KR102675988B1 - Composition for improving skin containing 3,3',4-tri-O-methylellagic acid as an active ingredient - Google Patents
Composition for improving skin containing 3,3',4-tri-O-methylellagic acid as an active ingredient Download PDFInfo
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- KR102675988B1 KR102675988B1 KR1020210074314A KR20210074314A KR102675988B1 KR 102675988 B1 KR102675988 B1 KR 102675988B1 KR 1020210074314 A KR1020210074314 A KR 1020210074314A KR 20210074314 A KR20210074314 A KR 20210074314A KR 102675988 B1 KR102675988 B1 KR 102675988B1
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- skin
- tri
- improving
- skin barrier
- acid
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
- A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
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- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
- A61K8/9783—Angiosperms [Magnoliophyta]
- A61K8/9789—Magnoliopsida [dicotyledons]
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- A—HUMAN NECESSITIES
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- A61Q19/00—Preparations for care of the skin
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/318—Foods, ingredients or supplements having a functional effect on health having an effect on skin health and hair or coat
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2250/00—Food ingredients
- A23V2250/20—Natural extracts
- A23V2250/21—Plant extracts
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2250/00—Food ingredients
- A23V2250/30—Other Organic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/74—Biological properties of particular ingredients
- A61K2800/78—Enzyme modulators, e.g. Enzyme agonists
- A61K2800/782—Enzyme inhibitors; Enzyme antagonists
Abstract
3,3',4-tri-O-methylellagic acid를 유효성분으로 포함하는 피부 개선용 조성물에 관한 것이다. 일 양상에 따른 일 양상에 따른 3,3',4-tri-O-methylellagic acid 화합물을 유효성분으로 포함하는 조성물은 콜라겐 합성을 촉진하고 콜라겐 분해를 억제하며 염증인자 발현을 감소시키고 피부장벽 관련 인자의 발현을 증가시켜 피부 개선에 효과적으로 사용될 수 있다.It relates to a composition for improving skin containing 3,3',4-tri-O-methylellagic acid as an active ingredient. According to one aspect, a composition containing a 3,3',4-tri-O-methylellagic acid compound as an active ingredient promotes collagen synthesis, inhibits collagen decomposition, reduces the expression of inflammatory factors, and reduces skin barrier-related factors. It can be effectively used to improve skin by increasing the expression of .
Description
3,3',4-tri-O-methylellagic acid를 유효성분으로 포함하는 피부 개선용 조성물에 관한 것이다.It relates to a composition for improving skin containing 3,3',4-tri-O-methylellagic acid as an active ingredient.
노령인구가 증가함에 따라 노화의 척도가 될 수 있는 피부미용 및 노화를 방지할 수 있는 항산화 분야가 주요 관심사로 떠오르고 있다. 노화로 인한 피부의 주름생성 및 체내의 항산화 활성 감소 등은 건강의 척도로 사용될 수 있다. 피부노화는 요인에 따라 내인성 노화(Intrinsic aging)와 외인성 노화(Extrinsic aging)로 구분할 수 있다. 내인성 노화는 나이에 따른 피부 표피 및 진피의 생리적 기능 변화가 원인이며, 외인성 노화는 대기오염, 자외선 노출, 스트레스 등의 환경으로부터 발생하는 피부의 생리적 기능 변화가 원인으로 알려져 있다. 이러한 노화의 메커니즘 중 자외선에 의해 유도되는 산화적 스트레스(Oxidative Stress)는 체내의 자유라디칼(Free Radical)을 증가시키고, 콜라겐(Collagen)을 분해하는 MMP-1 (Matrix Metalloproteinase-1), 히알루론산(Hyaluronic acid)을 분해하는 히아루론다제(Hyaluronidase)의 활성 증가로 피부 표피 및 진피 손상으로 설명될 수 있다.As the elderly population increases, skin care, which can be a measure of aging, and antioxidants, which can prevent aging, are emerging as major areas of interest. The formation of wrinkles on the skin and the decrease in antioxidant activity in the body due to aging can be used as a measure of health. Skin aging can be divided into intrinsic aging and extrinsic aging depending on the factors. Intrinsic aging is caused by changes in the physiological functions of the skin's epidermis and dermis with age, while extrinsic aging is known to be caused by changes in the physiological functions of the skin that occur from environments such as air pollution, exposure to ultraviolet rays, and stress. Among these aging mechanisms, oxidative stress induced by ultraviolet rays increases free radicals in the body, and MMP-1 (Matrix Metalloproteinase-1), which decomposes collagen, and hyaluronic acid ( This can be explained by damage to the skin epidermis and dermis due to increased activity of hyaluronidase, which decomposes hyaluronic acid.
피부의 각질층(Stratum corneum)은 피부에서 최외각 층에 존재하고, 외부환경에 직접 접하고 있어 외부의 물리적 화학적 스트레스로 부터 우리 몸을 보호하는 데 중요한 장벽기능(barrier function)을 담당하고 있다. 이러한 장벽기능은 표피의 항상성(homeostasis)에 의하여 유지된다. 표피 항상성은 기저층의 각질형성세포(keratinocytes)의 성장분열과 세포이동에 따른 분화 과정을 통해 최종 분화(terminal differentiation)를 거쳐 각질층으로 불리는 피부장벽을 형성함으로써 지속적인 피부 장벽 기능을 유지하는 것이다(Korean J. Food.Sci. Technol. 43:458-463, 2011).The stratum corneum of the skin exists in the outermost layer of the skin and is in direct contact with the external environment, so it plays an important barrier function in protecting our body from external physical and chemical stresses. This barrier function is maintained by epidermal homeostasis. Epidermal homeostasis maintains continuous skin barrier function by forming a skin barrier called the stratum corneum through terminal differentiation through growth division and cell migration of keratinocytes in the basal layer (Korean J Food. Sci. 43:458-463, 2011).
각질형성 세포가 분화함에 따라서 보습에 영향을 미치는 두 가지 요인을 생성한다. 첫째로, 각질형성세포가 분화하는 동안 그 세포막은 각질세포막(cornified envelope)이라는 구조물로 대체된다. 각질세포막은 로리크린(loricrin), 인볼루크린(involucrin), 필라그린(filaggrin)을 비롯한 여러 구조 단백질들이 가교를 형성한 막 구조물로서 외부환경에 대한 피부 보호기능을 제공함과 동시에 각질세포내의 수분증발을 억제한다(Nat. Rev. Mol. Cell Biol. 6(4):328-340, 2005). As keratinocytes differentiate, they produce two factors that affect moisturization. First, during keratinocyte differentiation, the cell membrane is replaced by a structure called the cornified envelope. The keratinocyte membrane is a membrane structure formed by cross-linking various structural proteins, including loricrin, involucrin, and filaggrin, and provides skin protection against the external environment while also preventing moisture evaporation within the keratinocytes. Inhibits (Nat. Rev. Mol. Cell Biol. 6(4):328-340, 2005).
또한, 각질세포의 분화 과정 중에 각질형성세포는 천연보습인자(Natural Moisturizing Factor; NMF)를 생성하면서 피부장벽 (skin barrier)으로서의 기능을 보유하게 한다. 천연보습인자들의 생성에 중요한 원천이 되는 단백질은 필라그린으로서, 필라그린은 CASP 14(caspase 14)에 의해 친수성 아미노산으로 분해되어 천연보습인자을 형성한다. 천연보습인자는 수분 보유 능력(water holding capacity)과 대기 중의 수분 흡습력(moistureabsorption)을 제공함으로써 피부 내 보습력을 유지하는 기능을 한다(J. Cell Sci. 122:1285-1294, 2009). 따라서 피부에 적절한 수준의 천연보습인자를 유지하는 것은 피부 장벽 기능을 통한 피부 건강에 매우 중요한 요소이다.Additionally, during the differentiation process of keratinocytes, keratinocytes produce Natural Moisturizing Factor (NMF) and maintain the function of a skin barrier. The protein that is an important source for the production of natural moisturizing factors is filaggrin, which is decomposed into hydrophilic amino acids by CASP 14 (caspase 14) to form natural moisturizing factors. Natural moisturizing factors function to maintain moisturizing power in the skin by providing water holding capacity and moisture absorption from the atmosphere (J. Cell Sci. 122:1285-1294, 2009). Therefore, maintaining an appropriate level of natural moisturizing factors in the skin is a very important factor for skin health through skin barrier function.
미세먼지는 지름이 10 μm 이하로 PM(Particulate Matter) 10 라고 하며 주로 자동차 배출가스나 공장 굴뚝 등을 통해 주로 배출되고, 중국의 황사나 심한 스모그때 날아온다. 이는 피부 모공의 약 20분의 1에 불과하기 때문에 피부에서 차단되지 못하고 모공 속으로 쉽게 침투되어 제거가 어렵다. 한 번 흡수된 미세먼지는 피부에 각종 화학자극을 일으키는 것은 물론 각질세포와 지질막 등에 악영향을 끼쳐 피부 면역력을 저하시키고 여드름 유발, 피부 건조, 주름 증가 및 색소 침착 등과 같은 피부 노화 현상을 더욱 가속화 시킨다. 따라서 미세먼지에 대한 피부 노출을 미리 차단하지 못하거나 침투된 미세먼지를 깨끗하게 제거하지 못하면 모공 속에서 염증 반응을 일으켜 피부 트러블이 발생할 확률이 높다.Fine dust is less than 10 μm in diameter and is called PM (Particulate Matter) 10. It is mainly emitted through automobile exhaust gases or factory chimneys, and is blown in during yellow dust or severe smog in China. Since it is only about 1/20th of the skin pores, it cannot be blocked by the skin and easily penetrates into the pores, making it difficult to remove. Once absorbed, fine dust not only causes various chemical irritations on the skin, but also has a negative effect on keratinocytes and lipid membranes, lowering skin immunity and further accelerating skin aging phenomena such as acne, skin dryness, increased wrinkles, and pigmentation. Therefore, if you do not prevent skin exposure to fine dust in advance or do not cleanly remove the fine dust that has penetrated, there is a high probability that skin problems will occur due to an inflammatory reaction in the pores.
피부가 미세먼지에 노출되었을 때 이를 방어하기 위한 작용으로 염증반응이 시작되며 다양한 면역세포와 염증 유도 사이토카인이 관여한다. IL-1β(interleukin-β), IL-8(interleukin-8), TNF-α(Tumor necrosis factor-α) 등이 대표적인 염증 유도 사이토카인으로 미세먼지 입자는 사람 각질형성세포에서 이러한 사이토카인의 발현을 증가시킨다.When the skin is exposed to fine dust, an inflammatory response begins as a defense mechanism, and various immune cells and inflammation-inducing cytokines are involved. Representative inflammation-inducing cytokines include interleukin-β (IL-1β), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α), and fine dust particles induce the expression of these cytokines in human keratinocytes. increases.
따라서, 이에 따른 자외선 또는 미세먼지에 의한 세포손상 억제 및 개선에 대한 기전 연구가 활발히 진행되어 왔으며 생화학적 효능, 효과를 나타내는 화장료 및 건강기능식품에 대한 연구가 진행되고 있다. 연구수준의 발달 및 기술력 증가로 실질적인 효능, 효과를 가진 소재들이 주 연구 대상이다.Therefore, research on mechanisms for suppressing and improving cell damage caused by ultraviolet rays or fine dust has been actively conducted, and research is being conducted on cosmetics and health functional foods that exhibit biochemical efficacy and effectiveness. With the development of research level and increase in technology, materials with practical efficacy and effectiveness are the main research targets.
식물유래 소재는 안전성 측면에서 우수하여 오랫동안 이용되었으며, 특히 국내의 경우 민간에서 이용되거나 혹은 한방에서 이용돼 식물 및 생약성분을 주로 한 기능성 소재 개발이 활발히 이루어지고 있다.Plant-derived materials are excellent in terms of safety and have been used for a long time. In particular, in Korea, the development of functional materials mainly made of plants and herbal medicines is being actively conducted, either in the private sector or in oriental medicine.
