KR101859499B1 - Cosmetic composition biomimetically designed from extracellular matrix for promoting the stemness of adipose-derived stem cell - Google Patents
Cosmetic composition biomimetically designed from extracellular matrix for promoting the stemness of adipose-derived stem cell Download PDFInfo
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- KR101859499B1 KR101859499B1 KR1020100120373A KR20100120373A KR101859499B1 KR 101859499 B1 KR101859499 B1 KR 101859499B1 KR 1020100120373 A KR1020100120373 A KR 1020100120373A KR 20100120373 A KR20100120373 A KR 20100120373A KR 101859499 B1 KR101859499 B1 KR 101859499B1
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Abstract
본 발명은 글리신-프롤린-하이드록시프롤린(Gly-Pro-Hyp)으로 구성된 트리펩타이드, 저분자량 히알루론산, 미네랄 및 비타민을 유효성분으로 함유하는 지방 유래 줄기세포의 줄기세포성 증진용 조성물을 제공한다. 본 발명의 조성물은 지방유래 줄기세포의 줄기세포성을 증진시킴으로써 미용 또는 성형 목적의 지방조직 증가에 유용하다. 그래서, 본 발명의 조성물은 피부 볼륨감을 증진시키고, 지방유래 줄기세포 재생을 촉진시키고 손상된 피하지방의 기능을 회복시켜 주므로 피부 볼륨감 증진용 미용 또는 성형용 조성물로 활용 가능하고, 피부외용제 조성물로 활용 가능하다. The present invention provides a composition for promoting stem cell activity in adipose derived stem cells comprising a tripeptide consisting of glycine-proline-hydroxy-proline (Gly-Pro-Hyp), low molecular weight hyaluronic acid, minerals and vitamins as active ingredients . The composition of the present invention is useful for increasing adipose tissue for cosmetic or cosmetic purposes by enhancing stem cell characteristics of adipose derived stem cells. Thus, the composition of the present invention improves skin volume, stimulates the regeneration of fat-derived stem cells, restores the function of damaged subcutaneous fat, and thus can be used as a cosmetic or molding composition for enhancing skin volume, It is possible.
Description
본 발명은 세포 외 기질을 모사하여 줄기세포의 특성을 유지 및 증진하게 하는 줄기세포성 증진용 조성물에 관한 것이다.The present invention relates to a composition for promoting stem cell performance, which maintains and promotes the characteristics of stem cells by simulating extracellular matrix.
피부는 표피, 진피 및 피하조직으로 구성되어 있고, 진피 조직에는 3차원의 지지체로서 무기염류, 영양분, 노폐물 등의 수용액과 거대 다당류 분자들이 포함된 세포외 기질(extracellular matrix: 이하 ECM) 성분이 있다. 이는 세포를 둘러싼 공간에서 네트워크를 형성해 조직의 형태를 유지하고 지탱하며, 세포간의 신호전달 및 세포의 성장과 분화를 조절하는 중요한 역할을 한다. The skin is composed of the epidermis, dermis and subcutaneous tissue. In the dermis tissue, there is extracellular matrix (ECM) component containing aqueous solution such as inorganic salts, nutrients, wastes and large polysaccharide molecules as a three-dimensional support . It forms a network in the space surrounding the cells to maintain and support the morphology of the tissue, and plays an important role in regulating cell signaling and cell growth and differentiation.
지금까지 모사된 ECM 성분은 대부분이 동물로부터 유래되었다. 하지만 동물유래 성분은 병원체 감염 등 안전성의 문제가 대두되면서 화장품에 사용하지 않는 추세이다.The ECM components that have been simulated so far are mostly derived from animals. However, animal-derived ingredients tend not to be used in cosmetics due to safety issues such as pathogen infection.
ECM 전체의 70~80%를 차지하는 주요 성분인 콜라겐은 길이가 긴 섬유구조 단백질 중의 하나로 피부 강도와 탄성을 조절하므로 피부 노화, 즉 탄력감소나 주름형성 등과 밀접한 관련이 있다고 알려져 있다. 그러나 현재 사용되고 있는 대부분의 콜라겐이 동물유래 원료이고, 분자량이 약 30만Da 가량의 고분자이기 때문에 피부를 통한 전달에 있어 콜라겐 자체로의 흡수는 한계가 있다.It is known that collagen, which is a major component of 70% ~ 80% of total ECM, is one of long fiber structure proteins and controls skin strength and elasticity, so it is known to be closely related to skin aging, such as elasticity and wrinkle formation. However, since most collagen currently used is an animal-derived raw material and has a molecular weight of about 300,000 Da, its absorption into collagen itself is limited in its transmission through the skin.
ECM 성분의 하나인 히알루론산(hyaluronic acid)은 피부 내 진피조직의 세포를 서로 결합시키고 영양분을 전달하는 역할을 하며 피부가 적절한 양의 수분을 유지할 수 있도록 한다. 하지만 히알루론산은 분자량이 수십만에서 수백만의 고분자이기 때문에 점도가 높아 화장품에 적용 시 사용량에 제한을 받으며, 피부에 직접 도포하여 피부를 투과하기가 매우 어렵다는 단점이 있다.One of the ECM components, hyaluronic acid, binds the cells of the dermis tissue in the skin and transports the nutrients, allowing the skin to maintain an adequate amount of moisture. However, since hyaluronic acid has a molecular weight of several hundred thousand to several millions, it is highly viscous and is limited in its application amount in cosmetics, and has a drawback in that it is very difficult to penetrate skin through direct application to the skin.
피부는 인체를 구성하고 있는 기관 중 가장 큰 기관으로, 우리 몸 부피의 약 16 %를 차지하고, 면적이 1.8 m2, 두께가 2~4 mm, 무게가 약 3 kg이며, 표피, 진피 및 피하지방층으로 구성되어 있다. 이러한 피부는 외부 환경과 직접 접하고 있으면서 인체 유해 미생물과 같은 다양한 유해인자들과 자외선 등과 같은 외부 자극으로부터 인체를 보호하는 중요한 보호막 역할을 담당하는 동시에 전신의 대사에 필요한 생화학적 기능을 영위하는 생명유지에 필수 불가결한 기관이다. 특히, 진피 아래에 존재하는 피하지방층은 지방세포(adipocyte)의 소엽으로 구성되어 있는데, 외부의 열에 대해 피부 내부의 기관의 보호 및 충격을 흡수하는 쿠션 역할을 하며 영양성분을 트리글리세라이드(Triglyceride)의 형태로 지방체(Lipid droplet)라는 세포 소기관에 저장하여 필요 시 에너지원으로 사용하기도 한다. 그러나 나이가 들어감에 따라 자연적인 요인과 각종 외부 자극에 의해 피부는 손상을 입게 되는데, 특히 진피에서 탄력을 담당하는 교원섬유(콜라겐), 탄력섬유(엘라스틴)의 활성 및 발현이 저하되며 탄력이 줄어듦과 동시에, 피하지방에서도 지방생성이 감소함으로써 결국에는 피부 전반적으로 각 구성 세포들의 본래 기능이 제대로 이루어지지 않게 된다. 그래서, 현재 널리 사용되고 있는 방법이 지방이식수술로 이는 튜립 니들(tulip needle) 모양의 끝이 날카롭지 않은 바늘을 갖는 주사기를 이용하여 자신의 지방을 채취해 탄력이 떨어져 보이는 피부의 각 부위에 이식하는 수술이다. 그러나, 지방이식수술 이후에 이식 부피의 40~60%가 다시 인체 내에 흡수된다는 것이 보고된 바 있고, 피부가 얇고 피하지방이 적은 부위에서의 지방이식수술은 세포 덩어리가 만져지는 등의 문제가 제기되며, 실제로 이식한 지방의 생존율과 생존기간이 기대에 미치지 못해 재이식이 필요한 경우가 발생한다. The skin is the largest organ of the human body, accounting for about 16% of our body volume, 1.8 m 2 in area, 2 ~ 4 mm in thickness, weighing about 3 kg, and the epidermis, dermis, . Such skin is in direct contact with the external environment and plays an important protective layer for protecting the human body from various harmful factors such as harmful microorganisms and ultraviolet rays, and at the same time, it has a biochemical function necessary for metabolism of the whole body. It is an indispensable institution. In particular, the subcutaneous fat layer below the dermis is composed of adipocyte lobules, which acts as a cushion to absorb the protection of the internal organs of the skin against external heat, and to absorb the nutrients of the triglyceride (Lipid droplet), which is stored in a cell organelle and used as an energy source when necessary. However, as the age increases, the skin becomes damaged due to natural factors and various external stimuli. In particular, the activity and expression of collagen (collagen) and elastic fiber (elastin) At the same time, the fat production in the subcutaneous fat is reduced, so that the original function of each constituent cell in the skin is not achieved properly. Therefore, the most widely used method is fat graft surgery, which uses a syringe having a needle with a tulip needle-shaped tip and grabs its own fat, to be. However, it has been reported that 40 to 60% of the transplant volume is resorbed into the human body after the fat transplant surgery, and fat transplant surgery in areas where the skin is thin and the subcutaneous fat is small causes problems such as cell mass being touched And the survival rate and the survival period of transplanted fat are not as expected, and re-transplantation may be necessary.
