KR20230152287A - Cosmetic composition and skin external application composition for improving skin condition and preventing or treating disorders of melanin hyperpigmentation comprising functional peptide - Google Patents
Cosmetic composition and skin external application composition for improving skin condition and preventing or treating disorders of melanin hyperpigmentation comprising functional peptide Download PDFInfo
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- KR20230152287A KR20230152287A KR1020220051825A KR20220051825A KR20230152287A KR 20230152287 A KR20230152287 A KR 20230152287A KR 1020220051825 A KR1020220051825 A KR 1020220051825A KR 20220051825 A KR20220051825 A KR 20220051825A KR 20230152287 A KR20230152287 A KR 20230152287A
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- tranexamoyl
- skin
- peptide
- composition
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
본 발명은 기능성 펩타이드를 함유하는 피부상태 개선 및 멜라닌 색소 과다 침착 질환 예방 또는 치료용 화장료 조성물 및 피부 외용제에 관한 것으로, 구체적으로 본 발명에서 제작한 3종의 트라넥사모일 펩타이드(Tranexamoyl-peptide) 트라넥사모일-GS, 트라넥사모일-GA 및 트라넥사모일-GSGA가 피부 세포에서 α-MSH에 의한 멜라닌 생성 억제하고, UV-B에 의한 세포사멸, 활성산소종(ROS) 생성, 콜라겐분해 및 염증 관련 유전자 발현을 억제하는 효과를 확인하였으므로, 상기 트라넥사모일 펩타이드는 피부상태 개선, 또는 멜라닌 색소 과다 침착 질환 예방 또는 치료 용도로 유용하게 이용될 수 있다.The present invention relates to a cosmetic composition containing functional peptides for improving skin condition and preventing or treating melanin hyperpigmentation diseases, as well as external skin preparations. Specifically, the three types of tranexamoyl-peptides produced in the present invention Nexamoyl-GS, tranexamoyl-GA, and tranexamoyl-GSGA inhibit melanin production by α-MSH in skin cells, and induce UV-B-induced apoptosis, reactive oxygen species (ROS) production, collagen degradation, and inflammation. Since the effect of suppressing the expression of related genes has been confirmed, the tranexamoyl peptide can be usefully used to improve skin condition or prevent or treat melanin hyperpigmentation disease.
Description
본 발명은 기능성 펩타이드를 함유하는 피부상태 개선 및 멜라닌 색소 과다 침착 질환 예방 또는 치료용 화장료 조성물 및 피부 외용제에 관한 것으로, 보다 상세하게는 기능성 펩타이드로 멜라닌 생성을 억제하고, UV-B에 의한 세포사멸, 활성산소종(ROS) 생성, 콜라겐분해 및 염증 관련 유전자 발현을 억제하는 트라넥사모일 펩타이드(Tranexamoyl-peptide)를 함유하는 피부상태 개선 및 멜라닌 색소 과다 침착 질환 예방 또는 치료용 화장료 조성물 및 피부 외용제에 관한 것이다.The present invention relates to a cosmetic composition containing a functional peptide for improving skin condition and preventing or treating melanin hyperpigmentation disease, and a skin external agent. More specifically, the present invention relates to a functional peptide that inhibits melanin production and inhibits cell death by UV-B. , Cosmetic compositions and external skin preparations for improving skin condition and preventing or treating melanin hyperpigmentation diseases containing tranexamoyl-peptide, which suppresses the production of reactive oxygen species (ROS), collagen decomposition, and inflammation-related gene expression. It's about.
피부의 노화는 크게 생물학적 과정에 따라 시간이 지나면서 나타나는 연대학적 노화(내인적인 노화)와 햇볕에 노출되는 부위에 일어나는 퇴행성 변화와 연대학적 노화가 복합적으로 발생하는 광노화(광인성 노화)로 구분된다. 광노화에서는 피부가 건조해지고 거칠어지며 두꺼워지는 반면 연대학적 노화에서는 오히려 피부가 얇고 매끄러워진다. 이 밖에도 광노화에서는 연대학적 노화와는 다르게 깊은 주름이 생기고 이완, 얼룩진 과색소 침착과 저색소 침착, 모세 혈관 확장, 자반, 가성반흔 등이 나타난다. 이외에도 연대학적 노화와 광노화는 여러 가지 임상 양상의 차이가 있다.Skin aging is largely divided into chronological aging (intrinsic aging), which occurs over time according to biological processes, and photoaging (photogenic aging), which occurs in combination with chronological aging and degenerative changes that occur in areas exposed to sunlight. . In photoaging, the skin becomes dry, rough, and thick, whereas in chronological aging, the skin becomes thinner and smoother. In addition, photoaging, unlike chronological aging, causes deep wrinkles, relaxation, patchy hyperpigmentation and hypopigmentation, capillary dilatation, purpura, and pseudoscars. In addition, chronological aging and photoaging have several clinical differences.
