KR20170099658A - Composition for improving skin - Google Patents
Composition for improving skin Download PDFInfo
- Publication number
- KR20170099658A KR20170099658A KR1020160022023A KR20160022023A KR20170099658A KR 20170099658 A KR20170099658 A KR 20170099658A KR 1020160022023 A KR1020160022023 A KR 1020160022023A KR 20160022023 A KR20160022023 A KR 20160022023A KR 20170099658 A KR20170099658 A KR 20170099658A
- Authority
- KR
- South Korea
- Prior art keywords
- skin
- composition
- stem cells
- formula
- compound represented
- Prior art date
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/318—Foods, ingredients or supplements having a functional effect on health having an effect on skin health and hair or coat
Abstract
Description
본 발명은 피부 재생, 피부결 개선, 줄기세포 활성 촉진 효과를 나타내는 피부 개선용 조성물에 관한 것이다. The present invention relates to a skin improving composition exhibiting skin regeneration, skin texture improvement, and stem cell activity promoting effect.
피부 표면의 형태인 피부결은 미세한 선에 의해 형성된 3차원 미세구조를 특징으로 하며 연령별·부위별로 유의하게 다르다. 피부결은 선의 깊이에 따라 1차(약 20-100 μm), 2차(약 5-40 μm), 3차(약 0.5 μm) 라인으로 구분되며, 좋은 피부일수록 각 라인들이 그물형태의 네트워크구조를 이루며 선들이 만나서 생기는 다각형과 별 모양(star formation)이 뚜렷하다는 특징을 지니고 있다[비특허문헌 1]. 그러나 나이가 들어감에 따라 또는 피부가 손상됨에 따라 촘촘하던 미세라인의 네트워크 구조가 무너져 미세 라인(2차, 3차 등)은 사라지고 1차 라인은 더욱 깊어져 주름이 생성되는 것으로 알려져 있다[비특허문헌 2]. 즉, 피부가 노화됨에 따라 나타나는 대표적인 징후인 주름은 이미 장기간에 걸쳐 일어나는 미세한 변화의 축적이다.The skin texture, which is the shape of the skin surface, is characterized by a three-dimensional microstructure formed by fine lines and is significantly different by age and area. The skin texture is divided into primary (about 20-100 μm), secondary (about 5-40 μm), and tertiary (about 0.5 μm) lines depending on the depth of the line. And has a characteristic that the polygons and star formation that occur when the lines meet meet [non-patent document 1]. However, as the age increases or the skin becomes damaged, the network structure of the dense fine lines collapses and fine lines (secondary, tertiary, etc.) disappear and the primary lines become deeper and wrinkles are known to be produced Literature 2]. In other words, wrinkles, a typical sign of skin aging, are accumulations of minute changes that have already occurred over a long period of time.
발생학적으로 사람 피부의 모든 구성성분은 외배엽이나 중배엽에서 유래되는 것으로 알려져 있다. 표피, 모낭, 피지선 및 땀샘선 등은 외배엽에서 기원하며, 멜라닌 세포, 신경 및 특수 감각 수용체는 신경외배엽에서 유래된다. 발생학적 시기에 따라 배아의 줄기세포는 분화를 거듭하여 각각의 조직 기능에 맞는 특성의 세포가 되고, 성체가 된 후에도 일정수의 줄기세포는 조직에 남게 되는데 피부에서는 주로 두 곳에 줄기세포들이 존재한다. 첫째는 모낭(hair follicle)에 존재한다. 이곳은 세포분화가 일어나기 전의 세포로 표피의 재생과 관련해 중요한 역할을 담당하는 것으로 알려져 있으며, 털의 재생과 성장에도 중요한 역할을 수행하고 있다. 둘째는 표피의 기저층(the basal layer of epidermis)이다. 이곳에 자리하고 있는 줄기세포는 표피는 물론 진피층의 섬유아세포까지 관장하여 피부 건강을 지키는 중요한 역할을 수행하고 있음이 밝혀졌다. 이곳의 줄기세포는 상대적으로 양이 많고 쉽게 얻을 수 있다는 장점이 있어 피부줄기세포 연구에 널리 사용되고 있다. 피부는 지속적으로 재생(renew)되며, 피부의 상피에 존재하는 줄기세포 즉, 피부의 상피줄기세포(epidermal stem cells)는 상처 후 상피의 복구에 관여한다[비특허문헌 3]. 상기 피부의 상피줄기세포는 피부줄기세포(skin stem cells)로도 칭해지며, 상기 피부줄기세포를 활성화시킬 경우, 외상 등의 피부상처를 치료하거나 상처 치료를 촉진할 수 있으며 피부의 주름완화 또한 기대할 수 있다. 피부줄기세포의 지표로는 인테그린β1(integrin β1) 및 인테그린 α6(integrin α6)이 사용되고 있고, 상피 형태 형성 및 분화에 필요한 피부줄기세포의 유지는 p63 단백질에 의해 조절된다고 보고되고 있다. Embryologically, all components of human skin are known to originate from ectoderm or mesodermal lobe. Epidermis, hair follicles, sebaceous glands and glands are originated from ectoderm, and melanocytes, nerves and special sensory receptors are derived from neuroepithelial cells. According to the developmental stage, the embryonic stem cells are repeatedly differentiated and become cells with the characteristics of each tissue function. After the embryo, a certain number of stem cells remain in the tissue. . The first is in the hair follicle. It is known to play an important role in the regeneration of the epidermis into cells before cell differentiation occurs, and plays an important role in hair regeneration and growth. The second is the basal layer of the epidermis. The stem cells found here play an important role in maintaining skin health by administering not only the epidermis but also the fibroblasts of the dermal layer. The stem cells here are relatively large in quantity and easy to obtain, making them widely used in the study of skin stem cells. The skin is constantly renewed, and stem cells present in the epithelium of the skin, that is, epidermal stem cells of the skin, are involved in the recovery of the epithelium after injury [Non-Patent Document 3]. The epithelial stem cells of the skin are also referred to as skin stem cells. When the skin stem cells are activated, it is possible to treat skin wounds such as trauma, promote wound healing, have. Integrin β1 and integrin α6 are used as indicators of dermal stem cells, and maintenance of skin stem cells necessary for epithelial morphogenesis and differentiation has been reported to be regulated by p63 protein.
피부줄기세포는 피부의 건강과 생리학적 및 생화학적인 항상성을 유지하는데 중요한 역할을 수행한다. 피부에 존재하는 줄기세포도 노화의 영향으로 인하여 기능에 이상이 발생하게 되고, 이에 따라 피부의 항상성이 깨지면서 여러 가지 문제가 발생된다. 따라서 이러한 줄기세포의 활성을 통하여 피부노화의 여러 현상을 개선할 수 있을 것이다[비특허문헌 4].Dermal stem cells play an important role in maintaining the health and physiological and biochemical homeostasis of the skin. Stem cells present in the skin are also abnormally functioned due to the effect of aging, and thus various problems arise as the homeostasis of the skin is broken. Therefore, it is possible to improve various phenomena of skin aging through the activation of stem cells [Non-Patent Document 4].
또한, 생체에 안전하고, 유효성분이 안정하며, 무엇보다도 기존의 피부 재생 및 피부결 개선 효과가 있는 물질보다 효과가 우수한 피부 재생 및 피부결 개선 활성을 지닌 성분의 개발이 절실히 요망되고 있다.In addition, development of a skin regeneration and skin texture improving activity that is more effective than a substance that is safe in the living body, stable in its active ingredient, and above all has the effect of regenerating the skin and improving the skin texture is desired.