이러한 문제점들이 있는 지방이식수술을 대체하면서 피하지방층을 충분히 증가시킬 수 있는 조성물에 대한 요구가 높아지고 있다. 또한 피부의 기본적인 구조는 피하지방조직에 의해서 유지되고, 이러한 피하지방조직은 피부의 볼륨과 강도를 좌우하는 역할을 하므로, 기존에 사용되고 있던 피부 외곽층의 진피나 표피에 탄력을 부여하는 방법보다 지방조직의 부피를 증가시키는 것이 피부의 볼륨감 유지에 좋은 해결책이 될 수 있다. There is a growing demand for a composition capable of sufficiently increasing the subcutaneous fat layer while replacing the fat transplant surgery with these problems. In addition, the basic structure of the skin is maintained by subcutaneous fat tissue, and since this subcutaneous fat tissue plays a role in the volume and intensity of the skin, it is more effective than the method of imparting elasticity to the dermis or epidermis of the skin outer- Increasing the volume of the tissue can be a good solution to maintain the volume of the skin.
따라서, 피부의 볼륨감 유지 및 증진을 위해 지방조직의 부피를 증가시킬 수 있는 조성물의 개발이 필요한 실정이었다. Therefore, it has been necessary to develop a composition capable of increasing the volume of adipose tissue in order to maintain and enhance the volume of the skin.
상기 문제점을 해결하기 위해, 본 발명은 지방조직을 증가시킬 수 있는 지방유래 줄기세포의 줄기세포성을 증진시키고 피부 볼륨감을 증가시킬 수 있는 조성물을 제공하는 것을 목적으로 한다.In order to solve the above problems, it is an object of the present invention to provide a composition capable of enhancing stem cell characteristics of fat-derived stem cells capable of increasing adipose tissue and increasing skin volume.
상기 목적을 달성하기 위해, 본 발명은 글리신-프롤린-하이드록시프롤린(Gly-Pro-Hyp)으로 구성된 트리펩타이드, 저분자량 히알루론산, 미네랄 및 비타민을 유효성분으로 함유하는 지방 유래 줄기세포의 줄기세포성 증진용 조성물을 제공한다. In order to achieve the above object, the present invention provides a stem cell comprising a tripeptide consisting of glycine-proline-hydroxy-proline (Gly-Pro-Hyp), a low molecular weight hyaluronic acid, a mineral and a vitamin Thereby providing a composition for improving sex.
또한 본 발명은 글리신-프롤린-하이드록시프롤린(Gly-Pro-Hyp)으로 구성된 트리펩타이드, 저분자량 히알루론산, 미네랄 및 비타민을 유효성분으로 함유하는 피부 볼륨감 증진용 미용 또는 성형용 조성물을 제공한다.The present invention also provides a cosmetic or molding composition for promoting skin volumizing, which comprises, as an active ingredient, a tripeptide composed of glycine-proline-hydroxyproline (Gly-Pro-Hyp), a low molecular weight hyaluronic acid, a mineral and a vitamin .
또한 본 발명은 글리신-프롤린-하이드록시프롤린(Gly-Pro-Hyp)으로 구성된 트리펩타이드, 저분자량 히알루론산, 미네랄 및 비타민을 유효성분으로 함유하는 피부 볼륨감 증진용 피부 외용제 조성물을 제공한다.The present invention also provides a composition for external application for skin, which comprises tripeptide consisting of glycine-proline-hydroxyproline (Gly-Pro-Hyp), low molecular weight hyaluronic acid, minerals and vitamins as active ingredients.
본 발명의 조성물은 트리펩타이드, 저분자량 히알루론산, 미네랄 성분 및 비타민 등이 세포를 둘러싼 공간에서 네트워크를 형성해 조직의 형태를 유지하고 지탱하며, 세포간의 신호전달 및 세포의 성장과 분화를 조절함으로써 지방유래 줄기세포의 줄기세포성을 증진시킴으로써 미용 또는 성형 목적의 지방조직 증가에 유용하다. 그래서, 본 발명의 조성물은 피부 볼륨감을 증진시키고, 지방유래 줄기세포 재생을 촉진시키고 손상된 피하지방의 기능을 회복시켜 주므로 피부 볼륨감 증진용 미용 또는 성형용 조성물로 활용 가능하고, 피부외용제 조성물로 활용 가능하다. The composition of the present invention comprises a tripeptide, a low-molecular-weight hyaluronic acid, a mineral component and a vitamin, forming a network in a space surrounding cells to maintain and support the morphology of the tissue, It is useful for increasing the adipose tissue for cosmetic or cosmetic purposes by promoting the stem cellity of the stem cell. Thus, the composition of the present invention improves skin volume, stimulates the regeneration of fat-derived stem cells, restores the function of damaged subcutaneous fat, and thus can be used as a cosmetic or molding composition for enhancing skin volume, It is possible.
도 1은 본 조성물의 세포독성을 파악하기 위하여 인간의 지방유래 줄기세포(human adipose derived stem cells, hADSCs)에 본 발명의 ECM 모사 조성물을 0.0001~10%의 농도로 처리하고 세포독성 정도를 CCK-8키트를 이용하여 확인한 결과를 나타낸 것이다. 리퀴덤(liquiderm)은 본 발명의 실시예 1의 조성물을 의미한다.
도 2는 지방유래 줄기세포 표지마커 유전자의 발현 수준을 측정하기 위해 CD29, 44, 73, 90, 105 유전자의 발현 패턴 변화를 나타낸 것이다. 리퀴덤은 본 발명의 실시예 1의 조성물을 의미한다.
도 3은 유세포 분석을 통해 지방유래 줄기세포를 발현하는 세포들의 숫자의 변화를 나타낸 것이다. 리퀴덤은 본 발명의 실시예 1의 조성물을 의미한다.