딱지꽃(Potentilla chinensis Ser.)은 일본, 만주, 아무르, 중국, 대만 등에서 분포하는 장미과의 여러해살이 풀이다. 식약처에서 고시한 식품원재료에 잎 부위가 식용가능부위로 명시되어 있으며, 한방에서는 위릉채라 하여 이질, 류마티스성 근골동통, 창개, 피부병 치료 등에 약용하였다. 또한 딱지꽃 부위 별 추출물이 항염, 미백, 주름 개선 및 보습에 대해 효과(한국화장품미용학회지, 2015, 5(3), 263-270)가 있는 것으로 보고된 바 있다. Potentilla chinensis Ser.) is a perennial plant of the Rosaceae family distributed in Japan, Manchuria, Amur, China, and Taiwan. In the food raw materials notified by the Ministry of Food and Drug Safety, the leaf part is specified as an edible part, and in oriental medicine, it is called Wireungchae and is used medicinally to treat dysentery, rheumatoid pain, itch, and skin diseases. In addition, it has been reported that extracts from each part of the scab flower have anti-inflammatory, whitening, wrinkle improvement, and moisturizing effects (Journal of the Korean Society of Cosmetics and Aesthetics, 2015, 5(3), 263-270).
3,3',4-tri-O-methylellagic acid는 딱지꽃 잎에서 발견되는 성분(약학회지, 1989, 33(6), 377-379)으로 분자량은 344.272 g/mol이며 IUPAC명은 2-Hydroxy-3,7,8-trimethoxychromeno[5,4,3-cde]chromene-5,10-dione이다. 이것의 기능성으로는 조혈모세포 성장촉진 효과(Molecules, 2014, 19(4), 5448-5458), 항당뇨효과(Planta Medicine, 2015, 81, PM_192)가 있는 것으로 보고된 바 있다.3,3',4-tri-O-methylellagic acid is a component found in scab leaves (Journal of Pharmaceutical Sciences, 1989, 33(6), 377-379). Its molecular weight is 344.272 g/mol and its IUPAC name is 2-Hydroxy- It is 3,7,8-trimethoxychromeno[5,4,3-cde]chromene-5,10-dione. Its functionality has been reported to include a hematopoietic stem cell growth promotion effect (Molecules, 2014, 19(4), 5448-5458) and an anti-diabetic effect (Planta Medicine, 2015, 81, PM_192).
하지만, 상기 성분은 피부 개선에 대한 직접적인 연구가 이루어지지 않은 실정이다. However, direct research on skin improvement has not been conducted with the above ingredients.
일 양상은 하기 화학식 1로 표시되는 3,3',4-tri-O-methylellagic acid 화합물 또는 이의 허용가능한 염을 유효성분으로 포함하는 피부 개선용 화장료 조성물을 제공하는 것이다:One aspect is to provide a cosmetic composition for improving skin containing a 3,3',4-tri-O-methylellagic acid compound represented by the following formula (1) or an acceptable salt thereof as an active ingredient:
[화학식 1][Formula 1]
. .
다른 양상은 상기 화학식 1로 표시되는 3,3',4-tri-O-methylellagic acid 화합물 또는 이의 허용가능한 염을 유효성분으로 포함하는 피부 개선용 건강기능식품 조성물을 제공하는 것이다.Another aspect is to provide a health functional food composition for improving skin containing the 3,3',4-tri-O-methylellagic acid compound represented by Chemical Formula 1 or an acceptable salt thereof as an active ingredient.
또 다른 양상은 상기 화학식 1로 표시되는 3,3',4-tri-O-methylellagic acid 화합물 또는 이의 허용가능한 염을 유효성분으로 포함하는 피부 손상 예방 또는 치료용 약학적 조성물을 제공하는 것이다.Another aspect is to provide a pharmaceutical composition for preventing or treating skin damage containing the 3,3',4-tri-O-methylellagic acid compound represented by Formula 1 or an acceptable salt thereof as an active ingredient.
또 다른 양상은 상기 화학식 1로 표시되는 3,3',4-tri-O-methylellagic acid 화합물 또는 이의 허용가능한 염을 유효성분으로 포함하는 피부 손상 예방 또는 개선용 피부 외용제를 제공하는 것이다. Another aspect is to provide an external skin preparation for preventing or improving skin damage containing the 3,3',4-tri-O-methylellagic acid compound represented by Chemical Formula 1 or an acceptable salt thereof as an active ingredient.
일 양상은 하기 화학식 1로 표시되는 3,3',4-tri-O-methylellagic acid 화합물 또는 이의 허용가능한 염을 유효성분으로 포함하는 피부 개선용 화장료 조성물을 제공한다:One aspect provides a cosmetic composition for skin improvement comprising a 3,3',4-tri-O-methylellagic acid compound represented by the following formula (1) or an acceptable salt thereof as an active ingredient:
[화학식 1][Formula 1]
. .
상기 3,3',4-tri-O-methylellagic acid 화합물은 시중에서 구입하여 사용할 수도 있고, 통상적인 방법에 따라 합성할 수도 있으며, 바람직하게는 천연물에서 분리 정제하여 사용할 수도 있다. 일 구체예에 있어서, 상기 3,3',4-tri-O-methylellagic acid는 딱지꽃(Potentilla chinensis Ser.) 추출물에서 분리된 것일 수 있다. The 3,3',4-tri-O-methylellagic acid compound can be purchased commercially or synthesized according to a conventional method, and preferably, it can be separated and purified from a natural product. In one embodiment, the 3,3',4-tri-O-methylellagic acid may be isolated from Potentilla chinensis Ser. extract.
상기 딱지꽃 추출물은 각각 그 수목의 지상부의 전체, 그 일부분, 또는 이들로부터 유래된 재료로부터 용매에 의하여 추출된 추출물일 수 있다. 상기 일부분은 수목의 줄기, 뿌리, 잎, 꽃, 꽃잎, 종실(씨앗), 과육, 열매 껍질 또는 열매일 수 있고 바람직하게는 잎일 수 있다. 추출에 사용된 상기 수목의 전체, 그 일부분, 또는 이들로부터 유래된 재료는 분쇄 또는 세절되거나 적당하게 건조된 것일 수 있다.The scab flower extract may be an extract extracted with a solvent from the entire above-ground part of the tree, a portion thereof, or materials derived from them. The part may be the stem, root, leaf, flower, petal, seed, pulp, fruit peel or fruit of the tree, and preferably may be a leaf. The whole tree, part thereof, or material derived therefrom used for extraction may be ground, shredded, or suitably dried.
상기 딱지꽃 추출물은 종래에 천연식물을 추출하기 위하여 이용된 열수추출, 용매추출, 증류추출, 초임계 추출 등 어떠한 추출방법으로도 추출될 수 있으며, 바람직하게는 물, 유기용매 또는 이들의 혼합용매로 추출되는 것을 특징으로 한다. 상기 유기용매는 탄소수 1 내지 4의 알코올, 예컨대 에탄올, 메탄올, 이소프로판올, 및 부탄올 등으로 이루어진 군에서 선택된 어느 하나 이상이 사용될 수 있으며, 바람직하게는 에탄올이 사용될 수 있으며, 더욱 바람직하게는 발효주정이 사용될 수 있다. The scab flower extract can be extracted by any extraction method conventionally used to extract natural plants, such as hot water extraction, solvent extraction, distillation extraction, or supercritical extraction, and is preferably extracted with water, organic solvents, or a mixed solvent thereof. It is characterized by being extracted as. The organic solvent may be one or more selected from the group consisting of alcohols having 1 to 4 carbon atoms, such as ethanol, methanol, isopropanol, and butanol, preferably ethanol, and more preferably fermented alcohol. can be used
상기 3,3',4-tri-O-methylellagic acid 화합물은 상기 딱지꽃 추출물의 분획물 일 수 있다. 상기 분획물(fraction)은 상기 추출물에 대하여 특정 성분을 포함하는 물질을 분리한 것을 말한다. 상기 3,3',4-tri-O-methylellagic acid 화합물은 컬럼 크로마토그래피를 이용하여 분리 정제될 수 있다. 상기 크로마토그래피는 실리카겔 컬럼 크로마토그래피(silica gel column chromatography), HP-20 컬럼 크로마토그래피(HP-20 column chromatography), RP-18 컬럼 크로마토그래피(RP-18 column chromatography), LH-20 컬럼 크로마토그래피(LH-20 column chromatography), 고성능 액체 크로마토그래피(High-performance liquid chromatography) 또는 그 조합을 선택하여 사용할 수 있다.The 3,3',4-tri-O-methylellagic acid compound may be a fraction of the scab extract. The fraction refers to separation of substances containing specific components from the extract. The 3,3',4-tri-O-methylellagic acid compound can be separated and purified using column chromatography. The chromatography includes silica gel column chromatography, HP-20 column chromatography, RP-18 column chromatography, and LH-20 column chromatography ( LH-20 column chromatography, high-performance liquid chromatography, or a combination thereof can be selected and used.
상기 피부 개선은 피부 장벽개선, 피부 손상 예방 또는 개선, 피부 보습, 피부 면역 개선, 피부 방어력 증진, 피부 염증 억제, 피부 진정 및 피부 재생으로 이루어진 군으로부터 선택된 하나 이상인 것일 수 있고, 상기 피부 개선용은 외부 자극으로부터의 피부 보호인 것일 수 있다. 또한, 상기 외부 자극은 자외선 또는 미세먼지인 것일 수 있으며, 상기 자외선 또는 미세먼지에 의해 인간 표피세포 및 진피세포가 손상되는 것일 수 있다.The skin improvement may be one or more selected from the group consisting of skin barrier improvement, skin damage prevention or improvement, skin moisturization, skin immunity improvement, skin defense enhancement, skin inflammation inhibition, skin soothing, and skin regeneration, and the skin improvement use may be one or more selected from the group consisting of: This may be to protect the skin from external stimulation. Additionally, the external stimulus may be ultraviolet rays or fine dust, and human epidermal cells and dermal cells may be damaged by the ultraviolet rays or fine dust.
이에, 본 발명자들은 상기 3,3',4-tri-O-methylellagic acid 화합물을 유효성분으로 포함하는 조성물이 손상된 표피세포 또는 진피세포를 증식 또는 복구시키고, MMP-1의 생성을 감소시키며, 프로콜라겐 생성량을 증가시킴으로써 피부를 개선시키는 효과가 있음을 확인하였고, 구체적으로 피부손상을 예방, 개선 또는 치료하고 피부를 재생시키는 효과가 있음을 확인하였다. 또한, 상기 3,3',4-tri-O-methylellagic acid 화합물을 유효성분으로 포함하는 조성물이 손상된 표피세포에서 필라그린, 인볼루크린, 로리크린 및/또는 CASP 14과 같은 피부장벽 단백질의 생성을 증가시킴으로써 피부를 개선시키는 효과가 있음을 확인하였고, 구체적으로 피부손상을 예방, 개선 또는 치료하고 피부 장벽 개선 효과가 있음을 확인하였다. 또한, 상기 3,3',4-tri-O-methylellagic acid 화합물을 유효성분으로 포함하는 조성물이 미세먼지로 손상된 표피세포에서 Interleukin-1β(IL-1β), Interleukin-8(IL-8) 및 Tumor necrosis factor-α(TNF-α)와 같은 염증인자를 감소시킴으로써 피부를 개선시키는 효과가 있음을 확인하였고, 구체적으로 피부손상을 예방, 개선 또는 치료하고 피부 면역 개선, 피부 방어력 증진 및/또는 피부 염증 억제 효과가 있음을 확인하였다. Accordingly, the present inventors have found that a composition containing the 3,3',4-tri-O-methylellagic acid compound as an active ingredient proliferates or repairs damaged epidermal cells or dermal cells, reduces the production of MMP-1, and It was confirmed that it has the effect of improving the skin by increasing collagen production, and specifically, it was confirmed that it has the effect of preventing, improving or treating skin damage and regenerating the skin. In addition, the composition containing the 3,3',4-tri-O-methylellagic acid compound as an active ingredient promotes the production of skin barrier proteins such as filaggrin, involucrin, loricrin and/or CASP 14 in damaged epidermal cells. It was confirmed that it has the effect of improving the skin by increasing , and specifically, it was confirmed that it prevents, improves, or treats skin damage and has the effect of improving the skin barrier. In addition, the composition containing the 3,3',4-tri-O-methylellagic acid compound as an active ingredient increases the levels of Interleukin-1β (IL-1β), Interleukin-8 (IL-8) and It was confirmed that it has the effect of improving the skin by reducing inflammatory factors such as tumor necrosis factor-α (TNF-α). Specifically, it prevents, improves, or treats skin damage, improves skin immunity, enhances skin defense, and/or skin damage. It was confirmed that it has an inflammation-inhibiting effect.
