KR102537521B1 - Composition for preventing hair loss and promoting hair growth - Google Patents
Composition for preventing hair loss and promoting hair growth Download PDFInfo
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- KR102537521B1 KR102537521B1 KR1020200147509A KR20200147509A KR102537521B1 KR 102537521 B1 KR102537521 B1 KR 102537521B1 KR 1020200147509 A KR1020200147509 A KR 1020200147509A KR 20200147509 A KR20200147509 A KR 20200147509A KR 102537521 B1 KR102537521 B1 KR 102537521B1
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- KR
- South Korea
- Prior art keywords
- hair
- composition
- hair growth
- promoting
- hair loss
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Abstract
본 발명은 탈모방지 및 모발성장 촉진용 조성물에 관한 것이다. 본 발명의 탈모방지 및 모발성장 촉진용 조성물은 모유두 세포의 증식을 촉진하고, Wnt/베타-카테닌 신호전달계를 활성화시켜, 탈모방지 및 모발성장 촉진 효과가 현저하게 우수하다. 또한, 본 발명의 탈모방지 및 모발성장 촉진용 조성물은 특정한 2 이상의 유효성분의 조합을 통해 탈모방지 및 모발성장 촉진에 현저한 상승 효과를 나타낼 수 있다.The present invention relates to a composition for preventing hair loss and promoting hair growth. The composition for preventing hair loss and promoting hair growth according to the present invention promotes the proliferation of dermal papilla cells and activates the Wnt/beta-catenin signaling system, thereby exhibiting remarkably excellent effects of preventing hair loss and promoting hair growth. In addition, the composition for preventing hair loss and stimulating hair growth of the present invention can exhibit a remarkable synergistic effect in preventing hair loss and stimulating hair growth through a combination of two or more specific active ingredients.
Description
본 발명은 모발 성장 촉진을 위한 조성물에 관한 것으로, 모발의 신규성장 또는 성장 촉진을 유도하는 성분을 함유하는 모발 성장 촉진을 위한 탈모 방지 및 발모 촉진용 조성물에 관한 것이다.The present invention relates to a composition for promoting hair growth, and relates to a composition for preventing hair loss and promoting hair growth for promoting hair growth, which contains a component that induces new growth or growth of hair.
시대가 변하면서 미용에 대한 관심이 날로 높아가는 과정에 모발은 중요한 한 부분을 차지하고 있다. 모발은 피부 표면에서 생산된 가늘고 각질화된 구조다. 이것은 외부 충격에 대한 쿠션 역할과 더불어 직사광선, 한랭, 마찰, 위험 등 외부 자극으로부터 인체를 보호하고 신체에 유해한 비소, 수은, 아연 등의 중금속이 체외로 배출되는 기능을 하며 현대에 와서는 장식의 미용 측면도 강조되고 있다. 그러나 식생활 변화나 내외적 스트레스 증가를 비롯하여 여러 원인에 의해 탈모를 호소하는 사람들이 늘어나고 있다. 탈모는 유전적 요인이 가장 주요한 원인으로 작용한다고 알려져 있지만 앞서 말한 바와 같이 사회적 스트레스의 증가, 환경오염, 잦은 파마와 염색, 및 잘못된 두피 관리들도 탈모의 원인으로 대두되고 있다.As the times change, hair takes up an important part in the process of increasing interest in beauty day by day. Hair is a thin, keratinized structure produced on the surface of the skin. It serves as a cushion against external impact, protects the human body from external stimuli such as direct sunlight, cold, friction, and danger, and discharges harmful heavy metals such as arsenic, mercury, and zinc to the outside of the body. Aspects are also emphasized. However, an increasing number of people complain of hair loss due to various causes, including changes in dietary life or increased internal and external stress. It is known that genetic factors act as the main cause of hair loss, but as mentioned above, increased social stress, environmental pollution, frequent perms and dyeing, and incorrect scalp management are also emerging as causes of hair loss.
사람의 모발은 약 10만-15만 개 정도이며, 각각의 모발은 서로 다른 성장 주기를 가진다. 발생 초기 모낭(hair follicle)의 형성은 베타-카테닌(β-catenin)의 작용에 의해 기저층 표피 세포에 의해 플라코드(placode)가 형성된다(Sarah E. Miller, 2002). 형성된 플라코드로부터 신호를 받은 진피 섬유아세포가 피부 응축체(dermal condensate)를 형성한다. 동시에 플라코드는 진피 방향으로 성장, 함입하여 피부 응축체와 합쳐 일차 모발 배종(primary hair germ)을 형성한다. 모발 배종을 형성한 표피 세포는 발생하는 진피 방향으로 길게 성장하고, 다층으로 이루어진 긴 기둥형태의 구조물인 헤어 페그(hair peg)를 형성하는 동시에 피부 응축체는 구형의 모유두(dermal papilla)로 형성된다. 헤어 페그의 끝쪽은 점점 두꺼워져 모구(hair bulb)가 형성되는데 모구는 모유두를 감싼 형태가 되어 모낭이 완성되고 모낭 내부의 표피 세포가 분화하여 모발이 생성된다. Human hair is about 100,000 to 150,000, and each hair has a different growth cycle. In the early stage of hair follicle formation, placodes are formed by basal layer epidermal cells by the action of β-catenin (Sarah E. Miller, 2002). Dermal fibroblasts receiving signals from the formed placodes form dermal condensates. At the same time, placodes grow and invade in the direction of the dermis and combine with skin condensates to form primary hair germs. Epidermal cells that form hair germs grow long in the direction of the developing dermis, and form hair pegs, which are long, multi-layered, columnar structures, while skin condensates are formed as spherical dermal papilla. . The end of the hair peg gradually becomes thicker to form a hair bulb. The hair bulb wraps around the dermal papilla, completes the hair follicle, and differentiates the epidermal cells inside the hair follicle to produce hair.
처음 생성된 모발은 성장기 시기를 거쳐 퇴화기, 휴지기로 들어가며, 이후 모발이 탈락된 후 다시 성장기로 들어가는 주기를 돈다. 모발 성장 주기는 3단계로 구성되는데, 모발이 가장 활발하게 성장하는 성장기(anagen stage), 모발의 퇴화가 시작되는 퇴화기(catagen stage), 및 모발의 성장이 멈추거나 휴식에 접어드는 휴지기(telogen stage)로 분류된다.The hair that is first generated goes through a growth phase, a degeneration phase, and a resting phase, and then goes through a cycle of falling out and entering the growth phase again. The hair growth cycle is composed of three stages: an anagen stage in which hair grows most actively, a catagen stage in which hair degeneration begins, and a telogen stage in which hair growth stops or enters rest. ) is classified as
이러한 모발의 성장 주기를 조절하는데 있어서, 모낭을 구성하는 모유두 세포 및 모낭 줄기세포를 포함한 외모근초 세포(outer root sheath cell)의 활성, 및 이들 세포에서 생산되는 다양한 사이토카인 및 성장 인자가 중요한 역할을 한다고 알려져 있다. 예를 들어 DKK-1(Dickkopf-1)은 모낭 성장 저해와 사멸에 중요한 역할을 한다(J Invest. Dermatol,2008:128(2)). 한편, 주기적인 모발 성장을 위해서는 모낭의 재생과 줄기세포의 활성화가 이루어져야 하며, 이는 Wnt/β-카테닌의 생성 및 활성화에 의해 이루어지는 것으로 알려져 있다(Nature 2007:447(7142)). In regulating the growth cycle of such hair, the activity of outer root sheath cells, including dermal papilla cells and hair follicle stem cells constituting the hair follicle, and various cytokines and growth factors produced by these cells play an important role. It is known to do For example, DKK-1 (Dickkopf-1) plays an important role in hair follicle growth inhibition and death (J Invest. Dermatol, 2008:128(2)). Meanwhile, regeneration of hair follicles and activation of stem cells are required for periodic hair growth, which is known to be achieved by the production and activation of Wnt/β-catenin (Nature 2007:447(7142)).
이외에도 VEGF, IGF-1, 또는 FGF 등의 성장인자는 모발의 성장기를 촉진시키는 것으로 알려져 있고, TGFb-1, EGF 등은 모낭의 퇴행기를 유도하는 성장 인자로 알려져 있다. In addition, growth factors such as VEGF, IGF-1, or FGF are known to promote the growth phase of hair, and TGFb-1, EGF, etc. are known as growth factors that induce the catagen phase of hair follicles.