도 4는 본 발명의 조성물이 지방유래 줄기세포의 성장인자 발현에 미치는 영향을 파악하기 위하여 성장인자 어레이를 실시한 결과를 나타낸 것이다. 리퀴덤은 본 발명의 실시예 1의 조성물을 의미한다.FIG. 1 is a graph showing the cytotoxicity of the composition according to the present invention. FIG. 1 is a graph showing the cytotoxicity of CCM-1 in human adipose derived stem cells (hADSCs) treated with 0.0001-10% 8 kit. ≪ tb >< TABLE > Liquidum refers to the composition of Example 1 of the present invention.
FIG. 2 shows the expression patterns of the CD29, 44, 73, 90 and 105 genes in order to measure the expression level of the marker gene of the stem cell marker in fat. Liquidum means the composition of Example 1 of the present invention.
FIG. 3 shows changes in numbers of cells expressing adipose-derived stem cells through flow cytometry. Liquidum means the composition of Example 1 of the present invention.
FIG. 4 shows the results of a growth factor array to understand the effect of the composition of the present invention on the expression of growth factors of adipose-derived stem cells. Liquidum means the composition of Example 1 of the present invention.
이하, 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail.
글리신-프롤린-하이드록시프롤린(Gly-Pro-Hyp)으로 구성된 트리펩타이드, 저분자량 히알루론산, 미네랄 및 비타민을 유효성분으로 함유하는 지방 유래 줄기세포의 줄기세포성 증진용 조성물을 제공한다. 상기 줄기세포성(stemness) 이란 줄기세포의 자기재생능력과 항상성을 지니며 줄기세포의 활성이 있는 상태를 말하며 줄기세포성 증진이란 줄기세포성이 유지되거나 줄기세포의 활성이 증가하는 것을 의미한다.A stem cell comprising a tripeptide consisting of glycine-proline-hydroxy-proline (Gly-Pro-Hyp), low molecular weight hyaluronic acid, minerals and vitamins as effective ingredients. The term "stemness" refers to a state of stem cells having self-renewal ability and homeostasis of stem cells, and the term "stem cell growth" means that stem cell activity is maintained or the activity of stem cells is increased.
본 발명의 일 실시예에서 상기 조성물은 세포외 기질(extracellular matrix, ECM)을 모사한 것으로 동물 유래의 ECM과는 달리 식물 유래이거나 합성 물질로 구성된 ECM 모사 조성물이다.In one embodiment of the present invention, the composition mimics an extracellular matrix (ECM) and is an ECM mimetic composition, which is a plant-derived or synthetic material, unlike an animal-derived ECM.
본 발명의 일 실시예에서 상기 지방유래 줄기세포(Adipose derived stem cell: ADSC)는 인간의 지방유래 줄기세포(human adipose derived stem cells, hADSCs)이다.In one embodiment of the present invention, the adipose derived stem cell (ADSC) is human adipose derived stem cells (hADSCs).
본 발명의 일 실시예에서 상기 조성물은 지방조직을 증가시켜서 피부에 볼륨감을 증대시킨다. 상기 조성물은 지방유래 줄기세포를 지방세포로 분화하는 것을 촉진하여 지방체(Lipid droplet)을 생성시킨다. 그래서 지방조직을 증가시켜 특정 부위의 피부에 볼륨감을 증대시킨다. In one embodiment of the present invention, the composition increases fat tissue and increases the volume feel on the skin. The composition promotes the differentiation of adipose-derived stem cells into adipocytes to produce lipid droplets. So it increases the fat tissue and increases the volume feeling on the skin of the specific area.
본 발명의 일 실시예에서 상기 조성물은 지방유래 줄기세포 표지마커인 분화 클러스터 29(Cluster of Differentiation 29: 이하 CD29), 분화 클러스터 44(Cluster of Differentiation 44: 이하 CD44), 분화 클러스터 73(Cluster of Differentiation 73: 이하 CD73), 분화 클러스터 90(Cluster of Differentiation 90: 이하 CD90) 또는 분화 클러스터 105(Cluster of Differentiation 105: 이하 CD105)의 발현량을 증가시킬 수 있다. 음성 대조군과 비교하여 CD29, CD44, CD73, CD90 또는 CD105의 발현량 증가는 지방유래 줄기세포의 활성이 증가된다는 것을 의미한다. CD29는 인테그린 베타 1(integrin beta 1)의 다른 이름으로 지방 유래 줄기세포의 표지 마커이고, CD44는 Wnt 시그날링(signaling) 활성을 통해 지방 유래 줄기세포의 활성을 증가시킨다. CD73은 5'-뉴클레오타이다제(5`-nucleotidase)의 다른 이름으로 뉴클레오타이드를 뉴클레오사이드로 전환시키는 효소이고 지방유래 줄기세포의 표지마커이고, CD90은 티1(Thy1)의 다른 이름으로 줄기세포의 대표적인 표지마커 이며, CD105는 엔도그린(Endoglin)의 다른 이름으로 TGFb의 리셉터의 한 부분으로 지방유래 줄기세포의 표지마커이다.In one embodiment of the present invention, the composition comprises at least one of a cluster of differentiation markers 29 (CD29), a cluster of differentiation 44 (hereinafter referred to as CD44), a cluster of differentiation 73: hereinafter CD73), Cluster of Differentiation 90 (hereinafter referred to as CD90), or Cluster of Differentiation 105 (hereinafter referred to as CD105). The increase in the expression level of CD29, CD44, CD73, CD90 or CD105 as compared with the negative control means that the activity of adipose stem cells is increased. CD29 is another marker for
본 발명의 일 실시예에서 상기 조성물은 지방유래 줄기세포 성장인자, 상세하게는 줄기 세포 인자(Stem cell factor: 이하 SCF)의 발현량을 증가시킬 수 있다. 음성 대조군과 비교하여 성장인자의 발현량 증가는 지방유래 줄기세포의 활성이 증가된다는 것을 의미한다.In one embodiment of the present invention, the composition may increase the expression level of adipose-derived stem cell growth factor, in particular, stem cell factor (SCF). The increase in the expression level of the growth factor as compared with the negative control means that the activity of adipose stem cells is increased.
본 발명의 일 실시예에서 상기 조성물은 조성물 총 중량에 대하여 트리펩타이드 0.001~3 중량%, 저분자량 히알루론산 0.01~50 중량%, 미네랄 0.001~3 중량% 및 비타민 0.001~3 중량%를 함유할 수 있다. In one embodiment of the present invention, the composition may contain from 0.001 to 3% by weight of tripeptide, from 0.01 to 50% by weight of low molecular weight hyaluronic acid, from 0.001 to 3% by weight of minerals and from 0.001 to 3% by weight of vitamins, have.
본 발명의 트리펩타이드는 조성물 총 중량에 대하여 0.001 중량% 미만이면 그 효과가 미미하고, 3 중량%을 초과하면 그 함량 증가에 비해 효능 증가가 크지 않고 가격 경쟁력을 상실한다. If the tripeptide of the present invention is less than 0.001% by weight based on the total weight of the composition, the effect thereof is insignificant. If it exceeds 3% by weight, the tripeptide of the present invention does not increase in efficacy as much as its content and loses its price competitiveness.
