KR100954216B1 - Composition for treating atopic dermatitis comprising agents inhibiting immune response of type Th1 and type Th2 - Google Patents
Composition for treating atopic dermatitis comprising agents inhibiting immune response of type Th1 and type Th2 Download PDFInfo
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- KR100954216B1 KR100954216B1 KR1020070131531A KR20070131531A KR100954216B1 KR 100954216 B1 KR100954216 B1 KR 100954216B1 KR 1020070131531 A KR1020070131531 A KR 1020070131531A KR 20070131531 A KR20070131531 A KR 20070131531A KR 100954216 B1 KR100954216 B1 KR 100954216B1
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Abstract
본 발명은 아토피성 피부염의 각 단계에 각각 작용하는 Th1 및 Th2 면역반응을 억제하고 또한 급만성 염증반응에 관여하는 NF-kB를 억제하여, 부작용이 없으며 효능이 뛰어난 아토피성 피부염 치료용 조성물을 제공한다. 보다 구체적으로는 오매, 창출, 고삼, 승마로 이루어진 군으로부터 오매를 필수적으로 포함하도록 하나 이상 선택된 약재를 포함하는 것을 특징으로 하는 조성물을 제공한다.The present invention inhibits Th1 and Th2 immune responses acting at each stage of atopic dermatitis, and also inhibits NF-kB involved in acute acute inflammatory reactions, thereby providing a composition for treating atopic dermatitis having no side effects and excellent efficacy. do. More specifically, it provides a composition characterized in that it comprises at least one selected medicinal herbs to include essentially ume from the group consisting of ume, creation, ginseng, horse riding.
아토피성 피부염, 오매, 창출, 고삼, 승마, Th1, Th2, NF-kB Atopic dermatitis, ume, creation, red ginseng, horse riding, Th1, Th2, NF-kB
Description
본 발명은 헬퍼 T1형(Th1) 및 헬퍼 T2형(Th2) 면역반응을 동시에 억제하고 NF-kB 활성을 억제하는 면역반응 및 염증 조절 조성물에 관한 것으로서, 특히 아토피성 피부염의 예방, 개선 또는 치료용 조성물에 관한 것이다. The present invention relates to an immune response and inflammation control composition that simultaneously inhibits helper type T1 (Th1) and helper type T2 (Th2) immune responses, and inhibits NF-kB activity, and particularly for the prevention, improvement or treatment of atopic dermatitis. It relates to a composition.
아토피성 피부염은 아토피 알러지를 가진 사람에게서 나타나는 질환으로, 가려움이 매우 심한 습진, 두껍고 거칠어 지는 피부, 재발되는 만성피부염 등의 증상을 보인다. 최근 환경오염물질의 노출이 증가하고 있어 아토피성 피부염 환자의 수는 날로 증가하고 있으며, 어린이의 20% 정도가 아토피성 피부염에 시달리고 있다. 한국에서의 피부 면역질환 발병률은 매년 증가하고 있어, 일례로 2004년 현재 아토피성 피부염으로 병원을 찾은 사람은 120여만 명이고 이 가운데 유아(1~4세)는 52만7000 여명으로 나타나 전체 유아의 18%를 차지하였다. 아토피성 피부염은 유전적, 면역학적, 환경적 요인이 관여한다고 알려져 있다. Atopic dermatitis is a disease that occurs in people with allergic atopic dermatitis, and itching has very severe eczema, thick, rough skin, and recurrent chronic dermatitis. With the recent increase in environmental pollutants, the number of patients with atopic dermatitis is increasing day by day, and about 20% of children suffer from atopic dermatitis. The incidence of skin immune diseases in Korea has been increasing every year. For example, as of 2004, more than 1.2 million people visited the hospital due to atopic dermatitis. Accounted for 18%. Atopic dermatitis is known to be involved in genetic, immunological and environmental factors.
아토피성 피부염은 대부분 IgE와 연관된 면역기전에 의해 발병되는데, T 세포 이상에 의한 면역반응이 관여한다는 보고가 많으며, 헬퍼 T세포 (Th cell)의 역할이 중요하다고 알려져 있다. 헬퍼 T세포에는 헬퍼 T1형(Th1) 세포와 헬퍼 T2형(Th2) 세포가 포함된다. Th1 세포가 분비하는 사이토카인은 세포매개형 면역반응에 관여하고, Th2 세포가 분비하는 사이토카인은 항체면역반응을 담당한다. 아토피성 피부염 병변에서 T 세포가 많이 발견되는데 이 중에서 Th2 세포에 의해 분비되는 사이토카인이 아토피 발병에 중요한 역할을 한다. Th2 세포가 분비하는 IL-4, IL-13은 IgE 생성을 촉진하며, IL-5는 호염구 반응을 증진시킨다 (International Immunology 2004, 16(8), p1155-1160). Atopic dermatitis is mostly caused by an immune mechanism associated with IgE, and there are many reports that an immune response caused by T cell abnormality is involved, and the role of helper T cells (Th cell) is known to be important. Helper T cells include helper T1 (Th1) cells and helper T2 (Th2) cells. Cytokines secreted by Th1 cells are involved in cell-mediated immune responses, and cytokines secreted by Th2 cells are responsible for antibody immune responses. Many T cells are found in atopic dermatitis lesions, and cytokines secreted by Th2 cells play an important role in the development of atopic dermatitis. IL-4 and IL-13 secreted by Th2 cells promote IgE production, and IL-5 enhances basophils (International Immunology 2004, 16 (8), p1155-1160).
Th2 세포 분비 사이토카인 뿐만 아니라 Th1 세포 분비 사이토카인인 인터페론감마도 아토피성피부염에 중요한 역할을 한다(Journal of Clinical Investigation 1999, 103(8), p1103-1111). 아토피성 피부염의 진전에 따라 면역반응이 달라지며, 급성 아토피성 피부염에는 Th2 세포가 관여하고, 만성 아토피성 피부염에는 Th1이 관여한다고 보고되었다. 즉, 초기에는 Th2에서 분비하는 IL-4와 IL-3가 중요하게 작용하는데, 가려움증이 생기면서 긁기 시작하면 Th1 세포가 증가한다(Journal of Clinical Investigation 2004, 113, pp651-657). Leung 등에 따르면, 집먼지진드기 알러겐에 의한 아토피성 피부염은 두 단계로 진전되는데, 초기 단계는 Th2세포에 의하여 IL-4가 주로 생성되며, 24-48시간 뒤에는 Th1 세포에 의하여 인터페론 감마가 생성된다(Lancet 2003, 361, p151-160). 따라서 효과적으로 아토피성 피부염을 예방, 치료 또는 개선하기 위해서는 Th1세포와 Th2 세포 모두에 영향을 미쳐 IL-4 및 인터페론감마의 생성을 억제할 수 있는 물질 또는 조성물이 효율적일 수 있다.In addition to Th2 cell secreting cytokines, interferongamma, a Th1 cell secreting cytokine, plays an important role in atopic dermatitis (Journal of Clinical Investigation 1999, 103 (8), p1103-1111). It is reported that the immune response varies according to the development of atopic dermatitis, Th2 cells are involved in acute atopic dermatitis, and Th1 is involved in chronic atopic dermatitis. In other words, IL-4 and IL-3, which are secreted from Th2, play an important role. Thitch cells increase when itching begins to scratch (Journal of Clinical Investigation 2004, 113, pp651-657). According to Leung et al., Atopic dermatitis caused by house dust mite allergens progresses in two stages, the initial stage of which mainly produces IL-4 by Th2 cells, and interferon gamma by Th1 cells after 24-48 hours ( Lancet 2003, 361, p151-160). Therefore, in order to effectively prevent, treat or improve atopic dermatitis, a substance or composition capable of affecting both Th1 and Th2 cells and inhibiting production of IL-4 and interferon gamma may be effective.
