없으나 예를 들어 물과 에탄올의 혼합 용매인 경우 5 내지 95 중량% 에탄올 수용액, 10 내지 90 중량% 에탄올 수용액, 20 내지 80 중량% 에탄올 수용액, 30 내지 70 중량% 에탄올 수용액이 이용될 수 있다.The mixed solvent does not need to be particularly limited, but for example, in the case of a mixed solvent of water and ethanol, 5 to 95 wt% ethanol aqueous solution, 10 to 90 wt% ethanol aqueous solution, 20 to 80 wt% ethanol aqueous solution, 30 to 70 wt% An aqueous ethanol solution may be used.
상기 물 추출물의 제조는 특별히 한정할 필요는 없으나 타임을 10 내지 100 ℃의 물로 2 내지 60 시간 동안 추출하여 제조할 수 있다.The preparation of the water extract does not need to be particularly limited, but may be prepared by extracting the time with water at 10 to 100° C. for 2 to 60 hours.
상기 알코올 추출물, 또는 물과 알코올의 혼합 용매의 추출물의 제조는 특별히 한정할 필요는 없으나 예를 들어 타임을 30 내지 70 중량%의 에탄올 수용액으로 20 내지 60 ℃에서 2 내지 48 시간 추출하여 제조할 수 있다.The preparation of the alcohol extract or the extract of a mixed solvent of water and alcohol does not need to be particularly limited, but for example, it can be prepared by extracting thyme with 30 to 70% by weight of an ethanol aqueous solution at 20 to 60° C. for 2 to 48 hours. have.
상기 물, 탄소수 1 내지 4의 알코올 또는 그들의 혼합 용매에 의한 추출물은, 물, 탄소수 1 내지 4의 알코올 또는 그들의 혼합 용매에 의한 추출물을 유기용매로 재분획한 분획물을 포함한다. 상기 유기용매는 탄소수 1 내지 4의 알코올, 헥산, 아세톤, 에틸아세테이트, 클로로포름 및 디에틸에테르 등에서 선택되는 하나 이상의 유기용매일 수 있고, 바람직하게는 헥산 또는 에틸아세테이트일 수 있다.The extract using water, an alcohol having 1 to 4 carbon atoms or a mixed solvent thereof includes a fraction obtained by refractionation of an extract using water, an alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof with an organic solvent. The organic solvent may be one or more organic solvents selected from alcohols having 1 to 4 carbon atoms, hexane, acetone, ethyl acetate, chloroform and diethyl ether, and preferably hexane or ethyl acetate.
본 발명에서 사용되는 용어 '추출물'은 상기 용매를 이용하여 타임(Thyme)에 포함된 성분을 추출한 추출물, 이들로부터 분획한 분획물, 이들 추출물 또는 분획물을 추가적으로 농축한 농축물, 이를 정제 또는 분리한 정제물도 포함하고, 상기 추출물, 분획물, 농축물 또는 정제물을 건조한 건조물 또는 그를 분쇄한 분말을 포함하는 의미로 사용된다. The term 'extract' used in the present invention is an extract obtained by extracting the components contained in thyme using the solvent, a fraction fractionated therefrom, a concentrate obtained by further concentrating these extracts or fractions, and a purified or separated tablet It also includes water, and is used in the sense of including a dried product of the extract, fraction, concentrate or purified product or a powder obtained by pulverizing the same.
상기 정제물의 제조를 위해 분자량 컷-오프 값을 갖는 한외 여과막을 통과시키거나, 또는 다양한 크로마토그래피(크기, 전하, 소수성 또는 친화성에 따른 분리를 위해 제작된 것)에 의한 분리 등, 추가적으로 실시된 다양한 정제 방법을 부가할 수 있다.For the preparation of the purified product, various additionally performed such as passing through an ultrafiltration membrane having a molecular weight cut-off value, or separation by various chromatography (those prepared for separation according to size, charge, hydrophobicity or affinity), etc. A purification method may be added.
본 발명에서 사용되는 용어 '알레르기성 또는 염증성 피부질환'은 피부에서 일어나는 알레르기성 또는 염증성 반응을 수분하는 피부질환을 제한없이 포함할 수 있으며, 예를 들어 피부 염증, 습진, 접촉성 피부염, 아토피 피부염, 지루성 피부염, 만성단순태선, 간찰진, 박탈 피부염, 구진상 두드러기, 건선, 건선관절염, 일광 피부염, 일광화상 및 여드름 중에서 선택되는 어느 하나의 피부질환일 수 있으며, 바람직하게는 만성 난치성 알레르기성 또는 염증성 피부질환인 아토피 피부염일 수 있다.The term 'allergic or inflammatory skin disease' used in the present invention may include, without limitation, skin diseases that pollinate an allergic or inflammatory reaction occurring in the skin, for example, skin inflammation, eczema, contact dermatitis, atopic dermatitis. , seborrheic dermatitis, chronic lichen simplex, hepatic dermatitis, exfoliative dermatitis, papular urticaria, psoriasis, psoriatic arthritis, solar dermatitis, sunburn and acne may be any one skin disease selected from, preferably chronic intractable allergic or It may be atopic dermatitis, an inflammatory skin disease.
상기 타임 추출물은 자주천인국 착즙액과 혼합하여 복합물로 경구 투여할 경우, 타임 추출물을 단독으로 경구 투여하는 경우에 비하여 알레르기성 또는 염증성 피부질환 치료 효능의 상승효과가 현저히 뛰어나다.When the thyme extract is orally administered as a complex by mixing it with the extract of the thyme extract, the synergistic effect of treating allergic or inflammatory skin diseases is remarkably excellent compared to the case of oral administration of the thyme extract alone.
상기 자주천인국 착즙액은 타임 추출물과 복합하여 경구 투여하는 경우, 물, 탄소수 1 내지 4의 알코올 또는 그들의 혼합 용매에 의한 자주천인국 수성 추출물이나, 또는 이들을 헥산, 에틸아세테이트 등으로 분획한 지용성 추출물에 비해 알레르기성 또는 염증성 피부질환 치료 효능이 현저히 뛰어나다.When administered orally in combination with the thyme extract, the extract of the cheonin soup is an aqueous extract of water, alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof, or a fat-soluble extract obtained by fractionating them with hexane, ethyl acetate, etc. It is very effective in treating allergic or inflammatory skin diseases.
상기 자주천인국 착즙액은 자주천인국(Echinacea purpurea)의 잎, 줄기 또는 이를 포함하는 지상부 전초의 추출물일 수 있으나, 경구 투여에 의한 알레르기성 또는 염증성 피부질환 감소 효능은 지상부 전초의 착즙액이 뛰어나다.The extract of purple cheoninguk ( Echinacea purpurea ) may be an extract of leaves, stems, or above-ground outpost containing the same, but the effect of reducing allergic or inflammatory skin diseases by oral administration is excellent.
본 발명에서 사용되는 용어 '착즙액'은 자주천인국 줄기, 잎 또는 지상부 전초를 압착, 또는 분쇄 및 압착하여 얻은 착즙액, 이들로부터 분획한 분획물, 이들 착즙액 또는 분획물을 추가적으로 농축한 농축물, 이를 정제 또는 분리한 정제물도 포함하고, 상기 착즙액, 분획물, 농축물 또는 정제물을 건조한 건조물 또는 그를 분쇄한 분말을 포함하는 의미로 사용된다. As used in the present invention, the term 'juice' refers to a juice obtained by pressing, pulverizing and pressing the stems, leaves, or above-ground parts of the stem, leaves or above-ground part of the sagebrush; It also includes purified or separated purified products, and is used in the sense of including a dried product obtained by drying the juice, a fraction, a concentrate, or a purified product or a powder obtained by pulverizing the juice.
상기 자주천인국 착즙액 분말 1 중량부를 제조하기 위해 건조되지 않은 자주천인국 약 20 내지 100 중량부, 바람직하게는 30 내지 60 중량부가 필요하고, 상기 자주천인국 착즙액 분말 1 중량부를 제조하기 위해 자주천인국 착즙액 10 내지 50 중량부, 바람직하게는 15 내지 30 중량부가 필요하다. About 20 to 100 parts by weight, preferably 30 to 60 parts by weight, of non-dried cheonin soup is required to prepare 1 part by weight of the self-propelled cheonin-guk juice powder, and to prepare 1 part by weight of the self-propelled cheonin-guk juice powder 10 to 50 parts by weight of the liquid, preferably 15 to 30 parts by weight, are required.
상기 타임 추출물 및 자주천인국 착즙액의 고형분 기준 혼합 비율은 1 : 99 중량비에서 99 : 1 중량비, 바람직하게는 5 : 95 중량비에서 95 : 5 중량비이고, 특별히 한정할 필요는 없으나 10 : 90 중량비, 20 : 80 중량비, 30 : 70 중량비, 40 : 60 중량비, 50 : 50 중량비, 60 : 40 중량비, 70 : 30 중량비, 80 : 20 중량비, 90 : 10 중량비 또는 이들 사이의 임의의 범위일 수 있다.The mixing ratio based on the solid content of the thyme extract and the juice of purple cheoninguk is 1:99 to 99: 1 by weight, preferably 5:95 to 95: 5 by weight, and there is no need to specifically limit it, but 10: 90 by weight, 20 : 80 weight ratio, 30: 70 weight ratio, 40: 60 weight ratio, 50: 50 weight ratio, 60: 40 weight ratio, 70: 30 weight ratio, 80: 20 weight ratio, 90: 10 weight ratio, or any range therebetween.
상기 '약학 조성물', '의약', '동물용 약학 조성물' 또는 '동물용 의약'은 유효성분으로 타임 추출물, 또는 타임 추출물 및 자주천인국 착즙액 이외에, 약학 조성물 등의 제조에 통상적으로 사용하는 적절한 담체, 부형제 및 희석제를 더 포함할 수 있다.The 'pharmaceutical composition', 'medicine', 'pharmaceutical composition for animals' or 'medicine for animals' is an active ingredient, in addition to thyme extract, or thyme extract and purple cheoninguk extract, suitable for use in the manufacture of pharmaceutical compositions, etc. It may further include carriers, excipients and diluents.
상기 '담체'는 세포 또는 조직 내로의 화합물의 부가를 용이하게 하는 화합물이다. 상기 '부형제'는 유효성분에 적당한 형태를 부여하여 제형화하거나 양을 증가시켜 사용하기 편리하게 하기 위해 첨가하는 화합물이다. 상기 '희석제'는 대상 화합물의 생물학적 활성 형태를 안정화시킬 뿐만 아니라, 화합물을 용해시키게 되는 물에서 희석되는 화합물이다. The 'carrier' is a compound that facilitates the addition of the compound into a cell or tissue. The 'excipient' is a compound added to make it easier to use by giving an appropriate form to the active ingredient, or by increasing the amount. The 'diluent' is a compound that is diluted in water to not only stabilize the biologically active form of the compound of interest, but also to dissolve the compound.
상기 담체, 부형제 및 희석제로는 특별히 한정할 필요는 없으나 예를 들어, 유당, 포도당, 설탕, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유 등을 들 수 있다.The carrier, excipient and diluent are not particularly limited, but for example, lactose, glucose, sugar, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose , methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methyl hydroxy benzoate, propyl hydroxy benzoate, talc, magnesium stearate and mineral oil.