상기 트리펩타이드(tripeptide)는 3개의 아미노산인 글리신-프롤린-하이드록시프롤린(Gly-Pro-Hyp)으로 구성되어 있으며 콜라겐의 생성을 촉진시키고 분자량이 낮기 때문에 피부 투과성이 높다. 또한, 상기 트리펩타이드는 합성으로 제조되기 때문에 순도가 높으며 동물 유래 성분이 아니므로 병원체 감염 등의 안전성 문제가 없다는 장점을 갖는다.The tripeptide is composed of three amino acids, glycine-proline-hydroxyproline (Gly-Pro-Hyp), promotes the production of collagen and has low permeability because of its low molecular weight. In addition, since the tripeptide is produced synthetically, it has high purity and is not an animal-derived component, so that it has an advantage that there is no safety problem such as pathogen infection.
콜라겐을 산으로 가수분해하면 다양한 단편이 생겨 트리펩타이드로 끊어내기가 어렵고, 효소를 이용하여 분해한다면 분자량을 작게 만드는데 한계점을 지니고 있다. 따라서, 본 발명은 아미노산을 기초로 하여 역으로 합성을 해나가는 방식을 이용함으로써 균질한 트리펩타이드를 수득할 수 있다. 본 발명의 트리펩타이드는 당업계에 통상적인 아미노산 합성 방법으로 제조될 수 있으며, 그 방법은 특별히 한정되지 않는다.Hydrolysis of collagen into acids results in various fragments that are difficult to break into tripeptides, and they have limitations in making the molecular weight smaller when degraded using enzymes. Therefore, the present invention can obtain a homogeneous tripeptide by using a method of reverse synthesis based on an amino acid. The tripeptide of the present invention can be produced by an amino acid synthesis method common in the art, and the method is not particularly limited.
본 발명의 저분자량 히알루론산은 조성물 총 중량에 대하여 0.001~50 중량%, 바람직하게는 0.01~10중량%로 사용될 수 있다. 상기 저분자량 히알루론산(hyaluronic acid)은 고분자 히알루론산보다 피부 흡수가 용이하며 우수한 피부 보습, 주름 개선, 상처 치유 및 항염 효과를 나타낸다. 본 발명의 저분자량 히알루론산은 500~10,000 달톤의 분자량을 가질 수 있다. 이는 500달톤 이하의 히알루론산은 제조 및 분리가 용이하지 않고, 10,000달톤을 초과하면 피부 투과가 어려워 그 효과를 나타내지 못하며 점도가 증가하여 제형 안정성이 나쁘기 때문이다.The low molecular weight hyaluronic acid of the present invention may be used in an amount of 0.001 to 50% by weight, preferably 0.01 to 10% by weight based on the total weight of the composition. The low molecular weight hyaluronic acid is more easily absorbed by the skin than the polymer hyaluronic acid and exhibits excellent skin moisturizing, wrinkle improvement, wound healing and anti-inflammatory effect. The low molecular weight hyaluronic acid of the present invention may have a molecular weight of 500 to 10,000 daltons. This is because the production and separation of hyaluronic acid of less than 500 daltons is not easy, and when it exceeds 10,000 daltons, skin permeation is difficult due to difficulty in exhibiting its effect, viscosity is increased, and formulation stability is poor.
상기 저분자량 히알루론산은 당업계에 통상적인 방법에 의해 제조될 수 있으며, 그 방법은 특별히 한정되지 않는다. 구체적인 예를 들면, 고온 가열 및 초음파를 이용하는 방법, 산 또는 염기 촉매에 의한 방법, 과황산암모늄 등의 분해 촉매를 이용한 방법 또는 히알루로니다아제 효소를 사용한 방법 등을 이용하여 고분자량의 히알루론산을 저분자화시킬 수 있다.The low-molecular-weight hyaluronic acid may be prepared by a conventional method in the art, and the method is not particularly limited. Specific examples thereof include a method using high temperature heating and ultrasonic waves, a method using an acid or base catalyst, a method using a decomposition catalyst such as ammonium persulfate, or a method using a hyaluronidase enzyme, and then a high molecular weight hyaluronic acid It can be reduced in molecular weight.
본 발명의 미네랄 성분은 조성물 총 중량에 대하여 0.001~3 중량%의 양으로 함유된다. 0.001 중량% 미만이면 그 효과가 미미하고, 3 중량%을 초과하면 피부의 항상성을 해칠 수 있기 때문에 바람직하지 않다.The mineral component of the present invention is contained in an amount of 0.001 to 3% by weight based on the total weight of the composition. If the amount is less than 0.001% by weight, the effect is insignificant. If the amount is more than 3% by weight, the homeostasis of the skin may be impaired.
상기 미네랄은 염화 마그네슘(magnesium chloride), 염화 칼슘(calcium chloride), 염화 칼륨(potassium chloride), 불화 마그네슘(Magnesium fluoride), 불화 망간(Manganese fluoride), 황산망간(Manganese sulfate), 황산 아연(zinc sulfate), 황산 마그네슘(magnesium sulfate) 및 황산 구리(copper sulfate)로 이루어진 군에서 선택된 1종 이상일 수 있으나, 이에 제한되지 않는다. The minerals may be selected from the group consisting of magnesium chloride, calcium chloride, potassium chloride, magnesium fluoride, manganese fluoride, manganese sulfate, zinc sulfate ), Magnesium sulfate, and copper sulfate. However, the present invention is not limited thereto.
상기 염화 마그네슘, 염화 칼슘 및 염화 칼륨은 표피 분화에 참여하고, 불화 마그네슘, 불화 망간, 황산 망간, 황산 아연, 황산 마그네슘 및 황산 구리와 같은 미네랄 성분은 세포 항상성과 피부 보호에 필요하다.The magnesium chloride, calcium chloride and potassium chloride participate in epidermal differentiation and mineral components such as magnesium fluoride, manganese fluoride, manganese sulfate, zinc sulfate, magnesium sulfate and copper sulfate are necessary for cell homeostasis and skin protection.
본 발명의 비타민은 조성물 총 중량에 대하여 0.001~3 중량%의 양으로 함유된다. 0.001 중량% 미만이면 그 효과가 미미하고, 3 중량%을 초과하면 변색, 변취 등을 일으켜 조성물의 안정도를 저해하기 때문이다.The vitamins of the present invention are contained in an amount of 0.001 to 3% by weight based on the total weight of the composition. If the amount is less than 0.001% by weight, the effect is insignificant. If the amount is more than 3% by weight, discoloration, deterioration, and the like are caused to deteriorate the stability of the composition.
상기 비타민은 이노시톨, 아스코르브산, 판토텐산, 니아신, 엽산, 티아민, 리보플라빈 및 이들의 유도체로 이루어진 군에서 선택된 1종 이상일 수 있으나, 이에 제한되지 않는다. The vitamin may be at least one selected from the group consisting of inositol, ascorbic acid, pantothenic acid, niacin, folic acid, thiamine, riboflavin and derivatives thereof, but is not limited thereto.
본 발명의 일 실시예는 글리신-프롤린-하이드록시프롤린(Gly-Pro-Hyp)으로 구성된 트리펩타이드, 저분자량 히알루론산, 미네랄 및 비타민을 유효성분으로 함유하는 피부 볼륨감 증진용 미용 또는 성형용 조성물을 제공한다.One embodiment of the present invention is a cosmetic or molding composition for enhancing the skin volume feeling comprising a tripeptide composed of glycine-proline-hydroxyproline (Gly-Pro-Hyp), a low molecular weight hyaluronic acid, a mineral and a vitamin as an active ingredient .
상기 유효성분은 조성물 총 중량에 대하여 0.0001~0.1 중량%, 상세하게는 0.0001~0.001 중량%를 함유될 수 있다. 0.0001 중량% 미만이면 효과가 미미하고, 0.1 중량% 초과하면 세포독성을 나타내는 문제가 있다.The active ingredient may contain 0.0001 to 0.1% by weight, more specifically 0.0001 to 0.001% by weight, based on the total weight of the composition. If the amount is less than 0.0001% by weight, the effect is insignificant. If the amount is more than 0.1% by weight, there is a problem of showing cytotoxicity.