본 명세서에 있어서, 용어 "피부 손상"이란 외부 자극, 예를 들어 자외선 또는 미세먼지에 의한 인간 피부세포의 사멸, 피부 세포 DNA 손상, 활성산소종 증가, 지질과산화 증가 등을 포함하며, 그 증상으로는 홍반, 일광화상, 색소침착, 광노화, 피부암 등을 포함할 수 있다. As used herein, the term "skin damage" includes death of human skin cells, skin cell DNA damage, increased reactive oxygen species, increased lipid peroxidation, etc. due to external stimuli such as ultraviolet rays or fine dust, and symptoms thereof include: This may include erythema, sunburn, pigmentation, photoaging, skin cancer, etc.
본 명세서 있어서, 용어 "피부 장벽 개선"은 피부 장벽 강화, 또는 보호 기능을 모두 포함하는 의미로, 여기서, 피부장벽(skin barrier)은 표피의 최외곽 층인 각질층(stratum corneum)은 주로 무핵의 편평한 각질세포(corneocyte)로 이루어져 있다. 정상적인 표피세포의 분열 및 분화과정을 통해 유지되는 피부장벽의 각질세포가 합성하는 세라마이드, 콜레스테롤, 및 지방산과 같은 세포간 지질로 형성된 다층지질막(multi lamella lipid layer)은 피부 내의 수분이 증발하지 않도록 방어막 역할을 한다. 한편, 이들 세포간 지질 중 오메가 히드록시 세라마이드는 각질세포(corneocyte) 외곽층의 단백질인 인볼루크린(involucrin)과 화학적 공유결합으로 연결되어 각질세포지질막(corneocyte lipid envelope, CLE)을 형성함으로써 다층 지질막 형태의 세포간 지질을 물리적으로 안정화시키는 역할을 하여 장벽기능을 강화시키는 역할을 하게 된다. 상기 피부 장벽 개선은 피부 장벽 기능이 약화됨에 따른 피부질환인 건선, 접촉성피부염, 습진성 피부염, 광선 피부염, 지루 피부염, 포진성 피부염, 편평태선, 경화태선, 괴저성 농피증, 천포창, 수포성 표피박리증, 전신성 경화증 또는 나병을 완화시키거나 손상된 피부 장벽 기능을 향상시키는 모든 작용을 의미할 수 있다.As used herein, the term "skin barrier improvement" is meant to include both skin barrier strengthening and protective functions. Here, the skin barrier refers to the stratum corneum, the outermost layer of the epidermis, which is mainly composed of inucleated flat keratin. It is made up of cells (corneocytes). The multi-lamella lipid layer, formed of intercellular lipids such as ceramide, cholesterol, and fatty acids synthesized by keratinocytes of the skin barrier maintained through the division and differentiation process of normal epidermal cells, acts as a barrier to prevent moisture in the skin from evaporating. It plays a role. Meanwhile, among these intercellular lipids, omega hydroxyceramide is connected to involucrin, a protein of the outer layer of corneocytes, through chemical covalent bonds to form the corneocyte lipid envelope (CLE), a multilayer lipid membrane. It plays a role in strengthening the barrier function by physically stabilizing the form of intercellular lipid. The skin barrier improvement is for skin diseases caused by weakened skin barrier function, such as psoriasis, contact dermatitis, eczematous dermatitis, actinic dermatitis, seborrheic dermatitis, dermatitis herpetiformis, lichen planus, lichen sclerosus, pyoderma gangrenosum, pemphigus, and epidermis bullous. It can refer to any action that alleviates exfoliation, systemic sclerosis or leprosy, or improves damaged skin barrier function.
본 명세서에서 용어 "허용가능한"이란 상기 조성물에 노출되는 세포나 인간에게 독성이 없는 특성을 나타내는 것을 의미한다.As used herein, the term “acceptable” means that the composition exhibits non-toxic properties to cells or humans exposed to the composition.
본 명세서에서 용어 "허용가능한 염"이란, 일 양상에 따른 특정 화합물과 비교적 무독성인 산 또는 염기를 이용해서 조제되는 염을 의미한다. 상기 화합물이 상대적으로 산성 관능기를 포함할 때, 순수 용액 또는 적합한 불활성 용매 중에서 충분한 양의 염기를 이러한 화합물의 중성 형태와 접촉시킴으로써 염기 부가염을 얻을 수 있다. 약학적으로 허용 가능한 염기 부가염은 나트륨, 칼륨, 칼슘, 암모늄, 유기 아민, 혹은 마그네슘의 염 또는 유사한 염이 포함된다. 상기 화합물이 상대적으로 염기성 관능기를 포함할 때, 순수 용액 또는 적합한 불활성 용매 중에서 충분한 양의 산을 이러한 화합물의 중성 형태와 접촉시킴으로써 산 부가염을 얻을 수 있다. 약학적으로 허용 가능한 산 부가염은 염산, 브롬화 수소산, 질산, 탄산, 탄산 수소 이온, 인산, 인산 1수소 이온, 인산 2수소 이온, 황산, 황산 수소 이온, 요오드화 수소산 또는 아인산 등의 무기산의 염, 그리고 아세트산, 프로피온산, 이소부티르산, 말레산, 말론산, 안식향산, 숙신산, 수베르산, 푸마르산, 락트산, 만델산, 프탈산, 벤젠술폰산, p-톨릴술폰산, 구연산, 주석산, 메탄술폰산 등의 유기산의 염을 들 수 있고, 나아가 아미노산(예를 들면 아르기닌 등)의 염 및 글루쿠론산 등의 유기산의 염도 포함된다.As used herein, the term “acceptable salt” refers to a salt prepared using a specific compound according to one aspect and a relatively non-toxic acid or base. When the compounds contain relatively acidic functional groups, base addition salts can be obtained by contacting the neutral form of these compounds with a sufficient amount of base in pure solution or a suitable inert solvent. Pharmaceutically acceptable base addition salts include salts of sodium, potassium, calcium, ammonium, organic amines, or magnesium or similar salts. When the compounds contain relatively basic functional groups, acid addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of acid in pure solution or a suitable inert solvent. Pharmaceutically acceptable acid addition salts include salts of inorganic acids such as hydrochloric acid, hydrobromic acid, nitric acid, carbonic acid, hydrogen carbonate ion, phosphoric acid, monohydrogen phosphate ion, dihydrogen phosphate ion, sulfuric acid, hydrogen sulfate ion, hydroiodic acid or phosphorous acid, and salts of organic acids such as acetic acid, propionic acid, isobutyric acid, maleic acid, malonic acid, benzoic acid, succinic acid, suberic acid, fumaric acid, lactic acid, mandelic acid, phthalic acid, benzenesulfonic acid, p-tolylsulfonic acid, citric acid, tartaric acid, and methanesulfonic acid. , and further include salts of amino acids (e.g., arginine, etc.) and salts of organic acids such as glucuronic acid.
상기 허용 가능한 염은 산성 또는 염기성 부분을 포함하는 모체 화합물로부터 통상적인 화학적 방법으로 합성할 수 있다. 일반적으로 이러한 염은 수중 또는 유기 용매 중 또는 이 2종의 혼합물 중에서, 이들 화합물의 유리산 또는 염기의 형태를 화학량론적으로 적량인 염기 또는 산과 반응시켜서 조제된다. 일반적으로 에테르, 아세트산에틸, 에탄올, 이소프로판올 또는 아세토니트릴 등의 비수성 매질이 바람직하다.The acceptable salts can be synthesized by conventional chemical methods from parent compounds containing an acidic or basic moiety. Generally, these salts are prepared by reacting the free acid or base form of these compounds with a stoichiometrically appropriate amount of base or acid in water or an organic solvent or a mixture of the two. Generally, non-aqueous media such as ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are preferred.
상기 3,3',4-tri-O-methylellagic acid 화합물은 상기 화장료 조성물 총 중량에 대하여 0.001 내지 10 중량%로 포함될 수 있다. 예를 들어, 0.001 내지 5 중량%, 0.001 내지 3 중량%, 0.001 내지 1 중량%, 0.01 내지 10 중량%, 0.01 내지 5 중량%, 0.01 내지 3 중량%, 0.01 내지 1 중량%, 0.1 내지 10 중량%, 0.1 내지 5 중량%, 0.1 내지 3 중량%, 0.1 내지 1 중량%로 포함될 수 있다. 또한, 상기 조성물에 딱지꽃 추출물을 더 포함할 수 있다.The 3,3',4-tri-O-methylellagic acid compound may be included in an amount of 0.001 to 10% by weight based on the total weight of the cosmetic composition. For example, 0.001 to 5% by weight, 0.001 to 3% by weight, 0.001 to 1% by weight, 0.01 to 10% by weight, 0.01 to 5% by weight, 0.01 to 3% by weight, 0.01 to 1% by weight, 0.1 to 10% by weight. %, 0.1 to 5% by weight, 0.1 to 3% by weight, and 0.1 to 1% by weight. Additionally, the composition may further include scab flower extract.
상기 화장료 조성물은 화장수(스킨로션), 스킨, 스킨소프너, 스킨토너, 아스트린젠트, 로션, 밀크로션, 모이스쳐 로션, 영양 로션, 마사지크림, 영양 크림, 모이스쳐 크림, 핸드크림, 손세정제, 파운데이션, 에센스, 영양 에센스, 팩, 비누, 클렌징폼, 클렌징로션, 클렌징크림, 바디로션, 바디클렌저, 현탁액, 겔, 분말, 페이스트, 마스크팩, 및 시트를 포함하는 제형으로 제조될 수 있다. 이러한 제형의 조성물은 당해 분야에서 통상적인 방법에 따라 제조될 수 있다. 상기 보습제 등의 추가 성분의 배합량은 본 발명의 목적 및 효과를 손상시키지 않는 범위 내에서 당업자가 용이하게 선정 가능하다.The cosmetic composition includes lotion (skin lotion), skin, skin softener, skin toner, astringent, lotion, milk lotion, moisture lotion, nutritional lotion, massage cream, nutritional cream, moisture cream, hand cream, hand sanitizer, foundation, essence, It can be manufactured into formulations including nutritional essence, pack, soap, cleansing foam, cleansing lotion, cleansing cream, body lotion, body cleanser, suspension, gel, powder, paste, mask pack, and sheet. Compositions of this dosage form can be prepared according to methods conventional in the art. The mixing amount of additional ingredients such as the above-mentioned moisturizer can be easily selected by a person skilled in the art within a range that does not impair the purpose and effect of the present invention.