NF-kB는 염증을 일으키는 유전자 발현 기구를 작동시켜 면역반응이나 염증반응에 관여하는 tumor necrosis factor(TNF), interleukin-1(IL-1), IL-6, IL-8, GM-CSF, inducible nitric oxide synthase(iNOS), intercellular adhesion molecule 1(ICAM-1), E-selectin, MHC class I, II 분자 등의 발현을 증가시키는 전사인자로 알려져 있다. 따라서 NF-kB의 활성 조절이 만성 및 급성 염증 질환의 치료에 유용하게 사용될 수 있으며, NF-kB 억제제는 아토피성 피부염치료효과를 나타낼 수 있다. NF-kB acts on the gene expression mechanism that causes inflammation, tumor necrosis factor (TNF), interleukin-1 (IL-1), IL-6, IL-8, GM-CSF, inducible It is known as a transcription factor that increases the expression of nitric oxide synthase (iNOS), intercellular adhesion molecule 1 (ICAM-1), E-selectin, MHC class I and II molecules. Therefore, the regulation of NF-kB activity can be usefully used for the treatment of chronic and acute inflammatory diseases, and the NF-kB inhibitor may have an atopic dermatitis therapeutic effect.
아토피성 피부염 치료제로는 면역억제제인 사이클로스포린 에이, FK-506, 스테로이드계 화합물 등이 사용되고 있다. 그러나 사이클로스포린 에이는 고혈압, 신독성, 약물상호작용 등의 심각한 부작용을 나타낸다. 스테로이드 기반 물질들은 심각한 부작용 때문에 의약품 외에 사용이 극히 제한되고 있으며. 실제로 일반적으로 널리 사용되고 있는 스테로이드계 아토피 치료제의 경우, 그 효과에 비해 높은 부작용 때문에 시장규모가 계속 축소되고 있다. FK-506은 호르몬 교란이 염려되는 것으로 알려져 있다. 따라서 이러한 부작용을 없애고 효능이 뛰어난 새로운 약제의 개발을 위하여 신규 아토피 개선제의 탐색 및 개발이 필요한 실정이다.As therapeutic agents for atopic dermatitis, cyclosporin A, FK-506, a steroid compound, etc., which are immunosuppressive agents, are used. However, cyclosporin A has serious side effects such as hypertension, nephrotoxicity, and drug interactions. Steroid-based substances are extremely limited to use in addition to medicines due to serious side effects. Indeed, the market size of steroid-based atopy drugs, which are generally widely used, continues to shrink due to their high side effects. FK-506 is known to be concerned about hormonal disturbances. Therefore, in order to eliminate these side effects and develop a new drug with excellent efficacy, it is necessary to search for and develop a new atopy improver.
따라서 천연약재로서 아토피 치료용 조성물의 개발이 시도되고 있으며, 문주란추출물(한국공개특허 제10-2007-0003365호), 향나무추출물(등록특허 제10-0614676호), 산양유추출물(등록특허 제10-0719761호)등이 보고되었으며, 생지황, 강활, 형개, 방풍, 창출, 천궁 등 다수의 약재를 포함하는 조성물(등록특허 제10-0682048호)이 있으나, 효능이 있으며 Th1 및 Th2 세포를 동시에 억제하며, 더불어 NF-kB 억제효과를 갖는 약재에 대한 연구는 지금까지 행해진 바가 없다. Therefore, the development of the composition for the treatment of atopy as a natural medicine has been attempted, Moonjuran extract (Korean Patent Publication No. 10-2007-0003365), juniper extract (Registration No. 10-0614676), Goat milk extract (Registration Patent No. 10- 0719761) has been reported, and there is a composition (Registration No. 10-0682048) containing a number of medicines, such as live yellow, vigor, mold opening, windproof, creation, cheongung, etc., but it is effective and simultaneously inhibits Th1 and Th2 cells In addition, no research has been conducted on medicinal herbs having NF-kB inhibitory effects.
본 발명에서는 아토피성 피부염의 각 단계에 각각 작용하는 Th1 및 Th2 면역반응을 억제하고 또한 급만성 염증반응에 관여하는 NF-kB를 억제하여, 부작용이 없으며 효능이 뛰어난 아토피성 피부염 치료용 조성물을 개발하는 것을 목적으로 한다. In the present invention, by inhibiting the Th1 and Th2 immune response acting at each stage of atopic dermatitis, and also inhibits NF-kB involved in acute acute inflammatory reaction, develop a composition for treating atopic dermatitis with no side effects and excellent efficacy It aims to do it.
상기 과제를 해결하기 위하여 본 발명은 오매, 창출, 고삼, 승마로 이루어진 군으로부터 오매를 필수적으로 포함하는 하나 이상 선택된 약재를 포함하는 것을 특징으로 하는 조성물을 제공한다.In order to solve the above problems, the present invention provides a composition comprising one or more selected medicinal herbs, which essentially comprises ume from the group consisting of ume, creation, ginseng, horse riding.
본 발명에 의한 조성물은 IL-4 및 인터페론감마의 생성을 억제하는 면역조절능과 함께 세포염증의 제일 중요한 인자인 NF-kB의 생성을 억제하는 염증억제능을 갖추어 우수한 아토피성 피부염의 예방, 치료, 개선을 위한 조성물로 사용할 수 있다.The composition according to the present invention has an immunomodulatory ability to inhibit the production of IL-4 and interferon gamma, and an inflammation inhibitory ability to inhibit the production of NF-kB, which is the most important factor of cell inflammation, to prevent, treat, and treat excellent atopic dermatitis. It can be used as a composition for improvement.
전술한 바와 같이, 본 발명은 오매, 창출, 고삼, 승마로 이루어진 군으로부 터 오매를 필수적으로 포함하는 하나 이상 선택된 약재를 포함하는 것을 특징으로 하는 아토피성 피부염의 예방, 치료, 개선을 위한 조성물에 관한 것이다. 또한 본 발명은 상기 조성물을 포함하는 의약품, 의약부외품, 식품, 화장품에 관한 것이다. 본 발명의 발명자들은 아토피성 피부염의 각 단계에 각각 작용하는 Th1 및 Th2 면역반응을 억제하고 또한 급만성 염증반응에 관여하는 NF-kB를 억제하는 생약재를 찾기 위하여 약200여가지의 생약재를 스크리닝한 결과, 오매, 창출, 고삼, 승마가 이러한 효능을 갖는다는 것을 밝혀내고 본 발명을 완성하기에 이르렀다. As described above, the present invention is a composition for the prevention, treatment, improvement of atopic dermatitis, characterized in that it comprises at least one selected medicament essentially comprising a mae from the group consisting of ume, creation, ginseng, horse riding It is about. The present invention also relates to pharmaceuticals, quasi-drugs, food, and cosmetics comprising the composition. The inventors of the present invention screened about 200 herbal medicines in order to find herbal medicines that inhibit Th1 and Th2 immune responses that act on each stage of atopic dermatitis and also inhibit NF-kB, which is involved in acute inflammatory reactions. As a result, it has been found that ume, generation, ginseng, horse riding have this effect, and came to complete the present invention.