일반적으로 탈모증이라 함은 이러한 주기 중에서 성장기의 모발 비율이 짧아지고 퇴행기 또는 휴지기의 모발이 많아져 비정상적으로 모발이 탈락하는 숫자가 많아지는 것을 일컫는다. 탈모는 정상적인 현상이나 정상인 사람이 성장기 상태의 모발이 많은 데 비해, 보통 탈모증(Alopecia)인 사람은 휴지기 상태의 모발이 많아 눈으로 보이는 탈모 현상이 나타내게 된다. 탈모증을 나타내는 사람들의 특징은 모발의 소형화에 있다. 탈모가 진행될수록 성장기의 기간이 짧아지고 퇴행기, 휴지기로의 이행이 촉진되며 뒤이은 모유두의 부피가 작아져 모낭은 점점 소형화된다. 따라서 탈모의 치료를 위해서는 휴지기 상태의 모낭을 성장기로 빨리 갈 수 있도록 하고, 짧아진 성장기를 늘려주는 것이 중요하다.In general, alopecia refers to an increase in the number of hairs that fall out abnormally because the hair ratio in the growth phase is shortened and the hair in the catagen or telogen phase increases during this cycle. Hair loss is a normal phenomenon, but a normal person has a lot of hair in the growth phase, whereas a person with alopecia usually has a lot of hair in the resting phase, resulting in visible hair loss. People with alopecia are characterized by miniaturization of the hair. As hair loss progresses, the anagen period is shortened, the transition to the catagen phase and the telogen phase is promoted, and the subsequent volume of the dermal papilla is reduced, resulting in a smaller hair follicle. Therefore, for the treatment of hair loss, it is important to allow hair follicles in the dormant phase to quickly go to the anagen phase and to lengthen the shortened anagen phase.
그 외에 가장 많은 탈모 환자가 속하고 있는 탈모증인 남성형 탈모증은 '안드로겐성 탈모증'으로도 불린다. 남성형 탈모증이 평균적으로 젊은 20∼30대의 남성에게서 많이 나타난다. 이는 안드로겐성 탈모증이 유전적 영향뿐만 아니라 남성호르몬의 작용 및 나이에 의하여 좌우되기 때문이다. 남성형 탈모증의 탈모 발생 주요원인으로 남성호르몬인 테스토스테론으로 연구되고 있으며, 탈모반의 형태와 진행 상태에 따라 다양하게 구분된다. 테스토스테론으로 인한 남성형 탈모증은 남성호르몬과 활성 효소인 5α-리덕타아제의 결합으로 발생된 디하이드로테스토스테론(DHT: Dihydro-testosterone)이 모낭에 작용하여 세포 분열을 억제시키고 모발의 성장을 저해하는 데에서 발생된다.In addition, androgenetic alopecia, which is the type of hair loss to which the largest number of hair loss patients belong, is also called 'androgenetic alopecia'. Androgenetic alopecia usually occurs in young men in their 20s and 30s. This is because androgenetic alopecia is influenced not only by genetic influences but also by the action of male hormones and age. Testosterone, a male hormone, is being studied as the main cause of hair loss in androgenetic alopecia, and it is classified in various ways according to the type and progress of the bald area. Testosterone-induced androgenetic alopecia is caused by the fact that dihydro-testosterone (DHT), generated by the combination of male hormone and the active enzyme 5α-reductase, acts on hair follicles to suppress cell division and inhibit hair growth. occurs
활성 효소인 5α-리덕타아제가 두피 상에 분포하는 양상에 따라 탈모의 형태가 다르게 나타난다. 활성 효소가 많이 분포하는 정수리 부위는 DHT의 영향으로 세포 분열이 둔화되고 모발의 모주기가 짧아져 모발의 연모화와 탈모 현상이 나타나지만, 측두부나 후두부의 경우에는 상대적으로 활성 효소의 활성도가 약하고 또한 여성호르몬의 영향을 받아 탈모가 쉽게 나타나지 않는다. 현재 남성형 탈모의 관리법으로 모발 이식술 또는 약물 요법 등이 활용되고 있다.Different forms of hair loss appear depending on the distribution of the active enzyme 5α-reductase on the scalp. In the parietal region, where active enzymes are abundantly distributed, cell division is slowed down due to the influence of DHT, and the hair cycle of hair is shortened, resulting in vellus hair and hair loss. Under the influence of female hormones, hair loss does not appear easily. Currently, hair transplantation or drug therapy is being used as a management method for male pattern baldness.
앞서 언급했듯이 탈모의 원인으로 남성호르몬 작용, 피지 분비 과다, 혈액순환 불량, 과산화물이나 세균 등에 의한 두피 기능 저하, 유전적 요인, 노화, 또는 스트레스 등이 논의되어 왔다. 그러나 현재까지 탈모에 관한 명확한 원인은 밝혀져 있지 않은 상태이며, 매우 복잡한 작용이 얽혀 있는 것으로 알려져 있다.As mentioned above, the cause of hair loss has been discussed as male hormone action, excessive sebum secretion, poor blood circulation, deterioration of scalp function due to peroxide or bacteria, genetic factors, aging, or stress. However, until now, the clear cause of hair loss has not been identified, and it is known that very complex effects are intertwined.
이처럼 다양하고 복잡한 탈모 원인에 대하여, 현재까지 알려진 탈모 방지 제품에는 유효성분으로 혈행 촉진, 모근 기능 강화, 두피 보습 효과, 비듬 방지 효과, 항산화 효과, 모발성장기 연장 효과, 또는 남성호르몬 작용 억제 등을 목적으로 하는 성분 등이 포함되어 있으나, 효과 면에서 뚜렷한 효과를 지닌 것은 아직까지 없는 상태이고 부작용의 문제가 제기되기도 한다.Regarding such diverse and complex causes of hair loss, hair loss prevention products known to date have been known to promote blood circulation, strengthen hair root function, moisturize the scalp, prevent dandruff, antioxidant effect, extend hair growth period, or inhibit the action of male hormones as active ingredients. However, there is still no clear effect in terms of effect, and the problem of side effects is raised.
한편, 에스신(escin)은 마로니에 추출물에 다량 함유되어 있는 사포닌 계열의 물질이며, 이는 항염작용, 혈관수축제, 또는 혈관보호제로 주로 사용된다. 하지만 본 발명의 이전에는 에스신의 탈모방지 개선, 발모촉진 효과에 관해서는 알려진 바가 없다.On the other hand, escin is a saponin-based substance that is contained in a large amount in horse chestnut extract, and is mainly used as an anti-inflammatory, vasoconstrictor, or vasoprotective agent. However, prior to the present invention, nothing was known about the anti-hair loss improvement and hair growth stimulating effect of Ssin.
현재 미국식품의약품안전청(FDA)에서 승인을 받은 도포제의 탈모 치료제는 미녹시딜(2,4-diamino-6-piperidinopyrimidine-3-oxide)이 유일하지만, 32주에서 48주 사용 시 그 효과가 각각 38% 및 13%로 만족스럽지 못한 실정이며(J Am Acad Dermatol. 2002. 47(3)), 앞머리에는 효과가 떨어진다는 단점이 있다. 또한, 경구용 탈모치료제인 피나스테라이드는 부작용 또는 사용상의 주의사항으로 인하여 사용에 많은 제약이 있다.Currently, minoxidil (2,4-diamino-6-piperidinopyrimidine-3-oxide) is the only topical hair loss treatment approved by the US Food and Drug Administration (FDA), but when used for 32 to 48 weeks, the effect is 38%, respectively. and 13%, which is unsatisfactory (J Am Acad Dermatol. 2002. 47(3)), and has a disadvantage that the effect is poor on the bangs. In addition, finasteride, an oral hair loss treatment agent, has many restrictions on its use due to side effects or precautions for use.
본 발명이 해결하고자 하는 과제는 우수한 탈모 방지 및/또는 모발 성장 효과를 갖는 탈모 방지 또는 모발 성장 촉진용 조성물을 제공하는 것이다.An object to be solved by the present invention is to provide a composition for preventing hair loss or promoting hair growth having excellent hair loss prevention and/or hair growth effects.
또한, 본 발명이 해결하고자 하는 과제는 상기 탈모 방지 또는 모발 성장 촉진용 조성물을 포함하는 헤어 또는 두피용 제품을 제공하는 것이다.In addition, the problem to be solved by the present invention is to provide a product for hair or scalp containing the composition for preventing hair loss or promoting hair growth.