상기 화장료 조성물에는 본 명세서에 개시된 유효성분 이외에 기능성 첨가물 및 일반적인 화장료 조성물에 포함되는 성분이 추가로 포함될 수 있으며, 통상적으로 사용되는 정제수, 점증제, 방부제, 안정화제, 용해화제, 계면활성제, 담체, 향료 또는 이들의 조합을 더 포함할 수 있다. 상기 기능성 첨가물로는 수용성 비타민, 유용성 비타민, 고분자 펩티드, 고분자 다당, 스핑고 지질 및 해초 엑기스로 이루어진 군에서 선택된 성분을 포함할 수 있다. 상기 담체로서는 알코올, 오일, 계면활성제, 지방산, 실리콘 오일, 습윤제, 보습제, 점성 변형제, 유제, 안정제, 자외선산란제, 자외선흡수제, 발색제, 향료 등이 예시될 수 있다. 상기 알코올, 오일, 계면활성제, 지방산, 실리콘 오일, 습윤제, 보습제, 점성 변형제, 유제, 안정제, 자외선산란제, 자외선흡수제, 발색제, 향료로 사용될 수 있는 화합물/조성물 등은 이미 당업계에 공지되어 있기 때문에 당업자라면 적절한 해당 물질/조성물을 선택하여 사용할 수 있다. 또한, 상기 화장료 조성물에는 필요에 따라 자외선 차단제, 산화 방지제(부틸히드록시아니솔, 갈릭산프로필, 엘리소르빈산, 토코페릴아세테이드, 부틸레이티드하이드록시톨루엔 등), 방부제(메칠파라벤, 부틸파라벤, 프로필파라벤, 페녹시에탄올, 이미다졸리디닐우레아, 클로르페네신 등), 착색제, pH 조절제(트리에탄올아민, 씨트릭애씨드, 시트르산, 시트르산나트륨, 말산, 말산나트륨, 프말산, 프말산나트륨, 숙신산, 숙신산나트륨, 수산화나트륨, 인산일수소나트륨 등), 보습제(글리세린, 솔비톨, 프로필렌 글라이콜, 부틸렌 글라이콜, 헥실렌 글라이콜, 디글리세린, 베타인, 글리세레스-26, 메칠글루세스-20 등), 윤활제 등의 성분을 더 첨가할 수 있다.In addition to the active ingredients disclosed herein, the cosmetic composition may further include functional additives and ingredients included in general cosmetic compositions, including commonly used purified water, thickeners, preservatives, stabilizers, solubilizers, surfactants, carriers, It may further include fragrance or a combination thereof. The functional additive may include ingredients selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, polymer peptides, polymer polysaccharides, sphingolipids, and seaweed extract. Examples of the carrier include alcohol, oil, surfactant, fatty acid, silicone oil, wetting agent, humectant, viscosity modifier, emulsion, stabilizer, ultraviolet scattering agent, ultraviolet absorber, coloring agent, fragrance, etc. Compounds/compositions that can be used as alcohols, oils, surfactants, fatty acids, silicone oils, wetting agents, moisturizers, viscosity modifiers, emulsions, stabilizers, UV scattering agents, UV absorbers, coloring agents, and fragrances are already known in the art. Therefore, a person skilled in the art can select and use the appropriate material/composition. In addition, the cosmetic composition may contain sunscreen, antioxidants (butylhydroxyanisole, propyl gallate, elisorbic acid, tocopheryl acetate, butylated hydroxytoluene, etc.), and preservatives (methylparaben, butylparaben) as necessary. , propylparaben, phenoxyethanol, imidazolidinyl urea, chlorphenesin, etc.), colorants, pH adjusters (triethanolamine, citric acid, citric acid, sodium citrate, malic acid, sodium malate, fmal acid, sodium fmalate, succinic acid) , sodium succinate, sodium hydroxide, sodium monohydrogen phosphate, etc.), moisturizers (glycerin, sorbitol, propylene glycol, butylene glycol, hexylene glycol, diglycerin, betaine, glycereth-26, methyl glue) Additional ingredients such as Seth-20, etc.) and lubricants can be added.
또한, 각 제형의 화장료 조성물에 있어서 화장료의 제형 또는 사용 목적에 따라 적절한 성분들을 선정하여 배합할 수 있다. 배합 성분 및 방법은 통상의 기술에 따를 수 있으므로 그 구체적인 설명은 본 명세서에서 생략한다.Additionally, in each type of cosmetic composition, appropriate ingredients can be selected and mixed depending on the formulation or purpose of use of the cosmetic. Since the mixing ingredients and methods may be in accordance with conventional techniques, detailed descriptions thereof are omitted in this specification.
다른 양상은 하기 화학식 1로 표시되는 3,3',4-tri-O-methylellagic acid 화합물 또는 이의 허용가능한 염을 유효성분으로 포함하는 피부 개선용 건강기능식품 조성물을 제공한다:Another aspect provides a health functional food composition for improving skin containing a 3,3',4-tri-O-methylellagic acid compound represented by the following formula (1) or an acceptable salt thereof as an active ingredient:
[화학식 1][Formula 1]
. .
일 구체예에 있어서, 상기 3,3',4-tri-O-methylellagic acid는 딱지꽃(Potentilla chinensis Ser.) 추출물에서 분리된 것일 수 있다.In one embodiment, the 3,3',4-tri-O-methylellagic acid may be isolated from Potentilla chinensis Ser. extract.
일 구체예에 있어서, 상기 피부 개선은 피부 장벽개선, 피부 손상 예방 또는 개선, 피부 보습, 피부 면역 개선, 피부 방어력 증진, 피부 염증 억제, 피부 진정 및 피부 재생으로 이루어진 군으로부터 선택된 하나 이상인 것일 수 있다.In one embodiment, the skin improvement may be one or more selected from the group consisting of skin barrier improvement, skin damage prevention or improvement, skin moisturizing, skin immunity improvement, skin defense enhancement, skin inflammation inhibition, skin soothing, and skin regeneration. .
상기 3,3',4-tri-O-methylellagic acid 화합물을 식품 첨가물로 사용할 경우, 상기 화합물을 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 유효성분의 혼합양은 사용 목적(예방, 건강 또는 치료적 처치)에 따라 적합하게 결정될 수 있다. 일반적으로, 식품 또는 음료의 제조 시에 본 발명의 화합물은 원료에 대하여 15 중량% 이하, 바람직하게는 10 중량% 이하의 양으로 첨가된다. 그러나, 건강 및 위생을 목적으로 하거나 또는 건강 조절을 목적으로 하는 장기간의 섭취의 경우에는 상기 범위 이하일 수 있으며, 안전성 면에서 아무런 문제가 없기 때문에 유효성분은 상기 범위 이상의 양으로도 사용될 수 있다.When using the 3,3',4-tri-O-methylellagic acid compound as a food additive, the compound can be added as is or used together with other foods or food ingredients, and can be used appropriately according to conventional methods. The mixing amount of the active ingredient can be appropriately determined depending on the purpose of use (prevention, health, or therapeutic treatment). Generally, when manufacturing food or beverages, the compound of the present invention is added in an amount of 15% by weight or less, preferably 10% by weight or less, based on the raw materials. However, in the case of long-term intake for the purpose of health and hygiene or health control, the amount may be below the above range, and since there is no problem in terms of safety, the active ingredient may be used in amounts above the above range.
상기 식품의 종류에는 특별한 제한은 없다. 상기 물질을 첨가할 수 있는 식품의 예로는 산제, 과립제, 정제, 캡슐제, 환제, 겔, 젤리, 현탁액, 에멀젼, 시럽제, 티백제, 침출차, 및 건강 음료로 이루어진 군으로부터 선택되는 제형 등이 있으며 통상적인 의미에서의 건강식품을 모두 포함한다.There are no special restrictions on the types of foods above. Examples of foods to which the above substances can be added include formulations selected from the group consisting of powders, granules, tablets, capsules, pills, gels, jellies, suspensions, emulsions, syrups, tea bags, leached teas, and health drinks. Includes all health foods in the conventional sense.
본 발명의 건강음료 조성물은 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 포함할 수 있다. 상술한 천연 탄수화물은 포도당, 과당과 같은 모노사카라이드, 말토오스, 수크로오스와 같은 디사카라이드, 및 덱스트린, 사이클로덱스트린과 같은 천연 감미제나, 사카린, 아스파르탐과 같은 합성 감미제 등을 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 ml 당 일반적으로 약 0.01 내지 10 g, 바람직하게는 약 0.01 내지 0.1 g 이다.The health drink composition of the present invention may include various flavoring agents or natural carbohydrates as additional ingredients, like conventional drinks. The above-mentioned natural carbohydrates may include monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, natural sweeteners such as dextrin and cyclodextrin, and synthetic sweeteners such as saccharin and aspartame. The proportion of natural carbohydrates is generally about 0.01 to 10 g, preferably about 0.01 to 0.1 g, per 100 ml of the composition of the present invention.
상기 외에 본 발명의 조성물은 여러 가지 영양제, 비타민, 전해질, 풍미제, 착색제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산 음료에 사용되는 탄산화제 등을 포함할 수 있다. 그 밖에 본 발명의 조성물은 천연 과일주스, 과일주스 음료 및 야채 음료의 제조를 위한 과육을 포함할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 크게 중요하진 않지만 본 발명의 조성물 100 중량부 당 0.01 내지 0.1 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above, the composition of the present invention contains various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, It may include carbonating agents used in carbonated drinks. Additionally, the composition of the present invention may include pulp for the production of natural fruit juice, fruit juice beverages, and vegetable beverages. These ingredients can be used independently or in combination. The ratio of these additives is not very important, but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.
또 다른 양상은 하기 화학식 1로 표시되는 3,3',4-tri-O-methylellagic acid 화합물 또는 이의 허용가능한 염을 유효성분으로 포함하는 피부 손상 예방 또는 치료용 약학적 조성물을 제공한다:Another aspect provides a pharmaceutical composition for preventing or treating skin damage, comprising a 3,3',4-tri-O-methylellagic acid compound represented by the following formula (1) or an acceptable salt thereof as an active ingredient:
[화학식 1][Formula 1]
. .
용어 "약학적 조성물"은, 대상체로의 투여 시에 몇몇 유리한 효과를 부여하는 분자 또는 화합물을 지칭할 수 있다. 유리한 효과는 진단적 결정을 가능하게 하는 것; 질병, 증상, 장애 또는 병태의 개선; 질병, 증상, 장애 또는 질환의 발병의 감소 또는 예방; 및 일반적으로 질병, 증상, 장애 또는 병태의 대응을 포함할 수 있다.The term “pharmaceutical composition” may refer to a molecule or compound that imparts some beneficial effect upon administration to a subject. Beneficial effects include enabling diagnostic decisions; Improvement of a disease, symptom, disorder or condition; Reducing or preventing the onset of a disease, symptom, disorder or condition; and generally responding to a disease, symptom, disorder or condition.
용어 "예방(prevention)"은 질환, 장애, 또는 그의 부수적 증상의 발병 또는 재발을 부분적으로 또는 완전히 지연시키거나 방지하거나, 질환 또는 장애의 획득 또는 재획득을 막거나, 질환 또는 장애의 획득의 위험을 감소시키는 방법을 말한다. 예를 들어, 상기 예방은 본 발명에 따른 조성물의 투여로 피부 손상, 또는 증상의 발생을 억제 또는 지연시키는 모든 행위를 말한다.The term “prevention” means to partially or completely delay or prevent the onset or recurrence of a disease, disorder, or its concomitant symptoms, prevent the acquisition or re-acquisition of a disease or disorder, or reduce the risk of acquisition of a disease or disorder. refers to a method of reducing . For example, the above prevention refers to all actions that suppress or delay the occurrence of skin damage or symptoms by administering the composition according to the present invention.
용어 "치료"는 질병의 발전의 억제, 경감 또는 제거를 포함한다.The term “treatment” includes inhibiting, alleviating or eliminating the development of a disease.
용어 "개선"이란 상태의 완화 도는 치료와 관련된 파라미터, 예를 들면 증상의 정도를 적어도 감소시키는 모든 행위를 의미할 수 있다.The term “improvement” can mean any action that results in alleviation of a condition or at least reducing the severity of parameters associated with treatment, such as symptoms.
상기 약학적 조성물은 임상투여시 비경구로 투여가 가능하며 일반적인 의약품 제제의 형태로 사용될 수 있다. 비경구 투여는 직장, 정맥, 복막, 근육, 동맥, 경피, 비강(Nasal), 흡입, 안구 및 피하와 같은 경구 이외의 투여경로를 통한 투여를 의미할 수 있다. 본 발명의 상기 약학적 조성물을 의약품으로 사용하는 경우, 추가로 동일 또는 유사한 기능을 나타내는 유효성분을 1종 이상 함유할 수 있다.The pharmaceutical composition can be administered parenterally during clinical administration and can be used in the form of a general pharmaceutical preparation. Parenteral administration may mean administration through routes of administration other than oral, such as rectal, intravenous, peritoneal, muscular, arterial, transdermal, nasal, inhalation, ocular, and subcutaneous. When the pharmaceutical composition of the present invention is used as a medicine, it may additionally contain one or more active ingredients that exhibit the same or similar functions.