오매(烏梅)는 덜 익은 매실의 껍질을 벗긴 뒤 짚불 연기에 거무스름하게 그슬려 말린 것을 일컫는데, 항균제와 지혈제로 사용되어 왔다. 동의보감은 오매를 '갈증과 가래를 없애고 구토와 설사를 그치게 하며 술독을 풀어주는 약'으로 설명한다. 오매는 홍삼과 같이 외부가열에 의해 효능이 향상되어 매실 자체로는 갖지 못하는 효과가 짚불연기에 거무스름하게 말리면서 생성된다. 오매는 헬리코박터 필로리균의 우레아제 활성억제효과가 있는 것으로 보고되었다 (공개특허공보 제10-2006-0040254호).Ome (烏梅) refers to the peeling of unripe plums and darkened with straw smoke, which has been used as an antibacterial and hemostatic agent. Dongbogam describes omae as a medicine that eliminates thirst and sputum, stops vomiting and diarrhea, and dissolves alcohol. Omae is enhanced by external heating like red ginseng, which is not produced by the plum itself. It has been reported that the hawk has an inhibitory effect on the urease activity of Helicobacter pylori (Unexamined Patent Publication No. 10-2006-0040254).
창출은 삽주의 긴뿌리를 잔뿌리만 다듬고 말린 것으로서, 삽주는 오래 먹으면 무병장수할 수 있는 약초로 널리 알려져 있다. Creation is the long root of the shovel which is trimmed and dried Shochu is widely known as a herb that can be long and disease-free.
고삼(Sophora flavescens Ait.)은 콩과에 속하는 산기슭이나 양지바른 들의 풀밭, 평원, 길가, 모래땅, 햇볕이 잘드는 황토땅에서 자라는 여러 해살이 풀로서, 어릴 때의 뿌리 모양이 인삼과 비슷하고 그 치료 효능이 인삼과 같은 효과가 있으면서 쓴맛이 나기 때문에 고삼(苦蔘)이라한다. 세균성 이질, 급성 위장염, 급성 전 염성 간염, 소아 폐렴, 급성 편도선염, 만성 기관지염, 장 트리코모나스, 트리코모나스 질염, 주혈흡충병에 의한 복수, Lamblia intestinalis, 살충, 혈리, 이뇨, 농작물 해충 구제, 소말의 피부 기생충 구제, 무좀, 땀띠, 악성 종기, 식욕촉진, 습기제거, 몽정, 유정, 활정, 식체, 직장궤양출혈, 황달, 급성 편도선염, 나병, 변비, 치루, 탈항, 피부가려움증, 옴으로 인하여 생긴 악창, 나력, 화상에 효험 과 같이 광범위한 질환에 한의학적으로 사용되고 있다.Ginseng (Sophora flavescens Ait.) Is a grass that grows in the foothills or sunny meadows of the legumes, on the grassland, plains, roadsides, sandy soils, and sunny ocher soils. The therapeutic effect is called ginseng because it has the same effect as ginseng and bitter taste. Bacterial dysentery, acute gastroenteritis, acute infectious hepatitis, pediatric pneumonia, acute tonsillitis, chronic bronchitis, intestinal trichomoniasis, trichomoniasis vaginitis, ascites caused by schistosomiasis, lamblia intestinalis, insecticidal, hemolysis, diuresis, crop pest control, skin worm parasite Remedies, athlete's foot, sweat, malignant boils, appetite promotion, dehumidification, dream tablets, oil wells, bowels, caries, rectal ulcers, jaundice, acute tonsillitis, leprosy, constipation, erosion, prolapse, itching, swelling caused by mange It is used in Korean medicine for a wide range of diseases, such as efficacy in burns and burns.
승마는 해열제로 쓰이며, 미아리과에 속하므로 많은 사포닌 성분에 의해 효능이 나타나는 것으로 생각된다.Horse riding is used as an antipyretic and belongs to the family of Mia family.
그러나 이들 또는 이들의 조합이 Th1 및 Th2 사이토카인을 억제하며, NF-kB 를 억제함으로써 아토피성 피부염을 치료할 수 있다는 것에 대해서는 알려진 바가 없었다. However, it is not known that these or combinations thereof can inhibit Th1 and Th2 cytokines and treat atopic dermatitis by inhibiting NF-kB.
본 발명의 발명자들은 면역세포를 사용한 실험을 통하여 오매, 창출, 고삼, 승마 및 이들의 혼합물이 인터페론-감마, IL-4 및 NF-kB 를 억제하며, 상기 활성이 항염증제로 상용화되어 있는 목단피(botanpi)나 사이클로스포린보다 크다는 것을 확인하였다(도1, 도3 및 도5). 특히 오매의 경우 그 활성이 더욱 우수하였으며, 이는 매실의 활성과 비교하여 놀라울 정도로 큰 것이었다(도2 및 도4). 오매의 이러한 활성은 임상시험에서 아토피성피부염 치료효과로 나타났다(도7).The inventors of the present invention, through the experiment using immune cells, berry, production, ginseng, horse riding and mixtures thereof inhibit interferon-gamma, IL-4 and NF-kB, and the activity is commercialized as anti-inflammatory (botanpi) ) Or greater than cyclosporin (FIGS. 1, 3 and 5). In particular, the activity of the umeru was better, which was surprisingly large compared to the activity of the plum (Fig. 2 and 4). This activity of maeja appeared to treat atopic dermatitis in clinical trials (Fig. 7).
이러한 실험결과를 바탕으로 본 발명은 다음에 기재된 사항을 제공한다.Based on the experimental results, the present invention provides the following items.
[1] 오매, 창출, 고삼, 승마로 이루어진 군으로부터 오매를 필수적으로 포함하도록 하나 이상 선택된 약재를 포함하는 것을 특징으로 하는 아토피성 피부염 치 료 또는 개선용 조성물.[1] composition for treating or improving atopic dermatitis, comprising at least one selected medicinal herb from the group consisting of ume, generation, ginseng and horse riding.
[2] [1]에 있어서, 상기 약재들이 물, 에탄올, 부탄올, 에틸아세테이트, 헥산 및 이들의 혼합물로 구성된 군에서 선택된 용매를 사용한 추출물의 형태로 포함되는 것인 조성물.[2] The composition of [1], wherein the medicines are included in the form of an extract using a solvent selected from the group consisting of water, ethanol, butanol, ethyl acetate, hexane, and mixtures thereof.
[3] [1]에 있어서, 경구로 투여되는 것인 조성물.[3] The composition of [1], which is administered orally.
[4] [1]에 있어서, 피부에 적용되는 것인 조성물.[4] The composition of [1], which is applied to the skin.
[5] [1] 내지 [4] 중 어느 하나의 조성물을 포함하는 의약품.[5] A pharmaceutical product comprising the composition of any one of [1] to [4].
[6] [1] 내지 [4] 중 어느 하나의 조성물을 포함하는 의약부외품.[6] An quasi drug containing the composition of any one of [1] to [4].
[7] [1] 내지 [3] 중 어느 하나의 조성물을 포함하는 식품.[7] A food comprising the composition of any one of [1] to [3].
[8] [1], [2] 및 [4] 중 어느 하나의 조성물을 포함하는 화장품.[8] A cosmetic comprising the composition of any one of [1], [2] and [4].