본 발명자들은 종래의 탈모 치료제의 부작용 및 사용상의 주의사항 등의 문제점을 개선하고 탈모 방지/양모제의 발모 촉진 효과가 미약한 등의 단점 없이, 인체에 대해 안전하면서도 모발 성장 및 발모 촉진에 효과적으로 작용할 수 있는 조성물을 개발하고자 예의 노력한 결과, 에스신이 탈모 방지 및 모발 성장 촉진에 현저하게 우수한 효과가 있음을 발견하였다.The inventors of the present invention can improve problems such as side effects and precautions for use of conventional hair loss treatments, and can act effectively in promoting hair growth and hair growth while being safe for the human body without disadvantages such as weak hair growth promoting effects of hair loss prevention / hair growth agents. As a result of diligent efforts to develop a composition having a composition, it was found that Escin has a remarkably excellent effect on preventing hair loss and promoting hair growth.
구체적으로, 본 발명의 발명자들은 에스신이 모유두 세포에서 Wnt/β-카테닌 신호전달계의 활성을 촉진시키고, 모유두 세포의 증식을 촉진시키며, β-카테닌의 발현량을 증가시킴을 확인하였다. 즉, 에스신이 모유두 세포의 Wnt/β-카테닌 신호 전달을 증폭시킴을 통해, 모발의 생리주기를 퇴행기에서 활성기로 가는데 중요한 역할을 담당하는 것을 인비트로(in-vitro) 실험을 통해 확인하였다. 또한, 본 발명의 발명자들은 에스신을 포함하는 탈모 치료용 조성물을 탈모증 환자에게 처리할 때, 모발의 굵기, 밀집 정도 및 탄력성을 개선하는데 현저하게 우수한 효과가 있음을 확인하였다. 추가적으로, 시판되는 제품인 미녹시딜과 비교 실험한 결과, 본 발명의 에스신을 포함하는 탈모 치료용 조성물은 탈모 방지 및 발모 효과가 미녹시딜에 비해 유사하거나 우수함을 확인하였다.Specifically, the inventors of the present invention confirmed that aescin promotes the activity of the Wnt/β-catenin signaling pathway in dermal papilla cells, promotes the proliferation of dermal papilla cells, and increases the expression level of β-catenin. That is, through in vitro experiments, it was confirmed that aescin plays an important role in amplifying the Wnt/β-catenin signal transduction of dermal papilla cells, and going from the catagen phase to the active phase of the menstrual cycle of hair. In addition, the inventors of the present invention confirmed that there is a remarkably excellent effect in improving the thickness, density and elasticity of hair when the composition for treating hair loss containing escin is treated with alopecia patients. Additionally, as a result of a comparative experiment with minoxidil, a commercially available product, it was confirmed that the composition for treating hair loss containing EScin of the present invention has similar or superior effects to minoxidil in preventing hair loss and hair growth.
나아가, 본 발명자들은 에스신에 아데노신(Adenosine), 알란토인(Allantoin), 병풀(Centella asiatica) 추출물, 덱스판테놀(Dexpanthenol), 나이아신아마이드(Niacinamide), 살리실산(Salicylic acid), 퀘르시트린(Quercitrin), 클로로젠산(Chlorogenic acid), 레인(Rhein), 및 리보플라빈 5'-포스페이트(Riboflavin 5’-phosphate)로 이루어진 군으로부터 선택된 1종 이상을 조합하는 경우, 놀랍게도 탈모 방지 및 모발 성장 촉진에 현저한 상승 효과가 나타남을 발견하여 본 발명을 완성하게 되었다.Furthermore, the present inventors found that adenosine, allantoin, centella asiatica extract, dexpanthenol, niacinamide, salicylic acid, quercitrin, clo When combining at least one selected from the group consisting of chlorogenic acid, rhein, and riboflavin 5'-phosphate, there is surprisingly a remarkable synergistic effect in preventing hair loss and promoting hair growth. The discovery of the appearance led to the completion of the present invention.
본 발명은 에스신; 및 아데노신, 알란토인, 병풀 추출물, 덱스판테놀, 나이아신아마이드, 살리실산, 퀘르시트린, 클로로젠산, 레인, 및 리보플라빈 5'-포스페이트로 이루어진 군으로부터 선택된 1종 이상을 유효성분으로 포함하는 탈모 방지 또는 모발 성장 촉진용 조성물을 제공한다. 또한, 본 발명의 조성물은 상기 유효성분들의 약학적으로 또는 화장품학적으로 허용 가능한 염을 포함할 수 있다.The present invention is an escin; and at least one selected from the group consisting of adenosine, allantoin, centella asiatica extract, dexpanthenol, niacinamide, salicylic acid, quercitrin, chlorogenic acid, lane, and riboflavin 5'-phosphate as an active ingredient for preventing hair loss or growing hair. A composition for promotion is provided. In addition, the composition of the present invention may include pharmaceutically or cosmetically acceptable salts of the active ingredients.
구체적으로, 본 발명의 발명자들은 상기 각각의 유효성분들이 모유두 세포의 활성을 촉진시키고 Wnt/베타-카테닌 신호전달계의 활성을 증진시켜, 모발의 생리주기를 퇴행기 내지 휴지기에서 성장기(활성기)로 가는데 중요한 역할을 담당하는 것을 인비트로(in-vitro) 실험을 통해 확인하였다. 본 발명의 탈모 방지 또는 모발 성장 촉진용 조성물은 상기 효과를 통해 모발의 성장 주기 중 휴지기에서 성장기로 이행되는 주기를 단축시킴으로써 모발의 성장을 촉진시키고 퇴행기로의 전환을 늦추어 탈모를 방지하고 모발 성장을 촉진하는 것으로 예상된다. 그러나 본 발명은 이러한 기전에 한정되는 것은 아니다. 또한, 본 발명의 발명자들은 체외 조직 배양 실험을 통해 상기 유효성분들이 모발의 길이를 생장시키는 효과가 현저하게 우수함을 확인하였다.Specifically, the inventors of the present invention found that each of the above active ingredients promotes the activity of dermal papilla cells and promotes the activity of the Wnt/beta-catenin signaling system, which is important for the menstrual cycle of hair to go from the catagen phase to the telogen phase to the growth phase (active phase). It was confirmed through an in-vitro experiment that it plays a role. The composition for preventing hair loss or promoting hair growth according to the present invention promotes hair growth by shortening the cycle from the telogen phase to the anagen phase of the hair growth cycle through the above effects and delays the transition to the catagen phase to prevent hair loss and promote hair growth. expected to promote However, the present invention is not limited to this mechanism. In addition, the inventors of the present invention confirmed through in vitro tissue culture experiments that the effect of the active ingredients in growing the length of hair is remarkably excellent.
일 실시예에서, 상기 에스신; 및 아데노신, 알란토인, 병풀 추출물, 덱스판테놀, 나이아신아마이드, 살리실산, 퀘르시트린, 클로로젠산, 레인, 및 리보플라빈 5'-포스페이트로 이루어진 군으로부터 선택된 1종 이상은 조성물 총 중량 대비 0.001 내지 10 중량%, 바람직하게 0.01 내지 5 중량%로 포함될 수 있다. 각 성분의 함량이 0.001 중량% 미만일 경우에는 모발의 성장을 유도하는 효과가 미약하고, 10 중량% 초과일 경우에는 제형의 안정성이 떨어질 수 있다.In one embodiment, the escine; And at least one selected from the group consisting of adenosine, allantoin, centella asiatica extract, dexpanthenol, niacinamide, salicylic acid, quercitrin, chlorogenic acid, lane, and riboflavin 5'-phosphate is 0.001 to 10% by weight relative to the total weight of the composition, It may preferably be included in 0.01 to 5% by weight. If the content of each component is less than 0.001% by weight, the effect of inducing hair growth is weak, and if it is more than 10% by weight, the stability of the formulation may be reduced.