상기 약학 조성물, 의약, 동물용 약학 조성물 또는 동물용 의약의 사용량은 환자 또는 치료대상 동물의 나이, 성별, 체중에 따라 달라질 수 있으며, 무엇보다도, 치료대상 개체의 상태, 치료 대상 질환의 특정한 카테고리 또는 종류, 투여 경로, 사용되는 치료제의 속성에 의존적일 것이다.The amount of the pharmaceutical composition, medicament, pharmaceutical composition for animals or veterinary medicine may vary depending on the age, sex, and weight of the patient or animal to be treated, and above all, the condition of the subject to be treated, a specific category of the disease to be treated, or It will depend on the type, route of administration, and the nature of the therapeutic agent used.
상기 약학 조성물, 의약, 동물용 약학 조성물 또는 동물용 의약은 체내에서 활성성분의 흡수도, 배설속도, 환자 또는 치료대상 동물의 연령 및 체중, 성별 및 상태, 치료할 질병의 중증정도 등에 따라 적절히 선택되나, 일반적으로 1 일 10 내지 5,000 mg, 바람직하게는 50 내지 4,000 mg, 더욱 바람직하게는 100 내지 3,000 mg, 가장 바람직하게는 200 내지 2,000 mg으로 투여하는 것이 바람직하다. 이렇게 제형화된 단위 투여형 제제는 필요에 따라 일정시간 간격으로 수회 투여할 수 있다.The pharmaceutical composition, medicament, pharmaceutical composition for animals or medicament for animals is appropriately selected according to the absorption rate of the active ingredient in the body, the rate of excretion, the age and weight of the patient or the animal to be treated, sex and condition, the severity of the disease to be treated, etc. , it is generally preferred to administer in an amount of 10 to 5,000 mg, preferably 50 to 4,000 mg, more preferably 100 to 3,000 mg, and most preferably 200 to 2,000 mg per day. The unit dosage form formulated in this way can be administered several times at regular time intervals as needed.
상기 약학 조성물, 의약, 동물용 약학 조성물 또는 동물용 의약은 개별적으로 예방제 또는 치료제로서 투여하거나 다른 치료제와 병용하여 투여될 수 있고, 종래의 치료제와는 순차적 또는 동시에 투여될 수 있다.The pharmaceutical composition, medicament, pharmaceutical composition for animals or medicament for animals may be administered individually as a prophylactic or therapeutic agent, or may be administered in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents.
상기 약학 조성물, 의약, 동물용 약학 조성물 또는 동물용 의약은 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 트로키제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구용 제제로 제형화하여 사용될 수 있다. 제형화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제될 수 있다.The pharmaceutical composition, medicine, pharmaceutical composition for animals or medicine for animals may be formulated into oral preparations such as powders, granules, tablets, capsules, troches, suspensions, emulsions, syrups, aerosols, etc. can In the case of formulation, it can be prepared using a diluent or excipient such as a filler, extender, binder, wetting agent, disintegrant, surfactant, etc. commonly used.
경구 투여를 위한 고형 제제에는 정제, 환제, 산제, 과립제, 캡슐제, 트로키제 등이 포함되며, 이러한 고형 제제는 상기 화합물에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘 카보네이트, 설탕 또는 유당, 젤라틴 등을 섞어 조제될 수 있다. 또한 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크 같은 윤활제들도 사용될 수 있다. 경구를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다.Solid preparations for oral administration include tablets, pills, powders, granules, capsules, troches, and the like, and such solid preparations include at least one excipient to the compound, for example, starch, calcium carbonate, sugar or lactose, gelatin. It can be prepared by mixing and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Liquid formulations for oral use include suspensions, solutions, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, fragrances, preservatives, etc. may be included. .
상기 알레르기성 또는 염증성 피부질환의 치료방법은 인간, 또는 인간을 제외한 동물, 특히 포유동물에게 상기 조성물을 경구 투여하는 것으로, 예를 들어 알레르기성 또는 염증성 피부질환을 가진 치료대상 개체에게 상기 조성물을 경구 투여하는 것이다.The method for treating allergic or inflammatory skin disease is by orally administering the composition to a human or non-human animal, particularly a mammal, for example, orally administering the composition to a subject to be treated with an allergic or inflammatory skin disease. is to administer
상기 치료를 위한 투여량, 투여 방법 및 투여 횟수는 상기 약학 조성물, 의약, 동물용 약학 조성물 또는 동물용 의약의 투여량, 투여 방법 및 투여 횟수를 참고할 수 있다.The dosage, administration method, and frequency of administration for the treatment may refer to the dosage, administration method and frequency of administration of the pharmaceutical composition, medicine, pharmaceutical composition for animals or medicament for animals.
본 발명은 타임 추출물, 또는 타임 추출물 및 자주천인국 착즙액을 유효성분으로 포함하는 알레르기성 또는 염증성 피부질환 개선용 식품 조성물에 관한 것이다.The present invention relates to a food composition for alleviating allergic or inflammatory skin diseases, comprising a thyme extract, or a thyme extract, and a juice of purple cheoninguk as an active ingredient.
상기 '식품 조성물'은 유효성분으로 타임 추출물, 또는 타임 추출물 및 자주천인국 착즙액 이외에, 식품 제조에 통상적으로 사용되는 식품의 기준 및 규격('식품공전')에 기재된 식품으로 사용가능한 식품 원료, 식품첨가물 공전에 기재된 식품첨가물을 포함할 수 있다.The 'food composition' as an active ingredient, in addition to thyme extract, or thyme extract, and juice of purple cheoninguk, food raw materials that can be used as foods described in the standards and standards ('Food Code') of foods commonly used in food production, food It may contain food additives described in the additive notice.
상기 식품 조성물은 특별히 한정할 필요는 없으나 예를 들어 탄수화물 및 향미제를 포함할 수 있다. 상기 탄수화물은 단당류, 예를 들어, 포도당, 과당 등; 이당류, 예를 들어 말토스, 설탕, 유당 등; 올리고당 또는 폴리사카라이드, 예를 들어 덱스트린, 물엿, 사이클로덱스트린 등; 당알코올, 예를 들어 자일리톨, 소르비톨, 에리트리톨 등을 사용할 수 있다. 상기 향미제는 천연 향미제[타우마틴, 스테비아 추출물(예를 들어 레바우디오시드 A, 글리시르히진 등)] 및 합성 향미제(사카린, 아스파르탐 등)를 사용할 수 있다.The food composition is not particularly limited, but may include, for example, carbohydrates and flavoring agents. The carbohydrates include monosaccharides such as glucose, fructose, and the like; disaccharides such as maltose, sugar, lactose and the like; oligosaccharides or polysaccharides such as dextrin, starch syrup, cyclodextrin and the like; Sugar alcohols such as xylitol, sorbitol, erythritol and the like can be used. As the flavoring agent, natural flavoring agents [taumatin, stevia extract (eg, rebaudioside A, glycyrrhizin, etc.)] and synthetic flavoring agents (saccharin, aspartame, etc.) may be used.
상기 타임 추출물, 또는 타임 추출물 및 자주천인국 착즙액을 유효성분으로 식품 조성물을 제조하는 경우 타임 추출물, 또는 타임 추출물 및 자주천인국 착즙액은 알레르기성 또는 염증성 피부질환 개선 효능을 나타내는 함량이면 특별히 한정할 필요는 없으나, 예를 들어 0.1 내지 99 중량%, 0.5 내지 95 중량%, 1 내지 90 중량%, 2 내지 80 중량%, 3 내지 70 중량%, 4 내지 60 중량%, 5 내지 50 중량%로 포함될 수 있다.In the case of manufacturing a food composition using the thyme extract, or thyme extract and purple cheoninguk extract as an active ingredient, the thyme extract, or thyme extract and thyme extract and thyme extract and thyme extract and thyme extract need to be specifically limited if the content exhibits the efficacy of improving allergic or inflammatory skin diseases. However, for example, 0.1 to 99% by weight, 0.5 to 95% by weight, 1 to 90% by weight, 2 to 80% by weight, 3 to 70% by weight, 4 to 60% by weight, 5 to 50% by weight may be included. have.
상기 식품 조성물에서 유효성분인 타임 추출물, 또는 타임 추출물 및 자주천인국 착즙액은 섭취자의 상태, 체중, 질병의 유무나 정도 및 기간에 따라 다르지만, 통상의 기술자에 의해 적절하게 선택될 수 있다. 예를 들어 1 일 투여량을 기준으로 1 일 10 내지 5,000 mg, 바람직하게는 50 내지 4,000 mg, 더욱 바람직하게는 100 내지 3,000 mg, 가장 바람직하게는 200 내지 2,000 mg일 수 있고, 투여 횟수는 특별히 한정할 필요는 없으나 1 일 3 회 내지 1 주일에 1 회의 범위 내에서 통상의 기술자가 조절할 수 있다. 건강 및 위생을 목적으로 하거나 또는 건강 조절을 목적으로 하는 장기간의 섭취의 경우에는 상기 범위 이하일 수 있다.The active ingredient in the food composition, the thyme extract, or the thyme extract and the extract and the juice of jasmine cheoninguk varies depending on the condition, weight, presence or absence of disease, and duration of the ingestion, but may be appropriately selected by those skilled in the art. For example, it may be 10 to 5,000 mg, preferably 50 to 4,000 mg, more preferably 100 to 3,000 mg, and most preferably 200 to 2,000 mg per day based on the daily dose, and the number of administration is particularly Although it is not necessary to limit, a person skilled in the art can adjust it within the range of 3 times a day to 1 time a week. In the case of long-term intake for the purpose of health and hygiene or health control, it may be less than the above range.
상기 식품 조성물은 특별히 한정할 필요는 없으나 예를 들어 산제, 과립제, 정제, 캡슐제, 환제, 엑스제, 젤리 제형, 티백 제형 또는 음료 제형일 수 있다.The food composition is not particularly limited, but may be, for example, a powder, granules, tablets, capsules, pills, extracts, jelly formulations, tea bag formulations or beverage formulations.
또한 일반 식품에 알레르기성 또는 염증성 피부질환 개선 기능성을 부여하기 위하여 상기 타임 추출물, 또는 타임 추출물 및 자주천인국 착즙액을 첨가할 수 있다. 첨가가 가능한 식품은, 특별히 한정할 필요는 없으나 예를 들어 식품위생법 제7조에 따른 식품의 기준 및 규격('식품공전')에 예시된 과자류, 빵 또는 떡류, 코코아가공품류 또는 초콜릿류, 식육 또는 알가공품, 어육가공품, 두부류 또는 묵류, 면류, 다류, 커피, 음료류, 특수용도식품, 장류, 조미식품, 드레싱류, 김치류, 젓갈류, 절임식품, 조림식품, 주류, 건포류, 기타 식품류 등에 첨가될 수 있다. 또한 축산물위생관리법 제4조에 따른 축산물의 가공기준 및 성분규격('축산물공전')에 예시된 유가공품, 식육가공품 및 포장육, 알가공품에 첨가될 수 있다.In addition, the thyme extract, or the thyme extract and the juice of purple cheoninguk may be added in order to give general food the function of improving allergic or inflammatory skin disease. Foods that can be added do not need to be particularly limited, but for example, confectionery, bread or rice cakes, cocoa processed products or chocolates, edible meat or Processed eggs, processed fish meat products, tofu or jelly, noodles, tea, coffee, beverages, special purpose foods, soy sauce, seasonings, dressings, kimchi, salted fish, pickled foods, stewed foods, alcoholic beverages, raisins, and other foods, etc. can be In addition, it can be added to dairy products, processed meat products, packaged meat, and processed egg products exemplified in the processing standards and ingredient specifications of livestock products according to Article 4 of the Livestock Products Sanitation Control Act ('Livestock Products Code').