본 발명에 따른 아토피성 피부염 치료용 조성물에 함유되는 생약재는 여러 가지 형태로 조성물에 함유될 수 있다. 예를 들어, 생약재를 완전히 건조한 후 미세하게 분말화하거나, 용매를 사용하여 추출하여 조성물에 함유시킬 수 있다. 용매로는 물이나 에탄올 메탄올, 부탄올, 에틸아세테이트, 헥산 및 이들의 혼합물 등을 사용할 수 있으나 이것으로 제한되는 것은 아니다. 혼합 용매의 경우, 예를 들어 물:에탄올을 20%:80% 내지 99%:1%로 혼합하여 사용할 수 있으나 이것으로 제한되는 것은 아니다. 본 발명의 생약재를 추출하기 위한 추출방법으로는 상대적으로 낮은 온도에서 일정시간 침출하는 냉침법, 35-45oC에서 침출하는 온침법, 60-120oC에서 침출하는 가열추출법, 퍼콜레이터(percolater)를 사용하는 방법, 증류냉각추출법 등이 사용될 수 있으나, 이에 제한되는 것은 아니다. 생약의 추출물은 생약들을 통상의 방법에 의해 각각 추출하거나, 또는 생약들을 혼합한 후 한꺼번에 추출할 수 있다. 필요한 경우 이를 농축하여 분말화 할 수 있다. The herbal medicine contained in the composition for treating atopic dermatitis according to the present invention may be contained in the composition in various forms. For example, the herbal medicine may be completely dried and then finely powdered, or extracted with a solvent to be included in the composition. Water or ethanol as solvent Methanol, butanol, ethyl acetate, hexane and mixtures thereof may be used, but is not limited thereto. In the case of a mixed solvent, for example, water: ethanol is mixed at 20%: 80% to 99%: 1% Can be used but is not limited to this. Extraction methods for extracting the herbal medicines of the present invention include a cold leaching method for leaching at a relatively low temperature for a predetermined time, a warm leaching method for leaching at 35-45 o C, a heat extraction method for leaching at 60-120 o C, percolater ), Distillation cooling extraction, etc. may be used, but is not limited thereto. The extracts of the herbal medicines may be extracted individually by a conventional method, or all at once after mixing the herbal medicines. If necessary, it can be concentrated and powdered.
본 발명에 따른 조성물은 생약재 성분 이외에 약제학적, 식품학적 또는 화장품학적으로 허용되는 성분을 추가로 함유할 수 있다. 예를 들어 결합제, 활택제, 붕해제, 부형제, 가용화제, 안정화제, 기제, 윤활제, 보존제, 습윤제, 유화제, 현탁화제, 점도조절제, 방부제, 계면활성제, 산화방지제, 보습제, 향료, 색소 등을 추가로 함유할 수 있다. 또한 종래의 아토피피부 치료제에 많이 사용되어온 세라마이드 등 보습제 또는 지질성분이나 하이드로코티손 등의 스테로이드, 레티닐팔미테이트 등의 비타민 A 유도체, 토코페폴, 기타 식물추출물 등을 추가로 함유할 수 있다. 본 발명의 조성물은 경구로 또는 국소에 적용할 수 있으며, 정제, 산제, 캅셀제, 과립제, 환제, 액제, 현탁화제, 연고제, 크림제, 로숀타입, 화장수타입, 팩타입 등 뿐만 아니라, 비누, 세안폼과 같은 세안료 등 여러 가지 형태로 제조할 수 있다. 또한 리포좀 형태로 만드는 것도 가능하다. The composition according to the present invention may further contain pharmaceutically, food or cosmetically acceptable ingredients in addition to the herbal ingredients. For example, binders, lubricants, disintegrants, excipients, solubilizers, stabilizers, bases, lubricants, preservatives, wetting agents, emulsifiers, suspending agents, viscosity regulators, preservatives, surfactants, antioxidants, moisturizers, fragrances, pigments, etc. It may further contain. In addition, it may further contain a moisturizer such as ceramide or a lipid component, a steroid such as hydrocortisone, a vitamin A derivative such as retinyl palmitate, tocopepol, and other plant extracts, which have been frequently used in conventional atopic skin treatments. The composition of the present invention can be applied orally or topically, tablets, powders, capsules, granules, pills, solutions, suspending agents, ointments, creams, lotion type, lotion type, pack type and the like, as well as soap, face wash It can be manufactured in various forms such as face washes such as foams. It is also possible to make liposomes.
본 발명에 따른 조성물의 투여량은 이를 적용받는 사람의 체중, 연령, 성별, 건강상태, 소화상태 등에 따라 적절히 조절할 수 있으며, 통상적인 1회 투여량은 체중 1kg당 0.1mg 내지 100mg 으로 투여할 수 있다. 본 발명의 조성물을 피부에 바르는 외용제의 형태로 제조하는 경우, 피부 외용제 중의 생약재 추출물의 배합량은 전체의 0.05%~50.0 중량%, 바람직하게는 0.1~10.0 중량%로 할 수 있다. The dosage of the composition according to the present invention can be appropriately adjusted according to the weight, age, sex, health status, digestive status, etc. of the person to which it is applied, and a typical single dosage can be administered at 0.1mg to 100mg per kg of body weight. have. When the composition of the present invention is prepared in the form of an external preparation applied to the skin, the blending amount of the herbal extract in the external preparation for skin may be 0.05% to 50.0% by weight of the total, preferably 0.1 to 10.0% by weight.
본 발명의 조성물은 아토피성 피부염의 예방 및 경감을 위한 의약부외품에 다양하게 이용될 수 있다. 또한, 본 발명의 조성물은 아토피성 피부염의 예방 및 경감을 위한 식품에 다양하게 이용할 수 있다. 본 발명의 조성물은 식품으로 복용할 수 있는 어떠한 제형으로도 적용하여 사용할 수 있으며, 그 예로 분말, 과립제, 정제, 환제, 캅셀제, 연질캅셀제, 또는 액제 등을 포함한다. 이러한 본 발명의 조성물을 첨가할 수 있는 식품으로는, 예를 들어, 각종 식품류, 육류, 차 등의 음료수, 스낵류, 과자류, 라면류, 기타면류, 캔디, 초콜릿, 아이스크림류, 껌, 비타민 복합체, 건강기능식품류 등이 있다.The composition of the present invention can be used in various quasi-drugs for the prevention and alleviation of atopic dermatitis. In addition, the composition of the present invention can be used in a variety of foods for the prevention and reduction of atopic dermatitis. The composition of the present invention can be applied to any formulation that can be taken as a food, and examples thereof include powders, granules, tablets, pills, capsules, soft capsules, or liquids. Examples of the food to which the composition of the present invention can be added include, for example, various foods, meats, beverages such as tea, snacks, confectionery, ramen, other noodles, candy, chocolate, ice cream, gum, vitamin complex, and health. Functional foods;
이하, 본 발명을 실시예 등을 통하여 보다 구체적으로 설명하나, 본 발명에 따른 실시예들은 여러 가지 다른 형태로 변형될 수 있으며 발명의 범위가 이에 의하여 한정되는 것은 아니다.Hereinafter, the present invention will be described in more detail with reference to examples and the like, but embodiments according to the present invention can be modified in many different forms and the scope of the invention is not limited thereto.