상기 조성물은 비제한적인 예로 유방 조직 형성을 통한 가슴 확대, 미세지방 이식술, 자가지방 이식술 등 얼굴에 피부 볼륨감을 증진시켜 팔자 주름 및 미간주름 제거 및 탄력 유지를 목적으로 사용할 수도 있다.The composition may be used, for example, for the purpose of removing wrinkles and wrinkles and maintaining elasticity by enhancing the volume feeling on the face such as breast enlargement through breast tissue formation, micro fat grafting, autologous fat transplantation.
상기 조성물은 약학적 분야에서 통상의 방법에 따라 환자의 신체 내 투여에 적합한 단위투여형의 제제로 제형화시켜 투여할 수 있다. 이러한 목적에 적합한 제형으로는 비경구투여 제제로서 주사제 또는 국소 투여용 제제 등이 바람직하다. 주사용 제형은 등장성 수용액 또는 현탁액이 바람직하다. 그러나, 이때, 일반적으로 사용되는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 함께 사용할 수 있다. The composition may be formulated into a unit dosage form suitable for administration to a patient in the body according to conventional methods in the pharmaceutical field. As a formulation suitable for such purpose, an injectable preparation or a preparation for topical administration is preferably used as the parenteral administration preparation. The injectable formulations are preferably isotonic aqueous solutions or suspensions. However, at this time, diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, surfactants and the like can be used together.
이렇게 제조된 본 발명의 제제는 통상의 방법에 따라 비경구적으로, 예를 들면 특정 부위에 직접 투여할 수 있다. 이때, 조성물의 주입은 주사기를 이용하여 이루어진다. 상기 조성물의 1일 투여량은 1× 105 내지 1× 107세포/kg 체중, 바람직하게는 5× 105 내지 5× 106 세포/kg 체중이며, 1회 또는 수회로 나누어 투여할 수 있다. 그러나, 유효성분의 실제 투여량은 분화 및 증식시키고자 하는 지방세포의 양, 투여경로, 환자의 체중, 연령 및 성별 등 여러 관련 인자에 비추어 결정되어야 하는 것으로 이해되어야 하며, 따라서, 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다.The thus prepared preparation of the present invention can be administered parenterally according to a conventional method, for example, directly to a specific site. At this time, the composition is injected using a syringe. The daily dose of the composition is 1 × 10 5 to 1 × 10 7 cells / kg body weight, preferably 5 × 10 5 to 5 × 10 6 cells / kg body weight, and can be administered once or several times . It should be understood, however, that the actual dosage of the active ingredient should be determined in light of various relevant factors such as the amount of fat cells to differentiate and proliferate, the route of administration, the weight of the patient, age and sex, And are not intended to limit the scope of the invention in any way.
본 발명의 일 실시예는 글리신-프롤린-하이드록시프롤린(Gly-Pro-Hyp)으로 구성된 트리펩타이드, 저분자량 히알루론산, 미네랄 및 비타민을 유효성분으로 함유하는 피부 볼륨감 증진용 피부 외용제 조성물을 제공한다.One embodiment of the present invention provides a skin external composition composition for enhancing skin volume feeling comprising tripeptide consisting of glycine-proline-hydroxyproline (Gly-Pro-Hyp), low molecular weight hyaluronic acid, minerals and vitamins as active ingredients do.
상기 유효성분은 조성물 총 중량에 대하여 0.0001~0.1 중량%, 상세하게는 0.0001~0.001 중량%를 함유될 수 있다. 0.0001 중량% 미만이면 효과가 미미하고, 0.1 중량% 초과하면 세포독성을 나타내는 문제가 있다.The active ingredient may contain 0.0001 to 0.1% by weight, more specifically 0.0001 to 0.001% by weight, based on the total weight of the composition. If the amount is less than 0.0001% by weight, the effect is insignificant. If the amount is more than 0.1% by weight, there is a problem of showing cytotoxicity.
상기 피부 외용제 조성물은 화장료 조성물 또는 약학 조성물일 수 있다. The composition for external application for skin may be a cosmetic composition or a pharmaceutical composition.
상기 화장료 조성물의 제형은 특별히 제한되지 않으며, 목적하는 바에 따라 적절히 선택할 수 있다. 예를 들어 유연 화장수, 영양화장수, 마사지 크림, 에센스, 영양크림, 팩 등의 제형으로 제조할 수 있으나, 이에 제한되지 않는다.The formulation of the cosmetic composition is not particularly limited and may be appropriately selected according to the purpose. For example, it can be manufactured by a formulation such as a soft lotion, a nutritional lotion, a massage cream, an essence, a nutrition cream, a pack, and the like, but is not limited thereto.
상기 약학 조성물은 로션, 연고, 겔, 크림, 패취 또는 분무제와 같은 경피 투여형 제형일 수 있으나, 이에 제한되지 않는다.The pharmaceutical compositions may be in a transdermal dosage form such as, but not limited to, lotions, ointments, gels, creams, patches or sprays.
각 제형에 의한 피부 외용제 조성물에 있어서, 상기한 본 발명의 조성물 이외의 다른 성분들을 기타 피부 외용제의 제형 또는 사용 목적 등에 따라 당업자가 어려움 없이 적의 선정하여 배합할 수 있으며, 이 경우 다른 원료와 동시에 적용할 경우 상승효과가 일어날 수 있다.In the composition for external application for skin according to each formulation, components other than the composition of the present invention may be mixed and selected without difficulty by those skilled in the art depending on the formulation or use purpose of other external preparation for skin, etc. In this case, A synergistic effect can occur.
또한, 본 발명에 의한 조성물이 약학 조성물로 사용될 경우에, 방부제, 안정화제, 수화제 또는 유화 촉진제, 삼투업 조절을 위한 염 또는 완충제 등의 약학적 보조제 및 기타 치료적으로 유용한 물질을 추가로 함유할 수 있으며, 통상적인 방법에 따라 다양한 경구 또는 비경구 투여 형태로 제형화할 수 있다. Further, when the composition according to the present invention is used as a pharmaceutical composition, it may further contain a preservative, a stabilizer, a wetting agent or an emulsifying accelerator, a pharmaceutical adjuvant such as a salt or buffer for controlling the osmotic pressure, and other therapeutically useful substances And can be formulated into various oral or parenteral dosage forms according to conventional methods.
유효성분의 실제 투여량은 증상의 중증도, 선택된 투여 경로, 대상의 연령, 성별, 체중 및 건강상태 등의 여러 관련 인자에 비추어 결정되어야 하는 것으로 이해되어야 한다.It should be understood that the actual dosage of the active ingredient should be determined in light of various relevant factors such as the severity of the symptoms, the route of administration selected, the age, sex, weight and health status of the subject.
일반적으로 유효성분의 투여량은 0.001mg/kg/일 내지 대략 2000mg/kg/일의 범위이다. 더 바람직한 투여량은 0.5mg/kg/일 내지2.5mg/kg/일이다.Generally, the dosage of active ingredient is in the range of 0.001 mg / kg / day to about 2000 mg / kg / day. A more preferred dosage is 0.5 mg / kg / day to 2.5 mg / kg / day.