한편 상기 타임 추출물, 또는 타임 추출물 및 자주천인국 착즙액을 유효성분으로 하는 식품 조성물은 알레르기성 또는 염증성 피부질환 개선용 건강기능식품, 예를 들어 아토피 피부염 개선용 건강기능식품, "과민면역반응 완화에 도움을 주는 건강기능식품" 또는 "면역과민반응에 의한 피부상태 개선에 도움을 주는 건강기능식품"으로 이용될 수 있다. On the other hand, the food composition comprising the thyme extract, or thyme extract and jasmine extract and extract as an active ingredient is a health functional food for improving allergic or inflammatory skin disease, for example, a health functional food for improving atopic dermatitis, "for alleviating hypersensitivity immune reaction" It can be used as "health functional food that helps" or "health functional food that helps improve skin condition due to immune hypersensitivity reaction".
상기 '건강기능식품'은 인체에 유용한 기능성을 가진 원료나 성분을 사용하여 법적 기준에 따라 제조(가공을 포함)한 식품(건강기능식품에 관한 법률 제3조 제1호)을 말한다. 상기 '건강기능식품'은 국가마다 용어나 범위에 차이가 있을 수 있으나, 미국의 '식이 보충제(Dietary Supplement)', 유럽의 '식품 보충제(Food Supplemnet)', 일본의 '보건기능식품' 또는 '특정보건용식품(Food for Special Health Use, FoSHU)', 중국의 '보건식품' 등에 해당할 수 있다.The above 'health functional food' refers to food manufactured (including processing) according to legal standards using raw materials or ingredients useful for the human body (Health Functional Food Act Article 3 No. 1). The above 'health functional food' may have different terms or scope in each country, but 'Dietary Supplement' in the US, 'Food Supplement in Europe', 'Health functional food' or 'Health functional food' in Japan It may correspond to 'Food for Special Health Use (FoSHU)' and 'health food' in China.
상기 식품 조성물 또는 건강기능식품은 식품첨가물을 추가로 포함할 수 있으며, 식품첨가물로서의 적합여부는 다른 규정이 없는 한 '식품첨가물공전'의 총칙 및 일반시험법 등에 따라 해당 품목에 관한 규격 및 기준에 따른다.The food composition or health functional food may additionally contain food additives, and the suitability as a food additive is determined by the standards and standards for the relevant item in accordance with the general rules and general test methods of the 'Food Additives Codex', unless otherwise specified. follow
또한 상기 건강기능식품에는 타임 추출물, 또는 타임 추출물 및 자주천인국 착즙액과 함께 "과잉면역반응 완화에 도움을 주는 건강기능식품" 또는 "면역과민반응에 의한 피부상태 개선에 도움을 주는 건강기능식품"에 사용되는 '기능성 원료'로 고시된 원료 또는 개별인정된 원료로서, Enterococcus feacalis 가열처리건조분말, 구아바잎추출물 등 복합물, 다래추출물, 소엽추출물, 피카오프레토 분말 등 복합물, 합성 PLAG, L. sakei Probio 65, 감마리놀렌산 함유 유지, 과채유래유산균(L. plantarum CJLP133), 프로바이오틱스ATP 등의 과잉면역반응 완화와 관련된 건강기능식품 소재를 복합하여 사용할 수 있다.In addition, the health functional food includes "health functional food that helps alleviate over-immune reaction" or "health functional food that helps improve skin condition due to immune hypersensitivity reaction" together with thyme extract, or thyme extract and juice extract of thyme extract. Raw materials notified as 'functional raw materials' or individually recognized raw materials used for Health functional food materials related to alleviation of excessive immune response such as Probio 65, oil containing gamma-linolenic acid, fruit and vegetable-derived lactic acid bacteria ( L. plantarum CJLP133), and probiotic ATP can be used in combination.
본 발명은 타임 추출물, 또는 타임 추출물 및 자주천인국 착즙액을 유효성분으로 포함하는 알레르기성 또는 염증성 피부질환 개선용 사료 조성물에 관한 것이다.The present invention relates to a feed composition for alleviating allergic or inflammatory skin diseases, comprising a thyme extract, or a thyme extract, and a thyme extract and extract of purple cheoninguk as active ingredients.
상기 '사료 조성물'은 유효성분으로 타임 추출물, 또는 타임 추출물 및 자주천인국 착즙액 이외에, 식품의 기준 및 규격('식품공전')에 기재된 식품으로 사용가능한 식품 원료, 식품첨가물 공전에 기재된 식품첨가물을 사용할 수 있고, 식품으로 사용가능한 식품 원료 또는 식품첨가물이 아니더라도 '사료 등의 기준 및 규격' 별표 1의 단미사료의 범위에 해당하는 원료, 별표 2의 보조사료의 범위에 해당하는 원료를 사용할 수 있다.The 'feed composition' contains thyme extract, or thyme extract, and juice of japanese cheoninguk as an active ingredient, as well as food ingredients and food additives that can be used as foods described in the Food Standards and Specifications ('Food Codex'). Even if it is not a food raw material or food additive that can be used as food, raw materials that fall within the range of single feed in Attached Table 1 of 'Standards and Specifications for Feed, etc.' .
상기 '사료 조성물'은 '사료 등의 기준 및 규격'에 따른 보조사료 중 추출제일 수 있고, 상기 보조사료를 포함하는 배합사료일 수 있다.The 'feed composition' may be an extractant among auxiliary feeds according to the 'standards and specifications for feed, etc.', and may be a compound feed including the auxiliary feed.
상기 타임 추출물, 또는 타임 추출물 및 자주천인국 착즙액을 유효성분으로 사료 조성물을 제조하는 경우 타임 추출물, 또는 타임 추출물 및 자주천인국 착즙액은 알레르기성 또는 염증성 피부질환 개선 효능을 나타내는 함량이면 특별히 한정할 필요는 없으나, 예를 들어 0.1 내지 99 중량%, 0.5 내지 95 중량%, 1 내지 90 중량%, 2 내지 80 중량%, 3 내지 70 중량%, 4 내지 60 중량%, 5 내지 50 중량%로 포함될 수 있다.In the case of preparing a feed composition using the thyme extract or thyme extract and thyme extract and thyme extract and thyme extract as an active ingredient, the thyme extract, or thyme extract and thyme extract and thyme extract and thyme extract and thyme extract need to be particularly limited as long as the content exhibits the efficacy of improving allergic or inflammatory skin diseases. However, for example, 0.1 to 99% by weight, 0.5 to 95% by weight, 1 to 90% by weight, 2 to 80% by weight, 3 to 70% by weight, 4 to 60% by weight, 5 to 50% by weight may be included. have.
상기 사료 조성물에서 유효성분인 타임 추출물, 또는 타임 추출물 및 자주천인국 착즙액은 섭취 동물의 상태, 체중, 질병의 유무나 정도 및 기간에 따라 다르지만, 통상의 기술자에 의해 적절하게 선택될 수 있다. 예를 들어 1 일 투여량을 기준으로 1 내지 5,000 mg, 바람직하게는 5 내지 2,000 mg, 더욱 바람직하게는 10 내지 1,000 mg, 더더욱 바람직하게는 20 내지 800 mg, 가장 바람직하게는 50 내지 500 mg일 수 있고, 투여 횟수는 특별히 한정할 필요는 없으나 1 일 3 회 내지 1 주일에 1회의 범위 내에서 통상의 기술자가 조절할 수 있다. 건강 및 위생을 목적으로 하거나 또는 건강 조절을 목적으로 하는 장기간의 섭취의 경우에는 상기 범위 이하일 수 있다.The active ingredient in the feed composition, the thyme extract, or the thyme extract and the extract of cheoninguk japonica varies depending on the condition, weight, presence or severity and duration of the ingested animal, but may be appropriately selected by those skilled in the art. For example, 1 to 5,000 mg, preferably 5 to 2,000 mg, more preferably 10 to 1,000 mg, still more preferably 20 to 800 mg, most preferably 50 to 500 mg, based on a daily dose and the number of administration does not need to be particularly limited, but may be adjusted by those skilled in the art within the range of 3 times a day to once a week. In the case of long-term intake for the purpose of health and hygiene or health control, it may be less than the above range.
이하, 바람직한 실시예를 들어 본 발명을 더욱 상세하게 설명한다. 그러나 이들 실시예는 본 발명을 보다 구체적으로 설명하기 위한 것으로, 본 발명의 범위가 이에 의하여 제한되지 않는다는 것은 당업계의 통상의 지식을 가진 자에게 자명할 것이다.Hereinafter, the present invention will be described in more detail with reference to preferred embodiments. However, these Examples are intended to illustrate the present invention in more detail, and it will be apparent to those skilled in the art that the scope of the present invention is not limited thereby.
제조예 1: 타임 물 추출물(TVWE) 분말Preparation Example 1: Thyme Water Extract (TVWE) Powder
핀젤버르그사의 "모델번호: 0 196 120; Thyme dry extract"를 구매하여 타임 물 추출물(TVWE) 분말로 사용하였다. 상기 타임 물 추출물(TVWE) 분말은 타임 지상부 전초의 물 추출물로서, 타임 물 추출물 고형분 함량은 70 중량%이었다."Model No.: 0 196 120; Thyme dry extract" from Finselberg was purchased and used as a thyme water extract (TVWE) powder. The thyme water extract (TVWE) powder was a water extract of an aerial part of thyme, and the solid content of the thyme water extract was 70% by weight.
제조예 2: 타임 에탄올 추출물(TVEE) 분말Preparation Example 2: Thyme Ethanol Extract (TVEE) Powder
핀젤버르그사의 "모델번호: 0 196 360; Thyme dry extract"를 구매하여 타임 에탄올 추출물(TVEE) 분말로 사용하였다. 상기 타임 에탄올 추출물(TVEE) 분말은 타임 지상부 전초의 70 중량% 에탄올 수용액 추출물로서, 타임 에탄올 추출물 고형분 함량은 80 중량%이었다. "Model No.: 0 196 360; Thyme dry extract" from Finselberg was purchased and used as a thyme ethanol extract (TVEE) powder. The thyme ethanol extract (TVEE) powder was a 70% by weight ethanol aqueous solution extract of an aerial part of thyme, and the solid content of the thyme ethanol extract was 80% by weight.
제조예 3: 자주천인국 착즙액(EPJ) 분말Preparation Example 3: Purple Cheonin Guk Extract (EPJ) Powder
핀젤버르그사의 "모델번호: 0 347 318; Echinacea dried pressed juice(95 % native)"를 구매하여 자주천인국 착즙액(EPJ) 분말로 사용하였다. 상기 자주천인국 착즙액(EPJ) 분말은 전초를 착즙한 착즙액을 건조한 것이고, 자주천인국 착즙액 고형분 함량은 95 중량%이었다.I purchased "Model Number: 0 347 318; Echinacea dried pressed juice (95 % native)" from Finselberg and used it as EPJ powder. The EPJ powder was obtained by drying the juice extracted from whole herbs, and the solid content of the juice extracted from the purple cheonin-guk was 95% by weight.