또한, 본 발명은 상기 탈모 방지 또는 모발 성장 촉진용 조성물을 포함하는 의약 조성물, 의약외품용 조성물, 화장료 조성물 또는 건강기능식품 조성물을 제공한다. 본 발명의 조성물은 통상적으로 피부에 적용시킬 수 있는 어떠한 형태로도 제형화될 수 있으나, 바람직하게 피부 외용제의 형태로 제형화될 수 있다. 본 발명의 조성물은 예를 들어 액상, 크림상, 페이스트상, 또는 고체상 등 피부에 적용시킬 수 있는 제형으로 제조될 수 있다.In addition, the present invention provides a pharmaceutical composition, a quasi-drug composition, a cosmetic composition, or a health functional food composition containing the composition for preventing hair loss or promoting hair growth. The composition of the present invention may be formulated in any form that can be applied to the skin in general, but may be formulated in the form of an external preparation for skin. The composition of the present invention may be formulated into a formulation that can be applied to the skin, such as, for example, liquid, cream, paste, or solid.
본 발명의 에스신; 및 아데노신, 알란토인, 병풀 추출물, 덱스판테놀, 나이아신아마이드, 살리실산, 퀘르시트린, 클로로젠산, 레인, 및 리보플라빈 5'-포스페이트로 이루어진 군으로부터 선택된 1종 이상은 상기 조성물 또는 제형에 탈모 방지제 또는 모발 성장 촉진제로 포함될 수 있다.the escin of the present invention; And at least one member selected from the group consisting of adenosine, allantoin, centella asiatica extract, dexpanthenol, niacinamide, salicylic acid, quercitrin, chlorogenic acid, lane, and riboflavin 5'-phosphate is added to the composition or formulation as an anti-hair loss agent or hair growth agent Can be included as an accelerator.
일 실시예에서, 본 발명의 제형이 액상인 경우에는 담체 성분으로 용매, 용해화제 또는 유탁화제 등이 사용될 수 있다. 예를 들어 상기 담체 성분으로 물, 알코올, 에틸 카보네이트, 에틸 아세테이트, 벤질 알코올, 벤질 벤조에이트, 프로필렌글리콜, 1,3-부틸글리콜 오일, 글리세롤 지방족 에스테르, 폴리에틸렌 글리콜 또는 소르비탄의 지방산 에스테르 등이 사용될 수 있다. 상기 알코올은 알코올 중 1종 이상을 의미하며, 바람직하게는 선형 또는 분지형의 C2-C4 모노알코올이며, 더욱 바람직하게는 에탄올 또는 이소프로판올을 사용할 수 있다. 특히 에탄올 또는 이소프로판올을 담체성분으로 사용하게되면 탈모 방지 또는 모발 성장 촉진용 조성물의 경피 흡수를 촉진할 수 있다.In one embodiment, when the formulation of the present invention is liquid, a solvent, a solubilizing agent, or an emulsifying agent may be used as a carrier component. For example, water, alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan fatty acid ester may be used as the carrier component. can The alcohol refers to one or more types of alcohol, preferably a linear or branched C 2 -C 4 monoalcohol, and more preferably ethanol or isopropanol. In particular, when ethanol or isopropanol is used as a carrier component, transdermal absorption of the composition for preventing hair loss or promoting hair growth can be promoted.
일 실시예에서, 본 발명의 제형이 페이스트, 크림 또는 젤인 경우에는 담체 성분으로서 알코올, 동물성유, 식물성유, 왁스, 파라핀, 전분, 트라칸트, 셀룰로오스 유도체, 폴리에틸렌글리콜, 실리콘, 벤토나이트, 실리카, 탈크 또는 산화아연 등이 사용될 수 있으며, 바람직하게는 알코올이 사용될 수 있고, 더욱 바람직하게는 상기 알코올은 이소프로판올일 수 있다.In one embodiment, when the formulation of the present invention is a paste, cream or gel, alcohol, animal oil, vegetable oil, wax, paraffin, starch, tracanth, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc as a carrier component Alternatively, zinc oxide may be used, preferably alcohol may be used, and more preferably, the alcohol may be isopropanol.
일 실시예에서, 본 발명의 제형이 파우더 또는 스프레이인 경우에는 담체 성분으로서 락토스, 탈크, 실리카, 알루미늄 히드록시드, 칼슘 실리케이트 또는 폴리아미드 파우더 등이 이용될 수 있다. 특히 스프레이 제형인 경우에는 추가적으로 클로로플루오로히드로카본, 프로판/부탄 또는 디메틸 에테르 등과 같은 추진체를 포함할 수 있다.In one embodiment, when the formulation of the present invention is a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component. In particular, in the case of a spray formulation, a propellant such as chlorofluorohydrocarbon, propane/butane or dimethyl ether may be additionally included.
일 실시예에서, 본 발명의 조성물은 에스신; 및 아데노신, 알란토인, 병풀 추출물, 덱스판테놀, 나이아신아마이드, 살리실산, 퀘르시트린, 클로로젠산, 레인, 및 리보플라빈 5'-포스페이트로 이루어진 군으로부터 선택된 1종 이상 외에 피부에 적용시킬 수 있는 외용제에 통상적으로 이용되는 성분들을 포함할 수 있다. 예를 들어 물, 계면활성제, 보습제, 저급알코올, 킬레이트제, 살균제, 산화방지제, 방부제, 색소 및 향료 등으로 이루어지는 군으로부터 선택되는 하나 이상의 첨가제가 추가로 포함될 수 있다.In one embodiment, a composition of the present invention comprises escin; and at least one selected from the group consisting of adenosine, allantoin, centella asiatica extract, dexpanthenol, niacinamide, salicylic acid, quercitrin, chlorogenic acid, lane, and riboflavin 5'-phosphate. Ingredients used may be included. For example, one or more additives selected from the group consisting of water, surfactants, humectants, lower alcohols, chelating agents, bactericides, antioxidants, preservatives, coloring agents, and fragrances may be further included.
또한 본 발명은 상기 탈모 방지 또는 모발 성장 촉진용 조성물을 포함하는 헤어 또는 두피용 제품을 제공한다. 상기 헤어 또는 두피용 제품은 발모제, 두피클리닉제, 두피스케일링제, 두피마사지제, 두피케어제, 세정제, 샴푸, 토닉, 헤어컨디셔너, 헤어로션, 젤, 팩, 크림, 에센스, 파우더, 스프레이, 오일, 비누, 연고, 헤어스타일링제, 염모제 및 펌제 등으로 이루어진 군으로부터 선택된 어느 하나일 수 있으나, 이에 한정되지 않는다.In addition, the present invention provides a product for hair or scalp containing the composition for preventing hair loss or promoting hair growth. The hair or scalp products include hair growth agents, scalp clinic agents, scalp scaling agents, scalp massage agents, scalp care agents, detergents, shampoos, tonics, hair conditioners, hair lotions, gels, packs, creams, essences, powders, sprays, and oils. , It may be any one selected from the group consisting of soap, ointment, hair styling agent, hair dye and perm agent, etc., but is not limited thereto.
일 실시예에서, 본 발명의 탈모 방지 또는 모발 성장 촉진용 조성물은 헤어토닉 또는 헤어로션의 제형으로 제조될 수 있다. 본 발명의 모발 성장 촉진용 조성물은 바람직하게 피부에 직접 도포하거나 살포하는 등의 경피 투여 방법으로 사용될 수 있다. In one embodiment, the composition for preventing hair loss or stimulating hair growth of the present invention may be prepared in the form of a hair tonic or hair lotion. The composition for promoting hair growth of the present invention may be preferably used as a transdermal administration method such as direct application or spraying to the skin.
또한 본 발명은 상기 탈모 방지 또는 모발 성장 촉진용 조성물을 포함하는 건강기능식품 조성물을 제공한다. 상기 건강기능식품은 당업계에서 통상적으로 사용되는 방법에 의하여 제조가능하며, 상기 제조시에는 당업계에서 통상적으로 첨가하는 원료 및 성분을 첨가하여 제조할 수 있다. 또한 상기 건강기능식품의 제형 또한 건강기능식품으로 인정되는 제형이면 제한 없이 제조될 수 있다. 본 발명의 건강기능식품은 다양한 형태의 제형으로 제조될 수 있으며, 일반 약품과는 달리 식품을 원료로 하여 약품의 장기 복용 시 발생할 수 있는 부작용 등이 없는 장점이 있고, 휴대성이 뛰어나, 본 발명의 건강기능식품은 탈모 방지 및 발모 촉진 효과를 증진시키기 위한 보조제로 섭취가 가능하다.In addition, the present invention provides a health functional food composition comprising the composition for preventing hair loss or promoting hair growth. The health functional food can be prepared by a method commonly used in the art, and can be prepared by adding raw materials and components commonly added in the art during the manufacture. In addition, the formulation of the health functional food may also be manufactured without limitation as long as the formulation is recognized as a health functional food. The health functional food of the present invention can be manufactured in various types of formulations, and unlike general drugs, it has the advantage of using food as a raw material and free from side effects that may occur when taking drugs for a long time, and has excellent portability, so the present invention The health functional food of can be consumed as a supplement to prevent hair loss and promote hair growth.