이에, 본 발명자들은 하기 화학식 1로 표시되는 화합물이 피부줄기세포의 증식을 촉진하고 줄기세포성을 유지하여 피부의 재생을 촉진시키고, 피부 밝기 개선으로 인한 피부결 개선 효과와 함께, 피부줄기세포의 증식을 촉진하고, 줄기세포성 유지 효과를 나타내고 있어 줄기세포 활성 촉진 효과를 확인함으로써 본 발명을 완성하게 되었다.Accordingly, the present inventors have found that a compound represented by the following formula (1) promotes proliferation of dermal stem cells, promotes regeneration of the skin by maintaining stem cell characteristics, enhances skin texture by improving skin brightness, Promoting proliferation, exhibiting a stem cell-maintaining effect, and confirming the effect of promoting stem cell activity, thereby completing the present invention.
[화학식 1][Chemical Formula 1]
따라서, 본 발명의 목적은 화학식 1로 표시되는 화합물 또는 이의 허용 가능한 염을 유효성분으로 포함하는 피부 재생 및/또는 피부결 개선용 조성물을 제공하는데 있다.Accordingly, an object of the present invention is to provide a composition for improving skin regeneration and / or skin texture comprising the compound represented by the general formula (1) or an acceptable salt thereof as an active ingredient.
또한, 본 발명의 다른 목적은 화학식 1로 표시되는 화합물 또는 이의 허용 가능한 염을 유효성분으로 포함하는 줄기세포 활성 촉진용 조성물을 제공하는데 있다.Another object of the present invention is to provide a composition for stimulating stem cell activity comprising the compound represented by the formula (I) or an acceptable salt thereof as an active ingredient.
상기 과제를 해결하기 위한 수단으로서, 본 발명은 의약, 화장료 또는 식품 제조를 위한, 하기 화학식 1로 표시되는 화합물 또는 이의 허용 가능한 염을 유효성분으로 포함하는 피부 재생 및/또는 피부결 개선용 조성물을 제공한다.As a means for solving the above problems, the present invention relates to a composition for skin regeneration and / or skin texture improvement comprising a compound represented by the following formula (1) or an acceptable salt thereof as an active ingredient for the manufacture of medicines, to provide.
[화학식 1][Chemical Formula 1]
상기 과제를 해결하기 위한 다른 수단으로서, 본 발명은 화장료 제형 제조를 위한, 하기 화학식 1로 표시되는 화합물 또는 이의 허용 가능한 염을 유효성분으로 포함하는 줄기세포 활성 촉진용 조성물을 제공한다.As another means for solving the above problems, the present invention provides a composition for stimulating stem cell activity comprising, as an active ingredient, a compound represented by the following general formula (1) or an acceptable salt thereof for producing a cosmetic formulation.
[화학식 1][Chemical Formula 1]
본 발명에 따른 화학식 1로 표시되는 화합물은 피부줄기세포의 증식을 촉진하고 줄기세포성을 유지하여 피부의 재생을 촉진시키고 피부 밝기 개선으로 인한 피부결 개선 효과를 나타냄으로써, 의약, 화장료 또는 식품 제조에 사용할 수 있다.The compound represented by formula (I) according to the present invention promotes the proliferation of dermal stem cells, promotes regeneration of skin by maintaining stem cell characteristics, and exhibits an effect of improving skin texture due to improvement in skin brightness. .
또한, 화학식 1로 표시되는 화합물은 피부줄기세포의 증식을 촉진하고, 줄기세포성 유지 효과를 나타내고 있어 줄기세포 활성 촉진용 화장료 제형 제조에 사용할 수 있다. In addition, the compound represented by the formula (1) promotes the proliferation of dermal stem cells and exhibits a stem cell-retaining effect, and can be used in the production of cosmetic formulations for promoting stem cell activity.
이하, 본 발명의 구성을 구체적으로 설명한다.Hereinafter, the configuration of the present invention will be described in detail.
피부 재생 및 피부결 개선 성분이 실제 피부에 적용 시 우수한 효과를 발휘하기 위해서는 저농도에서 고활성의 피부 재생 및 피부결 개선 활성을 나타내고, 피부를 투과하여 흡수되는 능력이 우수하고, 피부 재생 및 피부결 개선 효과를 나타내기에 충분한 시간 동안 머무를 수 있도록 휘발성이 낮고, 조성물이나 피부 상에서 활성 성분이 안정하게 유지되고, 의약, 화장료 또는 식품 등으로의 제조가 용이하며, 또한 피부에 안전한 것이 바람직하다. 그러나, 공지의 성분 중 상기 특성을 모두 만족시키는 성분은 흔치 않다. 예를 들어, 몇몇 피부 재생, 주름 개선 및 피부결 개선 성분들은 시험관 내 실험 시 저농도에서도 피부 재생 및 피부결 개선 활성은 우수하나, 피부를 투과하여 흡수되는 능력이 떨어져 실제 피부에 적용하기엔 어렵다. 또 다른 활성 성분들은 친수성이 낮아 의약이나 화장품, 식품으로 제형화가 어렵다. 또한, 몇몇 피부 재생 및 피부결 개선 성분들은 열, 광, 또는 산소에 노출되었을 때 상기 활성 성분이 분해되거나 다른 화합물로 변형되어 피부에 적용하기 전에 이미 효과가 사라지는 경우도 있다. In order to exert an excellent effect when the skin regeneration and skin texture improving ingredient is applied to actual skin, it exhibits high activity of skin regeneration and skin texture improving activity at a low concentration, has excellent ability to permeate and absorb the skin, It is preferable to have a low volatility so as to be able to stay for a sufficient time to exhibit the improvement effect, to keep the active ingredient stable on the composition or the skin, to be easily produced into medicines, cosmetics or foods, and to be safe for the skin. However, the components satisfying all of the above-mentioned characteristics among the known components are not common. For example, some skin regeneration, wrinkle improvement, and skin tone improving agents have excellent skin regeneration and skin texture improving activity even at low concentrations in vitro, but they are difficult to apply to actual skin because of their ability to permeate and absorb skin. Other active ingredients have low hydrophilicity, making them difficult to formulate into medicines, cosmetics, and foods. In addition, some skin regeneration and skin regeneration components may be degraded or transformed into other compounds when exposed to heat, light, or oxygen, and the effect may already be lost before application to the skin.
하기 실시예에서 확인할 수 있는 바와 같이, 화학식 1로 표시되는 화합물은 저농도에서 월등히 우수한 피부 줄기세포의 증식 촉진 효과 및 피부 밝기 개선 효과를 나타내므로 피부 재생 및 피부결 개선을 위한 의약, 화장료 또는 식품 조성물의 유효성분으로 사용할 수 있다. As can be seen from the following examples, the compound represented by the formula (1) exhibits the effect of promoting the proliferation and skin brightness of skin stem cells remarkably superior at a low concentration. Therefore, the medicinal, cosmetic or food composition Can be used as an active ingredient of the present invention.
따라서, 본 발명은 하기 화학식 1로 표시되는 화합물인 리쏘스페르믹산(Lithospermic acid)을 유효성분으로 포함하는 피부 재생 및 피부결 개선용 조성물을 제공한다.Accordingly, the present invention provides a composition for improving skin regeneration and skin texture comprising, as an active ingredient, Lithospermic acid, a compound represented by the following formula (1).