제조예 4: 타임 추출물 및 자주천인국 착즙액 혼합물(TEmix1) 분말의 제조Preparation Example 4: Preparation of thyme extract and purple cheonin-guk juice mixture (TEmix1) powder
제조예 1의 타임 물 추출물(TVWE) 분말 및 제조예 3의 자주천인국 착즙액(EPJ) 분말을 타임 물 추출물 및 자주천인국 착즙액의 고형분 기준으로 1 : 1 중량비로 혼합하여 타임 추출물 및 자주천인국 착즙액 혼합물(TEmix1) 분말을 제조하였다. The thyme water extract (TVWE) powder of Preparation Example 1 and the EPJ powder of Preparation Example 3 were mixed in a 1:1 weight ratio based on the solid content of the thyme water extract and the purple cheonin-guk extract to extract the thyme extract and the purple cheonin-guk juice. A liquid mixture (TEmix1) powder was prepared.
제조예 5: 타임 추출물 및 자주천인국 착즙액 혼합물(TEmix2) 분말의 제조Preparation Example 5: Preparation of thyme extract and purple cheoninguk juice mixture (TEmix2) powder
제조예 2의 타임 에탄올 추출물(TVEE) 분말 및 제조예 3의 자주천인국 착즙액(EPJ) 분말을 타임 에탄올 추출물 및 자주천인국 착즙액의 고형분 기준으로 1 : 1 중량비로 혼합하여 타임 추출물 및 자주천인국 착즙액 혼합물(TEmix2) 분말을 제조하였다. The thyme ethanol extract (TVEE) powder of Preparation Example 2 and the thyme extract (EPJ) powder of Preparation Example 3 were mixed in a 1:1 weight ratio based on the solid content of the thyme ethanol extract and the purple cheoninguk extract to extract the thyme extract and the juice A liquid mixture (TEmix2) powder was prepared.
실험예 1Experimental Example 1
1. 실험동물 및 시료의 준비1. Preparation of laboratory animals and samples
양성대조군 1로 "과잉면역반응 완화에 도움을 주는 건강기능식품"에 사용되는 '기능성 원료'로 고시된 '다래추출물'을 구입하여 사용하였다. 상기 다래추출물은 갈색의 분말로 추출물 고형분 함량은 41 중량%이었다.As positive control group 1, 'Actinidia extract' announced as a 'functional raw material' used in "health functional food that helps relieve hyperimmune reaction" was purchased and used. The extract was a brown powder, and the solid content of the extract was 41% by weight.
양성대조군 2로 '덱사메타손정(DEX)'을 구입하여 사용하였다. 상기 덱사메타손정은 흰색의 원형 정제로 정당 0.5 mg의 덱사메타손(dexamethasone)이 함유되어 있다. As positive control group 2, 'dexamethasone tablet (DEX)' was purchased and used. The dexamethasone tablet is a white round tablet containing 0.5 mg of dexamethasone per sugar.
실험동물은 재팬 에스엘씨(Japan SLC, Inc., Japan)에서 Nc/Nga 마우스(4주령, 숫컷)를 공급받아 사용하였다. NC/Nga 마우스는 IgE의 과생성에 의해 동반된 아토피성 피부염의 형태가 임상적으로나 조직학적으로 인간의 아토피 피부염의 병변과 매우 흡사한 양태를 나타내고, 종래 아토피 피부염 동물 모델로 활용된 사례가 많아 선택하였다. Experimental animals were supplied with Nc/Nga mice (4 weeks old, male) from Japan SLC, Inc., and used. In NC/Nga mice, the form of atopic dermatitis accompanied by IgE overproduction is clinically and histologically very similar to human atopic dermatitis lesions, and there are many cases that have been used as animal models for conventional atopic dermatitis. selected.
고형사료와 물을 충분히 공급하고 온도 23±2 ℃, 상대습도 55±10 %, 환기횟수 10 내지 20 회/hr, 12 시간-12 시간(light-dark cycle) 및 조도 150 내지 300 Lux의 환경에서 사육하였다. Sufficient supply of solid feed and water, temperature 23±2 ℃, relative humidity 55±10%, ventilation frequency 10 to 20 times/hr, 12 hours to 12 hours (light-dark cycle), and illumination in an environment of 150 to 300 Lux bred.
사육 개시 전 NC/Nga 마우스의 귓바퀴 및 목뒤 부분을 면도기로 제모한 후, 제모제를 적량 도포하여 제모하였다. 시험물질 투여 전, 아토피 피부염을 유도하기 위해 1, 5, 8 및 12 일차에 총 4 회, 아토피 피부염 유발시약(Biostir AD, Biostir Inc., Japan)을 귓바퀴, 경배부 및 앞다리 위치의 등 부위에 균일하게 도포하였다. 14 일차에 피부 임상지수를 평가하고 순위화한 아토피 피부염 유발 수준에 따라 각 군의 평균수준이 최대한 균일하게 분포하도록 무작위법으로 분배하였다.Before starting breeding, the auricle and the back of the neck of NC/Nga mice were shaved with a razor, and then an appropriate amount of a hair removal agent was applied to remove hair. Before administration of the test substance, atopic dermatitis inducing reagent (Biostir AD, Biostir Inc., Japan) was applied to the auricle, dorsal area and forelimbs in the dorsal area 4 times on days 1, 5, 8 and 12 to induce atopic dermatitis. It was applied uniformly. On the 14th day, the skin clinical index was evaluated and randomly distributed so that the average level of each group was distributed as evenly as possible according to the ranked atopic dermatitis induction level.
시험물질 투여 개시 이후에도 아토피 피부염을 지속적으로 유발하기 위해 15, 19, 22, 26, 29, 33, 36, 40, 43 및 47 일차에 총 10 회, 아토피 피부염 유발시약을 귓바퀴, 경배부 및 앞다리 위치의 등 부위에 균일하게 도포하였다.In order to continuously induce atopic dermatitis even after the start of administration of the test substance, atopic dermatitis-inducing reagents were applied 10 times on days 15, 19, 22, 26, 29, 33, 36, 40, 43 and 47 in the auricle, dorsal region and forelimb position. It was uniformly applied to the back of the
모든 동물실험 과정은 NIH(National Institutes of Health)의 실험동물관리 규정(Principle of Laboratory Animal Care)을 준수하여 수행하였다.All animal testing procedures were performed in compliance with the Principle of Laboratory Animal Care of the National Institutes of Health (NIH).
아래 표 1과 같이 이들 중 1군은 아토피 피부염을 유발시키지 않은 정상대조군, 나머지 7군에 대해서는 2 주간 아토피 피부염을 유발시킨 후, 시험물질 투여를 개시하고 5 주간 계속 아토피 피부염을 유발하면서 제1-3군 내지 제1-6군은 부형제를 제외한 타임 단독 추출물 또는 타임 추출물 및 자주천인국 착즙액 혼합물 고형분을 기준으로 200 mg/kg, 그리고 제1-7군은 '다래추출물'의 추출물 고형분을 기준으로 200 mg/kg, 제1-8군은 '덱사메타손' 유효성분을 기준으로 2 mg/kg을 10 mL/kg 투여 액량을 기준으로 1 일 1 회 경구 투여하였다. 정상대조군 및 음성대조군은 비히클로 생리식염수를 10 mL/kg 경구 투여하였다.As shown in Table 1 below, one of these groups was a normal control group that did not induce atopic dermatitis, and the remaining 7 groups induced atopic dermatitis for 2 weeks, then started administration of the test substance and continued to induce atopic dermatitis for 5 weeks. Groups 3 to 1-6 were 200 mg/kg based on the solid content of thyme extract alone or a mixture of thyme extract and purple cheonin-guk juice excluding excipients, and groups 1-7 were based on the extract solid content of 'Actinidia extract' 200 mg/kg, groups 1-8 were orally administered once a day at a dose of 2 mg/kg based on the active ingredient 'dexamethasone' based on a 10 mL/kg dose. The normal control group and the negative control group were orally administered with 10 mL/kg of physiological saline as a vehicle.
2. 체중 측정 결과2. Weighing results
아토피 피부염 유발 개시 1, 14, 28, 42 및 49 일차 체중(g)을 측정하여 표 2 및 3에 나타내었다. The body weights (g) at the 1st, 14th, 28th, 42nd and 49th days of atopic dermatitis induction were measured and shown in Tables 2 and 3.
제1-1군의 정상대조군과 제1-2군 내지 제1-8군 사이의 유의차는 * p<0.05, ** p<0.01, *** p<0.001; 제1-2군의 음성대조군과 제1-3군 내지 제1-8군 사이의 유의차는 # p<0.05, ## p<0.01Significant differences between the normal control group in group 1-1 and groups 1-2 to 1-8 were * p<0.05, ** p<0.01, *** p<0.001; The significant difference between the negative control group in Group 1-2 and Groups 1-3 to 1-8 was # p<0.05, ## p<0.01
아토피 피부염 유발 개시 14 일차에는 전체 시험군을 통틀어 통계적으로 유의한 체중 차이는 관찰되지 않았다.At the 14th day after the induction of atopic dermatitis, no statistically significant difference in body weight was observed across the entire test group.
아토피 피부염 유발 개시 28 일차(시험물질 투여 14 일차)에 모든 시험물질 투여군인 제1-3군 내지 제1-8군의 체중은 정상대조군인 제1-1군에 비하여 유의하게 낮았고(p<0.01, p<0.05, p<0.01, p<0.05, p<0.05 및 p<0.001), 특히 덱사메타손을 투여한 제1-8군의 체중은 음성대조군인 제1-2군에 비해서도 유의하게 낮았다(p<0.01). At the 28th day of atopic dermatitis induction (14th day of administration of the test substance), the body weights of all test substance groups, groups 1-3 to 1-8, were significantly lower than those of the normal control group, group 1-1 (p<0.01). , p<0.05, p<0.01, p<0.05, p<0.05 and p<0.001), in particular, the body weight of groups 1-8 administered with dexamethasone was significantly lower than that of group 1-2, a negative control group (p <0.01).
아토피 피부염 유발 개시 42 일차(시험물질 투여 28 일차)에 제1-3군, 제1-5군 및 제1-8군의 체중은 정상대조군인 제1-1군에 비하여 유의하게 낮았고(p<0.05, p<0.05 및 p<0.001), 덱사메타손을 투여한 제1-8군의 체중은 제1-2군의 음성대조군에 비해서도 유의하게 낮았다(p<0.01). At the 42nd day of atopic dermatitis induction (the 28th day of administration of the test substance), the body weights of groups 1-3, 1-5, and 1-8 were significantly lower than those of the normal control group, group 1-1 (p< 0.05, p<0.05 and p<0.001), the body weight of groups 1-8 treated with dexamethasone was significantly lower than that of the negative control group of group 1-2 (p<0.01).
아토피 피부염 유발 개시 49 일차(시험물질 투여 35 일차)에 제1-3군, 제1-5군, 제1-7군 및 제1-8군의 체중은 정상대조군인 제1-1군에 비하여 유의하게 낮았고(p<0.01, p<0.01, p<0.01 및 p<0.001), 덱사메타손을 투여한 제1-8군의 체중은 제1-2군의 음성대조군에 비해서도 유의하게 낮았다(p<0.01). On the 49th day of the induction of atopic dermatitis (the 35th day of administration of the test substance), the body weights of groups 1-3, 1-5, 1-7, and 1-8 were lower than that of group 1-1, the normal control group. It was significantly lower (p<0.01, p<0.01, p<0.01 and p<0.001), and the body weight of groups 1-8 administered with dexamethasone was significantly lower than that of the negative control group of groups 1-2 (p<0.01). ).