본 발명에 의한 지방유래 줄기세포의 줄기세포성을 증진시키는 조성물의 적용 부위는 신체의 모든 지방 조직을 포함하며, 특정 부위에 한정하지는 않지만, 예를 들면, 지방층이 적은 얼굴 부위를 포함할 수 있다. 또한 상기 지방조직의 증가 효과로는 미용 또는 성형 목적의 지방조직 증가 효과로 인해 피부 볼륨감 증가 효과가 있으나, 이에 한정되지는 않는다. The application site of the composition for promoting stem cell function of the adipose-derived stem cells according to the present invention includes all the adipose tissues of the body and may include, for example, . In addition, the effect of increasing the amount of adipose tissue may be an effect of increasing the volume of skin due to the effect of increasing adipose tissue for cosmetic or cosmetic purposes, but is not limited thereto.
이하 하기 실시예 및 시험예를 들어 본 발명을 보다 구체적으로 설명하지만, 이는 본 발명을 예시하기 위한 것일 뿐 본 발명의 범위가 이들만으로 한정되는 것은 아니다.
Hereinafter, the present invention will be described in more detail with reference to the following Examples and Test Examples, which should not be construed as limiting the scope of the present invention.
[실시예 1] [Example 1]
하기 표 1의 조성으로 세포 외 기질(ECM)을 모사한 조성물을 제조하였다. 이노시톨, 아스코르브산은 각각 비타민 B, C로, 니아신아마이드는 비타민 B3인 니아신의 유도체로 사용되었다. 황산아연, 염화칼륨, 염화칼슘, 황산마그네슘 및 황산구리는 미네랄 성분으로 사용되었다. 올리고 히알루론산은 ㈜바이오랜드, 트리펩타이드는 에이앤팹(A&PEP) (주)에서 구입하여 사용하였다.A composition having an extracellular matrix (ECM) replicated in the composition of Table 1 below was prepared. Inositol and ascorbic acid were used as vitamins B and C, respectively, and niacinamide was used as a derivative of niacin, vitamin B3. Zinc sulfate, potassium chloride, calcium chloride, magnesium sulfate and copper sulfate were used as minerals. Oligo hyaluronic acid was purchased from Biorand Co., and tripeptide was purchased from A & PEP Co., Ltd.
무게평균분자량 5,000달톤Oligo hyaluronic acid (Oligo hyaluronic acid)
Weight average molecular weight 5,000 daltons
[시험예 1] 인간 지방유래 줄기세포에서의 세포독성 파악[Test Example 1] Cytotoxicity of human adipose derived stem cells
지방유래 줄기세포를 75 cm2 T-flask에 계대배양을 하여, CO2 배양기 (CO2 Incubator)에서 37°C, 5% CO2 조건하에서 배양을 하였다. 통상적으로 두 번째 또는 세 번째에서 세포의 계대 배양(passage)을 진행하였다. Fat-derived stem cells were subcultured in a 75 cm 2 T-flask and cultured in a CO 2 incubator (CO2 Incubator) at 37 ° C and 5% CO 2 . Typically, passage of cells was performed in the second or third cycle.
인간의 지방유래 줄기세포(human adipose derived stem cells, hADSCs)를 론자사(Lonza, Inc. Walkersville, MD, USA)에서 구입하여 론자사의 지침서에 따라 배양하였다. 본 조성물의 세포독성을 파악하기 위하여 0.0001~10%의 농도로 처리하고 세포독성 정도를 CCK-8키트 (Dojindo)를 이용하여 확인하였다. 도 1의 결과를 보면, 0.001%의 농도 처리시 세포독성 없이 약 10% 정도의 세포분열증진 효과를 확인할 수 있었다.
Human adipose derived stem cells (hADSCs) were purchased from Lonza, Inc. (Walkersville, MD, USA) and cultured according to Lonza's guidelines. To determine the cytotoxicity of the composition, the concentration was 0.0001-10%, and the degree of cytotoxicity was confirmed using a CCK-8 kit (Dojindo). As shown in FIG. 1, about 10% cell division enhancement was observed without treatment of cytotoxicity at a concentration of 0.001%.
[시험예 2] 지방유래 줄기세포 표지 마커 유전자의 발현 수준에 대한 효과 측정 [Test Example 2] Measurement of the effect of expression level of adipose-derived stem cell marker marker gene
지방유래 줄기세포의 산화스트레스는 과산화수소수 (H2O2)를 200 uM 농도로 24시간 처리하였고, 지방유래 줄기세포의 줄기세포성 증진효과를 파악하기 위해서 본 조성물을 0.001%로 배지에 첨가하였다. 지방유래 줄기세포의 세포 배양액을 제거하고, 2 ml의 인산염 완충액(Phosphate Buffered Saline, PBS)으로 세포를 세척한다음, 이후, 트리졸 시약(Trizol reagent, Invitrogen, Carlsbad, CA, USA)을 사용하여 세포 내의 RNA를 분리하였다. The oxidative stress of the adipose-derived stem cells was treated with hydrogen peroxide (H 2 O 2 ) at a concentration of 200 uM for 24 hours, and the composition was added to the medium in an amount of 0.001% in order to evaluate the stem cell growth effect of the adipose-derived stem cells . The cells were washed with 2 ml of phosphate buffered saline (PBS) and then treated with triazol reagent (Invitrogen, Carlsbad, Calif., USA) RNA was isolated from the cells.
분리된 RNA를 키아젠사의 RNA 키트(QIAGEN RNeasy kt, QIAGEN, Valencia, CA)로 한번 더 정제한 후, 애질런트사의 바이오어낼라이저 2100 모델 기기(Agilent 2100 BioAnalyzer, Agilent Technologies, Santa Clara, CA, USA)를 사용하여 RNA의 질(quality)을 확인하였다. 인비트로젠사의 역전사키트(Superscript Reverse Transcriptase (RT) kit, Invitrogen, Carlsbad, CA)를 이용하여 상기 RNA로부터 cDNA를 합성하였고, 이를 실시간 역전사 중합 효소 연쇄반응(real time-reverse transcription polymerase chain reaction, Q-RT-PCR)을 통해 정량적으로 분석하였다. (Agilent 2100 BioAnalyzer, Agilent Technologies, Santa Clara, Calif., USA) after purification of the separated RNA with an RNA kit (QIAGEN RNeasykt, QIAGEN, Valencia, CA) Were used to confirm the quality of the RNA. CDNA was synthesized from the RNA using a reverse transcription kit (Superscript Reverse Transcriptase (RT) kit, Invitrogen, Carlsbad, Calif.), And the cDNA was synthesized using real time reverse transcription polymerase chain reaction -RT-PCR).
지방유래 줄기세포에서 CD29, 44, 73, 90, 105 유전자의 발현 패턴 변화를 어플라이드바이오시스템사의 택맨 유전자 발현 시스템(TaqMangene expression assay kit, Applied Biosystems, Foster City, CA) (CD29 유전자 프라이머: Hs00559595_m1, CD44 유전자 프라이머: Hs01075861_m1, CD73 유전자 프라이머: Hs01573922_m1, CD90 유전자 프라이머: Hs00174816_m1, CD105 유전자 프라이머: Hs00923996_m1)을 이용하여 평가하였으며, 그 결과를 도 2에 나타내었다. 각 유전자의 발현 양이 음성대조군 대비, 약 50% 정도 증가함을 확인하였다. 이러한 증가는 통계적으로 유의하였으며, 통계는 양측 스튜던트 t 테스트로 검증하였으며, p 값이 0.05 이하일 때 유의적인 차이가 있다고 표시하였다.