햇빛에 의한 손상은 피부노화의 주요 원인으로 광노화를 발생시키는 주요 원인은 자외선이다. 자외선은 그 파장의 길이에 따라 UV-A, B, C로 나눌 수 있는데, 이중 UV-A(320-400 nm)는 피부에 대한 자극이 미약하여 UV-B보다는 피부에 해가 적지만 오랫동안 노출될 경우 기미나 검버섯 등의 색소 침착이 일어나고 피부 노화를 심화시킬뿐 아니라, 심한 경우 피부암까지 발생시킬 수 있다. UV-C(200-280 nm)는 X선과 근접한 파장을 가진 광선으로 발암성이 매우 높지만 오존층에 의해 모두 차단되므로 별도로 차단해야 할 필요는 없다. UV-B(280-320 nm)는 인체에 가장 쉽고 빠르게 영향을 나타내어 피부손상에 관여하며 건조 및 피부홍반, 색소침착, 표피비후 등의 현상과 산화적 스트레스 및 항산화 기전의 불균형 유발을 통해 피부를 구성하는 지질, 단백질, 효소 등을 손상시킴으로써 염증반응과 피부암 및 광노화를 심화시켜 피부손상을 초래한다. 특히 UV-B 노출에 의해 생성이 유도되는 활성산소종(reactive oxygen species, ROS)은 광노화 주요원인 중 하나로 세포내 신호전달 체계를 자극하여 DNA와 지질 및 단백질과 같은 생체분자에 산화적 스트레스 유발을 통한 피부조직 손상을 야기한다. 또한 활성산소종은 표피 각질세포와 진피 섬유아세포의 자극으로 활성화 단백질(activator protein-1, AP-1) 및 핵인자 카파 B(nuclear factor kappa-light-chain-enhancer of activated B cells, NF-κB)의 전사인자를 활성화하고 염증 관련 사이토카인(cytokine)을 분비토록 하여 콜라겐 분해효소들(matrix metalloproteinase, MMPs)의 발현을 증가시킨다. 증가된 콜라겐 분해효소들(MMPs)은 피부의 콜라겐을 분해한다. 콜라겐은 피부의 주요 구성 성분으로 진피층의 경우 90%를 차지하고 있고 피부에 강도와 장력을 부여하며 이로 인해 외부의 자극이나 힘으로부터 피부를 보호하는 역할을 하고 있기 때문에 자외선 노출에 의한 콜라겐 분해효소들(MMPs)의 발현증가에 따른 콜라겐의 감소는 피부 노화와 주름형성을 유발한다. Damage from sunlight is the main cause of skin aging, and the main cause of photoaging is ultraviolet rays. Ultraviolet rays can be divided into UV-A, B, and C depending on the length of the wavelength. Among them, UV-A (320-400 nm) is less irritating to the skin and is less harmful to the skin than UV-B, but is exposed for a long time. If this happens, pigmentation such as freckles and age spots can occur, which not only worsens skin aging, but in severe cases can even cause skin cancer. UV-C (200-280 nm) is a ray with a wavelength close to X-rays and is highly carcinogenic, but it is completely blocked by the ozone layer, so there is no need to block it separately. UV-B (280-320 nm) has the easiest and fastest effect on the human body and is involved in skin damage. It damages the skin by causing dryness, skin erythema, pigmentation, and epidermal thickening, as well as oxidative stress and imbalance in antioxidant mechanisms. By damaging the constituent lipids, proteins, and enzymes, it intensifies inflammatory reactions, skin cancer, and photoaging, resulting in skin damage. In particular, reactive oxygen species (ROS), the production of which is induced by UV-B exposure, is one of the main causes of photoaging and stimulates the intracellular signaling system, causing oxidative stress in biomolecules such as DNA, lipids, and proteins. It causes skin tissue damage through In addition, reactive oxygen species stimulate epidermal keratinocytes and dermal fibroblasts to produce activator protein-1 (AP-1) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). ) and secrete inflammation-related cytokines, thereby increasing the expression of matrix metalloproteinase (MMPs). Increased collagenases (MMPs) break down collagen in the skin. Collagen is a major component of the skin, accounting for 90% of the dermal layer, and provides strength and tension to the skin. As a result, it plays a role in protecting the skin from external stimulation or force. Therefore, collagen decomposition enzymes caused by exposure to ultraviolet rays ( A decrease in collagen due to increased expression of MMPs causes skin aging and wrinkle formation.
항노화를 위한 대표적인 피부 주름 개선 물질로 알려진 레티놀, 레티노이드 및 그 유도체들의 경우 콜라겐 분해효소(MMP-1)를 억제해 콜라겐 손실을 방지하여 내인성 및 광노화를 방지하고 회복시키는 것으로 알려져 있으나 홍반, 가려움, 건선 등의 국소적 피부 부작용을 일으킬 수 있다고 알려져 있다.Retinol, retinoids, and their derivatives, which are known as representative skin wrinkle improvement substances for anti-aging, are known to prevent and restore endogenous and photoaging by inhibiting collagen degrading enzyme (MMP-1) to prevent collagen loss, but it is also known to prevent and restore intrinsic and photoaging. It is known that it can cause local skin side effects such as psoriasis.