아토피 피부염 유발 개시 28 일차부터 49 일차까지 나타난 제1-8군의 유의적인 체중 감소는 면역억제제의 전신적 투여에 따른 부작용인 것으로 평가되었으며, 그 외 시험물질 투여군에서 관찰된 제1-1군 대비 체중의 감소는 대부분의 날짜에서 제1-2군 대비 유의한 차이가 관찰되지 않았기에, 시험물질의 투여에 의한 것은 아닌 것으로 평가된다.The significant weight loss of groups 1-8, which appeared from the 28th to the 49th day of the induction of atopic dermatitis, was evaluated as a side effect of the systemic administration of the immunosuppressant, compared to group 1-1 observed in the other test substance administration groups. Since no significant difference was observed for most of the days compared to Group 1-2, it is evaluated that it is not due to the administration of the test substance.
3. 귀 부종 측정 결과3. Ear edema measurement result
아토피 피부염 유발 개시 1, 14, 28, 42 및 49 일차 귀 두께(mm)를 캘리퍼스로 측정하여 귀 부종 발생을 확인하여 표 4 및 5에 나타내었다.On the 1st, 14th, 28th, 42nd, and 49th days of the induction of atopic dermatitis, the ear thickness (mm) was measured with a caliper to confirm the occurrence of ear edema, and are shown in Tables 4 and 5.
제1-1군의 정상대조군과 제1-2군 내지 제1-8군 사이의 유의차는 * p<0.05, ** p<0.01, *** p<0.001; 제1-2군의 음성대조군과 제1-3군 내지 제1-8군 사이의 유의차는 # p<0.05, ## p<0.01Significant differences between the normal control group in group 1-1 and groups 1-2 to 1-8 were * p<0.05, ** p<0.01, *** p<0.001; The significant difference between the negative control group in Group 1-2 and Groups 1-3 to 1-8 was # p<0.05, ## p<0.01
아토피 피부염이 지속적으로 유발됨에 따라 아토피 피부염 유발 개시 28일차(시험물질 투여 14 일차)부터 시험 종료 시까지 제1-8군을 제외한 모든 아토피 유발군의 귀 두께 수준은 제1-1군에 비하여 유의하게 높았고(p<0.001, p<0.01 또는 p<0.05), 제1-8군의 귀 두께 수준은 제1-2군의 음성대조군에 비하여 유의하게 낮았다(p<0.001 또는 p<0.01). As atopic dermatitis is continuously induced, from the 28th day (14th day of administration of the test substance) to the end of the test, the ear thickness level of all atopic-inducing groups except for groups 1-8 was significantly higher than that of group 1-1. was significantly higher (p<0.001, p<0.01, or p<0.05), and the ear thickness level of Groups 1-8 was significantly lower than that of the negative control group of Groups 1-2 (p<0.001 or p<0.01).
제1-3군의 타임 추출물(TEWE) 투여군 및 제1-6군의 타임 추출물 및 자주천인국 착즙액 혼합물(TEmix2) 투여군은 제1-2군의 음성대조군에 비해 다소 귀 두께가 감소하는 경향을 보이고, 제1-7군의 다래추출물 투여군과 유사한 경향을 나타내었다.The group administered with thyme extract (TEWE) of group 1-3 and group administered with thyme extract and thyme extract and purple chrysanthemum extract (TEmix2) of group 1-6 showed a slight decrease in ear thickness compared to the negative control group of group 1-2. and showed a similar trend to that of the group 1-7 group treated with Actinidia extract.
4. 비장 중량 측정 결과4. Spleen Gravimetric Results
아토피 피부염 유발 개시 49 일차의 부검일에 비장을 적출하여 무게를 측정하고, 체중 및 체중에 대한 비율과 함께 표 6 및 7에 나타내었다. On the 49th day of autopsy on the 49th day of the induction of atopic dermatitis, the spleen was removed and the weight was measured, and the weight and weight-to-weight ratio are shown in Tables 6 and 7.
제1-1군의 정상대조군과 제1-2군 내지 제1-8군 사이의 유의차는 * p<0.05, ** p<0.01, *** p<0.001; 제1-2군의 음성대조군과 제1-3군 내지 제1-8군 사이의 유의차는 # p<0.05, ## p<0.01Significant differences between the normal control group in group 1-1 and groups 1-2 to 1-8 were * p<0.05, ** p<0.01, *** p<0.001; The significant difference between the negative control group in Group 1-2 and Groups 1-3 to 1-8 was # p<0.05, ## p<0.01
제1-1군의 정상대조군에 비하여 제1-2군의 음성대조군의 절대 및 상대 비장 중량은 모두 증가되는 양상으로 나타났으나, 제1-3군 내지 제1-7군의 시험물질 투여군 중에서 제1-2군 대비 통계적으로 유의한 비장 무게 감소를 나타내지 않았다. The absolute and relative spleen weights of the negative control group of Group 1-2 were both increased compared to the normal control group of Group 1-1, but among the test substance administration groups of Groups 1-3 to 1-7, There was no statistically significant decrease in spleen weight compared to Group 1-2.
그러나 제1-8군의 덱사메타손 투여군의 경우, 비장 절대중량 및 상대중량수준 모두 제1-1군 및 제1-2군에 비하여 유의하게 낮았으며(p<0.001 및 p<0.01), 절대 중량의 경우 제1-2군 대비 약 25 % 수준에 불과한 것으로 나타나 덱사메타손에 의한 강력한 면역억제. 효과가 비장의 축소로 이어진 것을 확인할 수 있었다.However, in the case of the dexamethasone administration group of Groups 1-8, both the absolute and relative weight levels of the spleen were significantly lower than those of Groups 1-1 and 1-2 (p<0.001 and p<0.01). Cases showed only about 25% of the level compared to group 1-2, so strong immunosuppression by dexamethasone. It was confirmed that the effect led to the reduction of the spleen.
5. 전체 백혈구, 호중구, 호산구 및 IgE 측정 결과5. Total Leukocyte, Neutrophil, Eosinophil and IgE Measurement Results
아토피 피부염 유발 개시 49 일차의 부검일에 채취한 혈액을 이용하여, 자동세포수 계산기(TC20 Automated Cell Counter, Bio rad)로 전체 백혈구수를 측정하고, 플로우 사이토메트리(flow cytometry)로 호중구 및 호산구를 측정하며, ELISA 분석법으로 혈중 IgE 농도를 측정하여 표 8 및 9에 나타내었다.Using the blood collected on the day of autopsy on the 49th day of the induction of atopic dermatitis, the total white blood cell count was measured using an automatic cell count calculator (TC20 Automated Cell Counter, Bio rad), and neutrophils and eosinophils were measured by flow cytometry. was measured, and the blood IgE concentration was measured by ELISA, and is shown in Tables 8 and 9.
(×103 세포/㎕)total white blood cells
(×10 3 cells/μl)
(×103 세포/㎕)neutrophils
(×10 3 cells/μl)
(×102 세포/㎕)eosinophils
(×10 2 cells/μl)
(㎍/㎖)IgE
(μg/ml)
(×103 세포/㎕)total white blood cells
(×10 3 cells/μl)
(×103 세포/㎕)neutrophils
(×10 3 cells/μl)
(×102 세포/㎕)eosinophils
(×10 2 cells/μl)
(㎍/㎖)IgE
(μg/ml)
제1-1군의 정상대조군과 제1-2군 내지 제1-8군 사이의 유의차는 * p<0.05, ** p<0.01, *** p<0.001; 제1-2군의 음성대조군과 제1-3군 내지 제1-8군 사이의 유의차는 # p<0.05, ## p<0.01Significant differences between the normal control group in group 1-1 and groups 1-2 to 1-8 were * p<0.05, ** p<0.01, *** p<0.001; The significant difference between the negative control group in Group 1-2 and Groups 1-3 to 1-8 was # p<0.05, ## p<0.01
전체 백혈구수를 측정한 결과, 제1-4군의 타임 추출물 투여군, 제1-5군의 타임 추출물 및 자주천인국 착즙액 혼합물(TEmix1) 투여군, 제1-6군의 타임 추출물 및 자주천인국 착즙액 혼합물(TEmix2) 투여군 및 제1-8군의 덱사메타손 투여군에서 제1-2군의 음성대조군에 비하여 전체 백혈구 수준이 유의하게 낮게 나타났다(모두 p<0.01). As a result of measuring the total white blood cell count, the thyme extract administered group of groups 1-4, the thyme extract of groups 1-5 and the thyme extract and purple cheonin-guk juice mixture (TEmix1) administration group, the thyme extract of group 1-6 and the thyme extract of group 1-6 The total leukocyte level was significantly lower in the mixture (TEmix2) administration group and the dexamethasone administration group in Groups 1-8 compared to the negative control group in Group 1-2 (both p<0.01).
호중구의 경우, 제1-3군의 타임 추출물 투여군, 제1-5군의 타임 추출물 및 자주천인국 착즙액 혼합물(TEmix1) 투여군, 제1-6군의 타임 추출물 및 자주천인국 착즙액 혼합물(TEmix2) 투여군 및 제1-8군의 덱사메타손 투여군에서 제1-2군의 음성대조군에 비하여 전체 백혈구 수준이 유의하게 낮게 나타났다(p<0.05, p<0.01, p<0.01 및 p<0.01). In the case of neutrophils, the thyme extract administered group of group 1-5, the thyme extract of groups 1-5, and the thyme extract and purple chrysanthemum juice mixture (TEmix1) administration group, the thyme extract of group 1-6 and the thyme extract of group 1-6 and thyme extract mixture (TEmix2) of neutrophils The total leukocyte levels were significantly lower in the administration group and the dexamethasone administration group in the 1-8 group compared to the negative control group in the 1-2 group (p<0.05, p<0.01, p<0.01, and p<0.01).
또한 호산구의 경우, 제1-2군의 음성대조군 및 제1-7군의 다래추출물 투여군은 제1-1군의 양성대조군에 비하여 유의하게 높았으나(p<0.001 및 p<0.01), 제1-3군 및 제1-4군의 타임 추출물 투여군, 제1-5군의 타임 추출물 및 자주천인국 착즙액 혼합물(TEmix1) 투여군, 제1-6군의 타임 추출물 및 자주천인국 착즙액 혼합물(TEmix2) 투여군 및 제1-8군의 덱사메타손 투여군은 제1-2군의 음성대조군에 비하여 유의하게 낮았다(모두 p<0.001). In addition, in the case of eosinophils, the negative control group of group 1-2 and the group 1-7 treated with the extract was significantly higher than that of the positive control group of group 1-1 (p<0.001 and p<0.01), but the first -Groups 3 and 1-4 administered thyme extract, Groups 1-5 administered thyme extract and purple cheoninguk juice mixture (TEmix1), Group 1-6 thyme extract and thyme extract and purple chrysanthemum extract mixture (TEmix2) The administration group and the dexamethasone administration group of groups 1-8 were significantly lower than the negative control group of groups 1-2 (both p<0.001).