The expression patterns of the CD29, 44, 73, 90 and 105 genes in adipose-derived stem cells were measured using a TaqMangene Expression Assay Kit (Applied Biosystems, Foster City, Calif.) (Applied Biosystems, Foster City, Calif .; Hs00559595_m1, CD44 Gene primer: Hs01075861_m1, CD73 gene primer: Hs01573922_m1, CD90 gene primer: Hs00174816_m1, CD105 gene primer: Hs00923996_m1). The results are shown in FIG. The expression level of each gene was increased by about 50% as compared with the negative control. These increases were statistically significant, and statistical tests were verified by both Student's t test, indicating a significant difference when the p-value was less than 0.05.
[시험예 3] 유세포 분석을 통한 지방유래 줄기세포의 측정[Test Example 3] Measurement of fat-derived stem cells through flow cytometry
인간 지방유래줄기세포를 0.25 % 트립신(Trypsin -EDTA)으로 75 cm2 Ti 플라스크로부터 분리한 뒤 1500 rpm에서 5분간 세포를 가라앉힌 다음, 배양액을 제거한 뒤에 3 ml의 차단버퍼: Blocking buffer, 2% 우태아혈청(Fetal calf serum: FCS), 2% 소의 혈청 알부민(Bovine Serum Albumin(BSA) KGM-2)을 넣어주어 세포를 현탁하였다. Human adipose tissue-derived stem cells were separated from 75 cm 2 Ti flasks with 0.25% Trypsin-EDTA, and the cells were allowed to settle for 5 minutes at 1500 rpm. After removing the culture medium, 3 ml of blocking buffer: blocking buffer, 2% The cells were suspended by adding fetal calf serum (FCS) and 2% bovine serum albumin (BSA) KGM-2.
4°C에서 15분 동안 세포 (약 106 개의 세포)를 적용시킨 다음, FITC (Fluorescein isothiocyanate)가 부착된 CD44 항체(Cat No. 560977)(BD Pharmingen, CA, US)와 PE-Cy(phycoerythrin-cyanine)가 부착된 CD29 항체(Cat No. 559882) (BD Pharmingen, CA, US)을 각각 100: l로 넣어주어, 4°C 하에서 45분 동안 반응시켰다. 한편, 음성 대조군으로 사용되는 세포에는 FITC Rat IgG2a, k 아이소타이프(isotype)(Cat No. 555742)와PE-Cy5 mouse IgG1 k 아이소타이프(Cat No. 555750)를 역시 100: l로 넣어주어, 4°C 하에서 45분 동안 반응시켰다.Cells (approximately 10 6 cells) were applied for 15 min at 4 ° C and then stained with FITC (Fluorescein isothiocyanate) -containing CD44 antibody (Cat No. 560977) (BD Pharmingen, CA, US) and PE- (cat. No. 559882) (BD Pharmingen, CA, US) with 100 ng / ml-Cyanine was added to each well and reacted at 4 ° C for 45 minutes. FITC Rat IgG2a, k isotype (Cat No. 555742) and PE-Cy5 mouse IgG1 k isotype (Cat No. 555750) were also added to the cells used as the negative control, Gt; C < / RTI > for 45 minutes.
반응이 끝난 후 3 ml의 워싱 버퍼(2% Bovine Serum Albumin (BSA) KGM-2)로 두 번 세척한 후, 세포를 현탁하였다. 이후 FACSCalibur(BD Bioscience, San Jose, CA, U.S)로 지방유래 줄기세포에서 CD29, 44을 발현하는 세포들의 숫자의 변화를 관찰하고, 이를 도 3, 표 2에 나타내었다. After the reaction was completed, the cells were washed twice with 3 ml of washing buffer (2% Bovine Serum Albumin (BSA) KGM-2), and then the cells were suspended. Thereafter, changes in the number of cells expressing CD29, 44 in adipose-derived stem cells were observed with FACSCalibur (BD Bioscience, San Jose, Calif., U. S.) and are shown in FIG.
도 3과 표 2을 참조하면, 음성대조군에 비해서 CD29는85%. CD44는 42% 증가하였음을 확인할 수 있다.
Referring to FIG. 3 and Table 2, CD29 was 85% as compared to negative control. CD44 was increased by 42% .
[시험예 4] 지방유래 줄기세포의 성장인자 발현 확인[Test Example 4] Expression of Growth Factor in Fat-Derived Stem Cells
본 발명의 조성물이 지방유래 줄기세포의 성장인자 발현에 미치는 영향을 파악하기 위하여 성장인자 어레이 (Growth factor array, Raybio)를 실시하였다.Growth factor arrays (Growth factor array, Raybio) were performed to understand the effect of the composition of the present invention on the expression of growth factors in adipose derived stem cells.
각 조건별로 배양한 지방유래 줄기세포의 배양액(conditioned medium)을 수획하여 성장인자 어레이를 수행하였다. 2ml의 차단 버퍼를 실온에서 30분 처리한 후 1ml의 배양액을 상온에서 2시간 처리하였다. 이후 2ml의 워싱버퍼로 5분간 5회 세척하고 바이오틴(Biotin)이 결합된 항성장인자(anti-growth factor) 항체로 상온에서 2시간 반응시킨다. 추가적으로 2ml의 워싱버퍼로 5분간 5회 세척하고 HRP가 결합한 스트렙토아비딘(streptoavidin)을 2ml 처리하여 2시간 반응하고 워싱버퍼로 세척후 디텍션(detection) 버퍼로 반응시켜 LAS-3000 (Fujifilm)기기로 현상하였다. Growth factor arrays were performed by collecting the conditioned medium of adipose - derived stem cells cultured under each condition. 2 ml of blocking buffer was treated at room temperature for 30 minutes and then 1 ml of the culture was treated at room temperature for 2 hours. The cells were then washed 5 times with 2 ml of wash buffer and reacted with biotin-conjugated anti-growth factor antibody for 2 hours at room temperature. After washing with 2 ml of washing buffer 5 times for 5 minutes, 2 ml of HRP-conjugated streptoavidin was treated for 2 hours, washed with washing buffer, and reacted with detection buffer to obtain LAS-3000 (Fujifilm) Respectively.
도 4에 의하면 총 41종의 성장인자를 분석한 결과, 산화 스트레스에 의해 분비량이 10%이상 감소하고 본 조성물 처리에 의해 10% 이상 증가한 성장인자는 Stem cell factor (SCF)가 분석되었다. 이러한 증가는 통계적으로 유의하였으며, 통계는 양측 스튜던트 t 테스트로 검증하였으며, p 값이 0.05 이하일 때 유의적인 차이가 있다고 표시하였다.
As shown in FIG. 4, when the growth factor was analyzed by 41 kinds of growth factors, the amount of secretion was decreased by 10% or more by oxidative stress, and the growth factor which was increased by 10% or more by the present composition treatment was analyzed for the stem cell factor (SCF). These increases were statistically significant, and statistical tests were verified by both Student's t test, indicating a significant difference when the p-value was less than 0.05.
[제형예 1] 유연화장수[Formulation Example 1] Flexible longevity
상기 실시예 1을 함유하는 유연화장수 제형을 하기 표 3에 나타낸 조성으로 통상의 제조 방법에 따라 제조하였다.The formulated softening water containing the above-mentioned Example 1 was prepared according to a conventional production method with the composition shown in Table 3 below.
[제형예 2] 영양화장수[Formulation Example 2] Nutritional lotion
상기 실시예 1을 함유하는 영양화장수 제형을 하기 표 4에 나타낸 조성으로 통상의 제조 방법에 따라 제조하였다.A nutritional lotion formulation containing the above Example 1 was prepared according to a conventional preparation method with the composition shown in Table 4 below.