[화학식 1][Chemical Formula 1]
상기 화학식 1의 화합물의 화합물명은 (2S,3S)-4-[(E)-3-[(1R)-1-카복시-2-(3,4-디하이드록시페닐)에톡시]-3-옥소프로프-1-엔일]-2-(3,4-디하이드록시페닐)-7-하이드록시-2,3-디하이드로-1-벤조퓨란-3-카복실산 ((2S,3S)-4-[(E)-3-[(1R)-1-carboxy-2-(3,4-dihydroxyphenyl)ethoxy]-3-oxoprop-1-enyl]-2-(3,4-dihydroxyphenyl)-7-hydroxy-2,3-dihydro-1-benzofuran-3-carboxylic acid)이며, 일명 모나르딕산 에이(monardic acid A)라 한다.The compound of the above formula (1) is named (2S, 3S) -4 - [(E) -3 - [(1R) -1-carboxy-2- (3,4-dihydroxyphenyl) ethoxy] -3- 3-carboxylic acid ((2S, 3S) -4, 5-dihydroxy- - [(E) -3 - [(1 R) -1-carboxy-2- (3,4-dihydroxyphenyl) ethoxy] -3-oxoprop-1-enyl] -2- hydroxy-2,3-dihydro-1-benzofuran-3-carboxylic acid, also known as monardic acid A.
상기 화학식 1로 표시되는 화합물은 합성하여 이용하거나, 시판되고 있는 화합물을 이용할 수 있다.The compound represented by the formula (1) may be synthesized or a commercially available compound may be used.
또한, 본 발명의 조성물은 상기 화학식 1로 표시되는 화합물의 허용 가능한 염을 포함할 수 있다. 상기 화학식 1로 표시되는 화합물의 허용 가능한 염은 약제학, 화장학 또는 식품학적으로 허용 가능한 염일 수 있으며, 상기 약제학, 화장학 또는 식품학적으로 허용 가능한 염은 유기산 또는 무기산을 이용하여 형성된 산 부가염일 수 있으며, 상기 유기산은, 예를 들면 포름산, 아세트산, 프로피온산, 락트산, 부티르산, 이소부티르산, 트리플루오로아세트산, 말산, 말레산, 말론산, 푸마르산, 숙신산, 숙신산 모노아미드, 글루탐산, 타르타르산, 옥살산, 시트르산, 글리콜산, 글루쿠론산, 아스코르브산, 벤조산, 프탈산, 살리실산, 안트라닐산, 디클로로아세트산, 아미노옥시 아세트산, 벤젠술폰산, p-톨루엔술폰산 및 메탄술폰산계 염을 포함하며 무기산은 예를 들면 염산, 브롬산, 황산, 인산, 질산, 탄산 및 붕산계 염을 포함한다. 바람직하게는 염산염 또는 아세트산염 형태일 수 있으며, 보다 바람직하게는 염산염 형태일 수 있다.In addition, the composition of the present invention may comprise an acceptable salt of the compound represented by the above formula (1). Acceptable salts of the compounds of formula 1 may be those of pharmacology, pharmacology or pharmacologically acceptable salts and the pharmacology, pharmacology or pharmacologically acceptable salts may be acid addition salts formed with organic or inorganic acids Wherein the organic acid is selected from the group consisting of formic acid, acetic acid, propionic acid, lactic acid, butyric acid, isobutyric acid, trifluoroacetic acid, malic acid, maleic acid, malonic acid, fumaric acid, succinic acid, succinic acid monoamide, glutamic acid, Examples of the inorganic acid include inorganic acids such as hydrochloric acid, bromic acid, phosphoric acid, phosphoric acid, nitric acid, phosphoric acid, Sulfuric acid, phosphoric acid, nitric acid, carbonic acid, and boric acid-based salts. Preferably in the hydrochloride or acetate form, more preferably in the hydrochloride form.
상기 언급된 산 부가염은 a) 상기 화학식 1로 표시되는 화합물 및 산을 직접 혼합하거나, b) 이들 중 한 가지를 용매 또는 함수 용매 중에 용해시키고 혼합시키거나, 또는 c) 화학식 1로 표시되는 화합물을 용매 또는 수하 용매 중의 산에 위치시키고 이들을 혼합하는 일반적인 염 제조방법으로 제조된다.The above-mentioned acid addition salts may be obtained by a) directly mixing the compound represented by the formula (1) and an acid, or b) dissolving and mixing one of them in a solvent or a water solvent, or c) Is placed in an acid in a solvent or an under-solvent and the mixture is mixed.
위와는 별도로 추가적으로 염이 가능한 형태는 가바염, 가바펜틴염, 프레가발린염, 니코틴산염, 아디페이트염, 헤미말론산염, 시스테인염, 아세틸시스테인염, 메티오닌염, 아르기닌염, 라이신염, 오르니틴염, 아스파르트산염 등이 있다. In addition to the above, additionally saltable forms include, but are not limited to, the salts of gabapentin, pregabalin, nicotinate, adipate, hemimarate, cysteine, acetylcysteine, methionine, arginine, Aspartate and the like.
본 발명에 있어서, '피부 재생 효과'라 함은 피부줄기세포의 활성이 촉진 됨에 따라, 피부 외부 및 내부 원인에 의한 손상에 대하여 피부 조직이 회복되는 것을 말한다. 이때, 상기 외부 원인에 의한 손상은 자외선, 외부 오염 물질, 창상 또는 외상 등을 들 수 있으며, 상기 내부 원인에 의한 손상은 스트레스 등을 들 수 있다. 바람직하게, 상기 피부 재생은 피부의 건강과 생리학적 및 생화학적 항상성을 유지하는데 중요한 역할을 수행하는 피부줄기세포와 관련되며, 상피 형태 형성 및 분화에 필요한 피부줄기세포성의 유지는 p63 단백질에 의해 조절된다. 따라서, 본원발명의 유효성분을 처리함으로써 피부줄기세포의 증식을 촉진하고 피부줄기세포성을 유지시킴을 통해 피부 재생 효과가 현저하게 증진될 수 있다.In the present invention, the term 'skin regeneration effect' refers to the recovery of skin tissue against damage caused by external or internal causes of skin as the activity of skin stem cells is promoted. At this time, the damage caused by the external cause may include ultraviolet rays, external pollutants, wound or trauma, and the damage caused by the internal cause may be stress. Preferably, the skin regeneration is associated with dermal stem cells which play an important role in maintaining the health and physiological and biochemical homeostasis of the skin. The maintenance of the skin stem cell state necessary for epithelial morphogenesis and differentiation is regulated by the p63 protein do. Accordingly, by treating the active ingredient of the present invention, the skin regeneration effect can be remarkably enhanced by promoting the proliferation of the dermal stem cells and maintaining the dermal cellularity.
본 발명에 있어서, '피부결 개선 효과'라 함은 노화, 스트레스 등의 영향으로 피부 표면이 거칠어지는 것을 억제 또는 저해함으로써 피부 표면을 매끄럽게 하고, 광택을 부여하며, 피부 톤을 밝게 개선하는 것을 말한다.In the present invention, the term " skin texture improving effect " refers to smoothing the skin surface, imparting gloss, and brightening the skin tone by inhibiting or inhibiting roughness of the skin surface due to aging, stress, .
본 발명의 조성물은 의약 제형 제조를 위해 사용할 수 있다.The compositions of the present invention may be used for the manufacture of pharmaceutical formulations.
상기 의약 제형은 오일 또는 수성 매질중의 용액, 현탁액 또는 유화액의 형태이거나, 엑스제, 분말제, 과립제, 정제 또는 캅셀제의 형태일 수 있다.The pharmaceutical formulations may be in the form of solutions, suspensions or emulsions in oils or aqueous media, or in the form of excipients, powders, granules, tablets or capsules.