실험예Experimental Example 1: One: 생약재Herbal medicine 시료의 제조 Preparation of Sample
약 200여종의 생약재를 정선하여 세절한 후, 각 생약 10g 에 70% 알코올 50 ml를 넣고 21일 동안 4oC에서 추출 하였다. 이후 원심분리기(3000rpm, 5분)을 이용하여 분리하여 상등액을 회수하여 이를 시료원액으로 사용하였으며, 순차적으로 희석하여 시료 검색을 위한 시료로 제조하였다.After selecting about 200 kinds of herbal medicines and cutting them, 50 ml of 70% alcohol was added to each 10g of herbal medicines, and extracted at 4 o C for 21 days. Thereafter, a supernatant was collected by using a centrifuge (3000 rpm, 5 minutes), which was used as a sample stock solution, and serially diluted to prepare a sample for sample retrieval.
실험예Experimental Example 2: 마우스 2: mouse 비장세포의Splenocyte 추출 extraction
마우스 비장세포(mouse spleen cell)는 아래와 같은 방법으로 추출하였다. 마우스를 경추탈골 시킨 후 알코올로 소독하여 복부를 절개한 후 비장을 무균적으로 채취한다. 채취후 항생제가 첨가된 RPMI-complete media에 넣고 냉장보존한다. 1개의 비장(spleen)당 약 2ml의 동물세포 배지(RPMI media)를 넣고 비장을 완전히 분쇄한다. 0.84% 암모니움 클로라이드 용액을 10초간 처리하여 적혈구 세포를 제거한다. 배지로 적혈구 용혈 반응정지후 원심분리후 가라앉은 세포를 채취한다. 얻은 세포분획을 하루동안 배양 후 실험에 사용하였다.Mouse spleen cells were extracted by the following method. The mouse is cervical distal bone, sterilized with alcohol and incised abdomen, and the spleen is aseptically collected. After collection, put in antibiotic-added RPMI-complete media and refrigerate. Approximately 2 ml of animal cell medium (RPMI media) is added per spleen and the spleen is completely ground. Red blood cells are removed by treatment with 0.84% ammonium chloride solution for 10 seconds. Stop the erythrocyte hemolysis reaction with the medium, and then settle the cells after centrifugation. The obtained cell fraction was used for the experiment after incubation for one day.
실험예Experimental Example 3: 인터페론-감마 3: interferon-gamma 어세이Assay
피토헤마글루티닌(Phytohemagglutinin; PHA) Stock Solution 은 살균된 인산완충용액PBS 1 ml 당 PHA 0.5mg을 넣고 용해하여 제조하였다.Phytohemagglutinin (PHA) Stock Solution was prepared by dissolving 0.5 mg of PHA per 1 ml of sterilized phosphate buffer solution PBS.
PMA Stock Solution 은 DMSO 1 mL당 PMA 100 ug를 넣고 용해하여 제조하였다.PMA Stock Solution was prepared by dissolving 100 ug of PMA per mL of DMSO.
Cyclosporin Stock solution은 에탄올 1ml 당 사이클로스포린 1mg 을 넣고 용해하여 제조하였으며, 목단피 및 본 발명의 생약재 추출물의 stock solution은 실험예1의 방법으로 제조한 시료원액을 사용하였다.Cyclosporin Stock Solution was prepared by dissolving 1 mg of cyclosporin per 1 ml of ethanol, and the stock solution of the extract of the herbaceous extract and the herbal medicine of the present invention was used as a sample stock solution prepared in Experimental Example 1.
2.5 ml 의 Jurkat cell culture, 마우스 비장세포, EL-4 세포주 (1 x 106 cells/ml, 1 x 107 cells/ml, 5 x 106 cells/ml) 와 2.5 ml 의 배지(RPMI 1640 + 10% fetal calf serum containing 10 ml/L penicillin-streptomycin) 을 25T flask에 넣고 배양하였다. 상기 세포배양액 150 ul를 96웰에 분주한 후, PHA stock solution을 15 ul 씩 첨가하고 동시에 약재 stock solution을 15 ul 씩 첨가하였다. 18 시간 배양 후 상등액을 원심분리한 후에 ELISA법을 이용하여 당일날 사이토카인을 분석하였다.2.5 ml of Jurkat cell culture, mouse splenocytes, EL-4 cell line (1 x 10 6 cells / ml, 1 x 10 7 cells / ml, 5 x 10 6 cells / ml) and 2.5 ml of medium (RPMI 1640 + 10) 10 ml / L penicillin-streptomycin) containing% fetal calf serum was incubated in a 25T flask. After dispensing 150 ul of the cell culture solution into 96 wells, 15 ul of PHA stock solution was added and 15 ul of medicinal stock solution was added at the same time. After 18 hours of incubation, the supernatant was centrifuged and analyzed for cytokines on the day by ELISA.
Th1 사이토카인인 인터페론-감마(IFN-γ)를 측정하기 위하여 ELISA 방법을 사용하였다. 바이오소스(BIOSOURCE)사의 IFN-γ immunoassay kit를 사용하였다. 96-웰플레이트의 각 웰을 IFN-γ의 포획항체로 코팅하였다. 이후 세척하고, 적절히 희석한 세포배양상등액 100 ul 및 50ul의Incubation Buffer를 첨가하고, 50 ul의 biotinylated detection antibody (Biotin Conjugate) solution을 넣고 2시간 상온에 방치하였다. 완전히 용액을 제거하고 4번 세척한 후, 100 ul의 Streptavidin-HRP Working Solution 을 넣고 30분간 상온에 방치하고 완전히 용액을 제거하고 세척한다. 100 ul의 Stabilized Chromogen을 넣고 30분 상온방치 후, 100 의 Stop Solution을 넣고 450 nm 에서 데이터 값을 읽었다.The ELISA method was used to measure the Th1 cytokine interferon-gamma (IFN-γ). BIOSOURCE's IFN-γ immunoassay kit was used. Each well of a 96-well plate was coated with capture antibody of IFN-γ. Thereafter, 100 ul and 50 ul of Incubation Buffer were added to the appropriately diluted cell culture supernatant, and 50 ul of biotinylated detection antibody (Biotin Conjugate) solution was added thereto and left at room temperature for 2 hours. After completely removing the solution and washing four times, add 100 ul of Streptavidin-HRP Working Solution, and leave it at room temperature for 30 minutes. Completely remove the solution and wash. 100 ul of Stabilized Chromogen was added and allowed to stand at room temperature for 30 minutes. Then, 100 Stop Solution was added and data were read at 450 nm.
도1은 생약재 추출물의 IFN-gamma 억제율을 나타낸다. 항염증제로 현재 상용되고 있는 목단피(보탄피 추출액)와 비교할 때, 오매, 고삼, 승마, 창출 및 이들의 혼합물 (오매:창출:고삼:승마=4:1:1:2)에 있어서 목단피보다 억제효과가 좋았으며, 생지황, 형개, 방풍, 치자, 금은화 등은 목단피보다 억제활성이 낮았다.Figure 1 shows the IFN-gamma inhibition rate of herbal extracts. Inhibitory effect on bark skins in buckwheat, red ginseng, horseback riding, creation, and mixtures thereof (oil: creation: red ginseng: horseback riding = 4: 1: 1: 2) compared to the bark skins currently used as anti-inflammatory agents Saenghwanghwang, mold opening, windproof, gardenia, gold and silver flower had lower inhibitory activity than bark skin.
특히 오매는 매실에 비하여 인터페론감마의 억제율이 약6배 높았다(도2). 매실을 오매로 만드는 과정에서 생기는 새로운 물질에 의한 것으로 추측된다. In particular, ume was about 6 times higher in inhibition rate of interferon-gamma than plum (Fig. 2). It is presumed to be due to a new substance that is produced in the process of making plums errant.