[제형예 3] 크림[Formulation Example 3] Cream
상기 실시예 1을 함유하는 크림 제형을 하기 표 5에 나타낸 조성으로 통상의 제조 방법에 따라 제조하였다.The cream formulations containing Example 1 were prepared according to the usual preparation methods with the compositions shown in Table 5 below.
이상으로 본 발명의 특정한 부분을 상세히 기술하였는 바, 당업계의 통상의 지식을 가진 자에게 있어서 이러한 구체적인 기술은 단지 바람직한 구현예일 뿐이며, 이에 본 발명의 범위가 제한되는 것이 아닌 점은 명백하다. 따라서, 본 발명의 실질적인 범위는 첨부된 청구항과 그의 등가물에 의하여 정의된다고 할 것이다.While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the same is by way of illustration and example only and is not to be construed as limiting the scope of the present invention. Accordingly, the actual scope of the present invention will be defined by the appended claims and their equivalents.
Claims (15)
상기 조성물은 지방조직을 증가시켜 피부에 볼륨감을 증진시키는 것이고,
상기 조성물은 지방유래 줄기세포 표지마커인 CD29, CD44, CD73, CD90 또는 CD105의 발현량을 증가시키고,
상기 조성물은 줄기세포 인자(SCF, Stem Cell Factor)의 발현량을 증가시키고,
상기 조성물은 조성물 총 중량에 대하여 트리펩타이드 0.001~3 중량%, 히알루론산 0.01~50 중량%, 미네랄 0.001~3 중량% 및 비타민 0.001~3 중량%를 함유하는 것이고,
상기 조성물은 트리펩타이드와 히알루론산의 중량비가 1 : 2 내지 50,000이고,
상기 조성물은 조성물 총 중량에 대하여 트리펩타이드 및 히알루론산의 중량의 합이 미네랄 및 비타민의 중량의 합보다 큰 것인, 줄기세포성 증진용 미용 또는 성형용 조성물. A tripeptide consisting of glycine-proline-hydroxyproline (Gly-Pro-Hyp), hyaluronic acid having a molecular weight of 500 to 10,000 daltons, a stem cell enhancer for fat-derived stem cells containing minerals and vitamins as active ingredients Or a composition for molding,
The composition is intended to increase the volume of the skin by increasing adipose tissue,
The composition increases the expression level of adipose-derived stem cell markers CD29, CD44, CD73, CD90 or CD105,
The composition increases the expression level of stem cell factor (SCF, Stem Cell Factor)
The composition contains 0.001 to 3% by weight of tripeptide, 0.01 to 50% by weight of hyaluronic acid, 0.001 to 3% by weight of minerals and 0.001 to 3% by weight of vitamins based on the total weight of the composition,
Wherein the weight ratio of tripeptide to hyaluronic acid is 1: 2 to 50,000,
Wherein the composition is such that the sum of the weights of the tripeptide and hyaluronic acid with respect to the total weight of the composition is greater than the sum of the weights of minerals and vitamins.
상기 조성물은 세포외 기질(extracellular matrix: 이하 ECM)을 모사한 것을 특징으로 하는 줄기세포성 증진용 미용 또는 성형용 조성물.The method according to claim 1,
Wherein the composition is an extracellular matrix (hereinafter referred to as " ECM ").
상기 지방유래 줄기세포는 인간의 지방유래 줄기세포(human adipose derived stem cells: 이하 hADSCs)인 것을 특징으로 하는 줄기세포성 증진용 미용 또는 성형용 조성물.The method according to claim 1,
Wherein the adipose-derived stem cells are human adipose derived stem cells (hereinafter, referred to as " hADSCs ").
상기 미네랄은 염화 마그네슘(magnesium chloride), 염화 칼슘(calcium chloride), 염화 칼륨(potassium chloride), 불화 마그네슘(Magnesium fluoride), 불화 망간(Manganese fluoride), 황산망간(Manganese sulfate), 황산 아연(zinc sulfate), 황산 마그네슘(magnesium sulfate) 및 황산 구리(copper sulfate)로 이루어진 군에서 선택된 1종 이상인 것을 특징으로 하는 줄기세포성 증진용 미용 또는 성형용 조성물.The method according to claim 1,
The minerals may be selected from the group consisting of magnesium chloride, calcium chloride, potassium chloride, magnesium fluoride, manganese fluoride, manganese sulfate, zinc sulfate Wherein the composition is at least one selected from the group consisting of magnesium sulfate, and copper sulfate.
상기 비타민은 이노시톨, 아스코르브산, 판토텐산, 니아신, 엽산, 티아민, 리보플라빈 및 이들의 유도체로 이루어진 군에서 선택된 1종 이상인 것을 특징으로 하는 줄기세포성 증진용 미용 또는 성형용 조성물.The method according to claim 1,
Wherein the vitamin is at least one selected from the group consisting of inositol, ascorbic acid, pantothenic acid, niacin, folic acid, thiamine, riboflavin and derivatives thereof.
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| CN201110385108.3A CN102475636B (en) | 2010-11-30 | 2011-11-28 | The stem cell property enhancement composition of the adipose-derived stem cells of analog cell epimatrix |
| HK12110837.2A HK1169959B (en) | 2010-11-30 | 2012-10-30 | Extracellular matrix-mimetic composition for promoting the stemness of adipose-derived stem cell |
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| KR102087136B1 (en) * | 2013-07-31 | 2020-03-10 | (주)아모레퍼시픽 | Skin external composition comprising bio water mimic fluid |
| CN107468704A (en) * | 2017-09-14 | 2017-12-15 | 上海市第十人民医院 | Application of the magnesium sulfate in soft tissue swelling disease and its eye mask patch containing magnesium sulfate |
| CN113728091B (en) * | 2019-06-10 | 2024-04-12 | 布瑞克斯奥根株式会社 | Compositions for promoting stem cell-derived exosome production and increasing dryness |
| KR102123268B1 (en) * | 2019-06-11 | 2020-06-17 | 브렉소젠 주식회사 | Composition For Promoting Production of Stem Cell-derived Exosomes and Increasing Stemness comprising Hyaluronic acid |
| KR20220091295A (en) * | 2020-12-23 | 2022-06-30 | 주식회사 엘지에너지솔루션 | Re-injection method of electrolyte and secondary battery capable of re-injecting electrolyte |
| AU2022238571A1 (en) | 2021-03-18 | 2023-09-14 | Seagen Inc. | Selective drug release from internalized conjugates of biologically active compounds |
| CN116836227B (en) * | 2023-05-24 | 2023-12-08 | 艾一生命科技(广东)有限公司 | Application of synthetic polypeptide in maintaining stem cell dryness |
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| US20030068297A1 (en) * | 2001-08-18 | 2003-04-10 | Deepak Jain | Composition and methods for skin rejuvenation and repair |
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| KR20100036389A (en) * | 2006-01-27 | 2010-04-07 | (주)프로스테믹스 | Cosmetic composition containing conditioned media of adipose-derived stem cell |
| WO2008003321A2 (en) * | 2006-07-07 | 2008-01-10 | Novozymes Biopolymer A/S | Compositions with several hyaluronic acid fractions for cosmetic use |
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| SOFW-Journal. Vol. 134, Edition 11-2008, pp. 1-5 (2008)* |
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| CN102475636B (en) | 2016-05-18 |
| KR20120058866A (en) | 2012-06-08 |
| CN102475636A (en) | 2012-05-30 |
| HK1169959A1 (en) | 2013-02-15 |
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