또한, 상기 조성물은 추가로 동일 또는 유사한 기능을 나타내는 유효성분을 1종 이상 함유할 수 있다. 예컨대, 공지의 피부 재생 및/또는 피부결 개선 성분을 포함할 수 있을 것이다. 추가적인 피부 재생 및/또는 피부결 개선 성분을 포함하게 되면 본 발명의 조성물의 피부 재생 및/또는 피부결 개선 효과는 더욱 증진될 수 있을 것이다. 상기 성분 추가 시에는 복합 사용에 따른 피부 안전성, 제형화의 용이성, 유효성분들의 안정성을 고려할 수 있다. 본 발명의 한 구체예에서, 상기 조성물은 당업계에 공지된 피부 재생 성분으로서, 레티노산, TGF, 동물 태반 유래의 단백질, 베튤린산 및 클로렐라 추출물, 당업계에 공지된 항산화 성분으로서, 토코페롤, 셀레늄, 비타민 C 및 페놀성 화합물, 당업계에 공지된 미백 성분으로서, 코지산(Kojic acid), 알부틴(Arbutin) 등과 같은 티로시나제 효소활성을 억제하는 물질, 하이드로퀴논(Hydroquinone), 비타민-C(L-Ascorbic acid) 및 이들의 유도체와 각종 식물 추출물로 구성되는 군으로부터 선택되는 1종 또는 2종 이상의 성분을 추가로 포함할 수 있다. 추가의 성분은 전체 조성물 중량에 대하여 0.0001 중량% 내지 10 중량%로 포함될 수 있을 것이며, 상기 함량 범위는 피부 안전성, 상기 화학식 1로 표시되는 화합물의 제형화 시의 용이성 등의 요건에 따라 조절될 수 있을 것이다.In addition, the composition may further contain one or more active ingredients showing the same or similar functions. For example, it may contain known skin regeneration and / or skin tone improving ingredients. The skin regeneration and / or skin texture improving effect of the composition of the present invention may be further enhanced by including additional skin regeneration and / or skin regeneration improving component. When the above ingredients are added, skin safety, easiness of formulation, and stability of effective ingredients can be considered according to the combined use. In one embodiment of the present invention, the composition is a skin regeneration component known in the art comprising retinoic acid, TGF, protein from animal placenta, betulinic acid and chlorella extract, antioxidant components known in the art, such as tocopherol, selenium , Vitamin C and phenolic compounds, whitening ingredients known in the art, substances inhibiting the activity of tyrosinase enzymes such as kojic acid and arbutin, hydroquinone, vitamin C (L- Ascorbic acid, derivatives thereof, and various plant extracts. The additional component may be included in an amount of 0.0001 to 10% by weight based on the total weight of the composition, and the content may be adjusted according to requirements such as skin safety and ease of formulation of the compound represented by Formula 1 There will be.
또한, 본 발명의 조성물은 약학적으로 허용 가능한 담체를 더 포함할 수 있다.In addition, the composition of the present invention may further comprise a pharmaceutically acceptable carrier.
약학적으로 허용 가능한 담체는 완충액, 주사용 멸균수, 일반 식염수 또는 인산염 완충 식염수, 슈크로스, 히스티딘, 염 및 폴리솔베이트 등과 같은 여러 성분을 함유할 수 있다.Pharmaceutically acceptable carriers may contain a variety of ingredients such as buffer, injectable sterile water, normal saline or phosphate buffered saline, sucrose, histidine, salts and polysorbates, and the like.
본 발명의 조성물은 경구 또는 비경구로 투여할 수 있으며, 일반 약학 제제의 형태, 예를 들어, 임상 투여 시 경구 및 비경구의 여러 가지 제형으로 투여될 수 있는데, 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제될 수 있다.The composition of the present invention can be administered orally or parenterally, and can be administered in the form of a general pharmaceutical preparation, for example, various forms of oral and parenteral administration at the time of clinical administration. In the case of formulation, a filler, , A binder, a wetting agent, a disintegrant, a surfactant, and the like.
경구 투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 본 발명의 의약 조성물에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘 카보네이트(Calcium carbonate), 수크로스(Sucrose) 또는 락토오스(Lactose), 젤라틴 등을 섞어 조제될 수 있다.Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like. These solid preparations can be prepared by mixing the pharmaceutical composition of the present invention with at least one excipient such as starch, calcium carbonate, Sucrose, lactose, gelatin and the like can be prepared.
단순한 부형제 이외에 마그네슘 스티레이트 탈크 같은 윤활제들도 사용된다. 경구를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다.In addition to simple excipients, lubricants such as magnesium stearate talc are also used. Examples of liquid formulations for oral administration include suspensions, solutions, emulsions, syrups and the like. Various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included in addition to water and liquid paraffin, which are commonly used simple diluents.
비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제제, 좌제가 포함된다. 비수성용제, 현탁용제로는 프로필렌 글리콜(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, 라우린지, 글리세로제라틴 등이 사용될 수 있다.Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used as the non-aqueous solvent and suspension agent. Examples of the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.
본 발명의 의약 제형은 피부 외용제 제형을 포함할 수 있다. The pharmaceutical formulations of the present invention may include external preparation for skin.
상기 화학식 1로 표시되는 화합물을 피부외용제로 사용하는 경우, 추가로 지방 물질, 유기 용매, 용해제, 농축제 및 겔화제, 연화제, 항산화제, 현탁화제, 안정화제, 발포제(foaming agent), 방향제, 계면활성제, 물, 이온형 또는 비이온형 유화제, 충전제, 금속이온봉쇄제 및 킬레이트화제, 보존제, 비타민, 차단제, 습윤화제, 필수 오일, 염료, 안료, 친수성 또는 친유성 활성제, 지질 소낭 또는 피부용 외용제에 통상적으로 사용되는 임의의 다른 성분과 같은 피부 과학 분야에서 통상적으로 사용되는 보조제를 함유할 수 있다. 또한 상기 성분들은 피부 과학 분야에서 일반적으로 사용되는 양으로 도입될 수 있다. When the compound represented by the above formula (1) is used as an external preparation for skin, it may further contain at least one selected from the group consisting of fatty substances, organic solvents, solubilizers, thickeners and gelling agents, softeners, antioxidants, suspending agents, stabilizers, foaming agents, Surfactants, water, ionic or nonionic emulsifiers, fillers, sequestering agents and chelating agents, preservatives, vitamins, blocking agents, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic active agents, lipid vesicles or external preparations for skin Such as any other ingredients conventionally used in the field of skin science. The components can also be introduced in amounts commonly used in the field of dermatology.
상기 화학식 1로 표시되는 화합물이 피부 외용제 제형으로 제공될 경우, 이에 제한되는 것은 아니나, 연고, 패취, 겔, 크림 또는 분무제와 같은 제형을 가질 수 있다.When the compound represented by Formula 1 is provided as an external preparation for skin, it may have a formulation such as, but not limited to, an ointment, a patch, a gel, a cream or a spray.
또한, 본 발명의 피부 재생 및/또는 피부결 개선용 조성물은 화장료 제형 제조를 위해 사용될 수 있다.In addition, the composition for improving skin regeneration and / or skin texture of the present invention can be used for the production of cosmetic formulations.