실험예Experimental Example 4: 4: ILIL -4 -4 어세이Assay
실험예 3의 세포배양물에서 Th2 사이토카인인 인터루킨-4(IL-4)를 측정하기 위하여 ELISA 방법을 사용하였다. BIOSOURCE사의 immunoassay kit을 사용하였으며, WHO reference preparation 86/504 (NIBSC, Hertfordshire, UK, EN6 3QG)를 준수하였다. 약 200여종의 한약재의 추출물 중 대표적인 후보물질의 값을 도시하였다(도3). An ELISA method was used to measure Interleukin-4 (IL-4), a Th2 cytokine in the cell culture of Experimental Example 3. BIOSOURCE's immunoassay kit was used and WHO reference preparation 86/504 (NIBSC, Hertfordshire, UK, EN6 3QG) was observed. Values of representative candidates among extracts of about 200 kinds of herbal medicines are shown (FIG. 3).
IL-4를 효과적으로 억제하는 물질군은 오매, 창출, 고삼, 승마 및 이들의 혼합물(오매:창출:고삼:승마=4:1:1:2)으로서 대표적 항염물질인 목단피보다 더 좋은 IL-4 억제율을 보인다. 특히 오매의 경우 IL-4수치가 거의 사이클로스포린 수준인 것으로 확인되었다. 일반 매실보다 오매의 경우 월등한 효능 향상효과를 보여주었다(도4). 매실을 오매로 만드는 과정에서 생기는 새로운 물질에 의한 것으로 추측된다. Groups of substances that effectively inhibit IL-4 are mae, generation, gosam, horse riding, and mixtures thereof (omega: creation: gosam: equestrian = 4: 1: 1: 2), which is better than the typical anti-inflammatory material, bark skin. Inhibition rate is shown. In particular, IL-4 levels were found to be nearly cyclosporine levels. In the case of umeol than normal plum showed a superior efficacy improvement effect (Fig. 4). It is presumed to be due to a new substance that is produced in the process of making plums errant.
실험예Experimental Example 5: 5: NFNF -- kBkB 어세이Assay
세포염증에 있어 제일 중요한 인자인 NF-kB를 적은 비용으로 많은 시료를 분석하기 위해 Luciferase(루시퍼레이즈)를 사용한 분석법을 확립하였다. 이 방법은 실험스텝이 짧으므로 데이터 재현성이 높고 많은 시료 물질을 동시에 처리할 수 있다. 세포주로는 Panomics사의 NIH3T3-luc 세포주를 사용하였으며, 예비실험을 통한 NF-kB의 발현여부와 각 후보물질에 의한 억제도를 확인하였다. 유도원(TNF-alpha)에 의해 약 12~17배의 루시퍼레이즈(NF-kB)가 유도되었으며, 실험 재현성이 우수함을 확인하였다. Panomics사의 NIH3T3 (Rev A 060820 Stable Cell Line: NIH3T3/NFkB-luc 1); Stable Cell Line: NIH3T3/NFkB-luc 을 사용하였다. The NIH3T3/NFkB-luc cell line은 세포 기반의 NFkB transcription factor를 확인하기 위해 고안된 시스템으로 pNFkB-luc (Panomics P/N LR0051)와 pHyg 벡터가 동시 Transfection을 통하여 확립된 세포주이다. pHyg의 성질을 이용하여 hygromycin 분리법을 이용하여 선택한다. 이러한 방법으로 인하여 세포 크로모좀에 루시퍼레이즈 유전자가 삽입된다. 각각의 배지 제조 방법은 아래와 같다.To analyze NF-kB, the most important factor in cell inflammation, and to analyze many samples at low cost, an assay using Luciferase was established. This method has a short experimental step, so the data is highly reproducible and many sample materials can be processed simultaneously. As the cell line, NIH3T3-luc cell line of Panomics was used. The preliminary experiments confirmed the expression of NF-kB and the inhibition by each candidate. About 12-17 times of luciferase (NF-kB) was induced by the induction source (TNF-alpha), and it was confirmed that the experimental reproducibility was excellent. NIH3T3 from Panomics (Rev A 060820 Stable Cell Line: NIH3T3 / NFkB-luc 1); Stable Cell Line: NIH3T3 / NFkB-luc was used. The NIH3T3 / NFkB-luc cell line is a system designed to identify cell-based NFkB transcription factors, a cell line in which pNFkB-luc (Panomics P / N LR0051) and pHyg vectors are established through simultaneous transfection. It is selected using hygromycin separation method using the property of pHyg. This method inserts the luciferase gene into the cell chromosome. Each medium production method is as follows.
100-mm culture dish나 T-75 flask에 15mL의 미리 데워진 Growth 배지를 넣고, 세포주를 미리 준비된 배양접시에 넣어 세포주를 잘 분산시킨다. 배양접시를 습기가 공급되는 37oC (5% CO2) 배양기에 넣고, 2~3일마다 배지를 교환한다. 90% confluency에 도달하면 동결 보존할 Stock를 만들고 계속 배양한다. 세포는 계대배양법에 따라 배양하여 세포주를 보존한다. Put 15 mL of pre-warmed Growth medium in a 100-mm culture dish or T-75 flask, and add the cell line to the prepared culture dish to disperse the cell line well. Place the culture dish in a humidified 37 ° C. (5% CO 2 ) incubator and change the medium every 2-3 days. Once the 90% confluency is reached, create a stock to cryopreserve and continue incubating. Cells are cultured according to passage method to preserve cell lines.