또한, UV-B 조사는 각질형성세포(keratinocyte)가 종양괴사인자-알파(tumour necrosis factor-α, TNF-α), 인터루킨-1베타(interleukin-1β, IL-1β), IL-6, IL-10 와 IL-8을 세포 외로 분비하도록 자극하여 염증을 유도한다. 특히 TNF-α는 초기 자극에 대한 중요한 염증 유발인자로서 염증반응을 유도해 유도형 NO 생성효소(inducible NO synthase, iNOS) 발현을 증가시키고 iNOS에 의해 생성된 염증매개 물질인 NO는 피부세포에서 콜라겐 생성에 중요한 영향을 끼칠 뿐 아니라 피부세포성장에 주요한 역할을 한다고도 알려져 있다.In addition, UV-B irradiation causes keratinocytes to produce tumor necrosis factor-alpha (TNF-α), interleukin-1beta (interleukin-1β, IL-1β), IL-6, and IL-6. It induces inflammation by stimulating extracellular secretion of -10 and IL-8. In particular, TNF-α is an important inflammatory trigger in response to initial stimulation and induces an inflammatory response to increase the expression of inducible NO synthase (iNOS). NO, an inflammatory mediator produced by iNOS, causes collagen in skin cells. It is known that it not only has an important effect on the formation of skin cells, but also plays a major role in skin cell growth.
현재까지 항염의 목적으로 이용되고 있는 물질로는 비스테로이드계로 플루페나믹산(flufenamic acid), 이부프로펜(ibuprofen), 벤지다민(benzydamine), 인도메타신(indomethacin)등이 있고, 스테로이드 계통으로 프레드니솔론(prednisolone), 덱사메타손(dexamethasone) 등이 있다. 또한, 알란토인, 아즈엔, 하이드로코티손 등이 항염증에 효과가 있는 것으로 알려져 있으나, 이들 물질은 피부에 대한 안전성의 문제로 사용량의 제한이 있거나, 효과가 미미하여 실질적으로 염증 완화 효과를 기대할 수 없는 문제점이 있다.Substances currently used for anti-inflammatory purposes include non-steroids such as flufenamic acid, ibuprofen, benzydamine, and indomethacin, and steroids such as prednisolone. ), dexamethasone, etc. In addition, allantoin, Azn, hydrocortisone, etc. are known to be effective in anti-inflammatory, but the amount of use of these substances is limited due to safety issues on the skin, or the effect is so minimal that it is not possible to expect a practical effect of alleviating inflammation. There is.
한편, 사람의 피부색을 결정하는 멜라닌(melanin)은 멜라노사이트(melanocyte)에서 생성된다. 구체적으로 멜라닌은 생체 내 존재하는 아미노산인 티로신(tyrosine)을 기질로 하여, 멜라노사이트에 존재하는 티로시나제(tyrosinase) 등의 효소에 의한 중합화 산화 반응으로 형성되는 흑갈색의 색소이다. 이렇게 형성된 멜라닌은 멜라노사이트의 수지상 돌기를 통하여 케라티노사이트(keratinocyte)라는 표피세포로 이동하게 된다. 케라티노사이트로 이동한 멜라닌은 케라티노사이트가 표피에서 떨어져 나갈 때에 피부에서 함께 떨어져 나감으로써 제거될 수 있다. 그러나 생체 내에 멜라닌을 분해하는 효소가 없기 때문에 한번 형성된 멜라닌은 생체 내에서는 분해되지 않는다. 따라서, 피부를 밝게 하기 위해서는 멜라닌의 생성을 억제하는 것이 관건이라 할 수 있다.Meanwhile, melanin, which determines human skin color, is produced in melanocytes. Specifically, melanin is a dark brown pigment formed through polymerization and oxidation reaction by enzymes such as tyrosinase present in melanocytes using tyrosine, an amino acid that exists in the body, as a substrate. The melanin formed in this way moves to epidermal cells called keratinocytes through the dendrites of melanocytes. Melanin that has moved to the keratinocytes can be removed by falling off the skin when the keratinocytes fall off the epidermis. However, since there is no enzyme to decompose melanin in the living body, melanin once formed is not decomposed in the living body. Therefore, the key to brightening the skin is to suppress the production of melanin.