또한, 본 발명은 에스신; 및 아데노신, 알란토인, 병풀 추출물, 덱스판테놀, 나이아신아마이드, 살리실산, 퀘르시트린, 클로로젠산, 레인, 및 리보플라빈 5'-포스페이트로 이루어진 군으로부터 선택된 1종 이상을 유효성분으로 포함하는 탈모 방지 또는 모발 성장 촉진용 조성물을 환자에 투여하는 단계를 포함하는 탈모 방지 또는 모발 성장 촉진 방법을 제공한다.In addition, the present invention is an escin; and at least one selected from the group consisting of adenosine, allantoin, centella asiatica extract, dexpanthenol, niacinamide, salicylic acid, quercitrin, chlorogenic acid, lane, and riboflavin 5'-phosphate as an active ingredient for preventing hair loss or growing hair. Provided is a method for preventing hair loss or promoting hair growth comprising administering a composition for promoting to a patient.
본 발명에서 사용되는 용어, "투여"는 어떠한 적절한 방법으로 본 발명의 조성물을 도입하는 것을 의미할 수 있다. 본 발명의 조성물의 투여 경로는 목적 조직에 도달할 수 있는 한 어떠한 일반적인 경로를 통하여 투여될 수 있다. 본 발명의 조성물은 경피 또는 경구 투여가 가능하며, 바람직하게는 경피 투여할 수 있으며, 그 중에서도 국소 도포가 가장 바람직하다. 본 발명의 조성물의 적용 횟수는 처방, 필요 또는 원하는 바에 따라 결정될 수 있다.As used herein, the term "administration" may mean introducing the composition of the present invention by any suitable method. The administration route of the composition of the present invention may be administered through any general route as long as it can reach the target tissue. The composition of the present invention can be administered transdermally or orally, preferably transdermally, and among them, topical application is most preferred. The number of applications of the composition of the present invention may be determined according to prescription, necessity or desire.
본 발명에 기재된 모든 성분은, 바람직하게는, 한국, 중국, 미국, 유럽, 일본 등의 관련 법규, 규범 (예를 들어, 화장품 안전 기준 등에 관한 규정(한국), 화장품 안전 기술 규범(중국), 식품공전(한국), 식품첨가물공전(한국), 건강기능식품공전(한국)) 등에서 규정한 최대 사용치를 초과하지 않는다. 즉, 바람직하게, 본 발명에 따른 화장료, 식품, 또는 퍼스널 케어용 조성물은 각국의 관련 법규, 규범에서 허용되는 함량 한도로 본 발명에 따른 성분들을 포함한다.All ingredients described in the present invention are preferably, related laws and regulations of Korea, China, the United States, Europe, Japan, etc. Do not exceed the maximum use value stipulated in the Food Codex (Korea), Food Additives Codex (Korea), Health Functional Food Codex (Korea)), etc. That is, preferably, the cosmetic, food, or personal care composition according to the present invention contains the components according to the present invention within the limits of the content permitted by the relevant laws and regulations of each country.
본 발명은 인비트로 실험을 통해 본 발명의 조성물에 포함되는 에스신; 및 아데노신, 알란토인, 병풀 추출물, 덱스판테놀, 나이아신아마이드, 살리실산, 퀘르시트린, 클로로젠산, 레인, 및 리보플라빈 5'-포스페이트로 이루어진 군으로부터 선택된 1종 이상이 모유두 세포의 활성을 증진시키고 Wnt/베타-카테닌 신호 전달 증폭을 통해 모발의 생리 주기를 퇴행기 내지 휴지기에서 활성기로 가는데 중요한 역할을 담당하여, 모발의 길이 생장을 촉진시킴을 확인하였다(실험예 6 내지 8).The present invention is an escin included in the composition of the present invention through in vitro experiments; And at least one selected from the group consisting of adenosine, allantoin, centella asiatica extract, dexpanthenol, niacinamide, salicylic acid, quercitrin, chlorogenic acid, lane, and riboflavin 5'-phosphate enhances the activity of dermal papilla cells and promotes Wnt/beta - It was confirmed that it plays an important role in the menstrual cycle of hair from the catagen phase to the telogen phase through the amplification of catenin signal transmission, thereby promoting the growth of the length of the hair (Experimental Examples 6 to 8).
본 발명의 조성물의 사용량은 연령, 병변의 정도 등의 개인 차이나 제형에 따라 적절하게 조절될 수 있으며, 통상 1일 1회 내지 수회 적당량을 두피에 도포시켜 1주일 내지 수개월 사용하는 것이 바람직하다. 본 발명의 실험예에서는 탈모 치료 또는 모발 성장 촉진용 조성물을 1주에 5회씩 6개월 동안 사용하였으며, 그 결과 우수한 모발 성장 촉진 효과가 나타났음을 확인하였다(실험예 4).The amount of the composition of the present invention can be appropriately adjusted according to individual differences such as age, severity of lesions, etc., or formulation, and it is preferable to apply an appropriate amount to the scalp once or several times a day and use it for one week to several months. In the experimental example of the present invention, the composition for treating hair loss or promoting hair growth was used 5 times a week for 6 months, and as a result, it was confirmed that an excellent hair growth promoting effect was exhibited (Experimental Example 4).
본 발명의 탈모 방지 및 모발 성장 촉진용 조성물은 에스신 등을 포함하는 유효성분에 의하여, 모발의 성장 주기 중 휴지기에서 성장기로 이행되는 주기를 단축시킴으로써 모발의 성장을 촉진시키고 퇴행기로의 전환을 늦추어 탈모 방지 및 모발 성장 촉진 효과가 우수하다.The composition for preventing hair loss and promoting hair growth of the present invention promotes hair growth and slows down the transition to the catagen phase by shortening the cycle transitioning from the telogen phase to the anagen phase of the hair growth cycle by using active ingredients including Scin, etc. It is excellent in preventing hair loss and promoting hair growth.
도 1은 모유두 세포에서 에스신의 Wnt/β-카테닌 프로모터 활성도 증폭 효과에 대한 분석 결과를 나타낸다.
도 2는 모유두 세포에서 에스신에 의한 β-카테닌의 발현량 증가를 확인한 실험 결과를 나타낸다.Figure 1 shows the analysis results for the effect of Wnt / β-catenin promoter activity amplification of escin in dermal papilla cells.
Figure 2 shows the experimental results confirming the increase in the expression of β-catenin by aescin in dermal papilla cells.
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 본 발명이 속한 분야에서 평균적인 지식을 가진 자에게 본 발명을 보다 완전하게 설명하기 위해 제공되는 것이다.Hereinafter, examples and the like will be described in detail to aid understanding of the present invention. However, the embodiments according to the present invention can be modified in many different forms, and the scope of the present invention should not be construed as being limited to the following examples. Embodiments of the present invention are provided to more completely explain the present invention to those skilled in the art.
제조예 1: 탈모 치료 및/또는 발모 촉진용 조성물(헤어토닉)Preparation Example 1: Composition for treating hair loss and/or promoting hair growth (hair tonic)
하기 표 1에 나타난 처방에 따라 통상의 방법으로 에스신을 포함하는 실시예 및 비교예의 헤어토닉을 제조하였다. 본 발명의 실험에 사용된 물질 및 시약들은 화장품 원료 제조사 및 상업용 공급 업체에서 구입하여 사용하였다. According to the prescriptions shown in Table 1 below, hair tonics of Examples and Comparative Examples containing EScin were prepared in a conventional manner. Materials and reagents used in the experiments of the present invention were purchased from cosmetic raw material manufacturers and commercial suppliers.
제조예 2: 탈모 치료 및/또는 발모 촉진용 조성물(헤어로션)Preparation Example 2: Composition for treating hair loss and/or promoting hair growth (hair lotion)
하기 표 2에 나타난 처방에 따라 통상의 방법으로 에스신을 포함하는 헤어로션을 제조하였다.According to the prescription shown in Table 2 below, a hair lotion containing EScin was prepared in a conventional manner.