제1-3군의 타임 추출물 투여군, 제1-5군의 타임 추출물 및 자주천인국 착즙액 혼합물(TEmix1) 투여군, 제1-6군의 타임 추출물 및 자주천인국 착즙액 혼합물(TEmix2) 투여군은 아토피 피부염의 병리기전에서 중요한 역할을 하는 호중구와 호산구 모두를 유의하게 감소시켰으며, 특히 양성대조군 1인 제1-7군의 다래추출물 투여군보다 현저히 우수하고, 양성대조군 2인 제1-8군의 덱사메타손 투여군과 유사한 수준으로 확인되었다. Atopic dermatitis in the group administered with the thyme extract of Groups 1-3, the group administered with the thyme extract of Groups 1-5 and the extract mixture (TEmix1), and the group administered with the thyme extract and the extract of Group 1-6 with the extract and extract of the purple chrysanthemum (TEmix2). Both neutrophils and eosinophils, which play an important role in the pathological mechanism of was found to be at a similar level to
한편 혈중 IgE 농도는, 제1-8군을 제외한 모든 아토피 유발군에서 제1-1군의 정상대조군에 비하여 유의하게 높았으나(p<0.001), 제1-3군 및 제1-4군의 타임 추출물 투여군, 제1-5군의 타임 추출물 및 자주천인국 착즙액 혼합물(TEmix1) 투여군 및 제1-6군의 타임 추출물 및 자주천인국 착즙액 혼합물(TEmix2) 투여군은 제1-2군의 음성대조군에 비하여 유의하게 낮았다(p<0.01, p<0.01, p<0.001 및 p<0.001). 상기 결과로부터 제1-3군 및 제1-4군의 타임 추출물, 특히 제1-5군의 타임 추출물 및 자주천인국 착즙액 혼합물(TEmix1) 투여군 및 제1-6군의 타임 추출물 및 자주천인국 착즙액 혼합물(TEmix2) 투여군은 양성대조군 1의 다래추출물보다 알레르기 반응의 핵심인자인 IgE 생성 억제에 매우 효과적인 것으로 확인되었다. On the other hand, the blood IgE concentration was significantly higher in all atopy-inducing groups except for groups 1-8 than in the normal control group in group 1-1 (p<0.001), but in groups 1-3 and 1-4 The thyme extract administration group, the group 1-5 administered thyme extract and the thyme extract and the thyme extract, and the thyme extract and the thyme extract and the thyme extract of the group 1-6 (TEmix2) administration group were the negative control groups of the 1,2 group. was significantly lower than that (p<0.01, p<0.01, p<0.001, and p<0.001). From the above results, the thyme extracts of groups 1-3 and 1-4, especially the thyme extract of groups 1-5 and the thyme extract of groups 1-5, and the thyme extract of groups 1-6 and the thyme extract of groups 1-6 and extract It was confirmed that the liquid mixture (TEmix2) administration group was more effective in inhibiting the production of IgE, a key factor in allergic reactions, than the extract of Actinidia in the positive control group 1.
6. 표피 내 염증세포 침윤 수준 및 비만세포 침윤 수준 측정 결과6. Measurement result of inflammatory cell infiltration level and mast cell infiltration level in the epidermis
아토피 피부염 유발 개시 49 일차의 부검일에 채취한 조직을 조직병리학적 검사를 위한 검체를 제작한 뒤, Hematoxylin & Eosin(H&E) 및 톨루이딘 블루(Toluidine blue) 염색을 실시하고, 광학 현미경(Olympus BX53, Japan)을 이용하여 조직병리학적 변화를 관찰하였다. After preparing a specimen for histopathological examination of the tissue collected on the day of autopsy on the 49th day of the induction of atopic dermatitis, Hematoxylin & Eosin (H&E) and Toluidine blue staining was performed, and an optical microscope (Olympus BX53, Japan) was used to observe histopathological changes.
Hematoxylin & Eosin(H&E) 염색 슬라이드를 이용한 조직병리학적 평가의 경우, 가장 심한 병변 부위를 선정한 다음, 표피층(epidermis)의 염증세포 침윤 수준을 평가하였고, 톨루이딘 블루 염색 슬라이드를 이용한 조직병리학적 평가의 경우, 가장 심한 병변 부위를 선정한 다음, 비만세포 수를 계수하여 표 10 및 11에 나타내었다.For histopathological evaluation using Hematoxylin & Eosin (H&E) stained slides, the most severe lesion site was selected and then the level of inflammatory cell infiltration in the epidermis was evaluated. For histopathological evaluation using toluidine blue stained slides , the most severe lesion site was selected, and the number of mast cells was counted and shown in Tables 10 and 11.
제1-1군의 정상대조군과 제1-2군 내지 제1-8군 사이의 유의차는 * p<0.05, ** p<0.01, *** p<0.001; 제1-2군의 음성대조군과 제1-3군 내지 제1-8군 사이의 유의차는 # p<0.05, ## p<0.01Significant differences between the normal control group in group 1-1 and groups 1-2 to 1-8 were * p<0.05, ** p<0.01, *** p<0.001; The significant difference between the negative control group in Group 1-2 and Groups 1-3 to 1-8 was # p<0.05, ## p<0.01
제1-2군의 음성대조군, 제1-3군 및 제1-4군의 타임 추출물 투여군 및 제1-7군의 다래추출물 투여군은 표피 내 염증세포 침윤 수준은 제1-1군의 정상대조군에 비하여 유의하게 높았다(p<0.001, p<0.01, p<0.05 및 p<0.001). In the negative control group of Group 1-2, the thyme extract administration group of Groups 1-3 and 1-4, and the Actinaceae extract administration group of Group 1-7, the level of inflammatory cell infiltration in the epidermis was the normal control group of Group 1-1. was significantly higher than that of . (p<0.001, p<0.01, p<0.05 and p<0.001).
나아가 제1-5군의 타임 추출물 및 자주천인국 착즙액 혼합물(TEmix1) 투여군 및 제1-8군의 덱사메타손 투여군은 제1-2군의 음성대조군에 비하여 유의하게 낮았다(p<0.05 및 p<0.001). 제1-6군의 경우에도 유의적이지는 않으나 표피 내 염증세포 침윤이 감소되는 경향을 보였다.Furthermore, the group 1-5 administered with thyme extract and thyme extract and extract (TEmix1) and the group 1-8 administered with dexamethasone were significantly lower than the negative control group of groups 1-2 (p<0.05 and p<0.001). ). In the case of groups 1-6, although not significant, the infiltration of inflammatory cells in the epidermis showed a tendency to decrease.
한편, 비만세포의 침윤 수준을 확인한 결과, 제1-5군의 타임 추출물 및 자주천인국 착즙액 혼합물(TEmix1) 투여군, 제1-6군의 타임 추출물 및 자주천인국 착즙액 혼합물(TEmix2) 투여군, 제1-7군의 다래추출물 투여군 및 제1-8군의 덱사메타손 투여군에서 비만세포수가 제1-2군의 음성대조군에 비해 유의하게 낮았다(p<0.05, p<0.05, p<0.01 및 p<0.001). On the other hand, as a result of confirming the level of infiltration of mast cells, the group 1-5 administered with a thyme extract and purple cheonin-guk juice mixture (TEmix1), the group 1-6 administered with the thyme extract and the thyme extract and purple cheonin-guk juice mixture (TEmix2), the first The number of mast cells was significantly lower in the group 1-7 treated with the extract of Actinidia and dexamethasone of group 1-8 compared to the negative control group of group 1-2 (p<0.05, p<0.05, p<0.01, and p<0.001). ).
실험예 2Experimental Example 2
1. 마우스 유래 대식세포 RAW264.7에서 추출물의 항염증 활성 비교1. Comparison of anti-inflammatory activity of extracts in mouse-derived macrophages RAW264.7
제조예 2의 타임 에탄올 추출물(TVEE)과 제조예 2에 기재된 방법을 그대로 이용하여 제조한 백리향(Thymus quinquecostatus) 에탄올 추출물(TQEE)의 항염증 활성을 비교하였다.The anti-inflammatory activity of the thyme ethanol extract (TVEE) of Preparation Example 2 and the thymus quinquecostatus ethanol extract (TQEE) prepared using the method described in Preparation Example 2 as it is was compared.
마우스 유래 대식세포인 RAW264.7 세포를 24-well plate에 4×105 cells/well 세포수로 분주하여 24 시간 동안 배양하였다. 배양배지를 제거한 후 무혈청 배지에 희석한 TVEE와 TQEE를 각각 250 μg/mL 농도로 처리하였다. 이와 동시에 무혈청 배지에 희석한 LPS(lipopolysaccharide)를 최종농도 500 ng/mL로 처리하여 24 시간 동안 배양하였다. 배양 후 배양액은 원심분리(5,000 rpm, 3 분, 4 ℃)하여 부유세포를 제거하고 상등액을 이용하여 LPS에 의해 분비된 염증 매개물질인 산화질소(nitric oxide, NO)와 염증성 사이토카인인 IL-1β 및 IL-6의 분비량을 측정하였다. RAW264.7 cells, which are mouse-derived macrophages, were seeded in a 24-well plate at 4×10 5 cells/well and cultured for 24 hours. After removing the culture medium, TVEE and TQEE diluted in serum-free medium were each treated at a concentration of 250 μg/mL. At the same time, LPS (lipopolysaccharide) diluted in serum-free medium was treated to a final concentration of 500 ng/mL and cultured for 24 hours. After incubation, the culture medium is centrifuged (5,000 rpm, 3 minutes, 4 ℃) to remove suspended cells, and the supernatant is used to obtain nitric oxide (NO), an inflammatory mediator secreted by LPS, and IL-, an inflammatory cytokine. The secretion amount of 1β and IL-6 was measured.
산화질소 분비량 측정은 96-well plate에 50 μL Griess's reagent와 50 μL의 상등액을 혼합하여 15 분 동안 상온에서 반응시킨 후 microplate reader를 이용해 540 nm에서 흡광도를 측정하여 산화질소 분비량을 정량하였고, 염증성 사이토카인인 IL-6 및 IL-1β 분비량은 ELISA 키트(KOMA BIOTECH Co., Korea)를 이용하여 분석하였다.Nitric oxide secretion was measured by mixing 50 μL of Griess’ reagent and 50 μL of supernatant in a 96-well plate, reacting at room temperature for 15 minutes, and then measuring the absorbance at 540 nm using a microplate reader to quantify the secretion of nitric oxide, The secretion levels of kinases IL-6 and IL-1β were analyzed using an ELISA kit (KOMA BIOTECH Co., Korea).
또한 랫드 유래 비만세포(mast cell)인 RBL-2H3(rat mast cell line) 세포를 American Type Culture Collection(ATCC, USA)에서 구입하여 배양하였다. 상기 RBL-2H3 세포에서 시료 처리에 따른 TNF-α 분비량을 측정하기 위해 24-well plate에 2×105 cells/well 세포수로 분주하여 24 시간 동안 배양하였다. 배양배지를 제거한 후 무혈청 배지에 희석한 시료를 농도별로 처리하였다. 이와 동시에 A23187 1 μM, PMA 50 nM으로 18 시간 동안 처리하여 비만세포를 감작시켰다. 배양 후 배양액을 원심분리(5,000 rpm, 3 분, 4 ℃)하여 분비된 TNF-α를 ELISA Kit(KOMA BIOTECH Co., Korea)를 이용하여 정량하였다.In addition, rat-derived mast cells, RBL-2H3 (rat mast cell line) cells were purchased from the American Type Culture Collection (ATCC, USA) and cultured. In order to measure the amount of TNF-α secretion according to the sample treatment in the RBL-2H3 cells, 2×10 5 cells/well cells were dispensed into a 24-well plate and cultured for 24 hours. After removing the culture medium, samples diluted in serum-free medium were treated for each concentration. At the same time, mast cells were sensitized by treatment with 1 μM of A23187 and 50 nM of PMA for 18 hours. After incubation, the culture medium was centrifuged (5,000 rpm, 3 minutes, 4° C.) and secreted TNF-α was quantified using an ELISA Kit (KOMA BIOTECH Co., Korea).