상기 활성 성분을 개체 내로 전달할 수 있는 약학적 활성 성분의 종류는 항암제, 조영제(염료), 호르몬제, 항호르몬제, 비타민제, 칼슘제, 무기질 제제, 당류제, 유기산 제제, 단백질 아미노산 제제, 해독제, 효소 제제, 대사성 제제, 당뇨 병용제, 조직 부활 용약, 클로로필 제제, 색소제제, 종양 용약, 종양 치료제, 방사성 의약품, 조직 세포 진단제, 조직 세포 치료제, 항생 물질 제제, 항바이러스제, 복합항생물질제제, 화학요법제, 백신, 독소, 톡소이드, 항독소, 렙토스피라혈청, 혈액 제제, 생물학적 제제, 진통제, 면역원성 분자, 항히스타민제, 알레르기 용약, 비특이성 면역원 제제, 마취제, 각성제, 정신 신경 용제, 저분자 화합물, 핵산, 앱타머, 안티센스 핵산, 올리고뉴클레오타이드, 펩타이드, siRNA 및 마이크로 RNA 등을 포함할 수 있다. Types of pharmaceutically active ingredients that can deliver the active ingredient into the subject include anticancer agents, contrast agents (dyes), hormones, antihormones, vitamins, calcium agents, mineral agents, saccharides, organic acid agents, protein amino acid agents, detoxifiers, and enzymes. Preparations, metabolic preparations, concomitant drugs for diabetes, tissue revitalization drugs, chlorophyll preparations, dye preparations, tumor preparations, tumor treatment drugs, radiopharmaceuticals, tissue cell diagnostic agents, tissue cell therapeutic agents, antibiotic preparations, antivirals, combination antibiotic preparations, chemistry Therapeutics, vaccines, toxins, toxoids, antitoxins, leptospira serum, blood products, biological agents, analgesics, immunogenic molecules, antihistamines, allergy medications, non-specific immunogenic agents, anesthetics, stimulants, psychotropic agents, small molecule compounds, nucleic acids, It may include aptamers, antisense nucleic acids, oligonucleotides, peptides, siRNA, and micro RNA.
상기 약학적 조성물은, 추가로 약학적으로 허용 가능한 담체를 1종 이상 포함하여 제조할 수 있다. 약학적으로 허용 가능한 담체는 식염수, 멸균수, 링거액, 완충 식염수, 덱스트로오스 용액, 말토덱스트린 용액, 글리세롤, 에탄올 및 이들 성분 중 1 성분 이상을 혼합하여 사용할 수 있으며, 필요에 따라 항산화제, 완충액, 정균제 등 다른 통상의 첨가제를 첨가할 수 있다. 또한, 희석제, 분산제, 계면활성제, 결합제 및 윤활제를 부가적으로 첨가하여 수용액, 현탁액, 유탁액 등과 같은 주사용 제형, 환약, 캡슐, 과립 또는 정제로 제제화할 수 있다. 더 나아가 당 분야의 적정한 방법으로, 각 질환에 따라 또는 성분에 따라 바람직하게 제제화할 수 있다.The pharmaceutical composition may be prepared by additionally containing one or more pharmaceutically acceptable carriers. Pharmaceutically acceptable carriers can be saline solution, sterile water, Ringer's solution, buffered saline solution, dextrose solution, maltodextrin solution, glycerol, ethanol, and a mixture of one or more of these ingredients, and if necessary, antioxidants and buffer solutions. Other common additives such as bacteriostatic agents can be added. In addition, diluents, dispersants, surfactants, binders, and lubricants can be additionally added to formulate injectable formulations such as aqueous solutions, suspensions, emulsions, etc., pills, capsules, granules, or tablets. Furthermore, it can be preferably formulated according to each disease or ingredient using an appropriate method in the art.
상기 약학적 조성물을 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. 비경구투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제제, 좌제가 포함된다. 비수성용제, 현탁용제로는 프로필렌글리콜(Propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(Witepsol), 마크로골, 트윈(Tween) 61, 카카오지, 리우린지, 글리세로제라틴 등이 사용될 수 있다. When formulating the pharmaceutical composition, it is prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants. Preparations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate. As a base for suppositories, Witepsol, Macrogol, Tween 61, cacao, Liurinji, glycerogeratin, etc. can be used.
상기 약학적 조성물은 안정성이나 흡수성을 증가시키기 위하여 글루코스, 수크로스 또는 덱스트란과 같은 탄수화물, 아스코르브산(Ascorbic acid) 또는 글루타치온(Glutathione)과 같은 항산화제(Antioxidants), 킬레이트화제(Chelating agents), 저분자 단백질 또는 다른 안정화제(Stabilizers)들이 약제로 사용될 수 있다.The pharmaceutical composition contains carbohydrates such as glucose, sucrose or dextran, antioxidants such as ascorbic acid or glutathione, chelating agents, and small molecules to increase stability or absorption. Proteins or other stabilizers can be used as agents.
또 다른 양상은 상기 약학적 조성물을 개체에 투여하는 단계를 포함하는 피부 손상을 치료하는 방법을 제공한다.Another aspect provides a method of treating skin damage comprising administering the pharmaceutical composition to a subject.
용어 "투여"는 임의의 적절한 방법으로 개체에게 약학적 조성물을 제공하는 것을 의미한다.The term “administration” means providing a pharmaceutical composition to a subject by any suitable method.
상기 약학적 조성물의 약학적 유효량, 유효 투여량은 약학적 조성물의 제제화 방법, 투여 방식, 투여시간 및/또는 투여 경로 등에 의해 다양할 수 있다. 또한, 상기 약학 조성물의 투여로 달성하고자 하는 반응의 종류와 정도, 투여 대상이 되는 개체의 종류, 연령, 체중, 일반적인 건강 상태, 질병의 증세나 정도, 성별, 식이, 배설, 해당 개체에 동시 또는 이시에 함께 사용되는 약물 기타 조성물의 성분 등을 비롯한 여러 인자 및 의약 분야에서 잘 알려진 유사 인자에 따라 다양해질 수 있다. 당해 기술 분야에서 통상의 지식을 가진 자는 목적하는 치료에 효과적인 투여량을 용이하게 결정하고 처방할 수 있다. 본 발명에 따른 약학 조성물의 투여는 하루에 1회 투여될 수 있고, 수회에 나누어 투여될 수 있다. 따라서 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다. 약학적 조성물의 투여량은 1일 1 ug/kg/일 내지 1,OOO mg/kg/일일 수 있다. The pharmaceutically effective amount and effective dosage of the pharmaceutical composition may vary depending on the formulation method, administration method, administration time, and/or administration route of the pharmaceutical composition. In addition, the type and degree of response to be achieved by administration of the pharmaceutical composition, the type of subject to be administered, age, weight, general health condition, symptoms or degree of disease, gender, diet, excretion, simultaneous or It may vary depending on various factors including drugs used together and components of other compositions, and similar factors well known in the pharmaceutical field. A person skilled in the art can easily determine and prescribe an effective dosage for the desired treatment. The pharmaceutical composition according to the present invention can be administered once a day or divided into several times. Therefore, the above dosage does not limit the scope of the present invention in any way. The dosage of the pharmaceutical composition may be 1 ug/kg/day to 1,OOO mg/kg/day.
상기 개체는 포유동물, 예를 들면, 사람, 소, 말, 돼지, 개, 양, 염소, 또는 고양이일 수 있다. 상기 개체는 아토피 피부염의 치유를 필요로 하는 개체일 수 있다.The subject may be a mammal, such as a human, cow, horse, pig, dog, sheep, goat, or cat. The subject may be an individual in need of treatment for atopic dermatitis.
또 다른 양상은 하기 화학식 1로 표시되는 3,3',4-tri-O-methylellagic acid 화합물 또는 이의 허용가능한 염을 유효성분으로 포함하는 피부 손상 예방 또는 개선용 피부 외용제를 제공한다:Another aspect provides an external skin preparation for preventing or improving skin damage, comprising a 3,3',4-tri-O-methylellagic acid compound represented by the following formula (1) or an acceptable salt thereof as an active ingredient:
[화학식 1][Formula 1]
. .
상기 피부외용제는 크림, 겔, 연고, 피부 유화제, 피부 현탁액, 경피전달성 패치, 약물 함유 붕대, 로션, 또는 그 조합일 수 있다. 상기 피부외용제는 통상 화장품이나 의약품 등의 피부외용제에 사용되는 성분, 예를 들면 수성성분, 유성성분, 분말성분, 알코올류, 보습제, 증점제, 자외선흡수제, 미백제, 방부제, 산화방지제, 계면활성제, 향료, 색제, 각종 피부 영양제, 또는 이들의 조합과 필요에 따라서 적절하게 배합될 수 있다. 상기 피부외용제는, 에데트산이나트륨, 에데트산삼나트륨, 시트르산나트륨, 폴리인산나트륨, 메타인산나트륨, 글루콘산 등의 금속봉쇄제, 카페인, 탄닌, 벨라파밀, 감초추출물, 글라블리딘, 칼린의 과실의 열수추출물, 각종생약, 아세트산토코페롤, 글리틸리틴산, 트라넥삼산 및 그 유도체 또는 그 염등의 약제, 비타민 C, 아스코르브산인산마그네슘, 아스코르브산글루코시드, 알부틴, 코지산, 글루코스, 프룩토스, 트레할로스 등의 당류등도 적절하게 배합할 수 있다.The external skin preparation may be a cream, gel, ointment, skin emulsifier, skin suspension, transdermal delivery patch, drug-containing bandage, lotion, or a combination thereof. The skin external preparations include ingredients commonly used in skin external preparations such as cosmetics and medicines, such as aqueous ingredients, oil-based ingredients, powder ingredients, alcohols, moisturizers, thickeners, ultraviolet absorbers, whitening agents, preservatives, antioxidants, surfactants, and fragrances. , colorants, various skin nutrients, or a combination thereof may be appropriately mixed according to need. The skin external preparations include metal sequestrants such as disodium edetate, trisodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, and gluconic acid, caffeine, tannin, belafamil, licorice extract, glablidin, and calin. Hot water extract of fruit, various herbal medicines, drugs such as tocopherol acetate, glytylitinic acid, tranexamic acid and its derivatives or salts, vitamin C, magnesium ascorbate phosphate, ascorbate glucoside, arbutin, kojic acid, glucose, fructose, Sugars such as trehalose can also be appropriately mixed.
상기 피부는 얼굴, 손, 팔, 다리, 발, 가슴, 배, 등, 엉덩이, 및 두피를 포함하는 신체의 모든 피부 부위를 포함한다.The skin includes all skin areas of the body, including the face, hands, arms, legs, feet, chest, stomach, back, buttocks, and scalp.
상기 발명에 대해 기술한 용어, 방법 및 효과 등은 각 발명들 간에 동일하게 적용된다. The terms, methods, effects, etc. described for the above inventions apply equally to each invention.
일 양상에 따른 3,3',4-tri-O-methylellagic acid 화합물을 유효성분으로 포함하는 조성물은 콜라겐 합성을 촉진하고 콜라겐 분해를 억제하며 염증인자 발현을 감소시키고 피부장벽 관련 인자의 발현을 증가시켜 피부 개선에 효과적으로 사용될 수 있다. According to one aspect, a composition containing a 3,3',4-tri-O-methylellagic acid compound as an active ingredient promotes collagen synthesis, inhibits collagen decomposition, reduces the expression of inflammatory factors, and increases the expression of skin barrier-related factors. It can be effectively used to improve skin.
도 1은 3,3',4-tri-O-methylellagic acid 의 1H-NMR(DMSO-d6, D2O) 스펙트럼이다.
도 2는 3,3',4-tri-O-methylellagic acid 의 13C-NMR(DMSO-d6, D2O) 스펙트럼이다.
도 3은 딱지꽃 추출물 및 3,3',4-tri-O-methylellagic acid의 HPLC 스펙트럼이다.
도 4는 진피세포에서 딱지꽃 추출물 및 3,3',4-tri-O-methylellagic acid의 세포독성을 평가한 그래프이다.
도 5는 자외선으로 손상이 야기된 진피세포에서 딱지꽃 추출물 및 3,3',4-tri-O-methylellagic acid의 MMP-1 억제효능을 비교한 그래프이다.
도 6은 자외선으로 손상이 야기된 진피세포에서 딱지꽃 추출물 및 3,3',4-tri-O-methylellagic acid의 프로콜라겐 생성량을 비교한 그래프이다.