실험예 1: 모유두 세포 활성 신호(Wnt/β-카테닌)조절 효과Experimental Example 1: Dermal papilla cell activation signal (Wnt/β-catenin) regulatory effect
일반적으로 모유두에서 활성화 되는 wnt/β-카테닌 신호는 모발의 성장 주기 중 퇴행기에서 활성기로 넘어올 때, 즉 모발이 자라기 시작할 때부터 모발 생장이 일어나는 활성기 동안에 걸쳐 일어난다. 또 휴지기 및 퇴행기에는 wnt/β-카테닌 신호가 약해지거나 없어지게 되어, 모낭이 퇴화하며 모발이 빠지는 현상이 일어난다. 본 실험예에서는 에스신이 wnt/β-카테닌 신호증폭에 얼마나 기여를 하는지 확인하였다.In general, the wnt/β-catenin signal activated in the dermal papilla occurs when the hair moves from the catagen phase to the active phase during the hair growth cycle, that is, from the start of hair growth to the active phase in which hair growth occurs. In addition, in the telogen and catagen phases, the wnt/β-catenin signal is weakened or lost, causing hair follicles to degenerate and hair to fall out. In this experimental example, it was confirmed how much aescin contributes to wnt/β-catenin signal amplification.
Wnt/β-카테닌 신호를 증폭시키는 양성대조군으로 wnt3a 단백질을 사용하였으며, 음성대조군으로 DMSO를 사용하였다. 배양 96-웰 플레이트에 약 3x104의 Wnt 리포터 HEK293A 세포를 각 웰에 시딩(seeding)한 후, 에스신을 각각 5㎍/㎖, 10㎍/㎖, 20㎍/㎖의 농도로 처리하였다. 이후 Promega사의 루시퍼라제 분석 키트(Luciferase assay kit)(E1960)를 이용하여, 제조사의 실험방법을 따라서 리포터 분석을 진행하였다. luminometer Victor(PerkinElmer, Waltham, Massachusetts, USA)를 이용하여 Wnt/β-카테닌 프로모터 활성도를 측정하였고, 분석 결과는 도 1에 나타내었다.Wnt3a protein was used as a positive control to amplify the Wnt/β-catenin signal, and DMSO was used as a negative control. About 3×10 4 Wnt reporter HEK293A cells were seeded in each well in a 96-well culture plate, and then treated with Escyn at concentrations of 5 μg/ml, 10 μg/ml, and 20 μg/ml, respectively. Then, using Promega's Luciferase assay kit (E1960), reporter analysis was performed according to the manufacturer's experimental method. Wnt/β-catenin promoter activity was measured using a luminometer Victor (PerkinElmer, Waltham, Massachusetts, USA), and the analysis results are shown in FIG. 1 .
실험 결과를 볼 때, 에스신은 무처리군인 음성대조군 대비 Wnt/β-카테닌 신호를 11배 가량 증폭시켰다. 에스신을 포함하는 실험군은 농도 의존적인 양상을 보이지는 않았으나, 20 μg/ml의 농도 근처에서 반복적인 확실한 효과를 확인하였다. 특히 에스신은 Wnt/β-카테닌의 직접적인 수용체에 결합하는 양성대조군인 wnt3a 단백질보다 우수한 효능을 보이는 것으로 나타났다. 따라서, 에스신은 모낭 줄기세포의 모발 성장 촉진 신호인 Wnt/β-카테닌 신호전달계의 활성을 매우 촉진시킴으로써 현저하게 우수한 발모 촉진 효과가 있음을 확인할 수 있다.As a result of the experiment, EScin amplified the Wnt/β-catenin signal 11 times compared to the untreated negative control group. The experimental group containing aescin did not show a concentration-dependent pattern, but confirmed a repeatable effect at a concentration of around 20 μg/ml. In particular, aescin was found to exhibit superior efficacy than the positive control, wnt3a protein, which binds to the direct receptor of Wnt/β-catenin. Therefore, it can be confirmed that EScin has a remarkably excellent hair growth promoting effect by greatly promoting the activity of the Wnt/β-catenin signaling system, which is a hair growth promoting signal of hair follicle stem cells.
실험예 2: 모유두 세포 증식 촉진 효과Experimental Example 2: Dermal papilla cell proliferation promoting effect
인간 유래 모유두 세포(dermal papilla cells, DPCs)는 프로모셀사에서 구입하였다. 상기 DPCs을 프로모셀사에서 권장하는 Follicle Dermal Papilla Cell Growth Medium 및 supplement mix를 사용하여, 37℃ 및 5% CO2 조건하에 배양하였다. 배양한 DPCs 3,000 cells/well을 96-웰 플레이트에 분주한 뒤, 0.1% 혈청 조건에서 24시간 동안 배양하였다. 그 후, 배양한 세포에 무혈청 DMEM에 1:1000으로 희석한 DMSO(vehicle)을 대조군으로, 에스신을 각각 0.2, 0.5, 1,2 및 5㎍/㎖씩 1일 동안 처리하고 인큐베이션 하였다. 인큐베이션 후 CCK방법을 이용하여 세포의 증식 정도를 평가하였다. CCK-8을 배양액에 1:10으로 처리하여 1시간 동안 인큐베이션 하였다. 1시간 후, 각 웰의 흡광도 (absorbance)를 450nm으로 측정하였다. 모든 실험들은 3번씩 반복되었으며 흡광도 값의 평균을 계산하였다. 상기 결과들은 대조군을 100으로 하고 그에 비한 처리군의 퍼센트로 표현되었다. 실험 결과, 에스신을 처리하였을 경우 DPCs 증식 효과를 나타내어, 모유두 세포 증식 효과가 우수함을 확인하였다.Human-derived dermal papilla cells (DPCs) were purchased from Promocell. The DPCs were cultured at 37° C. and 5% CO 2 conditions using Follicle Dermal Papilla Cell Growth Medium and supplement mix recommended by Promocell. After dispensing 3,000 cells/well of the cultured DPCs into a 96-well plate, they were cultured for 24 hours in 0.1% serum condition. Thereafter, the cultured cells were treated with DMSO (vehicle) diluted 1:1000 in serum-free DMEM as a control, and each of 0.2, 0.5, 1,2 and 5 μg/ml of acecin was treated and incubated for 1 day. After incubation, the degree of cell proliferation was evaluated using the CCK method. CCK-8 was treated 1:10 in the culture medium and incubated for 1 hour. After 1 hour, the absorbance of each well was measured at 450 nm. All experiments were repeated three times and the average of the absorbance values was calculated. The results were expressed as a percentage of the treatment group relative to the control group being 100. As a result of the experiment, it was confirmed that the DPCs proliferative effect was exhibited when aescin was treated, and the dermal papilla cell proliferative effect was excellent.
실험예 3: 모유두 세포 β-카테닌의 발현 증가Experimental Example 3: Increased expression of β-catenin in dermal papilla cells
Wnt 신호가 억제되는 휴지기 및 퇴행기의 모유두 세포에서는 β-카테닌이 GSK3-베타에 의해 분해된다. 그러나 Wnt 신호가 증폭되는 활성기 모유두 세포에서는 GSK3-베타의 활성이 억제되기 때문에, β-카테닌이 분해되지 않아 β-카테닌의 발현량이 증가한다. 인간 모유두 세포를 약 500,000 cell/well로 6개 웰 플레이트에 분주한 후, 에스신을 각각 0.2, 0.5, 1,2 및 5㎍/㎖씩 1일 동안 처리하고 인큐베이션 하였다. 인큐베이션 후 M-PER 용해 버퍼를 이용해 세포를 용해시키고, 동량의 세포 용해물을 SDS-PAGE 겔에 로딩하였다. SDS-PAGE 겔에 로딩된 세포 용해물을 니트로셀룰로스 막으로 옮긴 후, 항-β-카테닌 항체를 니트로셀룰로스 막에 붙여 단백질을 검출하였다. GAPDH는 단백질양을 보정하는 control로 사용되었다. 에스신에 의해 증가한 β-카테닌의 양을 확인하였고, 그 결과는 도 2에 나타내었다. β-Catenin is degraded by GSK3-beta in resting and anagen-phase dermal papilla cells in which Wnt signaling is suppressed. However, since the activity of GSK3-beta is suppressed in active dermal papilla cells in which Wnt signals are amplified, β-catenin is not degraded and the expression level of β-catenin increases. After dispensing about 500,000 cells/well of human dermal papilla cells into a 6-well plate, they were treated with 0.2, 0.5, 1,2, and 5 μg/ml of EScin, respectively, and incubated for 1 day. After incubation, cells were lysed using M-PER lysis buffer, and the same amount of cell lysate was loaded on an SDS-PAGE gel. After transferring the cell lysate loaded on the SDS-PAGE gel to a nitrocellulose membrane, an anti-β-catenin antibody was applied to the nitrocellulose membrane to detect proteins. GAPDH was used as a control to correct the protein amount. The amount of β-catenin increased by aescin was confirmed, and the results are shown in FIG. 2 .