화장품으로서의 미백제의 연구는 최근 정서적으로 흰 피부를 선호하는 동양권의 생활 수준 향상과 더불어 피부 흑화가 자외선에 의한 피부 노화로 인식되면서 그 필요성이 점차 증대되고 있다. 그에 따라 아스코르빈산(ascorbic acid), 하이드로퀴논(hydroquinone), 글루타치온(glutathione), 알부틴(arbutin) 등의 티로시나아제 저해 활성을 나타내는 물질들이 화장료나 의약품에 배합되어 사용되어 왔으나, 이들 중 대부분의 것은 효과가 불충분하거나 제형상 불안정한 면이 있어 활용도가 떨어진다. 특히 하이드로퀴논과 같은 화합물은 강한 탈색 작용을 나타내며 그 자체가 피부 감작성을 가지고 있어 피부 알레르기 등을 유발할 수 있고, 정상적인 피부의 기능을 변화시켜 백반증을 유발하는 등의 부작용을 나타내어 피부에 대한 안전성 측면에서 그 사용이 제한되고 있다.The need for research on whitening agents as cosmetics is gradually increasing as the standard of living in Eastern countries, which emotionally prefer white skin, improves and skin darkening is recognized as skin aging caused by ultraviolet rays. Accordingly, substances showing tyrosinase inhibitory activity, such as ascorbic acid, hydroquinone, glutathione, and arbutin, have been used in cosmetics and pharmaceuticals, but most of these These have poor usability due to insufficient effectiveness or instability in the formulation. In particular, compounds such as hydroquinone exhibit a strong depigmentation effect and have skin sensitization properties themselves, which can cause skin allergies and other side effects such as changing normal skin function and causing vitiligo, making them safe for the skin. Its use is restricted.
이에, 본 발명자들은 세포 독성이 없고 피부상태 개선 효과가 우수한 물질을 개발하기 위해 노력한 결과, 3종의 트라넥사모일 펩타이드(Tranexamoyl-peptide) 트라넥사모일-GS, 트라넥사모일-GA 및 트라넥사모일-GSGA 각각이 피부 세포에서 α-MSH에 의한 멜라닌 생성 억제하고, UV-B에 의한 세포사멸, 활성산소종(ROS) 생성, 콜라겐분해 및 염증 관련 유전자 발현을 억제하는 효과를 확인하여, 상기 트라넥사모일 펩타이드를 피부상태 개선, 또는 멜라닌 색소 과다 침착 질환 예방 또는 치료 용도로 유용하게 이용할 수 있다는 점을 밝힘으로써, 본 발명의 출원에 이르렀다.Accordingly, the present inventors made efforts to develop a material that is non-cytotoxic and has excellent skin condition improvement effects, and as a result, three types of tranexamoyl peptides, tranexamoyl-GS, tranexamoyl-GA, and tranexamoyl, were found. -GSGA was confirmed to have the effect of suppressing melanin production by α-MSH in skin cells, and suppressing UV-B-induced apoptosis, reactive oxygen species (ROS) production, collagen decomposition, and inflammation-related gene expression, and the above tra By revealing that nexamoyl peptide can be usefully used to improve skin condition or prevent or treat melanin hyperpigmentation disease, the present invention has been filed.
본 발명의 목적은 기능성 펩타이드를 함유하는 피부상태 개선용 화장료 조성물 및 피부 외용제를 제공하는 것이다.The purpose of the present invention is to provide a cosmetic composition for improving skin condition and a skin external agent containing functional peptides.
본 발명의 다른 목적은 기능성 펩타이드를 함유하는 멜라닌 색소 과다 침착 질환의 예방, 치료 또는 개선용 조성물을 제공하는 것이다.Another object of the present invention is to provide a composition for preventing, treating or improving melanin hyperpigmentation disease containing a functional peptide.
본 발명의 목적을 달성하기 위하여, 본 발명은 트라넥사모일 펩타이드(Tranexamoyl-peptide)를 유효성분으로 함유하는 피부상태 개선용 화장료 조성물로서, 상기 트라넥사모일 펩타이드는 트라넥사모일-GS, 트라넥사모일-GA 및 트라넥사모일-GSGA로 이루어진 군에서 선택되는 것인 화장료 조성물을 제공한다.In order to achieve the object of the present invention, the present invention is a cosmetic composition for improving skin condition containing tranexamoyl peptide (Tranexamoyl-peptide) as an active ingredient, wherein the tranexamoyl peptide is tranexamoyl-GS, tranexamoyl Provided is a cosmetic composition selected from the group consisting of -GA and tranexamoyl-GSGA.
또한, 본 발명은 트라넥사모일 펩타이드를 유효성분으로 함유하는 피부상태 개선용 피부 외용제 조성물로서, 상기 트라넥사모일 펩타이드는 트라넥사모일-GS, 트라넥사모일-GA 및 트라넥사모일-GSGA로 이루어진 군에서 선택되는 것인 피부 외용제 조성물을 제공한다.In addition, the present invention is a skin external composition for improving skin condition containing tranexamoyl peptide as an active ingredient, wherein the tranexamoyl peptide is a group consisting of tranexamoyl-GS, tranexamoyl-GA and tranexamoyl-GSGA. Provides a composition for external application for skin selected from.