도 7은 표피세포에서 딱지꽃 추출물 및 3,3',4-tri-O-methylellagic acid의 세포독성을 비교한 그래프이다.
도 8은 자외선으로 손상이 야기된 표피세포에서 딱지꽃 추출물 및 3,3',4-tri-O-methylellagic acid의 필라그린 발현양 증가를 나타내는 그래프이다.
도 9는 자외선으로 손상이 야기된 표피세포에서 딱지꽃 추출물 및 3,3',4-tri-O-methylellagic acid의 인볼루크린 발현양 증가를 나타내는 그래프이다.
도 10은 자외선으로 손상이 야기된 표피세포에서 딱지꽃 추출물 및 3,3',4-tri-O-methylellagic acid의 로리크린 발현양 증가를 나타내는 그래프이다.
도 11은 자외선으로 손상이 야기된 표피세포에서 딱지꽃 추출물 및 3,3',4-tri-O-methylellagic acid의 CASP14 발현양 증가를 나타내는 그래프이다.
도 12는 미세먼지로 염증반응이 유발된 표피세포에서 딱지꽃 추출물 및 3,3',4-tri-O-methylellagic acid의 IL-1β 발현양 감소를 나타내는 그래프이다.
도 13은 미세먼지로 염증반응이 유발된 표피세포에서 딱지꽃 추출물 및 3,3',4-tri-O-methylellagic acid의 IL-8 발현양 감소를 나타내는 그래프이다.
도 14는 미세먼지로 염증반응이 유발된 표피세포에서 딱지꽃 추출물 및 3,3',4-tri-O-methylellagic acid의 TNF-α 발현양 감소를 나타내는 그래프이다.Figure 1 is a 1 H-NMR (DMSO-d6, D 2 O) spectrum of 3,3',4-tri-O-methylellagic acid.
Figure 2 is a 13 C-NMR (DMSO-d6, D 2 O) spectrum of 3,3',4-tri-O-methylellagic acid.
Figure 3 is the HPLC spectrum of scab extract and 3,3',4-tri-O-methylellagic acid.
Figure 4 is a graph evaluating the cytotoxicity of scab extract and 3,3',4-tri-O-methylellagic acid in dermal cells.
Figure 5 is a graph comparing the MMP-1 inhibitory effects of scab extract and 3,3',4-tri-O-methylellagic acid in dermal cells damaged by ultraviolet rays.
Figure 6 is a graph comparing the amount of procollagen produced by scab extract and 3,3',4-tri-O-methylellagic acid in dermal cells damaged by ultraviolet rays.
Figure 7 is a graph comparing the cytotoxicity of scab extract and 3,3',4-tri-O-methylellagic acid in epidermal cells.
Figure 8 is a graph showing the increase in the expression level of filaggrin in epidermal cells damaged by ultraviolet rays from scab extract and 3,3',4-tri-O-methylellagic acid.
Figure 9 is a graph showing the increase in the expression level of involucrin in epidermal cells damaged by ultraviolet rays from scab extract and 3,3',4-tri-O-methylellagic acid.
Figure 10 is a graph showing the increase in loricrin expression of scab extract and 3,3',4-tri-O-methylellagic acid in epidermal cells damaged by ultraviolet rays.
Figure 11 is a graph showing the increase in the expression level of CASP14 in epidermal cells damaged by ultraviolet rays due to scab extract and 3,3',4-tri-O-methylellagic acid.
Figure 12 is a graph showing the decrease in IL-1β expression of scab extract and 3,3',4-tri-O-methylellagic acid in epidermal cells in which an inflammatory response was induced by fine dust.
Figure 13 is a graph showing the decrease in IL-8 expression of scab extract and 3,3',4-tri-O-methylellagic acid in epidermal cells in which an inflammatory response was induced by fine dust.
Figure 14 is a graph showing the decrease in TNF-α expression of scab extract and 3,3',4-tri-O-methylellagic acid in epidermal cells in which an inflammatory response was induced by fine dust.
이하 실시예를 통하여 보다 상세하게 설명한다. 그러나, 이들 실시예는 하나 이상의 구체예를 예시적으로 설명하기 위한 것으로 본 발명의 범위가 이들 실시예에 한정되는 것은 아니다.This will be described in more detail through examples below. However, these examples are intended to illustrate one or more embodiments and the scope of the present invention is not limited to these examples.
실시예 1: 딱지꽃 (Example 1: Scab Flower ( Potentilla chinesisPotentilla chinesis ) 추출물의 제조) Preparation of extract
본 발명의 조성물에 함유되는 딱지꽃 추출물은 다음과 같은 과정에 의해 제조된다. 우선, 국내에서 자생하는 딱지꽃을 구입하여 증류수로 깨끗이 씻은 후, 햇빛이 없는 서늘한 곳에서 중량의 변화가 없을 때까지 완전히 건조시켰다. 그 후, 완전히 건조된 건조물에 30 % 발효주정(30배, w/w) 900 kg을 준비한 후, 상기 건조물을 30 kg 첨가하였다. 이때, 건조물과 30 % 발효주정의 혼합비율은, 중량비로 30 배수로 하였다. 다음으로, 상기 건조물과 혼합한 30 % 발효주정을 항온 수조에 넣어서 60 ℃, 5시간 동안 교반추출 하였다. 추출된 시료는 하우징필터 (10 ㎛)로 여과 후 감압 농축을 통하여 황갈색의 수용성 분말을 수득하였다.The scab extract contained in the composition of the present invention is prepared by the following process. First, we purchased scab flowers that grow naturally in Korea, washed them thoroughly with distilled water, and dried them completely in a cool place without sunlight until there was no change in weight. After that, 900 kg of 30% fermented alcohol (30 times, w/w) was prepared in the completely dried dried material, and then 30 kg of the dried material was added. At this time, the mixing ratio of the dried material and 30% fermented alcohol was set to 30 times the weight ratio. Next, 30% fermented alcohol mixed with the dried material was placed in a constant temperature water bath and stirred and extracted at 60°C for 5 hours. The extracted sample was filtered through a housing filter (10 ㎛) and then concentrated under reduced pressure to obtain a yellow-brown water-soluble powder.
실시예 2: 3,3',4-tri-O-methylellagic acid의 제조Example 2: Preparation of 3,3',4-tri-O-methylellagic acid
실시예 1로 얻어진 추출 분말에 3배수의 증류수를 첨가한 후, Silica gel 60을 이용하여 코팅을 진행하였다. 상기 코팅물에 각각 헥세인, 디클로로메테인, 메탄올을 이용해 추출물을 제조하였다. 그중 디클로로메테인 추출물에 Sephadex LH-20 레진을 사용해 gel filteration을 실시하였다. 전개용매는 [디클로로메테인:메탄올 = 1:1]혼합용액을 사용하여 용매분획 하였으며 7개의 소분획(Fr.1~7)으로 나누었다. 이중 소분획 3을 Sephadex LH-20 레진을 사용해 gel filteration을 실시하였다. 전개용매는 [헥세인:디클로로메테인 = 1:1 ~ 디클로로메테인:아세톤 = 1:1 ]혼합용액을 사용하여 용매분획 하여 총 3개의 소분획(Fr.3-1~3)으로 나누었다. 그중 소분획 3-1을 Silica gel 레진을 사용해 gel filteration을 실시하였다. 전개용매는 [클로로포름:에틸아세테이트 = 3:97 ~ 0:100 ]혼합용액을 사용하여 용매분획 하여 총 10개의 소분획(Fr.3-1-1~10)으로 나누었다. 그중 소분획 3-1-7에서 3,3',4-tri-O-methylellagic acid (화합물 1) 단일물질을 순수하게 수득하였다.After adding three times the amount of distilled water to the extracted powder obtained in Example 1, coating was performed using Silica gel 60. Extracts were prepared from the coating using hexane, dichloromethane, and methanol, respectively. Among them, gel filtration was performed on the dichloromethane extract using Sephadex LH-20 resin. The developing solvent was solvent fractionated using a mixed solution of [dichloromethane:methanol = 1:1] and divided into 7 small fractions (Fr. 1 to 7). Among these, subfraction 3 was subjected to gel filtration using Sephadex LH-20 resin. The developing solvent was a mixed solution of [hexane:dichloromethane = 1:1 ~ dichloromethane:acetone = 1:1] and was divided into a total of 3 small fractions (Fr.3-1~3) through solvent fractionation. Among them, subfraction 3-1 was subjected to gel filtration using silica gel resin. The developing solvent was a mixed solution of [chloroform:ethyl acetate = 3:97 to 0:100], which was subjected to solvent fractionation and divided into a total of 10 subfractions (Fr.3-1-1 to 10). Among them, a single substance, 3,3',4-tri-O-methylellagic acid (Compound 1), was obtained pure from subfraction 3-1-7.
상기 화합물 1의 구조를 확인하기 위하여, 먼저 1H-NMR을 확인하였다. 도 1에 나타낸 바와 같이 δH 7.57에서 C-5에 기인하는 하나의 수소를 확인할 수 있었으며, δH 7.48에서 C-5'에 기인하는 singlet의 수소 하나를 확인하였다. δH 4.01 에서는 C3-OCH3에 해당하는 3개의 수소가 singlet으로 확인되었으며, δH 4.00 에서는 C3'-OCH3에 해당하는 3개의 수소, δH 3.96 에서는 C4'-OCH3에 해당하는 3개의 수소가 각각 singlet peak을 보이는 것을 알 수 있었다.To confirm the structure of Compound 1, 1 H-NMR was first performed. As shown in Figure 1, one hydrogen originating from C-5 was confirmed at δH 7.57, and one singlet hydrogen originating from C-5' was confirmed at δH 7.48. At δH 4.01, three hydrogens corresponding to C3-OCH 3 were confirmed as singlet, at δH 4.00, three hydrogens corresponding to C3'-OCH 3 , and at δH 3.96, three hydrogens corresponding to C4'-OCH 3 , respectively. It was found that a singlet peak was observed.
13C-NMR을 확인한 결과, 도 2에 나타낸 바와 같이 δC 57.24, δC 61.50, δC 61.83 에서 methoxy group에서 기인한 3개의 탄소로 각각 C4'-OCH3, C3-OCH3, C3'-OCH3 에 해당하는 것을 알수 있었다. δC 107.96 - δC 159.07에서 총 14개의 탄소를 확인할 수 있었으며, carbonyl group에서 기인한 피크 및 benzene group에 기인하는 탄소임을 확인할 수 있었다. 13 As a result of C-NMR, as shown in Figure 2, three carbons originating from the methoxy group at δC 57.24, δC 61.50, and δC 61.83 were C4'-OCH 3 , C3-OCH 3 , and C3'-OCH 3 , respectively. I was able to find out what was applicable. A total of 14 carbons were identified at δC 107.96 - δC 159.07, and it was confirmed that the peak originated from the carbonyl group and the carbon originated from the benzene group.
이상의 결과를 종합하여 문헌과 비교하여 볼 때, 화합물 1이 3,3',4-tri-O-methylellagic acid 라는 것을 확인 하였다 (Molecules 2012, 17, 13917-13922).By combining the above results and comparing them with the literature, it was confirmed that compound 1 was 3,3',4-tri-O-methylellagic acid ( Molecules 2012 , 17 , 13917-13922).