상기 화장료 제형은 일반적인 유화 제형 및 가용화 제형의 형태일 수 있다. 예컨대, 유연 화장수 또는 영양 화장수 등과 같은 화장수, 훼이셜 로션, 바디로션 등과 같은 유액, 영양 크림, 수분 크림, 아이 크림 등과 같은 크림, 에센스, 화장연고, 스프레이, 젤, 팩, 선 스크린, 메이크업 베이스, 액체 타입, 고체 타입 또는 스프레이 타입 등의 파운데이션, 파우더, 클렌징 크림, 클렌징 로션, 클렌징 오일과 같은 메이크업 제거제, 클렌징 폼, 비누, 바디 워쉬 등과 같은 세정제 등의 제형을 가질 수 있다. The cosmetic formulation may be in the form of a conventional emulsion formulation and a solubilized formulation. For example, creams, essences, cosmetic creams, sprays, gels, packs, sunscreens, make-up bases, liquids such as lotions such as lotion, facial lotion, body lotion, A powder, a cleansing lotion, a makeup removing agent such as a cleansing oil, a cleaning agent such as a cleansing foam, a soap, a body wash and the like.
또한, 상기 화장품은 화학식 1로 표시되는 화합물에 추가로 지방 물질, 유기 용매, 용해제, 농축제 및 겔화제, 연화제, 항산화제, 현탁화제, 안정화제, 발포제(foaming agent), 방향제, 계면활성제, 물, 이온형 또는 비이온형 유화제, 충전제, 금속이온봉쇄제 및 킬레이트화제, 보존제, 비타민, 차단제, 습윤화제, 필수 오일, 염료, 안료, 친수성 또는 친유성 활성제, 지질 소낭 또는 화장품에 통상적으로 사용되는 임의의 다른 성분과 같은 화장품학 분야에서 통상적으로 사용되는 보조제를 함유할 수 있다.The cosmetic composition may further contain, in addition to the compound represented by the formula (1), a lipid, an organic solvent, a solubilizing agent, a thickening agent and a gelling agent, a softening agent, an antioxidant, a suspending agent, a stabilizer, a foaming agent, Water, ionic or non-ionic emulsifiers, fillers, sequestering and chelating agents, preservatives, vitamins, blocking agents, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic active agents, lipid vesicles or cosmetics Such as, for example, cosmetics, cosmetics, pharmaceuticals, cosmetics, pharmaceuticals,
상기 화장료 제형은 유효성분이 단기간 내에 피부에 머무르게 되는 메이크업 제거제, 세정제 등과 같은 워쉬-오프(wash-off) 타입의 화장품의 경우에는 비교적 높은 농도의 상기 화학식 1로 표시되는 화합물을 포함할 수 있을 것이다. 반면, 유효성분이 장기간 동안 피부에 머무르게 되는 화장수, 유액, 크림, 에센스 등의 리브-온(leave-on) 타입의 화장품의 경우에는 워쉬-오프 타입의 화장품에 비해 낮은 농도의 상기 화학식 1로 표시되는 화합물을 포함해도 무방할 것이다. 이에 제한되는 것은 아니나, 본 발명의 한 구체예에서, 상기 조성물은 상기 화학식 1로 표시되는 화합물을 전체 조성물 중량에 대하여 0.0001 중량% 내지 10 중량%(바람직하게는 0.0001 중량% 내지 1 중량%)로 포함할 수 있다. 본 발명의 조성물이 상기 화학식 1로 표시되는 화합물을 0.0001 중량% 미만으로 포함할 경우에는 충분한 피부 재생 효과, 피부결 개선 효과를 기대할 수 없고, 10 중량%를 초과하여 포함할 경우에는 알러지 등 원치 않는 반응이 발생하거나 피부 안전성에 문제가 있을 수 있으므로 이를 방지하기 위한 것이다.The cosmetic formulation may contain a relatively high concentration of the compound represented by the above formula (1) in the case of a wash-off type cosmetic such as a make-up remover, a cleanser, etc. in which the active ingredient remains on the skin in a short period of time. On the other hand, in the case of leave-on type cosmetics, such as lotion, cream, essence, etc., in which the active ingredient remains on the skin for a long period of time, Compound. ≪ / RTI > Although not limited thereto, in one embodiment of the present invention, the composition contains 0.0001 to 10% by weight (preferably 0.0001 to 1% by weight) of the compound represented by the formula (1) . When the composition of the present invention contains less than 0.0001% by weight of the compound represented by the formula (1), sufficient skin regeneration effect and skin texture improving effect can not be expected. When the composition contains more than 10% by weight, This is to prevent a reaction or skin safety problem.
본 발명에 있어서, '유효량'이라 함은 손상된 피부의 재생을 촉진하거나, 피부결을 개선할 수 있는 화학식 1로 표시되는 화합물의 양을 의미한다. 본 발명의 조성물이 유효량의 상기 화학식 1로 표시되는 화합물을 포함할 때 바람직한 피부 재생 효과, 피부결 개선 효과를 제공할 수 있다. 본 발명의 조성물에 포함되는 상기 화학식 1로 표시되는 화합물의 유효량은 조성물이 제품화되는 형태, 상기 화합물이 피부에 적용되는 방법 및 피부에 머무르는 시간 등에 따라 달라질 것이다. 예컨대, 상기 조성물이 약학 제형으로 제품화되는 경우에는 일상적으로 피부에 적용하게 되는 화장품으로 제품화되는 경우에 비해 높은 농도로 상기 화학식 1로 표시되는 화합물을 포함할 수 있을 것이다. 따라서, 일일 투여량은 상기 화학식 1로 표시되는 화합물의 양을 기준으로 0.1 내지 100 ㎎/㎏이고, 바람직하게는 30 내지 80 ㎎/㎏이고, 더욱 바람직하게는 50 내지 60 mg/kg이며, 하루 1 ∼ 6 회 투여될 수 있다.In the present invention, the term "effective amount" means the amount of the compound represented by the formula (1) which can promote the regeneration of the damaged skin or improve the skin texture. When the composition of the present invention contains an effective amount of the compound represented by the above formula (1), it is possible to provide a desirable skin regeneration effect and skin texture improving effect. The effective amount of the compound represented by formula (1) contained in the composition of the present invention will vary depending on the form in which the composition is commercialized, the method in which the compound is applied to the skin, and the time on the skin. For example, when the composition is commercialized as a pharmaceutical formulation, it may contain a compound represented by the above formula (1) at a higher concentration than a cosmetic product that is routinely applied to skin. Therefore, the daily dose is 0.1 to 100 mg / kg, preferably 30 to 80 mg / kg, more preferably 50 to 60 mg / kg, It can be administered 1 to 6 times.
본 발명의 조성물은 단독으로, 또는 수술, 방사선 치료, 호르몬 치료, 화학 치료 및 생물학적 반응조절제를 사용하는 방법들과 병용하여 사용할 수 있다.The composition of the present invention may be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy, and biological response modifiers.
또한, 본 발명의 피부 재생 및/또는 피부결 개선용 조성물은 식품 제형 제조를 위해 사용될 수 있다.In addition, the composition for improving skin regeneration and / or skin texture of the present invention can be used for the production of food formulations.
상기 식품 제형은 상기 화학식 1로 표시되는 화합물을 음료, 차류, 향신료, 껌, 과자류 등의 식품 소재에 첨가하거나, 캡슐화, 분말화, 현탁액 등으로 제조한 식품을 의미한다. The food formulation refers to a food prepared by adding the compound represented by Formula 1 to food materials such as beverage, tea, spice, gum, confectionery, etc., or by encapsulation, powdering, suspension or the like.
상기 식품 제형은 일상적으로 섭취하는 것이 가능하기 때문에 높은 피부 재생 효과, 피부결 개선 효과를 기대할 수 있어 매우 유용하다.Since the food formulation can be ingested on a daily basis, a high skin regeneration effect and skin texture improvement effect can be expected, which is very useful.