또한, 본 발명은 트라넥사모일 펩타이드를 유효성분으로 함유하는 멜라닌 색소 과다 침착 질환의 예방 또는 치료용 약학 조성물로서, 상기 트라넥사모일 펩타이드는 트라넥사모일-GS, 트라넥사모일-GA 및 트라넥사모일-GSGA로 이루어진 군에서 선택되는 것인 약학 조성물을 제공한다.In addition, the present invention is a pharmaceutical composition for preventing or treating melanin hyperpigmentation disease containing tranexamoyl peptide as an active ingredient, wherein the tranexamoyl peptide is tranexamoyl-GS, tranexamoyl-GA and tranexamoyl. Provided is a pharmaceutical composition selected from the group consisting of -GSGA.
아울러, 본 발명은 트라넥사모일 펩타이드를 유효성분으로 함유하는 멜라닌 색소 과다 침착 질환의 예방 또는 개선용 건강기능식품 조성물로서, 상기 트라넥사모일 펩타이드는 트라넥사모일-GS, 트라넥사모일-GA 및 트라넥사모일-GSGA로 이루어진 군에서 선택되는 것인 건강기능식품 조성물을 제공한다.In addition, the present invention is a health functional food composition for preventing or improving melanin hyperpigmentation disease containing tranexamoyl peptide as an active ingredient, wherein the tranexamoyl peptide is tranexamoyl-GS, tranexamoyl-GA and tranexamoyl Provided is a health functional food composition selected from the group consisting of nexamoyl-GSGA.
본 발명에서는 3종의 트라넥사모일 펩타이드(Tranexamoyl-peptide)로 트라넥사모일-GS, 트라넥사모일-GA 및 트라넥사모일-GSGA를 제작하였고, 피부 세포에서 상기 트라넥사모일 펩타이드가 α-MSH에 의한 멜라닌 생성을 억제하고, UV-B에 의한 세포사멸, 활성산소종(ROS) 생성, 콜라겐분해 및 염증 관련 유전자 발현을 억제하는 효과를 확인하였으므로, 상기 트라넥사모일 펩타이드는 피부상태 개선, 또는 멜라닌 색소 과다 침착 질환 예방 또는 치료 용도로 유용하게 이용될 수 있다.In the present invention, tranexamoyl-GS, tranexamoyl-GA, and tranexamoyl-GSGA were produced from three types of tranexamoyl-peptides, and the tranexamoyl peptides were linked to α-MSH in skin cells. Since the effectiveness of suppressing melanin production by UV-B, apoptosis, reactive oxygen species (ROS) production, collagen decomposition, and inflammation-related gene expression was confirmed, the tranexamoyl peptide is effective in improving skin condition or melanin production. It can be useful for preventing or treating hyperpigmentation diseases.
도 1은 본 발명의 일 실시예에 따른 트라넥사모일 펩타이드(Tranexamoyl-peptide)의 제조 방법을 모식화한 도이다.
도 2는 본 발명의 일 실시예에 따른 트라넥사모일 펩타이드를 처리한 B16F1 세포에서 α-MSH에 의한 멜라닌 생성 억제를 확인한 도이다.
도 3은 HaCaT 세포에서 본 발명의 일 실시예에 따른 트라넥사모일 펩타이드의 세포독성을 확인한 도이다.
도 4는 본 발명의 일 실시예에 따른 트라넥사모일 펩타이드를 처리한 HaCaT 세포에서 UV-B에 의한 세포사멸 억제를 확인한 도이다.
도 5는 본 발명의 일 실시예에 따른 트라넥사모일 펩타이드를 처리한 HaCaT 세포에서 UV-B에 의한 활성산소종(ROS) 생성 억제를 확인한 도이다.
도 6은 본 발명의 일 실시예에 따른 트라넥사모일 펩타이드를 처리한 HaCaT 세포에서 UV-B에 의한 콜라겐분해 억제를 확인한 도이다.
도 7은 본 발명의 일 실시예에 따른 트라넥사모일 펩타이드를 처리한 HaCaT 세포에서 UV-B에 의한 염증 관련 유전자 발현 억제를 확인한 도이다.Figure 1 is a diagram schematically illustrating a method for producing tranexamoyl peptide (Tranexamoyl-peptide) according to an embodiment of the present invention.
Figure 2 is a diagram confirming the inhibition of melanin production by α-MSH in B16F1 cells treated with tranexamoyl peptide according to an embodiment of the present invention.
Figure 3 is a diagram confirming the cytotoxicity of tranexamoyl peptide according to an embodiment of the present invention in HaCaT cells.
Figure 4 is a diagram confirming the inhibition of apoptosis by UV-B in HaCaT cells treated with tranexamoyl peptide according to an embodiment of the present invention.
Figure 5 is a diagram confirming the inhibition of reactive oxygen species (ROS) production by UV-B in HaCaT cells treated with tranexamoyl peptide according to an embodiment of the present invention.
Figure 6 is a diagram confirming the inhibition of collagen degradation by UV-B in HaCaT cells treated with tranexamoyl peptide according to an embodiment of the present invention.