실험 결과, 무처리군에 비해 에스신을 처리한 군에서 매우 유의하게 β-카테닌의 양이 증가하는 것을 확인할 수 있었으며, 이는 모유두 세포의 Wnt/β-카테닌 신호가 증가한 것을 의미한다.As a result of the experiment, it was confirmed that the amount of β-catenin increased very significantly in the group treated with aescin compared to the untreated group, which means that the Wnt/β-catenin signal of dermal papilla cells increased.
실험예 4: 탈모 치료/발모용 조성물 1(헤어토닉)의 발모 효과 확인Experimental Example 4: Confirmation of hair growth effect of composition 1 (hair tonic) for hair loss treatment/hair growth
모발의 수가 정상에 비해 현저히 적거나 탈모 증상이 있는 모발이 약한 남녀 총 105명을 대상으로 본 발명의 탈모 치료/발모용 조성물 1(헤어토닉)의 발모 효과를 실험하였다. 상기 남녀 총 105명을 15명씩 7개 그룹으로 나누어 비교예 1 및 실시예 1 내지 6을 사용하였으며, 1주에 5회씩 6개월 동안 모발 및 두피에 사용하였다. 사용 후 모발의 굵기, 밀집 정도, 탄력성 및 전체적 평가 항목에 대하여 개선 정도 또는 손상 정도를 각각 5단계로 나누어 평가하였다(개선된 정도: +5, +4, +3, +2, +1, 개선 없음: 0, 손상된 정도: -1, -2, -3, -4, -5). 상기 평가는 사용 시작 6개월 경과 후 사용자 문진 결과의 평균값으로 판정하였으며, 그 결과를 표 4에 나타내었다.The hair growth effect of Composition 1 (Hair Tonic) for hair loss treatment/hair growth of the present invention was tested on a total of 105 men and women with weak hair having significantly less hair than normal or with hair loss symptoms. A total of 105 men and women were divided into 7 groups of 15 each, and Comparative Example 1 and Examples 1 to 6 were used, and they were used for hair and scalp 5 times a week for 6 months. After use, the degree of improvement or damage was evaluated in 5 stages for the thickness, density, elasticity, and overall evaluation items of the hair (degree of improvement: +5, +4, +3, +2, +1, improvement None: 0, degree of damage: -1, -2, -3, -4, -5). The evaluation was determined by the average value of the user questionnaire results after 6 months of use, and the results are shown in Table 4.
상기 결과에서 알 수 있듯이, 에스신을 함유하는 실시예 1 내지 6에서 높은 탈모 방지 및 모발 성장 효과가 나타나는 것을 확인하였다. 이를 통해, 에스신을 유효성분으로 포함하는 본 발명의 탈모 방지 모발 성장 촉진용 조성물이 탈모치료에 매우 효과적으로 사용될 수 있음을 입증하였다.As can be seen from the above results, it was confirmed that high hair loss prevention and hair growth effects appeared in Examples 1 to 6 containing escin. Through this, it was proved that the composition for preventing hair loss and stimulating hair growth of the present invention containing Escin as an active ingredient can be used very effectively for hair loss treatment.
실험예 5: 탈모 치료/발모용 조성물 1(헤어토닉)의 발모 효과 확인Experimental Example 5: Confirmation of hair growth effect of composition 1 (hair tonic) for hair loss treatment/hair growth
모발의 수가 정상에 비해 현저히 적거나 탈모 증상이 있는 모발이 약한 남녀 총 105명을 대상으로 본 발명의 탈모 치료/발모용 조성물 1(헤어토닉)의 발모 효과를 실험하였다. 상기 남녀 총 105명을 15명씩 7개 그룹으로 나누어 비교예 1 및 실시예 1 내지 6을 사용하였으며, 1주에 5회씩 6개월 동안 모발 및 두피에 사용하였다. 사용 후 임상사진 촬영을 통한 연구자 평가와 포토트리코그램을 통한 평가를 진행하였다. 임상 사진을 통한 연구자 평가는 도포 2, 4, 6개월 뒤 비교예와 실험예에 대해 'good', 'slight' 'no change'3개 항목에 대해 평가를 진행하였다 (Good: 50%~75% 호전됨, Slight: 25%~50% 호전됨, no change: 무변화). 포토트리코그램을 통한 단위면적당 모발의 개수와 평균 모발의 두께에 대한 평가는 도포 4, 6개월 뒤 비교예 및 실시예에 대해 측정을 진행하였으며, 그 결과를 표 5에 나타내었다.The hair growth effect of Composition 1 (Hair Tonic) for hair loss treatment/hair growth of the present invention was tested on a total of 105 men and women with weak hair having significantly less hair than normal or with hair loss symptoms. A total of 105 men and women were divided into 7 groups of 15 each, and Comparative Example 1 and Examples 1 to 6 were used, and they were used for hair and scalp 5 times a week for 6 months. After use, researcher evaluation through clinical picture taking and evaluation through phototricogram were conducted. As for the researcher's evaluation through clinical pictures, three items of 'good', 'slight' and 'no change' were evaluated for comparative and experimental examples 2, 4, and 6 months after application (Good: 50% to 75% Improved, Slight: 25%~50% improved, no change: no change). Evaluation of the number of hairs per unit area and average hair thickness through a phototricogram was performed on Comparative Examples and Examples 4 and 6 months after application, and the results are shown in Table 5.
(명)No change
(number of people)
(명)Slight
(number of people)
(명)Good
(number of people)
(μm)average hair thickness
(μm)
상기 결과에서 알 수 있듯이, 에스신을 함유하는 실시예 1 내지 6에서 높은 탈모 방지 및 모발 성장 효과가 나타나는 것을 확인하였다. 이를 통해, 에스신을 유효성분으로 포함하는 본 발명의 탈모 방지 모발 성장 촉진용 조성물이 탈모치료에 매우 효과적으로 사용될 수 있음을 입증하였다.As can be seen from the above results, it was confirmed that high hair loss prevention and hair growth effects appeared in Examples 1 to 6 containing escin. Through this, it was proved that the composition for preventing hair loss and stimulating hair growth of the present invention containing Escin as an active ingredient can be used very effectively for hair loss treatment.
상기 헤어토닉 또는 헤어로션과 같은 제형 예는 본 발명 모발성장 촉진용 조성물의 예시일 뿐, 본 발명 조성물의 범위가 이들 제형만으로 한정되지 않는다는 것은 당업계에서 통상의 지식을 가진 자에게 있어서 자명할 것이다.Formulation examples such as the hair tonic or hair lotion are only examples of the composition for promoting hair growth of the present invention, and it will be apparent to those skilled in the art that the scope of the composition of the present invention is not limited to these formulations only. .
실험예 6: 유효성분 조합의 모유두세포 증식능 평가Experimental Example 6: Evaluation of dermal papilla cell proliferation ability of active ingredient combination
실험예 2와 동일한 방식으로, 에스신; 및 아데노신, 알란토인, 병풀 추출물, 덱스판테놀, 나이아신아마이드, 살리실산, 퀘르시트린, 클로로젠산, 레인, 및 리보플라빈 5'-포스페이트로 이루어진 군으로부터 선택된 1종 조합의 모유두세포 증식능을 평가하였다.In the same manner as Experimental Example 2, Escyn; and adenosine, allantoin, centella asiatica extract, dexpanthenol, niacinamide, salicylic acid, quercitrin, chlorogenic acid, lane, and riboflavin 5'-phosphate.