NF-kB 측정은 다음과 같이 하였다. 세포를 Initial Growth Media에 5 x 10 5 / well 수준으로 12-well plate에 분주하고, 세포주가 바닥에 부착하도록 습기가 공급되는 5% CO2(37o C)에 넣고 24시간동안 배양한다. Serum이 함유되지 않은 새로운 배지로 교환한다. 약 8시간 동안 5% CO2(37 o C) 인큐베이터에 배양한 후, 배지를 제거하고 100 ul lysis buffer를 각각의 well에 넣어 Luciferase activity를 측정한다. 측정법은 Promega 사의 매뉴얼을 참고하여 실험한다. (Promega P/N E1500)NF-kB measurement was performed as follows. Dispense the cells into a 12-well plate at 5 x 10 5 / well level in Initial Growth Media, and incubate for 24 hours in moistened 5% CO 2 (37 o C) to allow cell lines to adhere to the bottom. Replace with fresh medium that does not contain Serum. After incubating in 5% CO 2 (37 o C) incubator for about 8 hours, the medium is removed and 100 ul lysis buffer is added to each well to measure Luciferase activity. For the measurement method, please refer to the Promega manual. (Promega P / N E1500)
96-Well 을 이용한 NF-kB 정량은 log-growth phase 상태에 있는 세포주를 트립신으로 처리한 후 5 x 104 cells / 100 ul 수준으로 맞춘후 96-well plate에 넣으며, 이때 적절히 희석된 후보물질 15 ul도 같이 넣는다. 37 oC로 맞춰진 5% CO2 배양기에 밤새 배양하고, NF-kB를 유도하는 약재(예 TNF-alpha를 15 ul volume 수준으로 처리하고, 배지를 제거한 후 50 ul lysis buffer (Promega P/N E1500)를 각각의 well에 넣고 처리한다. Lysis buffer넣은 상태로 2 분동안 상온에서 처리하고, Lysis Buffer가 충분히 녹여냈는지 확인한다. 0 oC 에 급속히 얼린 후 상온에서 녹여내고 2~3회 용액을 섞어준다. 20 ul 의 각각의 용해물(lysate)을 새로운 96-well에 옮기고, 20 ul의 luciferase substrate를 각각의 well에 넣고 2~3회 섞어 준 후, Luminometer를 이용하여 측정하였다.NF-kB quantification using 96-Well was carried out with trypsin-treated cell lines at 5 x 10 4 cells / 100 ul and placed in 96-well plates. Put ul together. Incubate overnight in a 5% CO 2 incubator set at 37 o C, treat NF-kB-derived medicinal products (eg TNF-alpha at 15 ul volume level, remove media and remove 50 ul lysis buffer (Promega P / N E1500 Process each well at room temperature for 2 minutes with Lysis buffer and check if Lysis Buffer is sufficiently dissolved After rapid freezing at 0 o C, melt at room temperature and
NF-kB의 정량 결과(Luciferase assay)를 각각의 생약 추출물과 상용화된 목단피(Botanpi), 사이클로스포린(CsA)을 적절하게 희석하여 효과를 비교하였다. 유도원에 의한 유도율은 19.44 배이었으며, 고삼, 창출, 승마, 오매 모두 높은 NF-kB 억제율을 나타내었다. 이들은 사이클로스포린보다 억제율이 컸으며, 항염능이 높은 것으로 알려진 목단피(Botanpi)와 비교하면, 오매, 창출, 승마의 경우 보탄피보다 우수한 NF-kB 억제능을 보여줬으며, 고삼의 경우 보탄피와 비슷한 NF-kB억제능을 나타내었다(도5).The quantitative results of NF-kB (Luciferase assay) were compared by diluting Botanpi and cyclosporin (CsA) commercially available with each herbal extract. The induction rate by induction source was 19.44 times, and high ginseng, production, horseback riding, and buckwheat showed high NF-kB inhibition rate. They showed higher inhibition rate than cyclosporin, and showed better NF-kB inhibition than Botanpi in berry, production, and horse riding compared to Botanpi, which is known to have high anti-inflammatory activity. Inhibitory activity was shown (FIG. 5).
실험예Experimental Example 6: 추출 용매에 따른 활성비교 6: Activity comparison by extraction solvent
오매, 창출, 고삼, 승마를 각각 물, 70%에탄올, 100% 에탄올을 사용하여 추출하고 각 추출물의 IL-4 억제율을 측정하여 활성정도를 비교하였다. 오매의 경우 70~100% Ethanol, 승마의 경우 70% Ethanol, 고삼의 경우 100% Ethanol, 그리고 창출의 경우 70~100%의 Ethanol에서 IL-4 억제율이 더 높은 것으로 보아 유효성분이 더 많이 추출되는 것을 확인할 수 있었다(도6).The extracts of five plums, wild ginseng, red ginseng and horse riding were extracted with water, 70% ethanol and 100% ethanol, respectively, and the IL-4 inhibition rate of each extract was measured to compare the activities. 70 ~ 100% Ethanol for buckwheat, 70% Ethanol for horseback riding, 100% Ethanol for ginseng, and 70 ~ 100% Ethanol for generation showed higher IL-4 inhibition rate. It could be confirmed (Fig. 6).
실험예Experimental Example 7: 오매의 아토피성 피부염의 치료효과 평가 7: Evaluation of the therapeutic effect of atopic dermatitis on omega
70% 에탄올을 사용한 오매추출물 100 ul를 1일 1회 아토피성 피부염이 발생한 부위에 3주간 도포하였다. 도7은 오매 추출물을 이용한 아토피성 피부염의 치료평가 실험 전 및 후의 사진이다. 사진에서 나타나는 바와 같이 본 발명의 오매 추출물은 아토피성 피부염의 치료에 탁월한 효능이 있음을 알 수 있다.100 ul of maeol extract using 70% ethanol was applied to the site of atopic dermatitis once a day for 3 weeks. Figure 7 is a photograph before and after the treatment evaluation experiment of atopic dermatitis using the ume extract. As shown in the picture, the mae extract of the present invention can be seen that the excellent efficacy in the treatment of atopic dermatitis.
제조예Production Example : 크림: cream
1) 오매추출물 1.0 중량%1) fruit extract 1.0% by weight
2) 창출추추물 1.0 중량%2) 1.0% by weight of creation extract
3) 스테아린산 2.0 중량%3) stearic acid 2.0% by weight
4) 스테아릴알코올 3.0 중량%4) stearyl alcohol 3.0 wt%
5) 1,3 부틸렌글리콜 5.0 중량%5) 1,3 butylene glycol 5.0 wt%
6) 모노스테아린산글리콜 4.0 중량%6) 4.0 wt% glycol monostearate
7) 수산화칼륨 0.1 중량%7) Potassium hydroxide 0.1% by weight
8) 정제수 77.9 중량%8) Purified water 77.9 wt%
9) 레시틴 5.0 중량%9) Lecithin 5.0% by weight
10) 콜레스테롤 1.0 중량%10) Cholesterol 1.0 wt%
유성성분과 수성성분을 75oC로 각각 가열한 다음 크림제조용 혼합기에서 균질화용 믹서를 이용하여 유화시킨 후, 탈기, 여과, 냉각하여 크림을 제조하였다.The oil and water components were heated to 75 ° C., respectively, and then emulsified using a homogenizing mixer in a cream manufacturing mixer, followed by degassing, filtration and cooling to prepare a cream.
제조예Production Example : 화장수: Lotion
1)오매 추출물 0.1 중량%1) Oil Extract 0.1% by weight
2) 1,3-부틸렌글리콜 8.0 중량%2) 1,3-butylene glycol 8.0% by weight
3) 글리세린 2.0 중량%3) glycerin 2.0% by weight
4) 크산탄검 0.02 중량%4) Xanthan gum 0.02 wt%
5) 구연산 0.01 중량%5) citric acid 0.01% by weight
6) 구연산나트륨 0.1 중량%6) Sodium Citrate 0.1% by weight
7) 에탄올 5.0 중량%7) Ethanol 5.0 wt%
8) 파라옥시안식향산메틸 0.1 중량%8) 0.1% by weight of methyl paraoxybenzoate
9) 폴리옥시에틸렌경화피마자유(40E.O.) 0.1 중량%9) 0.1% by weight of polyoxyethylene hardened castor oil (40E.O.)
10) 향료 0.1 중량%10) fragrance 0.1 wt%
11) 정제수 84.47 중량%11) 84.47 wt% of purified water
성분 1-6 및 11, 성분 7-10를 각각 균일하게 용해하여 양자를 혼합하고 여과하여 제조하였다.The components 1-6, 11, and 7-10 were melt | dissolved uniformly, respectively, and both were mixed and filtered.