Figure 7 is a diagram confirming the inhibition of inflammation-related gene expression by UV-B in HaCaT cells treated with tranexamoyl peptide according to an embodiment of the present invention.
이하, 본 발명을 보다 상세히 설명한다.Hereinafter, the present invention will be described in more detail.
본 발명에서 사용되는 용어 "펩타이드"는 펩타이드 결합에 의해 아미노산 잔기들이 서로 결합되어 형성된 선형의 분자를 의미하며, "트라넥사모일 펩타이드(Tranexamoyl-peptide)"는 트라넥삼산((Tranexamic acid)의 카르복실기와 펩타이드의 N-말단을 화학적으로 결합시켜 합성된 융합체의 형태를 말한다.As used in the present invention, the term "peptide" refers to a linear molecule formed by combining amino acid residues with each other through peptide bonds, and "tranexamoyl-peptide" refers to the carboxyl group of tranexamic acid. It refers to a form of fusion synthesized by chemically combining the N-terminus of a peptide with a peptide.
본 발명에서 사용되는 용어 "예방"은 본 발명의 조성물의 투여로 질환을 억제하거나 진행을 지연시키는 모든 행위를 의미한다.The term “prevention” used in the present invention refers to any action that suppresses or delays the progression of a disease by administering the composition of the present invention.
본 발명에서 사용되는 용어 "치료" 또는 "개선"은 본 발명의 조성물의 투여로 질환의 증상이 호전 또는 이롭게 변경되는 모든 행위를 의미한다.The term “treatment” or “improvement” used in the present invention refers to any action in which the symptoms of a disease are improved or beneficially changed by administration of the composition of the present invention.
본 발명에서 사용되는 용어 "투여"는 임의의 적절한 방법으로 개체에 본 발명의 조성물을 제공하는 것을 의미한다.As used herein, the term “administration” means providing a composition of the invention to a subject by any suitable method.
본 발명에서 사용되는 용어 "개체"는 본 발명의 조성물을 투여하여 질환의 증상이 호전될 수 있는 질환을 가진 인간, 원숭이, 개, 염소, 돼지 또는 쥐 등 모든 동물을 의미한다.The term “subject” used in the present invention refers to any animal, such as a human, monkey, dog, goat, pig, or rat, whose disease symptoms can be improved by administering the composition of the present invention.
본 발명은 트라넥사모일 펩타이드(Tranexamoyl-peptide)를 유효성분으로 함유하는 피부상태 개선용 화장료 조성물로서,The present invention is a cosmetic composition for improving skin condition containing tranexamoyl-peptide as an active ingredient,
상기 트라넥사모일 펩타이드는 트라넥사모일-GS, 트라넥사모일-GA 및 트라넥사모일-GSGA로 이루어진 군에서 선택되는 것인 화장료 조성물을 제공한다.The tranexamoyl peptide provides a cosmetic composition selected from the group consisting of tranexamoyl-GS, tranexamoyl-GA, and tranexamoyl-GSGA.
본 발명에서, 상기 트라넥사모일 펩타이드에 결합된 펩타이드는 2 또는 4개의 아미노산 잔기로 구성되어 매우 분자량이 작아 피부 침투율이 우수하다. 따라서, 본 발명의 트라넥사모일 펩타이드를 국소적으로 피부에 도포하는 경우 높은 피부 침투율로 인해 우수한 피부상태 개선 효과를 달성할 수 있다.In the present invention, the peptide bound to the tranexamoyl peptide is composed of 2 or 4 amino acid residues and has a very low molecular weight, resulting in excellent skin penetration rate. Therefore, when the tranexamoyl peptide of the present invention is applied topically to the skin, an excellent skin condition improvement effect can be achieved due to the high skin penetration rate.
구체적으로, 상기 피부상태 개선은 피부미백, 항노화, 자외선에 의한 피부보호, 항산화, 피부주름 개선, 피부탄력 개선 또는 항염증일 수 있다.Specifically, the skin condition improvement may be skin whitening, anti-aging, skin protection from ultraviolet rays, antioxidant, skin wrinkle improvement, skin elasticity improvement, or anti-inflammation.
보다 구체적으로, 본 발명의 트라넥사모일 펩타이드는 멜라닌 합성을 억제하여 피부 색상을 밝게 하고 피부톤을 일정하게 함으로써, 피부상태 개선으로 피부미백을 달성할 수 있다.More specifically, the tranexamoyl peptide of the present invention can suppress melanin synthesis to brighten skin color and maintain a consistent skin tone, thereby achieving skin whitening by improving skin condition.
또한, 본 발명의 트라넥사모일 펩타이드는 자외선에 의한 세포사멸 억제하여 피부상태 개선으로 항노화 및 자외선에 의한 피부보호를 달성할 수 있다.In addition, the tranexamoyl peptide of the present invention can achieve anti-aging and skin protection from ultraviolet rays by improving skin condition by inhibiting cell death caused by ultraviolet rays.