산화질소, IL-1β 및 IL-6 분비량 측정에서 제2-1군은 LPS로 세포에 염증을 유발하지 않은 정상대조군, 나머지 3군은 LPS로 염증을 유발시킨후 시험물질을 처리한 군으로 제2-2군은 생리식염수를 처리한 음성대조군, 제2-3군은 타임 에탄올 추출물(TVEE) 250μg/mL처리군, 그리고 제2-4군은 백리향 에탄올 추출물(TQEE) 250μg/mL 처리군이다. TNF-α 분비량 측정에서 제2-1군은 PMA로 비만세포를 감작시키지 않은 정상대조군, 나머지 3군은 PMA로 감작시킨후 시험물질을 처리한 군으로 제2-2군은 생리식염수를 처리한 음성대조군, 제2-3군은 타임 에탄올 추출물(TVEE) 250μg/mL처리군, 그리고 제2-4군은 백리향 에탄올 추출물(TQEE) 250μg/mL 처리군이다. In the measurement of nitric oxide, IL-1β, and IL-6 secretion, group 2-1 was a normal control group that did not induce inflammation in cells with LPS, and the other 3 groups were treated with the test substance after inflammation was induced with LPS. Group 2-2 is a negative control group treated with physiological saline, group 2-3 is a thyme ethanol extract (TVEE) 250 μg/mL group, and group 2-4 is a group treated with thyme ethanol extract (TQEE) 250 μg/mL . In the measurement of TNF-α secretion, group 2-1 was a normal control group that did not sensitize mast cells with PMA, group 3 was treated with a test substance after sensitization with PMA, and group 2-2 was treated with physiological saline. Negative control group, group 2-3 is thyme ethanol extract (TVEE) 250 μg/mL treatment group, and group 2-4 is thyme ethanol extract (TQEE) 250 μg/mL treatment group.
제2-1군의 정상대조군과 제2-2군 내지 제2-4군 사이의 유의차는 * p<0.05, ** p<0.01, *** p<0.001; 제2-2군의 음성대조군과 제2-3군 및 제2-4군 사이의 유의차는 # p<0.05, ## p<0.01Significant differences between the normal control group in group 2-1 and groups 2-2 to 2-4 were * p<0.05, ** p<0.01, *** p<0.001; Significant differences between the negative control group in group 2-2 and groups 2-3 and 2-4 were # p<0.05, ## p<0.01
LPS로 세포에 염증을 유발한 제2-2군의 음성대조군은 제2-1군의 정상대조군에 비해서 산화질소, IL-1β 및 IL-6 분비량이 현저히 증가하였다(p<0.01 또는 p<0.05). 또한 PMA로 비만세포를 감작시킨 제2-2군의 음성대조군도 제2-1군의 정상대조군에 비해 TNF-α 분비량이 현저히 증가하였다(p<0.05).The levels of nitric oxide, IL-1β and IL-6 secretion were significantly increased in the negative control group of group 2-2, which induced inflammation in cells with LPS, compared to the normal control group in group 2-1 (p<0.01 or p<0.05). ). In addition, the negative control group of group 2-2, which was sensitized to mast cells with PMA, also significantly increased TNF-α secretion compared to the normal control group of group 2-1 (p<0.05).
제2-3군의 타임 에탄올 추출물(TVEE) 처리군 및 제2-4군의 백리향 에탄올 추출물(TQEE) 처리군은 제2-2의 음성대조군에 비해 산화질소, IL-1β 및 IL-6를 현저히 감소시켰다(p<0.01 또는 p<0.05). 그 중에서도 제2-3군의 타임 에탄올 추출물(TVEE) 처리군은 제2-4군의 백리향 에탄올 추출물(TQEE) 처리군보다 LPS 처리로 현저히 증가된 IL-1β 및 IL-6 분비량을 더욱 낮게 낮추는 경향을 나타내었다.The thyme ethanol extract (TVEE) treatment group of group 2-3 and the thyme ethanol extract (TQEE) treatment group of group 2-4 showed nitric oxide, IL-1β and IL-6 compared to the negative control group of 2-2. significantly decreased (p<0.01 or p<0.05). Among them, the thyme ethanol extract (TVEE) treatment group of group 2-3 lowered the IL-1β and IL-6 secretion significantly increased by LPS treatment than the thyme ethanol extract (TQEE) treatment group of group 2-4. showed a trend.
또한 제2-3군의 타임 에탄올 추출물(TVEE) 처리군은 제2-2의 음성대조군에서 PMA 감작으로 현저히 증가된 TNF-α 분비량을 유의적으로 낮추었으나(p<0.05), 제2-4군의 백리향 에탄올 추출물(TQEE) 처리군은 TNF-α 분비량에서 제2-2의 음성대조군과 유의적인 차이가 없었다.In addition, the thyme ethanol extract (TVEE) treatment group of group 2-3 significantly lowered the TNF-α secretion significantly increased by PMA sensitization in the negative control group of group 2-2 (p<0.05), but group 2-4 The thyme ethanol extract (TQEE) treatment group had no significant difference from the negative control group of 2-2 in the amount of TNF-α secretion.
따라서 타임 에탄올 추출물(TVEE)은 백리향 에탄올 추출물(TQEE)에 비해 염증성 사이토카인 IL-6, IL-1β 및 TNF-α 분비량을 낮추는 항염증 효과가 뛰어나므로, 알레르기성 또는 염증성 피부질환 개선에 더욱 유리한 소재로 판단되었다.Therefore, thyme ethanol extract (TVEE) has an excellent anti-inflammatory effect in lowering the secretion of inflammatory cytokines IL-6, IL-1β and TNF-α compared to thyme ethanol extract (TQEE), so it is more advantageous for improving allergic or inflammatory skin diseases material was considered.
실험예 3Experimental Example 3
타임 추출물 단독과 타임 추출물에 자주천인국 착즙액을 혼합한 혼합물의 아토피 피부염과 관련성이 높은 호산구의 전체 백혈구 중 비율, 및 절대량을 측정하여 비교하였다.The ratio and absolute amount of eosinophils highly related to atopic dermatitis were measured and compared between the thyme extract alone and the mixture of the thyme extract and the thyme extract mixed with the extract.
제조예 3의 자주천인국 착즙액 추출물(EPJ)과 제조예 2의 타임 에탄올 추출물(TVEE)을 각각 자주천인국 착즙액 및 타임 에탄올 추출물의 고형분 기준으로 9 : 1, 7 : 3, 5 : 5, 3 : 7 및 1 : 9 중량비로 혼합하여 자주천인국 착즙액 및 타임 추출물 혼합물 분말을 제조하였다. The thyme ethanol extract (TVEE) of Preparation Example 3 and the thyme ethanol extract (TVEE) of Preparation Example 3 were respectively 9: 1, 7: 3, 5: 5, 3 based on the solid content of the thyme extract and the thyme ethanol extract. : 7 and 1 : 9 were mixed in a weight ratio to prepare a mixture powder of purple cheoninguk juice and thyme extract.
실험동물, 사육조건 및 아토피 피부염 유발 방법은 모두 실험예 1과 동일하게 진행하고, 정상대조군 및 음성대조군도 실험예 1과 동일하게 사용하였고, 모든 시료는 추출물, 착즙액 또는 이들의 혼합물의 고형분을 기준으로 200 mg/kg을 10 mL/kg 투여 액량을 기준으로 1 일 1 회씩 4 주간 경구 투여하였다. 정상대조군 및 음성대조군은 비히클로 생리식염수를 10 mL/kg 경구 투여하였다.Experimental animals, breeding conditions, and methods for inducing atopic dermatitis were all carried out in the same manner as in Experimental Example 1, and the normal and negative controls were also used in the same manner as in Experimental Example 1, and all samples were extracts, juices, or solids of a mixture thereof. As a standard, 200 mg/kg was orally administered once a day for 4 weeks based on a 10 mL/kg dose. The normal control group and the negative control group were orally administered with 10 mL/kg of physiological saline as a vehicle.
아토피 피부염 유발 개시 42 일차의 부검일에 채취한 혈액을 이용하여 백혈구의 비율을 확인하였다. 채혈한 혈액 중 일부를 항응고제인 EDTA-2K가 들어있는 CBC bottle에 주입한 후 자동혈액분석기(ADVIA 2120, SIEMENS, USA)를 이용하여 호산구(Eosinophil) 비율 및 절대량을 확인하여 표 13에 나타내었다.The percentage of leukocytes was confirmed using the blood collected on the day of autopsy on the 42nd day of the induction of atopic dermatitis. After injecting some of the blood collected into the CBC bottle containing EDTA-2K, an anticoagulant, the ratio and absolute amount of eosinophils were checked using an automatic hematology analyzer (ADVIA 2120, SIEMENS, USA), and it is shown in Table 13.
제3-1군의 정상대조군과 제3-2군 내지 제3-9군 사이의 유의차는 * p<0.05, ** p<0.01; 제3-2군의 음성대조군과 제3-3군 내지 제3-9군 사이의 유의차는 # p<0.05, ## p<0.01, ### p<0.001Significant differences between the normal control group in Group 3-1 and Groups 3-2 to 3-9 were * p<0.05, ** p<0.01; Significant differences between the negative control group in group 3-2 and groups 3-3 to 3-9 were # p<0.05, ## p<0.01, ### p<0.001
아토피 피부염에서 염증 관련 세포수, 특히 호산구의 비율이 증대되고, 호산구는 아토피 피부염의 병리기전에 중요한 역할을 하는 것으로 알려져 있다. In atopic dermatitis, the number of inflammation-related cells, particularly eosinophils, is increased, and eosinophils are known to play an important role in the pathogenesis of atopic dermatitis.
호산구의 비율 및 호산구의 절대량은 제3-1군의 정상대조군에 비해서 제3-2군의 음성대조군에서 유의적으로 현저히 증가하였고(p<0.01 및 p<0.05), 제3-3군 내지 제3-9군의 모든 시험물질 투여군에서 제3-2군의 음성대조군에 비해 유의적으로 감소하였다(p<0.05, p<0.01 및 p<0.001).The ratio of eosinophils and the absolute amount of eosinophils were significantly and significantly increased in the negative control group of group 3-2 compared to the normal control group of group 3-1 (p<0.01 and p<0.05), and groups 3-3 to group 3 All test substance administration groups of groups 3-9 significantly decreased compared to the negative control group of group 3-2 (p<0.05, p<0.01 and p<0.001).
타임 에탄올 추출물(TVEE)에 자주천인국 착즙액(EPJ)을 혼합한 시험군 중에서 자주천인국과 타임을 9 : 1로 혼합한 제3-5군에서 제3-3군의 타임 단독 투여군 및 제3-4군의 자주천인국 단독 투여군에 비해 호산구의 비율 및 호산구의 절대량이 유의적으로 감소하였음을 확인하였다. Among the test groups in which thyme ethanol extract (TVEE) was mixed with thyme extract (EPJ), in group 3-5, in which thyme was mixed with thyme in a ratio of 9: 1, thyme alone administered group and group 3- It was confirmed that the ratio of eosinophils and the absolute amount of eosinophils were significantly decreased compared to the group 4 administered alone.
따라서 아토피 피부염 치료를 위해서는 타임 추출물 단독으로도 효과가 있으나, 바람직하게는 타임 추출물과 자주천인국 착즙액을 고형분 기준으로 1 : 99 중량비에서 20 : 80 중량비, 바람직하게는 5 : 95 중량비에서 15 : 85 중량비로 혼합하는 것이 유리할 수 있을 것으로 판단된다.Therefore, for the treatment of atopic dermatitis, thyme extract alone is effective, but preferably, the thyme extract and the juice of purple cheoninguk are 1:99 in weight ratio 20:80 weight ratio, preferably 5:95 weight ratio 15:85 It is determined that mixing in a weight ratio may be advantageous.