상기 실험 결과, 에스신; 및 아데노신, 알란토인, 병풀 추출물, 덱스판테놀, 나이아신아마이드, 살리실산, 퀘르시트린, 클로로젠산, 레인, 및 리보플라빈 5'-포스페이트로 이루어진 군으로부터 선택된 1종 조합을 처리하였을 경우 모유두세포 증식능이 모두 현저하게 증가하였다. 특히 에스신 및 기타 1종을 포함하여 2종의 유효성분이 혼합된 실시예 18 내지 27은 단일 유효성분이 포함된 실시예 7 내지 17에 비해 모유두 세포 활성 증진 효과가 현저하게 우수하여, 2종의 유효성분의 조합을 통해 상승 효과가 발생함을 확인하였다.As a result of the above experiment, Ssin; And when treated with one combination selected from the group consisting of adenosine, allantoin, centella asiatica extract, dexpanthenol, niacinamide, salicylic acid, quercitrin, chlorogenic acid, lane, and riboflavin 5'-phosphate, all dermal papilla cell proliferative abilities were remarkably increased. In particular, Examples 18 to 27, in which two types of active ingredients were mixed, including Escin and one other, were significantly superior to Examples 7 to 17, which contained a single active ingredient, in enhancing the dermal papilla cell activity. It was confirmed that a synergistic effect occurred through the combination of components.
실험예 7: 유효성분 조합의 모유두 세포 활성 신호(Wnt/β-카테닌)조절 효과Experimental Example 7: Dermal papilla cell activation signal (Wnt/β-catenin) modulating effect of active ingredient combinations
실험예 1과 동일한 방식으로, 에스신; 및 아데노신, 알란토인, 병풀 추출물, 덱스판테놀, 나이아신아마이드, 살리실산, 퀘르시트린, 클로로젠산, 레인, 및 리보플라빈 5'-포스페이트로 이루어진 군으로부터 선택된 1종 조합의 Wnt/β-카테닌 신호 활성화 효과를 평가하였다.In the same manner as in Experimental Example 1, Escyn; And adenosine, allantoin, centella asiatica extract, dexpanthenol, niacinamide, salicylic acid, quercitrin, chlorogenic acid, lane, and riboflavin 5'-phosphate Wnt / β-catenin signal activation effect of one combination selected from the group consisting of did
상기 실험 결과를 볼 때, 에스신; 및 아데노신, 알란토인, 병풀 추출물, 덱스판테놀, 나이아신아마이드, 살리실산, 퀘르시트린, 클로로젠산, 레인, 및 리보플라빈 5'-포스페이트로 이루어진 군으로부터 선택된 1종의 조합을 처리하였을 경우 우수한 Wnt 신호 활성화 효과를 나타냄을 확인하였다. 특히 에스신 및 기타 1종을 포함하여 2종의 유효성분이 혼합된 실시예 39 내지 48은 단일 유효성분이 포함된 실시예 28 내지 38에 비해 Wnt 신호 활성화 효과가 현저하게 우수하여, 2종의 유효성분의 조합을 통해 상승 효과가 발생함을 확인하였다.Looking at the above experimental results, Ssin; and adenosine, allantoin, centella asiatica extract, dexpanthenol, niacinamide, salicylic acid, quercitrin, chlorogenic acid, lane, and riboflavin 5'-phosphate. It was confirmed that In particular, Examples 39 to 48 in which two types of active ingredients were mixed, including escin and one other, were significantly superior to Examples 28 to 38 containing a single active ingredient, and the Wnt signal activating effect was significantly superior, so that the two types of active ingredients It was confirmed that a synergistic effect occurred through the combination of .
따라서, 에스신; 및 아데노신, 알란토인, 병풀 추출물, 덱스판테놀, 나이아신아마이드, 살리실산, 퀘르시트린, 클로로젠산, 레인, 및 리보플라빈 5'-포스페이트로 이루어진 군으로부터 선택된 1종 이상 조합은 모낭 줄기 세포의 모발 성장 촉진 신호인 Wnt/베타-카테닌 신호전달계의 활성을 매우 우수하게 촉진시킴으로써 발모 촉진의 효과가 있음을 확인할 수 있었다.Thus, escin; And at least one combination selected from the group consisting of adenosine, allantoin, centella asiatica extract, dexpanthenol, niacinamide, salicylic acid, quercitrin, chlorogenic acid, lane, and riboflavin 5'-phosphate is a hair growth promoting signal of hair follicle stem cells. It was confirmed that there is an effect of promoting hair growth by promoting the activity of the Wnt/beta-catenin signaling system very well.
실험예 8: 모발 체외 조직 배양(Ex-vivo)시 모발 성장 효과 확인Experimental Example 8: Confirmation of hair growth effect during ex vivo tissue culture (Ex-vivo)
모낭은 피부과 두피수술 후 얻은 모낭으로 실험을 진행하였다. 개개의 분리된 모낭은 모낭 기저의 모유두 세포로부터 3-3.5mm 의 길이로 일정하게 절단하여 초기 길이를 맞추었다. 이후, willium's E medium (gibco)에 10ng/ml의 하이드로콜티손, 10mg/ml의 인슐린, 2mM의 L-glutamine, 및 antibiotic antimycotic solution을 포함한 배양배지에서 배양하였다. 37℃의 5% 이산화탄소 환경 조건에서 실시예 7 내지 27을 해당 농도로 포함하여 배양을 시작하였다. 2일에 한번씩 해당 배지를 새로 교체해 주었으며, 배양 7일 후 올림푸스 스테레오 현미경을 사용하여 길이를 측정하였다. 초기 길이에 비해 생장된 길이를 측정하여 각 실시예별로 수치화 하였다.The hair follicles were tested with hair follicles obtained after dermatological scalp surgery. Each isolated hair follicle was uniformly cut to a length of 3-3.5 mm from the dermal papilla cell at the base of the hair follicle to match the initial length. Then, they were cultured in a culture medium containing 10 ng/ml hydrocortisone, 10 mg/ml insulin, 2 mM L-glutamine, and an antibiotic antimycotic solution in willium's E medium (gibco). Cultivation was started by including Examples 7 to 27 at the corresponding concentration under 5% carbon dioxide environmental conditions at 37°C. The medium was newly replaced every 2 days, and after 7 days of culture, the length was measured using an Olympus stereo microscope. The length grown compared to the initial length was measured and quantified for each example.
상기 실험 결과를 볼 때, 에스신; 및, 아데노신, 알란토인, 병풀 추출물, 덱스판테놀, 나이아신아마이드, 살리실산, 퀘르시트린, 클로로젠산, 레인, 및 리보플라빈 5'-포스페이트로 이루어진 군으로부터 선택된 1종의 조합을 함유하는 경우 높은 모발 성장 효과가 나타남을 확인하였다. 특히 에스신 및 기타 1종을 포함하여 2종의 유효성분이 혼합된 실시예 18 내지 27는 단일 유효성분이 포함된 실시예 7 내지 17에 비해 모발 성장 효과가 현저하게 우수하여, 2종의 유효성분의 조합을 통해 상승 효과가 발생함을 확인하였다.Looking at the above experimental results, Ssin; And, when containing one combination selected from the group consisting of adenosine, allantoin, centella asiatica extract, dexpanthenol, niacinamide, salicylic acid, quercitrin, chlorogenic acid, lane, and riboflavin 5'-phosphate, high hair growth effect confirmed to appear. In particular, Examples 18 to 27 in which two types of active ingredients were mixed, including Escin and one other, had significantly better hair growth effects than Examples 7 to 17 containing a single active ingredient, so that the two types of active ingredients It was confirmed that a synergistic effect occurred through the combination.
상기 실험예들을 통해, 에스신; 및 아데노신, 알란토인, 병풀 추출물, 덱스판테놀, 나이아신아마이드, 살리실산, 퀘르시트린, 클로로젠산, 레인, 및 리보플라빈 5'-포스페이트로 이루어진 군으로부터 선택된 1종 이상을 유효성분으로 포함하는 본 발명의 탈모 방지 및/또는 모발 성장 촉진용 조성물이 탈모 치료에 매우 효과적으로 사용될 수 있음을 확인하였다.Through the above experimental examples, Ssin; and at least one selected from the group consisting of adenosine, allantoin, centella asiatica extract, dexpanthenol, niacinamide, salicylic acid, quercitrin, chlorogenic acid, lane, and riboflavin 5'-phosphate as an active ingredient to prevent hair loss of the present invention And / or it was confirmed that the composition for promoting hair growth can be used very effectively for the treatment of hair loss.
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