상기 화학식 1로 표시되는 화합물을 식품첨가물로 사용하는 경우, 상기 화학식 1로 표시되는 화합물을 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 유효성분의 혼합양은 그의 사용 목적(예방, 건강 또는 치료적 처치)에 따라 적합하게 결정될 수 있다. 일반적으로, 식품 또는 음료의 제조시에 본 발명의 조성물은 원료에 대하여 15 중량부 이하, 바람직하게는 10 중량부 이하의 양으로 첨가된다. 그러나, 건강 및 위생을 목적으로 하거나 또는 건강 조절을 목적으로 하는 장기간의 섭취의 경우에는 상기 양은 상기 범위 이하일 수 있으며, 안전성 면에서 아무런 문제가 없기 때문에 유효성분은 상기 범위 이상의 양으로도 사용될 수 있다.When the compound represented by the formula (1) is used as a food additive, the compound represented by the formula (1) may be added as it is, or may be used together with other food or food ingredients, and may be suitably used according to a conventional method. The amount of the active ingredient to be mixed can be suitably determined according to its intended use (prevention, health or therapeutic treatment). Generally, the composition of the present invention is added in an amount of not more than 15 parts by weight, preferably not more than 10 parts by weight, based on the raw material, when the food or beverage is produced. However, in the case of long-term consumption intended for health and hygiene purposes or for health control purposes, the amount may be less than the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount exceeding the above range .
상기 식품의 종류에는 특별한 제한은 없다. 상기 물질을 첨가할 수 있는 식품의 예로는 육류, 소세지, 빵, 초콜릿, 캔디류, 스넥류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 차, 드링크제, 알코올 음료 및 비타민 복합제 등이 있으며, 통상적인 의미에서의 건강식품을 모두 포함한다.There is no particular limitation on the kind of the food. Examples of the food to which the above substance can be added include dairy products including meat, sausage, bread, chocolate, candy, snack, confectionery, pizza, ramen, other noodles, gums, ice cream, various soups, drinks, tea, Alcoholic beverages, and vitamin complexes, all of which include health foods in a conventional sense.
식품 제형이 음료인 경우, 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물은 포도당, 과당과 같은 모노사카라이드, 말토스, 슈크로스와 같은 디사카라이드, 및 덱스트린, 사이클로덱스트린과 같은 폴리사카라이드, 자일리톨, 소르비톨, 에리트리톨 등의 당알코올이다. 감미제로서는 타우마틴, 스테비아 추출물과 같은 천연 감미제나, 사카린, 아스파르탐과 같은 합성 감미제 등을 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 mL당 일반적으로 약 0.01 ∼ 0.04 g, 바람직하게는 약 0.02 ∼ 0.03 g 이다.When the food is a beverage, various flavors or natural carbohydrates may be added as an additional ingredient such as a normal drink. The above-mentioned natural carbohydrates are sugar alcohols such as monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and xylitol, sorbitol and erythritol. Examples of sweeteners include natural sweeteners such as tau martin and stevia extract, synthetic sweeteners such as saccharin and aspartame, and the like. The ratio of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 mL of the composition of the present invention.
상기 외에 식품 제형은 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 함유할 수 있다. 그 밖에 식품 제형은 천연 과일주스, 과일주스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 혼합하여 사용할 수 있다. 이러한 첨가제의 비율은 크게 중요하진 않지만 본 발명의 조성물 100 중량부당 0.01 ~ 0.1 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above, the food formulations may contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and salts thereof, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, And the like. Other food formulations may contain flesh for the production of natural fruit juices, fruit juice drinks and vegetable drinks. These components may be used independently or in combination. The proportion of such additives is not critical, 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.
본 발명은 또한, 상기 화학식 1로 표시되는 화합물을 유효성분으로 포함하는 줄기세포 활성 촉진용 조성물을 제공한다.The present invention also provides a composition for stimulating stem cell activity comprising the compound represented by Formula 1 as an active ingredient.
본 발명에서 용어 ‘줄기세포’는 스스로 세포 분열을 할 수 있고, 매우 다양한 형태의 특이 세포 타입(specific cell type)으로 분화할 수 있는 능력을 갖는 세포이다. 이러한 줄기세포의 종류는 특별히 제한되지 않으며, 한 구체예에서, 상기 줄기세포는 피부줄기세포일 수 있다. 상기 ‘피부줄기세포’는 피부(표피, 진피 및 피하지방층)를 이루는 세포로 분화될 수 있는 줄기세포를 의미한다. 상기 피부를 이루는 세포는 표피에 존재하는 케라티노사이트(keratinocyte), 멜라노사이트(melanocyte) 및 진피에 존재하는 섬유아세포(콜라겐 및 엘라스틴의 생합성을 주로 담당)를 포함한다. The term 'stem cell' in the present invention is a cell capable of cell division by itself and capable of differentiating into a very specific type of specific cell type. The type of such stem cells is not particularly limited, and in one embodiment, the stem cells may be dermal stem cells. The term 'dermal stem cells' refers to stem cells that can be differentiated into cells constituting the skin (epidermis, dermis and subcutaneous fat layer). The cells that make up the skin include keratinocytes, melanocytes, and fibroblasts (mainly responsible for biosynthesis of collagen and elastin) present in the epidermis.
상기 피부줄기세포의 종류는 특별히 제한되지 않는다. 본 발명에서 사용되는 피부줄기세포는 그것이 어디로부터 유래한 것인지 관계없이 이용될 수 있다. 예를 들어, 피부줄기세포는 공지의 피부줄기세포 공급원, 예를 들어, 모낭 또는 표피의 기저층에서 얻을 수 있으며, 채취 대상인 동물은 포유동물일 수 있다. 한 구체예에서, 포유동물은 인간, 마우스, 랫트, 기니어 피그, 토끼, 원숭이, 돼지, 말, 소, 양, 영양, 개 또는 고양이를 포함할 수 있지만, 이에 한정되는 것은 아니다. 바람직하게 포유동물은 인간일 수 있다. 이러한, 피부줄기세포 공급원으로부터 피부줄기세포를 수득하는 방법에 대해서는 당업계에서 잘 알려져 있다.The kind of the skin stem cell is not particularly limited. The dermal stem cells used in the present invention can be used irrespective of where they originate from. For example, dermal stem cells may be obtained from a known source of dermal stem cells, e. G., From the basal layer of hair follicles or epidermis, and the animal to be harvested may be a mammal. In one embodiment, the mammal may include, but is not limited to, a human, a mouse, a rat, a guinea pig, a rabbit, a monkey, a pig, a horse, a cattle, a sheep, Preferably the mammal can be human. Such methods of obtaining dermal stem cells from dermal stem cell sources are well known in the art.
본 발명에 있어서, '줄기세포 활성 촉진 효과'라 함은 줄기세포 증식 촉진 효과, 및/또는 줄기세포의 특이적 지표 분자 및 자가 분열적 성질인 줄기세포성을 유지하는 효과를 포함하는 것을 말한다. 상기 줄기세포성 유지는 화학식 1로 표시되는 화합물을 줄기세포에 처리할 때 세포 내 전사인자로서 피부줄기세포의 유지 마커인 p63의 발현이 촉진됨으로써 나타나는 효과이다.In the present invention, the term 'promoting effect on stem cell activity' refers to an effect of promoting stem cell proliferation and / or an effect of maintaining stem cell characteristics, which is a specific indicator molecule and a self-cleaving property of stem cells. The stem cell maintenance is an effect produced by promoting the expression of p63, which is a maintenance marker of dermal stem cells, as an intracellular transcription factor when treating a stem cell with a compound represented by the formula (1).