또한, 본 발명의 트라넥사모일 펩타이드는 활성 산소, 예컨대 활성산소종(ROS) 생성을 억제하여 피부상태 개선으로 항산화를 달성할 수 있다.In addition, the tranexamoyl peptide of the present invention can achieve antioxidant properties by improving skin condition by suppressing the production of active oxygen, such as reactive oxygen species (ROS).
또한, 본 발명의 트라넥사모일 펩타이드는 콜라겐, 예컨대 타입 I 콜라겐의 합성을 촉진하고, 콜라겐분해효소, 예컨대 MMP-1(matrix metalloproteinase-1)의 발현을 억제하여 피부주름 개선 및 피부탄력 개선을 달성할 수 있다. In addition, the tranexamoyl peptide of the present invention promotes the synthesis of collagen, such as type I collagen, and inhibits the expression of collagenase, such as matrix metalloproteinase-1 (MMP-1), thereby improving skin wrinkles and improving skin elasticity. can do.
또한, 본 발명의 트라넥사모일 펩타이드는 염증 관련 인자, 예컨대 TNF-α 또는 iNOS의 발현을 억제하여 염증을 완화하거나 감소시키는 피부상태 개선 효과를 달성할 수 있다.In addition, the tranexamoyl peptide of the present invention can achieve the effect of improving skin condition by alleviating or reducing inflammation by inhibiting the expression of inflammation-related factors, such as TNF-α or iNOS.
본 발명의 구체적인 실시예에서, 본 발명자들은 3종의 트라넥사모일 펩타이드(Tranexamoyl-peptide)로 트라넥사모일-GS, 트라넥사모일-GA 및 트라넥사모일-GSGA를 제작하였다(표 1).In a specific example of the present invention, the present inventors prepared tranexamoyl-GS, tranexamoyl-GA, and tranexamoyl-GSGA from three types of tranexamoyl peptides (Table 1).
또한, 본 발명자들은 마우스 흑색종 세포주인 B16F1 세포에서 상기 3종의 트라넥사모일 펩타이드가 α-MSH에 의한 멜라닌 생성을 억제하는 효과를 확인하였다. 또한, 상기 3종의 트라넥사모일 펩타이드 각각은 트라넥삼산, 다이펩타이드(dipeptide) GS, GA 및 테트라펩타이드(tetrapeptide) GSGA 각각보다 우수한 멜라닌 생성 억제 효과를 나타냄을 확인하였다(도 2).Additionally, the present inventors confirmed the effect of the above three types of tranexamoyl peptides on inhibiting melanin production by α-MSH in B16F1 cells, a mouse melanoma cell line. In addition, it was confirmed that each of the three types of tranexamoyl peptides showed a superior melanin production inhibition effect than tranexamic acid, dipeptide GS, GA, and tetrapeptide GSGA (FIG. 2).
또한, 본 발명자들은 인간 각질세포주인 HaCaT 세포에서 상기 3종의 트라넥사모일 펩타이드가 세포독성이 없고(도 3), UV-B에 의한 세포사멸을 억제하는 효과를 확인하였다(도 4).In addition, the present inventors confirmed that the three types of tranexamoyl peptides were not cytotoxic in HaCaT cells, a human keratinocyte cell line (Figure 3), and were effective in suppressing apoptosis caused by UV-B (Figure 4).
또한, 본 발명자들은 인간 각질세포주인 HaCaT 세포에서 상기 3종의 트라넥사모일 펩타이드가 UV-B에 의한 활성산소종(ROS) 생성을 억제하는 효과를 확인하였다(도 5). In addition, the present inventors confirmed the effect of the above three types of tranexamoyl peptides on suppressing UV-B-induced reactive oxygen species (ROS) production in HaCaT cells, a human keratinocyte cell line (FIG. 5).
또한, 본 발명자들은 인간 각질세포주인 HaCaT 세포에서 상기 3종의 트라넥사모일 펩타이드가 UV-B에 의한 콜라겐 발현 감소 및 콜라겐분해효소 발현 증가를 억제하는 효과를 확인하였다(도 6).In addition, the present inventors confirmed the effect of the three tranexamoyl peptides on suppressing the decrease in collagen expression and increase in collagen decomposition enzyme expression caused by UV-B in HaCaT cells, a human keratinocyte cell line (FIG. 6).
아울러, 본 발명자들은 인간 각질세포주인 HaCaT 세포에서 상기 3종의 트라넥사모일 펩타이드가 UV-B에 의한 염증 관련 유전자 발현 증가를 억제하는 것을 확인하였다(도 7).In addition, the present inventors confirmed that the above three types of tranexamoyl peptides suppressed the increase in inflammation-related gene expression caused by UV-B in HaCaT cells, a human keratinocyte cell line (FIG. 7).