실험예 1: 딱지꽃 추출물의 3,3',4-tri-O-methylellagic acid 함량분석Experimental Example 1: Analysis of 3,3',4-tri-O-methylellagic acid content of scab flower extract
본 발명의 실시예 1 로 얻어진 추출 분말과 3,3',4-Tri-O-methylellagic acid는 고속액체크로마토그래피(HPLC)와 자외부흡광도검출기 (UV/Vis detector)로 분석을 실시하였다. HPLC 기기는 Waters e2695 Series system, Waters 24489 UV/Vis detector(Worcester, MA, USA), X select C18(5 ㎛, 250 Х 4.6 ㎜, waters, Milford, Massachusetts, USA) 컬럼을 사용하였으며 분석에 사용된 모든 용매는 J.T. Baker(Phillipsburg, NJ, USA)로부터 구입한 HPLC급 용매를 사용하였다. 분석 시 컬럼의 온도는 35 ℃, 주입 용량은 10 ㎕, 측정 파장은 360 ㎚로 설정하였다. 이동상은 아세토니트릴(ACN)과 3차 증류수(D.W)를 사용하였으며, 0.7 ㎖/분 의 속도로 ACN -D.W (1:9 - 10:0, v/v) 혼합 용액을 50분간 분석하였다. 분석 시료는 실시예 1로 얻어진 추출 분말 100 ㎎을 정밀히 칭량하여 메탄올 10 ㎖을 가한 후 20분간 초음파 진탕기에 넣어 용해하여 실온에서 방냉 후 상등액을 취해 0.45 ㎛ 멤브레인 필터로 여과하여 사용하였으며, 3,3', 4-Tri-O-methylellagic acid는 1 mg을 정밀히 칭량하여 메탄올 2 ㎖을 가한 후 20분간 초음파 진탕기에 넣어 용해하여 실온에서 방냉 후 메탄올을 가하여 0.45 ㎛ 멤브레인 필터로 여과하여 사용하였다. 각각의 분석시료는 360 ㎚에서 크로마토그램을 추출하여 딱지꽃 추출물 피크와 3,3', 4-Tri-O-methylellagic acid 피크를 비교 분석하여 도 3에 나타내었다.The extracted powder and 3,3',4-Tri-O-methylellagic acid obtained in Example 1 of the present invention were analyzed using high performance liquid chromatography (HPLC) and ultraviolet absorbance detector (UV/Vis detector). The HPLC equipment used was Waters e2695 Series system, Waters 24489 UV/Vis detector (Worcester, MA, USA), and X select C18 (5 ㎛, 250 Х 4.6 ㎜, waters, Milford, Massachusetts, USA) column. All solvents were purchased from J.T. HPLC grade solvent purchased from Baker (Phillipsburg, NJ, USA) was used. During analysis, the column temperature was set to 35°C, the injection volume was set to 10 μl, and the measurement wavelength was set to 360 nm. Acetonitrile (ACN) and tertiary distilled water (D.W) were used as mobile phases, and the ACN -D.W (1:9 - 10:0, v/v) mixed solution was analyzed for 50 minutes at a rate of 0.7 ml/min. For the analysis sample, 100 mg of the extract powder obtained in Example 1 was precisely weighed, 10 ml of methanol was added, and then dissolved in an ultrasonic shaker for 20 minutes. After cooling at room temperature, the supernatant was taken and filtered through a 0.45 ㎛ membrane filter for use. 3,3 ', 1 mg of 4-Tri-O-methylellagic acid was precisely weighed, added with 2 ml of methanol, dissolved in an ultrasonic shaker for 20 minutes, cooled at room temperature, added with methanol, and filtered through a 0.45 ㎛ membrane filter. For each analyzed sample, a chromatogram was extracted at 360 nm, and the peak of the scab extract and the 3,3', 4-Tri-O-methylellagic acid peak were compared and analyzed, and the results are shown in Figure 3.
실험예 2: 세포독성 평가Experimental Example 2: Cytotoxicity evaluation
상기 실시예 1 및 실시예 2에서 얻은 시료에 대하여 자외선에 노출시킨 진피세포 또는 표피세포의 손상을 복구할 수 있는지 측정하였다. 자외선에 의한 피부세포 손상 예방 또는 개선의 효능이 있는지 확인하기 위해, 1.0 X 104 cells/well의 농도로 진피세포(Hs68)를 96-웰 플레이트 상에 24 시간동안 부착시켜 안정화시켰다. 자외선을 조사하기 위해, 기존 배지를 제거하고, PBS 세척을 한 후 25 mJ/㎝2으로 UVB를 처리하였다. 이후 시료를 처리한 배지를 이용해 24시간 배양 후, MTT assay를 통해 세포 생존 정도를 측정하였다. MTT assay는 살아있는 세포의 미토콘드리아에 의해 환원된 MTT로부터 형성된 포마잔의 양을 측정하는 방법이다. 더 자세하게는, 5 ㎎/㎖ MTT 용액을 50 ㎕씩 각각의 세포에 처리하고 4시간동안 배양한 후, 용액을 완전히 제거하고 DMSO로 용해시킨 플레이트를 540㎚의 흡광도에서 측정하였다.The samples obtained in Examples 1 and 2 were tested to determine whether damage to dermal cells or epidermal cells exposed to ultraviolet rays could be repaired. To determine whether it is effective in preventing or improving skin cell damage caused by ultraviolet rays, dermal cells (Hs68) were stabilized by attaching them to a 96-well plate for 24 hours at a concentration of 1.0 To irradiate ultraviolet light, the existing medium was removed, washed with PBS, and treated with UVB at 25 mJ/cm 2 . After culturing for 24 hours using the medium treated with the sample, the degree of cell survival was measured through MTT assay. The MTT assay is a method to measure the amount of formazan formed from MTT reduced by the mitochondria of living cells. More specifically, 50 ㎕ of 5 mg/mL MTT solution was applied to each cell and cultured for 4 hours. Then, the solution was completely removed and the absorbance of the plate dissolved in DMSO was measured at 540 nm.
표피세포에 대한 세포독성을 확인하기 위하여 1.0 X 104 cells/well의 농도로 표피세포(HaCaT)를 96-웰 플레이트 상에 24시간동안 부착시켜 안정화시켰다. 이후 각 농도 시료를 처리한 배지로 교환하여 24 시간동안 배양하였다. 이후 MTT assay를 통해 세포 생존 정도를 측정하였다.To confirm cytotoxicity against epidermal cells , epidermal cells (HaCaT) were stabilized by attaching them to a 96-well plate for 24 hours at a concentration of 1.0 Afterwards, the samples of each concentration were replaced with the treated medium and cultured for 24 hours. Afterwards, the degree of cell survival was measured through MTT assay.
도 4 및 도 7에 도시된 것과 같이, 진피세포 또는 표피세포에서 실시예 1 및 실시예 2의 모든 시료가 세포독성을 나타내지 않았으며, 세포독성 시험에 근거하여 딱지꽃추출물 및 3,3', 4-Tri-O-methylellagic acid의 이후 실험예의 처리농도를 결정하였다.As shown in Figures 4 and 7, all samples of Examples 1 and 2 did not show cytotoxicity in dermal cells or epidermal cells, and based on the cytotoxicity test, the scab extract and 3,3', The treatment concentration of 4-Tri-O-methylellagic acid in the subsequent experimental example was determined.
실험예 3: MMP-1의 함량 변화 평가Experimental Example 3: Evaluation of changes in content of MMP-1
상기 실시예 1 또는 실시예 2에서 얻은 시료에 대하여 진피세포 Hs68 fibroblast에서 MMP-1의 분비를 억제시킬 수 있는지 측정하였다. 물질처리에 따라 MMP-1이 감소할 수 있는지 확인하기 위해, 1.0 X 105 cells/well의 농도로 각각의 세포들을 24-웰 플레이트 상에 분주하고 24시간동안 안정화시켰다. 자외선(UVB)을 조사하기 위해, 기존 배지를 제거하고, PBS 세척을 한 후 25 mJ/㎝2으로 UVB를 처리하였다. 이후 시료를 처리한 배지를 이용해 24시간 배양 후 상층액에서 MMP-1 Human ELISA Kit(ab100603, Abcam, US)를 사용하여 MMP-1의 분비 정도를 측정하였다. The samples obtained in Example 1 or Example 2 were tested to determine whether MMP-1 secretion could be inhibited from Hs68 fibroblast dermal cells. To confirm whether MMP-1 can be reduced according to material treatment, each cell was distributed on a 24-well plate at a concentration of 1.0 × 10 5 cells/well and stabilized for 24 hours. To irradiate ultraviolet rays (UVB), the existing medium was removed, washed with PBS, and treated with UVB at 25 mJ/cm 2 . After culturing the sample for 24 hours using the treated medium, the secretion level of MMP-1 was measured in the supernatant using the MMP-1 Human ELISA Kit (ab100603, Abcam, US).
도 5에 도시된 것과 같이 25 mJ/㎝2의 UVB로부터 손상이 야기된 진피세포에서 MMP-1의 농도가 증가되었고, 실시예 1 및 실시예 2의 시료가 MMP-1 생성을 농도 의존적으로 감소시켰다. 또한, 실시예 1 및 실시예 2의 시료의 MMP-1 생성 억제에 대한 효과가 유의적으로 나타난 것으로 보아, 실시예2가 자외선으로 인한 피부 손상 개선에 효과적이라는 것을 확인하였다.As shown in Figure 5, the concentration of MMP-1 increased in dermal cells damaged by UVB of 25 mJ/cm 2 , and the samples of Examples 1 and 2 decreased MMP-1 production in a concentration-dependent manner. I ordered it. In addition, the samples of Examples 1 and 2 showed a significant effect on inhibiting MMP-1 production, confirming that Example 2 was effective in improving skin damage caused by ultraviolet rays.
실험예 4: 프로콜라겐 타입 1의 함량 변화 평가Experimental Example 4: Evaluation of change in content of procollagen type 1
상기 실시예 1 또는 실시예 2에서 얻은 시료에 대하여 진피세포 Hs68 fibroblast에서 프로콜라겐 타입1을 증가시킬 수 있는지 측정하였다. 물질처리에 따라 프로콜라겐 타입1의 분비양이 증가할 수 있는지 확인하기 위해, 1.0 X 105 cells/well의 농도로 각각의 세포들을 24-웰 플레이트 상에 분주하고 24시간동안 안정화시켰다. UVB를 조사하기 위해, 기존 배지를 제거하고, PBS 세척을 한 후 25 mJ/㎝2으로 UVB를 처리하였다. 이후 시료를 처리한 배지를 이용해 24시간 배양 후 상층액에서 Procollagen Type I C-peptide(PIP) EIA kit(Mk101, Takara, japan)를 사용하여 프로콜라겐타입1의 분비 정도를 측정하였다. For the samples obtained in Example 1 or Example 2, it was measured whether procollagen type 1 could be increased in dermal cells Hs68 fibroblasts. To determine whether the secretion amount of procollagen type 1 could increase according to material treatment, each cell was distributed on a 24-well plate at a concentration of 1.0 × 10 5 cells/well and stabilized for 24 hours. To irradiate UVB, the existing medium was removed, washed with PBS, and treated with UVB at 25 mJ/cm 2 . After culturing the sample for 24 hours using the treated medium, the secretion level of procollagen type 1 was measured in the supernatant using the Procollagen Type I C-peptide (PIP) EIA kit (Mk101, Takara, Japan).
도 6에 도시된 것과 같이, 25 mJ/㎝2 UVB로부터 손상이 야기된 진피세포에서 실시예 1 및 실시예 2의 시료가 프로콜라겐 생성량을 증가시켰다. 또한, 실시예 1 및 실시예 2의 시료가 프로콜라겐 생성량을 유의적으로 농도에 따라 증가시킨 것으로 보아, 이로써, 실시예 2가 자외선으로부터 분해된 콜라겐 섬유들의 재생을 도와 자외선에 의한 피부 손상을 예방 또는 개선한다는 것을 확인하였다.As shown in Figure 6, the samples of Examples 1 and 2 increased the amount of procollagen production in dermal cells damaged by 25 mJ/cm 2 UVB. In addition, it appears that the samples of Examples 1 and 2 significantly increased the amount of procollagen production depending on the concentration, and thus, Example 2 prevents skin damage caused by ultraviolet rays by helping to regenerate collagen fibers decomposed from ultraviolet rays. Or it was confirmed that it was improving.
실험예 5: 피부장벽 관련 유전자 발현양 변화 평가Experimental Example 5: Evaluation of changes in skin barrier-related gene expression level
상기 실시예 1 또는 실시예 2에서 얻은 시료에 대하여 피부보습 효과를 확인하기 위하여 표피세포 HaCaT keratinocyte에 각 시료를 농도별로 처리하여 피부장벽 관련 유전자인 필라그린 및 인볼루크린, 로리크린, CASP 14의 발현양 변화를 확인하였다.In order to confirm the skin moisturizing effect of the samples obtained in Example 1 or Example 2, the epidermal cells HaCaT keratinocytes were treated with each sample at different concentrations to determine the skin barrier-related genes filaggrin, involucrin, loricrin, and CASP 14. Changes in expression level were confirmed.