통계분석statistical analysis
상기 실험 결과는 평균 ± 표준편차로 나타내고, 모수적인 다중비교의 경우, 자료의 정규성을 가정하고, 모수적 일원분산분석(One-way ANOVA)으로 검정하였으며, 그 결과가 유의할 경우, Dunnett's multiple comparison test를 이용하여 사후검정을 실시하여 시험군간 유의한 차이를 분석하였다. 비모수적인 다중비교의 경우, Kruskal-Wallis'H-test로 검정하여, 그 결과가 유의할 경우 사후분석인 Mann-Whitney U test를 이용하여 시험군간 유의한 차이를 분석하였다.The experimental results are expressed as mean ± standard deviation, and in the case of parametric multiple comparison, normality of the data was assumed, and it was tested by parametric one-way ANOVA. If the result is significant, Dunnett's multiple comparison test A post-hoc test was performed using In the case of non-parametric multiple comparisons, the Kruskal-Wallis'H-test was used, and if the results were significant, significant differences between the test groups were analyzed using the Mann-Whitney U test, which is a post-hoc analysis.
통계학적 분석은 Prism 7.04(GraphPad Software Inc., San Diego, CA, USA)을 이용하여 실시하였으며, p값이 0.05 미만일 경우, 통계학적으로 유의한 것으로 판정하였다. Statistical analysis was performed using Prism 7.04 (GraphPad Software Inc., San Diego, CA, USA), and when the p-value was less than 0.05, it was determined to be statistically significant.
아래에 본 발명의 타임 추출물, 또는 타임 추출물 및 자주천인국 착즙액의 혼합물을 포함하는 조성물의 제제예를 설명하나, 본 발명은 이를 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다.Examples of the formulation of the composition comprising the thyme extract of the present invention or a mixture of thyme extract and purple cheoninguk juice will be described below, but the present invention is not intended to be limited thereto, but only to be described in detail.
제제예 1: 산제의 제조Formulation Example 1: Preparation of powder
제조예 1의 타임 추출물(TVWE) 분말 20 mgThyme extract (TVWE) powder of Preparation Example 1 20 mg
유당 100 mgLactose 100 mg
탈크 10 mgtalc 10 mg
상기의 성분들을 혼합하고 기밀포에 충진하여 산제를 제조한다.The above ingredients are mixed and filled in an airtight bag to prepare a powder.
제제예 2: 정제의 제조Formulation Example 2: Preparation of tablets
제조예 2의 타임 추출물(TVEE) 분말 10 mg10 mg of thyme extract (TVEE) powder of Preparation Example 2
옥수수전분 100 mg100 mg cornstarch
유당 100 mgLactose 100 mg
스테아린산 마그네슘 2 mg2 mg magnesium stearate
상기의 성분들을 혼합한 후 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조한다.After mixing the above ingredients, tablets are prepared by tableting according to a conventional manufacturing method of tablets.
제제예 3: 캡슐제의 제조Formulation Example 3: Preparation of capsules
제조예 4의 타임 추출물 및 자주천인국 착즙액 분말 10 mg10 mg of thyme extract of Preparation Example 4 and extract powder of purple cheonin-guk
결정성 셀룰로오스 3 mg3 mg of crystalline cellulose
락토오스 14.8 mgLactose 14.8 mg
마그네슘 스테아레이트 0.2 mg0.2 mg magnesium stearate
통상의 캡슐제 제조방법에 따라 상기의 성분을 혼합하고 젤라틴 캡슐에 충전하여 캡슐제를 제조한다.According to a conventional capsule preparation method, the above ingredients are mixed and filled in a gelatin capsule to prepare a capsule.
제제예 4: 과립제의 제조Formulation Example 4: Preparation of granules
제조예 5의 타임 추출물 및 자주천인국 착즙액 분말 1,000 mg1,000 mg of thyme extract of Preparation Example 5 and extract powder of purple cheonin-guk
비타민 혼합물 적량appropriate amount of vitamin mixture
비타민 A 아세테이트 70 ㎍70 μg vitamin A acetate
비타민 E 1.0 mgVitamin E 1.0 mg
비타민 B1 0.13 mgVitamin B1 0.13 mg
비타민 B2 0.15 mgVitamin B2 0.15 mg
비타민 B6 0.5 mg0.5 mg of vitamin B6
비타민 B12 0.2 ㎍0.2 μg of vitamin B12
비타민 C 10 mgVitamin C 10 mg
비오틴 10 ㎍Biotin 10 μg
니코틴산아미드 1.7 mgNicotinamide 1.7 mg
엽산 50 ㎍50 μg folic acid
판토텐산 칼슘 0.5 mgCalcium pantothenate 0.5 mg
무기질 혼합물 적량Appropriate amount of inorganic mixture
황산제1철 1.75 mgferrous sulfate 1.75 mg
산화아연 0.82 mgZinc Oxide 0.82 mg
탄산마그네슘 25.3 mgMagnesium carbonate 25.3 mg
제1인산칼륨 15 mgPotassium monophosphate 15 mg
제2인산칼슘 55 mgDibasic calcium phosphate 55 mg
구연산칼륨 90 mgPotassium citrate 90 mg
탄산칼슘 100 mg100 mg calcium carbonate
염화마그네슘 24.8 mgMagnesium chloride 24.8 mg
상기의 비타민 및 미네랄 혼합물의 조성비는 건강기능식품에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상의 건강기능식품 제조방법에 따라 상기의 성분을 혼합한 다음, 과립을 제조하고, 통상의 방법에 따라 건강기능식품 조성물 제조에 사용할 수 있다.The composition ratio of the vitamin and mineral mixture is mixed with ingredients suitable for health functional food in a preferred embodiment, but the blending ratio may be arbitrarily modified, and the ingredients are mixed according to a conventional health functional food manufacturing method. Next, the granules can be prepared and used in the preparation of a health functional food composition according to a conventional method.
제제예 5: 음료 제형의 제조Formulation Example 5: Preparation of beverage formulations
제조예 1의 타임 추출물(TVWE) 분말 1,000 mg1,000 mg of thyme extract (TVWE) powder of Preparation Example 1
구연산 1,000 mg1,000 mg citric acid
올리고당 100 g100 g of oligosaccharides
매실농축액 2 g2 g of plum concentrate
타우린 1 g1 g taurine
정제수를 가하여 전체 900 mLAdd purified water to total 900 mL
통상의 음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1 시간 동안 85 ℃에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 2 L 용기에 취득하여 밀봉 멸균한After mixing the above ingredients according to a conventional beverage manufacturing method, after stirring and heating at 85 ° C for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2 L container, sealed and sterilized.
제제예 6: 사료 조성물의 제조Formulation Example 6: Preparation of feed composition
제조예 4의 타임 추출물 및 자주천인국 착즙액(TEmix1) 분말 0.1 kg, 옥수수 25.5 kg, 소맥 15.04 kg, 소맥분 8.15 kg, 미강 7.4 kg, 대두박 18 kg, 옥구르텐 1 kg, 닭부산물 14 kg, 동물성유지 9 kg, 가공염 0.3 kg, 인산제삼칼슘 0.3 kg, 석회석 1 kg, 염화콜린 0.01 kg, 비타민 0.05 kg, 미네랄 0.05 kg 및 소화효소제 0.1 kg을 혼합하여 동물(개, 애완견) 사료 조성물을 제조하였다. 0.1 kg of thyme extract of Preparation Example 4 and extract (TEmix1) powder, 25.5 kg of corn, 15.04 kg of wheat, 8.15 kg of wheat flour, 7.4 kg of rice bran, 18 kg of soybean meal, 1 kg of okgurten, 14 kg of chicken by-products, animal origin 9 kg of fat and oil, 0.3 kg of processed salt, 0.3 kg of tricalcium phosphate, 1 kg of limestone, 0.01 kg of choline chloride, 0.05 kg of vitamins, 0.05 kg of minerals and 0.1 kg of digestive enzymes were mixed to prepare an animal (dog, pet dog) feed composition.
Claims (15)
상기 자주천인국 착즙액은 자주천인국의 줄기, 잎 또는 지상부 전초의 착즙액이고,
상기 타임 추출물 및 자주천인국 착즙액의 고형분 기준 혼합비율은 1 : 9 중량비이며,
상기 약학 조성물은 경구용 제제인 것을 특징으로 하는 알레르기성 또는 염증성 피부질환 치료 또는 예방용 약학 조성물.In the pharmaceutical composition for the treatment or prevention of allergic or inflammatory skin disease comprising a thyme extract and the extract of purple chrysanthemum as an active ingredient,
The juice of the purple cheonin-guk is the juice of the stems, leaves or above-ground parts of the purple cheonin-guk,
The mixing ratio based on the solids content of the thyme extract and the juice of the thyme extract is 1: 9 by weight,
The pharmaceutical composition is a pharmaceutical composition for treating or preventing allergic or inflammatory skin disease, characterized in that it is an oral preparation.
상기 자주천인국 착즙액은 자주천인국의 줄기, 잎 또는 지상부 전초의 착즙액이고,
상기 타임 추출물 및 자주천인국 착즙액의 고형분 기준 혼합비율은 1 : 9 중량비이며,
상기 약학 조성물은 경구용 제제인 것을 특징으로 하는 알레르기성 또는 염증성 피부질환 치료 또는 예방용 동물용 약학 조성물.In the pharmaceutical composition for an animal for the treatment or prevention of allergic or inflammatory skin disease, comprising a thyme extract and extract of purple chrysanthemum as an active ingredient,
The juice of the purple cheonin-guk is the juice of the stems, leaves or above-ground parts of the purple cheonin-guk,
The mixing ratio based on the solids content of the thyme extract and the juice of the thyme extract is 1: 9 by weight,
The pharmaceutical composition is an animal pharmaceutical composition for treating or preventing allergic or inflammatory skin disease, characterized in that it is an oral preparation.
상기 자주천인국 착즙액은 자주천인국의 줄기, 잎 또는 지상부 전초의 착즙액이고,
상기 타임 추출물 및 자주천인국 착즙액의 고형분 기준 혼합비율은 1 : 9 중량비인 것을 특징으로 하는 알레르기성 또는 염증성 피부질환 개선용 식품 조성물.In a food composition for improving allergic or inflammatory skin diseases, comprising thyme extract and purple cheoninguk extract as active ingredients,
The juice of the purple cheonin-guk is the juice of the stems, leaves or above-ground parts of the purple cheonin-guk,
A food composition for alleviating allergic or inflammatory skin diseases, characterized in that the mixing ratio of the thyme extract and the juice extract of purple cheoninguk based on the solid content is 1 : 9 by weight.
상기 자주천인국 착즙액은 자주천인국의 줄기, 잎 또는 지상부 전초의 착즙액이고,
상기 타임 추출물 및 자주천인국 착즙액의 고형분 기준 혼합비율은 1 : 9 중량비인 것을 특징으로 하는 알레르기성 또는 염증성 피부질환 개선용 사료 조성물.In the feed composition for improving allergic or inflammatory skin disease comprising thyme extract and jasmine cheoninguk extract as active ingredients,
The juice of the purple cheonin-guk is the juice of the stems, leaves or above-ground parts of the purple cheonin-guk,
A feed composition for improving allergic or inflammatory skin diseases, characterized in that the mixing ratio of the thyme extract and the juice of jasmine cheoninguk juice based on the solid content is 1 : 9 by weight.
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