제조예Production Example : 연고: Ointment
1)오매추출물 1.0 중량%1) Oil Extract 1.0% by weight
2) 창출추출물 1.0 중량%2) Creation extract 1.0 wt%
3) 폴리옥시에틸렌세틸에테르 (30 E.O.) 2.0 중량%3) Polyoxyethylene Cetyl Ether (30 E.O.) 2.0 wt%
4) 모노스테아린산글리세린 10.0 중량%4) 10.0% by weight glycerin monostearate
5) 유동파라핀 5.0 중량%5) 5.0 wt% of liquid paraffin
6) 세탄올 6.0 중량%6) cetanol 6.0% by weight
7) 프로필렌글리콜 10.0 중량%7) 10.0 wt% propylene glycol
8) 파라옥시안식향산메틸 0.1 중량%8) 0.1% by weight of methyl paraoxybenzoate
9) 정제수 64.9 중량%9) Purified water 64.9 wt%
성분 3-6을 가열용해하여 혼합하고, 70oC를 유지하여 유상으로 만든다. 성분1,2 및 7-9를 가열용해하여 혼합하고, 75oC를 유지하여 수상으로 만든다. 유상과 수상을 합하여 유화시키고 30oC까지 냉각하여 제품화한다.Mix components 3-6 by dissolution by heating, and make oily phase at 70 °
제조예Production Example : 목욕용제: Bath Solvent
1) 오매추출물 5.0 중량%1) 5.0% by weight of berry extract
2) 탄산수소나트륨 50.0 중량%2) Sodium bicarbonate 50.0 wt%
3) 황색 202호 0.05 중량%3) Yellow 202 0.05% by weight
4) 향료 0.25 중량%4) 0.25% by weight fragrance
5) 무수황산나트륨 44.7 중량%5) 44.7% by weight of anhydrous sodium sulfate
1-5 성분을 균일하게 혼합한다.Mix 1-5 components evenly.
제조예Production Example : 음료: beverage
1) 오매추출물 1.0 중량%1) fruit extract 1.0% by weight
2) 구연산 5.0 중량%2) 5.0 wt% citric acid
3) 향료 0.1 중량%3) 0.1% by weight fragrance
성분1-3에 물을 혼합하여 전체 100 중량%으로 한다.Water is mixed with components 1-3 to make 100% by weight in total.
제조예Production Example : 정제: refine
1) 오매추출물 2.5 중량%1) Schisandra extract 2.5% by weight
2) 창출추출물 2.5 중량%2) 2.5% by weight of extract produced
3) 고삼추출물 2.5 중량%3) 2.5% by weight of red ginseng extract
4) 승마추출물 2.5 중량%4) Riding extract 2.5% by weight
5) 정제백당 20.0 중량%5) 20.0 wt% per tablet bag
6) 카르복시메틸셀룰로즈 20.0 중량%6) carboxymethylcellulose 20.0 wt%
7) 미세결정셀룰로즈 35.0 중량%7) 35.0 wt% of microcrystalline cellulose
8) 폴리비닐피롤리돈 5.0 중량%8) polyvinylpyrrolidone 5.0% by weight
9) 탈크 10.0 중량%9) Talc 10.0 wt%
성분 1-7을 혼합한 후, 성분8의 수용액을 결합제로서 첨가하여 통상의 방법으로 과립화한다. 여기에 활택제로서 성분9를 배합한 후, 정제로 타정한다.After mixing components 1-7, an aqueous solution of component 8 is added as a binder and granulated in a conventional manner. After blending the component 9 as a lubricant, it tablets by tablet.
도1은 생약재 추출물의 IFN-gamma 억제율을 나타낸다. 0.14 는 세포배양액에 시료원액이 0.14%(V/V) 들어갔음을 의미한다. 억제율 계산 방법은 다음과 같다.Figure 1 shows the IFN-gamma inhibition rate of herbal extracts. 0.14 means 0.14% (V / V) of the sample stock solution in the cell culture solution. The inhibition rate calculation method is as follows.
억제율 = {1-(시료처리군의 사이토카인 생성량 / 양성대조군의 사이토카인 생성량)} x 100Inhibition rate = {1- (cytokine production in the sample treatment group / cytokine production in the positive control group)} x 100
도2는 오매와 매실 추출물의 IFN-gamma 억제율을 비교한 것이다.Figure 2 compares the inhibition rate of IFN-gamma of ume and plum extract.
도3은 생약재 추출물의 IL-4의 억제율을 나타낸다. 억제율은 다음과 같이 계산한다.Figure 3 shows the inhibition rate of IL-4 of the herbal extracts. The inhibition rate is calculated as follows.
억제율 = {1-(시료처리군의 사이토카인 생성량 / 양성대조군의 사이토카인 생성량)} x 100Inhibition rate = {1- (cytokine production in the sample treatment group / cytokine production in the positive control group)} x 100
도4는 오매와 매실 추출물의 IL-4의 억제율을 비교한 것이다.Figure 4 compares the inhibition of IL-4 of the ume and plum extract.
도5는 생약재 추출물의 NF-kB 억제효과를 나타낸다.Figure 5 shows the NF-kB inhibitory effect of the herbal extracts.
CsA: 사이클로스포린, CON: 유도원을 투여한 대조군CsA: cyclosporin, CON: control group administered with induction
Y축의 fold는 유도원을 처리하지 않은 음성대조군의 NF-kB 생성량을 1 fold으로 한다.The fold of the Y-axis is 1 fold for the amount of NF-kB produced by the negative control group without the induction source.
도6은 추출 용매에 따른 IL-4 억제 활성증감효과를 나타낸 것이다.Figure 6 shows the effect of increasing the IL-4 inhibitory activity according to the extraction solvent.
도7은 아토피성피부염 부위에 오매를 처리하기 전 및 후의 사진이다.Figure 7 is a photograph before and after the treatment of the maeru atopic dermatitis site.
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KR20200110253A (en) | 2019-03-15 | 2020-09-23 | (주) 테라베스트 | Cell composition, preparing method thereof and pharmaceutical composition for preventing or treating atopic dermatitis |
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KR101736979B1 (en) | 2010-09-08 | 2017-05-19 | (주)아모레퍼시픽 | Composition for external application to the skin containing prunus mume extract |
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JPS57163307A (en) | 1981-03-30 | 1982-10-07 | Pola Chem Ind Inc | Cosmetic |
KR100354608B1 (en) * | 2000-01-03 | 2002-09-30 | 김형민 | Pharmaceutical compositions for preventing and treating allergic diseases and methods for preparation thereof |
US20030157126A1 (en) * | 2000-03-07 | 2003-08-21 | Xiu-Min Li | Herbal remedies for treating allergies and asthma |
KR20050014947A (en) * | 2003-08-01 | 2005-02-21 | 주식회사 에스티씨나라 | Cosmetic Composition for Improving Atopic Dermatitis Containing Extracts from Plants as Active Ingredient |
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JPS57163307A (en) | 1981-03-30 | 1982-10-07 | Pola Chem Ind Inc | Cosmetic |
KR100354608B1 (en) * | 2000-01-03 | 2002-09-30 | 김형민 | Pharmaceutical compositions for preventing and treating allergic diseases and methods for preparation thereof |
US20030157126A1 (en) * | 2000-03-07 | 2003-08-21 | Xiu-Min Li | Herbal remedies for treating allergies and asthma |
KR20050014947A (en) * | 2003-08-01 | 2005-02-21 | 주식회사 에스티씨나라 | Cosmetic Composition for Improving Atopic Dermatitis Containing Extracts from Plants as Active Ingredient |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
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KR20200110253A (en) | 2019-03-15 | 2020-09-23 | (주) 테라베스트 | Cell composition, preparing method thereof and pharmaceutical composition for preventing or treating atopic dermatitis |
KR20220061935A (en) | 2019-03-15 | 2022-05-13 | (주) 테라베스트 | Cell composition, preparing method thereof and pharmaceutical composition for preventing or treating atopic dermatitis |
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