또한, 본 발명의 조성물은 화장료 제형 제조를 위해 사용될 수 있다. 이러한 화장료 제형에 대해서는 앞서 화학식 1로 표시되는 화합물을 포함하는 화장료 제형에 관한 설명에 기재된 내용과 동일하다. In addition, the compositions of the present invention can be used for the production of cosmetic formulations. These cosmetic formulations are the same as those described in the description of the cosmetic formulation containing the compound of formula (1).
이하, 본 발명의 이해를 돕기 위하여 실시예 등을 들어 상세하게 설명하기로 한다. 그러나, 본 발명에 따른 실시예들은 여러 가지 다른 형태로 변형될 수 있으며, 본 발명의 범위가 하기 실시예들에 한정되는 것으로 해석되어서는 안 된다. 본 발명의 실시예들은 당업계에서 평균적인 지식을 가진 자에게 본 발명을 보다 완전하게 설명하기 위해 제공되는 것이다.Hereinafter, embodiments of the present invention will be described in detail to facilitate understanding of the present invention. However, the embodiments according to the present invention can be modified into various other forms, and the scope of the present invention should not be construed as being limited to the following embodiments. Embodiments of the invention are provided to more fully describe the present invention to those skilled in the art.
참조예Reference Example 1: One: LithospermicLithospermic acid 물질 정보 acid substance information
[화학식 1][Chemical Formula 1]
CAS No.: 28831-65-4CAS No .: 28831-65-4
구입처: Sichuan Hongjie Import&Export CO., LTDWhere to buy: Sichuan Hongjie Import & Export CO., LTD
참조예Reference Example 2: 2: 무혈청Serum-free 배지조건에서Under medium conditions 피부줄기세포의Of dermal stem cells 배양 culture
Cellntec 사에서 구입한 인간 피부줄기세포(Human epidermal stem cell)를 48-웰 플레이트(6×103 cells/well)에, 소태아혈청(fetal bovine serum)과 유사한 BPE(Bovine pituitary extract)가 첨가된 CNT-57 배지(Cellntec사)를 이용하여 24 시간 동안 5% CO2 및 37℃ 조건에서 배양하였다. 그 후, 배양액을 흡입관을 통하여 제거한 다음, PBS 용액(GibcoBRL 사)을 이용하여 배지 성분을 제거하고, BPE가 포함되지 않은 CNT-57 배지에 화학식 1로 표시되는 화합물 10 ㎍/mL을 처리하여 5％ CO2 및 37℃ 조건에서 72시간 동안 배양하였다.Human epidermal stem cells purchased from Cellntec were added to 48-well plates (6 × 10 3 cells / well), supplemented with BPE (bovine pituitary extract) similar to fetal bovine serum And cultured for 24 hours at 5% CO 2 and 37 ° C using CNT-57 medium (Cellntec). Thereafter, the culture medium was removed through a suction tube, and the medium was removed using a PBS solution (GibcoBRL). 10 ㎍ / mL of the compound represented by the formula (1) was treated with CNT-57 medium containing no BPE to prepare 5 in% CO 2 and 37 ℃ condition were cultured for 72 hours.
실시예Example 1: One: CCKCCK -8 평가법을 통한 -8 Through evaluation method 피부줄기세포Dermal stem cells 증식 촉진 효과 Proliferation promoting effect
상기 참조예 2에서 배양된 피부줄기세포에 CCK-8(Cell counting kit-8) 평가를 실시하였다. CCK-8 평가는 세포 내 전자전달계 내의 탈수소효소(Dehydrogenase)가 테트라졸리움 염(Tetrazolium Salt)를 분해하여 생성하는 포르마잔(Formazan)의 흡광도를 측정하여 살아있는 세포의 밀도를 간접적으로 나타내는 분석방법이다. The skin stem cells cultured in Reference Example 2 were evaluated for CCK-8 (Cell counting kit-8). The CCK-8 assay is an indirect method of measuring the density of living cells by measuring the absorbance of Formazan, a dehydrogenase in the intracellular electron transport system, produced by the decomposition of tetrazolium salt.
세포에 CCK-8 용액(배지 부피의 1/10을 처리)을 37℃에서 2시간 동안 처리한 후, 파장 450 nm에서의 흡광도를 측정함으로써 분광학적으로 측정하였다. 화학식 1의 화합물의 피부줄기세포의 증식 촉진 효과는 측정된 흡광도 값으로부터 대조군(BPE 첨가한 CNT-57 배지) 대비 하기 수학식 1에 따라 증식율(%)을 구하고, 그 값을 하기 표 1에 나타냈다.Cells were spectrophotometrically measured by treating CCK-8 solution (treated with 1/10 of the medium volume) at 37 ° C for 2 hours and then measuring the absorbance at 450 nm. The proliferation rate (%) of the compound of the formula (1) was determined from the measured absorbance value according to the following equation (1) with respect to the control group (CNT-57 medium supplemented with BPE) .
[수학식 1][Equation 1]
증식율(%) = (시료처리군의 흡광도/대조군의 흡광도) × 100Growth rate (%) = (absorbance of sample-treated group / absorbance of control group) x 100
표 1에 나타난 바와 같이, 화학식 1의 화합물을 처리한 배지조건에서의 피부줄기세포는 우수한 증식 촉진 효과를 나타내었다. As shown in Table 1, the skin stem cells under the medium condition treated with the compound of the formula (1) showed an excellent proliferation promoting effect.
실시예Example 2: 2: 피부줄기세포의Of dermal stem cells 줄기세포성( Stem cell ( stemnessstemness ) 유지 효과 확인) Confirm maintenance effect
상기 참조예 2에서 배양된 피부줄기세포의 줄기세포성 유지 효과 확인을 위해 p63 발현 정도를 평가하였다. p63은 세포 내 전사인자로서 피부줄기세포의 유지 마커로 잘 알려져 있다. 세포의 RNA를 분리하여 cDNA를 합성한 다음, Taqman 염색액으로 실시간-PCR을 수행하여 p63의 발현 정도를 측정하였다. 본 실험에서 RNA의 농도는 S16 리보솜 RNA로 표준화하였다.The expression level of p63 was evaluated in order to confirm the stem cell maintenance effect of the dermal stem cells cultured in Reference Example 2 above. p63 is an intracellular transcription factor and is well known as a maintenance marker for dermal stem cells. Cells were isolated and cDNA was synthesized. Then, real-PCR was performed with Taqman staining solution to measure the expression level of p63. The concentration of RNA in this experiment was normalized to S16 ribosomal RNA.
상기 실험 결과는 하기 표 2에 나타내었다. 하기 표 2에서 p63 증가 배수의 수치는 대조군(BPE 첨가한 CNT-57 배지) 대비 배수를 의미한다.The experimental results are shown in Table 2 below. In Table 2 below, the numerical value of the increase in p63 is a multiple of the control group (CNT-57 medium supplemented with BPE).
표 2에 나타난 바와 같이, 화학식 1의 화합물을 처리한 배지 조건은 피부줄기세포의 p63 발현을 촉진하여 줄기세포성 유지 효과가 우수하다.As shown in Table 2, the medium condition treated with the compound of Formula 1 promotes the expression of p63 in dermal stem cells, and thus has excellent stem cell retention effect.
실시예Example 3: 3: 각질박리(turn-over)개선에To improve the turn-over of the skin 대한 About 효능성Efficacy
하기 제제예 2의 영양크림에 대해서 건강한 20대에서 50대의 여성을 대상으로 각질 박리 개선 효과를 다음과 같이 시험하였다.About the nutritional cream of the following formulation example 2, the effect of the improvement of the exfoliation of the skin in the healthy twenties to 50 women was tested as follows.