구체적으로 HaCaT세포 1x106 cells을 6-웰 플레이트에 10 % FBS가 첨가된 DMEM배지 (Hyclone SH30243.01)로 분주하여 24시간동안 안정화시켰다. UVB를 조사하기 위해, 기존 배지를 제거하고, PBS 세척을 한 후 18 mJ/㎝2으로 UVB를 처리하였다. 이후 시료를 처리한 배지를 이용해 24시간 배양 후 기존 배지를 제거하고 혈청기아 상태로 24 시간동안 배양한 후 트립신(Trypsin)-EDTA로 처리하여 세포 펠렛(pellet)을 회수하였다. 그 후 얻어진 세포로부터 Trizol 시약을 이용하여 RNA를 추출하고, cDNA synthesis kit(Bio-Rad)를 사용하여 얻어진 RNA로부터 cDNA를 합성하여 이를 주형으로 하여 정량적 실시간-PCR (quantitative real time-PCR, qRT-PCR)을 실시하였다(LightCycler 96, Roche, Switzerland). RT-PCR 반응은 95 ℃ 600초 pre-incubation 후 95 ℃ 10초, 60 ℃ 10초, 72 ℃ 10초로 반복되는 40 사이클의 조건으로 수행하였다. 유전자의 발현양은 β-actin 유전자에 대한 보정을 통해 최종적으로 분석하였다.Specifically, 1x10 6 HaCaT cells were distributed in 6-well plates with DMEM medium (Hyclone SH30243.01) supplemented with 10% FBS and stabilized for 24 hours. To irradiate UVB, the existing medium was removed, washed with PBS, and treated with UVB at 18 mJ/cm 2 . After cultivating the sample for 24 hours using the treated medium, the existing medium was removed, cultured for 24 hours in serum starvation, and then treated with Trypsin-EDTA to recover the cell pellet. Afterwards, RNA was extracted from the obtained cells using Trizol reagent, and cDNA was synthesized from the obtained RNA using a cDNA synthesis kit (Bio-Rad), using this as a template for quantitative real-time-PCR (qRT- PCR) was performed (LightCycler 96, Roche, Switzerland). The RT-PCR reaction was performed under the conditions of 40 cycles of pre-incubation at 95°C for 600 seconds, followed by 95°C for 10 seconds, 60°C for 10 seconds, and 72°C for 10 seconds. The expression level of the gene was finally analyzed through correction for the β-actin gene.
qRT-PCR은 상기 표1에 나타낸 올리고머를 프라이머로 사용하여 수행하였다. 상기 프라이머 세트는 필라그린 및 인볼루크린, 로리크린, CASP 14 유전자에 특이적인 것으로서, 이들은 피부장벽 관련 유전자이다. 도 8에 도시된 것과 같이 자외선을 처리하였을 때 손상된 표피세포에서는 피부장벽 관련 유전자인 필라그린 및 인볼루크린, 로리크린, CASP 14의 발현양이 감소하였다. 그러나, 실시예 1 및 실시예 2의 시료가 피부장벽 관련 유전자를 모두 유의적으로 증가시키는 것으로 보아, 이로써, 실시예 2가 자외선으로부터 감소된 피부장벽 유전자의 발현을 증가시켜 자외선에 의한 피부 손상을 예방 또는 개선한다는 것을 확인하였다.qRT-PCR was performed using the oligomers shown in Table 1 above as primers. The primer set is specific for filaggrin, involucrin, loricrin, and CASP 14 genes, which are skin barrier-related genes. As shown in Figure 8, when treated with ultraviolet rays, the expression level of skin barrier-related genes filaggrin, involucrin, loricrin, and CASP 14 decreased in damaged epidermal cells. However, it was seen that the samples of Examples 1 and 2 significantly increased all skin barrier-related genes, and thus, Example 2 increased the expression of skin barrier genes reduced from ultraviolet rays, thereby preventing skin damage caused by ultraviolet rays. It was confirmed that it prevents or improves.
실험예 6: 미세먼지 관련 사이토카인 함량 변화 평가Experimental Example 6: Evaluation of changes in fine dust-related cytokine content
상기 실시예 1 또는 실시예 2에서 얻은 시료에 대하여 미세먼지에 대한 항염증 효과를 평가하기 위해 염증 유발 사이토카인인 IL-1β, IL-8 및 TNF-α에 대해 미세먼지(PM10)를 처치하여 그 발현량을 측정하였다. 구체적으로 HaCaT세포 1x106 cells을 6-웰 플레이트에 10 % FBS가 첨가된 DMEM배지 (Hyclone SH30243.01)로 분주하여 24시간동안 안정화시켰다. 미세먼지를 처리하기 위해, 기존 배지를 제거하고, PBS 세척을 한 후 100㎍/㎖의 미세먼지를 처리하였다. 이후 시료를 처리한 배지를 이용해 4시간동안 배양한 다음 세포 내에서 mRNA를 추출하여 cDNA로 합성하고, 타겟 주형(primer)을 사용하여 정량적 실시간-PCR을 실시하여 최종적으로 염증 사이토카인의 유전자 발현 정도를 평가하었다. In order to evaluate the anti-inflammatory effect of fine dust on the samples obtained in Example 1 or Example 2, fine dust (PM10) was applied to the inflammatory cytokines IL-1β, IL-8, and TNF-α. The expression level was measured. Specifically, 1x10 6 HaCaT cells were distributed in a 6-well plate with DMEM medium (Hyclone SH30243.01) supplemented with 10% FBS and stabilized for 24 hours. To treat fine dust, the existing medium was removed, washed with PBS, and then treated with 100 μg/ml of fine dust. Afterwards, the sample was cultured for 4 hours using the treated medium, then the mRNA was extracted from the cells, synthesized into cDNA, and quantitative real-time-PCR was performed using a target template (primer) to finally determine the gene expression level of inflammatory cytokines. was evaluated.
qRT-PCR은 상기 표2에 나타낸 올리고머를 프라이머로 사용하여 수행하였다. 상기 프라이머 세트는 IL-1β, IL-8 및 TNF-α유전자에 특이적인 것으로서, 이들은 미세먼지에 의해 증가된 염증 사이토카인 관련 유전자이다. 도 9에 도시된 것과 같이 미세먼지를 처리하였을 때 손상된 표피세포에서는 염증 사이토카인 관련 유전자인 IL-1β, IL-8 및 TNF-α의 발현양이 증가하였다. 그러나, 실시예 1및 실시예 2의 시료가 염증 사이토카인 관련 유전자를 모두 유의적으로 감소시키는 것으로 보아, 이로써, 실시예 2가 미세먼지에 의해 증가했던 사이토카인의 발현을 감소시켜 미세먼지에 의한 피부 손상을 예방 또는 개선한다는 것을 확인하였다.qRT-PCR was performed using the oligomers shown in Table 2 above as primers. The primer set is specific for IL-1β, IL-8, and TNF-α genes, which are genes related to inflammatory cytokines increased by fine dust. As shown in Figure 9, when treated with fine dust, the expression level of inflammatory cytokine-related genes IL-1β, IL-8, and TNF-α increased in damaged epidermal cells. However, it appears that the samples of Examples 1 and 2 significantly reduced the genes related to inflammatory cytokines. As a result, Example 2 reduced the expression of cytokines that had increased due to fine dust, thereby reducing the risk of inflammation caused by fine dust. It was confirmed that it prevents or improves skin damage.
상기 결과들은 딱지꽃추출물 및 3,3', 4-Tri-O-methylellagic acid이 자외선 또는 미세먼지에 의한 피부손상을 예방, 개선 또는 치료에 유용하게 사용될 수 있는 효과가 있음을 의미한다.The above results mean that scab extract and 3,3', 4-Tri-O-methylellagic acid can be useful in preventing, improving, or treating skin damage caused by ultraviolet rays or fine dust.
제형예 1: 정제의 제조Formulation Example 1: Preparation of tablets
상기 실시예 2에 대하여 통상의 정제 제조방법에 따라서 하기 표 3의 성분을 혼합하고 타정하여 정제를 제조하였다. For Example 2, tablets were manufactured by mixing the ingredients in Table 3 below and compressing them according to a conventional tablet manufacturing method.
제형예 2: 캡슐제의 제조Formulation Example 2: Preparation of capsules
상기 실시예 2에 대하여 통상의 캡슐제 제조방법에 따라서 하기 표 4의 성분을 혼합하고 젤라틴 캡슐에 충전하여 연질캡슐제를 제조하였다. For Example 2, soft capsules were prepared by mixing the ingredients in Table 4 below and filling them into gelatin capsules according to a typical capsule manufacturing method.
제형예 3: 액제의 제조Formulation Example 3: Preparation of liquid formulation
상기 실시예 2에 대하여 기호에 적합한 음료 제조방법에 따라서 하기 표 5의 성분을 혼합하고 과병 또는 파우치에 충전하여 액제를 제조하였다. For Example 2, a liquid preparation was prepared by mixing the ingredients in Table 5 below and filling them in a fruit bottle or pouch according to a beverage production method suited to one's preference.
제형예 4: 젤리의 제조Formulation Example 4: Preparation of jelly
상기 실시예 2에 대하여 기호에 적합한 젤리 제조방법에 따라서 하기 표 6의 성분을 혼합하고 삼면포에 충전하여 젤리를 제조하였다. Regarding Example 2, jelly was prepared by mixing the ingredients in Table 6 below and filling them in a three-sided cloth according to a jelly manufacturing method suitable to one's preference.
제형예 5: 영양크림의 제조Formulation Example 5: Preparation of nutritional cream
상기 실시예 2에 대하여 영양크림을 통상의 방법에 따라서 하기 표 7의 조성으로 제조하였다. For Example 2, nutritional cream was prepared with the composition shown in Table 7 below according to a conventional method.
상기의 조성비는 일반적으로 적합한 성분을 혼합하여 제형예로 조성하였지만, 필요에 따라서 그 배합비 및 원료를 임의로 변경 실시하여도 무방하다. The above composition ratio is generally prepared by mixing appropriate ingredients as a formulation example, but the mixing ratio and raw materials may be arbitrarily changed as needed.
본 발명의 추출물은 모든 제형예 시험 조건에서 안정하므로 제형의 안정성에는 문제가 없었다. The extract of the present invention was stable under all formulation test conditions, so there was no problem with the stability of the formulation.
Claims (14)
[화학식 1]
.A cosmetic composition for improving skin barrier or moisturizing skin containing 3,3',4-tri-O-methylellagic acid compound represented by the following formula (1) or an acceptable salt thereof as an active ingredient:
[Formula 1]
.
[화학식 1]
.A health functional food composition for improving skin barrier or moisturizing skin containing 3,3',4-tri-O-methylellagic acid compound represented by the following formula (1) or an acceptable salt thereof as an active ingredient:
[Formula 1]
.
[화학식 1]
.A pharmaceutical composition for improving the skin barrier containing a 3,3',4-tri-O-methylellagic acid compound represented by the following formula (1) or an acceptable salt thereof as an active ingredient, wherein the skin barrier improvement is used to treat psoriasis and contact dermatitis. Preventing or treating skin diseases selected from the group consisting of eczematous dermatitis, actinic dermatitis, seborrheic dermatitis, dermatitis herpetiformis, lichen planus, lichen sclerosus, pyoderma gangrenosum, pemphigus, epidermolysis bullosa, systemic sclerosis, and leprosy. , Pharmaceutical composition for improving skin barrier:
[Formula 1]
.
[화학식 1]
.An external skin preparation for improving the skin barrier containing a 3,3',4-tri-O-methylellagic acid compound represented by the following formula (1) or an acceptable salt thereof as an active ingredient, wherein the skin barrier improvement is used to treat psoriasis, contact dermatitis, Preventing or treating skin diseases selected from the group consisting of eczematous dermatitis, actinic dermatitis, seborrheic dermatitis, dermatitis herpetiformis, lichen planus, lichen sclerosus, pyoderma gangrenosum, pemphigus, epidermolysis bullosa, systemic sclerosis and leprosy, External skin preparations for improving skin barrier:
[Formula 1]
.
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