20세에서 50세까지의 여성 20명의 시험 부위에 DHA(Dihydroxyacetone, Sigma Aldrich, USA) 1.5% 용액을 8시간 동안 폐쇄첩포하여 침착시킨 후 제조예 영양크림을 매일 2회 시험 부위에 도포하였다. 도포 4일 후, 도포 8일 후, 도포 12일 후에 Chromameter CR-400(Minolta, Japan)을 이용하여 침착 부위의 피부 밝기에 대한 기기측정과 DSLR을 이용하여 사진 촬영을 실시하였다. 측정값은 최대값과 최소값을 제외한 3회의 평균값을 구하여 평가하였으며, 침착 부위의 피부 밝기 개선이 높을수록 각질 박리 개선 효과가 있음을 나타낸다. 결과는 하기 표 3에 나타내었다.Twenty of 20 women aged 20 to 50 years were given a 1.5% solution of DHA (Dihydroxyacetone, Sigma Aldrich, USA) for 8 hours, followed by deposition. The preparation cream was applied twice daily to the test site. After 4 days of application, 8 days after application, 12 days after application, photographs were taken using instrument Chromameter CR-400 (Minolta, Japan) and skin lightness of DSLR and DSLR. The measured values were evaluated by three mean values excluding the maximum value and the minimum value. The higher the improvement in the skin brightness of the deposition site, the better the improvement of the exfoliation. The results are shown in Table 3 below.
표 3에 나타난 바와 같이, 본 발명에 따른 영양크림을 사용한 경우 각질 박리 개선 효과가 있는 것으로 나타났다.As shown in Table 3, when the nutritional cream according to the present invention was used, it was found that the exfoliation of the skin was improved.
제제예Formulation example 1: 의약 제제의 제조 1: Manufacture of pharmaceutical preparations
1. 정제의 제조1. Preparation of tablets
화학식 1의 화합물 0.2㎎0.2 mg of the compound of formula (1)
옥수수전분 100㎎100 mg of corn starch
유 당 100㎎100 mg of milk
스테아린산 마그네슘 2㎎ 2 mg of magnesium stearate
상기의 성분을 혼합한 후, 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조하였다.After mixing the above components, tablets were prepared by tableting according to a conventional method for producing tablets.
제제예Formulation example 2: 화장품의 제조 2: Manufacture of cosmetics
1. 영양크림의 제조1. Manufacture of nutritional cream
하기 조성과 같이, 화학식 1의 화합물을 유효성분으로 포함하는 영양크림을 통상의 방법에 따라 제조하였다.A nutritional cream containing the compound of formula (1) as an active ingredient was prepared according to a conventional method, as shown below.
화학식 1의 화합물 0.2중량％0.2% by weight of the compound of formula (1)
베타-1,3-글루칸 5.0 중량％Beta-1,3-glucan 5.0 wt%
밀납 10.0 중량％Wax 10.0 wt%
폴리솔베이트60 1.5 중량％Polysorbate 60 1.5 wt%
피이지 60 경화피마자유 2.0 중량％≪ tb > < tb > < tb >
솔비탄세스퀴올레이트 0.5 중량％0.5% by weight of sorbitan sesquioleate
유동파라핀 10.0 중량％Liquid paraffin 10.0 wt%
스쿠알란 5.0 중량％Squalane 5.0 wt%
카프릴릭/카프릭트리글리세라이드 5.0 중량％Caprylic / capric triglyceride 5.0 wt%
글리세린 5.0 중량％Glycerin 5.0 wt%
부틸렌글리콜 3.0 중량％3.0% by weight of butylene glycol
프로필렌글리콜 3.0 중량％3.0% by weight of propylene glycol
트리에탄올아민 0.2 중량％0.2% by weight triethanolamine
방부제 0.05 중량％Preservative 0.05 wt%
색소 0.05 중량％0.05% by weight of pigment
향료 0.05 중량％0.05% by weight fragrance
정제수 to 100 중량％Purified water to 100%
제제예Formulation example 3: 피부 외용제의 제조 3: Preparation of external preparation for skin
1. 연고의 제조1. Manufacture of ointment
하기 조성과 같이, 화학식 1의 화합물을 유효성분으로 포함하는 연고를 통상의 방법에 따라 제조하였다.An ointment containing the compound of formula (I) as an active ingredient was prepared according to a conventional method, as shown below.
화학식 1의 화합물 0.5 중량％0.5% by weight of the compound of formula (1)
베타-1,3-글루칸 10.0 중량%Beta-1,3-glucan 10.0 wt%
밀납 10.0 중량%Wax 10.0 wt%
폴리솔베이트60 5.0 중량%Polysorbate 60 5.0 wt%
피이지 60 경화피마자유 2.0 중량%≪ tb > < tb > < tb >
솔비탄세스퀴올레이트 0.5 중량%0.5% by weight of sorbitan sesquioleate
바셀린 5.0 중량%Vaseline 5.0 wt%
유동파라핀 10.0 중량%Liquid paraffin 10.0 wt%
스쿠알란 5.0 중량%Squalane 5.0 wt%
쉐어버터 3.0 중량%SHARE BUTTER 3.0 wt%
카프릴릭/카프릭트리글리세라이드 5.0 중량%Caprylic / capric triglyceride 5.0 wt%
글리세린 10.0 중량%Glycerin 10.0 wt%
프로필렌글리콜 10.2 중량%Propylene glycol 10.2 wt%
트리에탄올아민 0.2 중량%0.2% by weight triethanolamine
방부제 0.05 중량％Preservative 0.05 wt%
색소 0.05 중량％0.05% by weight of pigment
향료 0.05 중량％0.05% by weight fragrance
정제수 to 100 중량%Purified water to 100%
Claims (8)
[화학식 1]
A composition for skin regeneration comprising a compound represented by the following formula (1) or an acceptable salt thereof as an active ingredient.
[Chemical Formula 1]
상기 조성물은 피부 재생용 의약, 화장료 또는 식품 제조를 위한 것인, 피부 재생용 조성물.
The method according to claim 1,
Wherein the composition is for the manufacture of a medicament for skin regeneration, a cosmetic preparation or a food product.
[화학식 1]
A composition for improving skin texture comprising a compound represented by the following formula (1) or an acceptable salt thereof as an active ingredient.
[Chemical Formula 1]
상기 조성물은 피부결 개선용 의약, 화장료 또는 식품 제조를 위한 것인, 피부결 개선용 조성물.
The method of claim 3,
Wherein the composition is for the manufacture of a medicament for the improvement of skin texture, a cosmetic composition or a food product.
[화학식 1]
A composition for stimulating stem cell activity comprising a compound represented by the following formula (1) or an acceptable salt thereof as an active ingredient.
[Chemical Formula 1]
상기 조성물은 줄기세포 증식 촉진 또는 줄기세포성 유지를 위한 것인, 줄기세포 활성 촉진용 조성물.
6. The method of claim 5,
Wherein the composition is for promoting stem cell proliferation or stem cell maintenance.
상기 조성물은 p63 유전자의 발현을 촉진시켜 줄기세포성을 유지하는 줄기세포 활성 촉진용 조성물.
6. The method of claim 5,
Wherein the composition promotes the expression of p63 gene to maintain stem cell characteristics.
조성물은 줄기세포 활성 촉진용 화장료 제조를 위한 것인, 줄기세포 활성 촉진용 조성물.6. The method of claim 5,
Wherein the composition is for the production of a cosmetic for promoting stem cell activity.
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