따라서, 본 발명자들은 본 발명에 따른 3종의 트라넥사모일 펩타이드가 피부 세포에서 α-MSH에 의한 멜라닌 생성을 억제하고, UV-B에 의한 세포사멸, 활성산소종(ROS) 생성, 콜라겐분해 및 염증 관련 유전자 발현을 억제하는 효과를 확인하였으므로, 상기 트라넥사모일 펩타이드는 피부상태 개선용 화장료 조성물로 유용하게 이용될 수 있다.Therefore, the present inventors found that the three types of tranexamoyl peptides according to the present invention inhibit melanin production by α-MSH in skin cells, and inhibit UV-B-induced apoptosis, reactive oxygen species (ROS) production, collagen decomposition and Since the effect of suppressing inflammation-related gene expression was confirmed, the tranexamoyl peptide can be usefully used as a cosmetic composition for improving skin condition.
본 발명의 화장료 조성물은 예를 들면 용액, 겔, 고체 또는 반죽 무수 생성물, 수상에 유상을 분산시켜 얻은 에멀젼, 현탁액, 마이크로에멀젼, 마이크로캡슐, 미세과립구 또는 이온형(리포좀), 비이온형의 소낭 분산제의 형태, 크림, 스킨, 로션, 파우더, 연고, 스프레이 또는 콘실 스틱의 형태로 제공될 수 있다. 또한, 포말(foam)의 형태 또는 압축된 추진제를 더 함유한 에어로졸 조성물의 형태로도 제조될 수 있다.The cosmetic composition of the present invention may be, for example, a solution, gel, solid or pasty anhydrous product, an emulsion obtained by dispersing an oil phase in an aqueous phase, a suspension, a microemulsion, a microcapsule, a microgranule, or an ionic (liposome) or non-ionic vesicle. It may be provided in the form of a dispersant, cream, skin, lotion, powder, ointment, spray or concealer stick. Additionally, it can be prepared in the form of foam or in the form of an aerosol composition further containing compressed propellant.
또한, 상기 화장료 조성물은 유효성분으로 본 발명의 트라넥사모일 펩타이드에 추가로 지방 물질, 유기 용매, 용해제, 농축제 및 겔화제, 연화제, 항산화제, 현탁화제, 안정화제, 발포제(foaming agent), 방향제, 계면활성제, 물, 이온형 또는 비이온형 유화제, 충전제, 금속 이온 봉쇄제 및 킬레이트화제, 보존제, 비타민, 차단제, 습윤화제, 필수 오일, 염료, 안료, 친수성 또는 친유성 활성제, 지질 소낭 또는 화장품에 통상적으로 사용되는 임의의 다른 성분과 같은 화장품 분야에서 통상적으로 사용되는 보조제를 함유할 수 있다.In addition, the cosmetic composition contains, in addition to the tranexamoyl peptide of the present invention as an active ingredient, fatty substances, organic solvents, solubilizers, thickeners and gelling agents, softeners, antioxidants, suspending agents, stabilizers, foaming agents, Fragrances, surfactants, water, ionic or non-ionic emulsifiers, fillers, sequestering agents and chelating agents, preservatives, vitamins, blocking agents, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic activators, lipid vesicles or It may contain auxiliaries commonly used in the cosmetics field, such as any other ingredients commonly used in cosmetics.
본 발명의 화장료 조성물에 있어서, 통상적으로 함유되는 화장료 조성물에 본 발명의 트라넥사모일 펩타이드는 0.01 내지 30 중량%, 바람직하게는 0.1 내지 10 중량%, 보다 바람직하게는 0.1 내지 5 중량%의 양으로 첨가될 수 있으나, 이에 제한되지 않는다.In the cosmetic composition of the present invention, the tranexamoyl peptide of the present invention is contained in an amount of 0.01 to 30% by weight, preferably 0.1 to 10% by weight, and more preferably 0.1 to 5% by weight in cosmetic compositions commonly contained. It may be added, but is not limited thereto.
또한, 본 발명은 트라넥사모일 펩타이드를 유효성분으로 함유하는 피부상태 개선용 피부 외용제 조성물로서,In addition, the present invention provides an external skin composition for improving skin condition containing tranexamoyl peptide as an active ingredient,
상기 트라넥사모일 펩타이드는 트라넥사모일-GS, 트라넥사모일-GA 및 트라넥사모일-GSGA로 이루어진 군에서 선택되는 것인 피부 외용제 조성물을 제공한다.The tranexamoyl peptide is selected from the group consisting of tranexamoyl-GS, tranexamoyl-GA, and tranexamoyl-GSGA.
본 발명에서, 상기 트라넥사모일 펩타이드 및 피부상태에 대해서는 상술한 바와 동일하므로, 구체적인 설명은 상기 내용을 원용하고, 이하에서는 피부 외용제 조성물의 특유한 구성에 대해서만 설명하도록 한다.In the present invention, since the tranexamoyl peptide and skin condition are the same as described above, the above content will be used for detailed description, and hereinafter, only the unique composition of the external skin composition will be described.
한편, 본 발명자들은 본 발명에 따른 3종의 트라넥사모일 펩타이드가 피부 세포에서 α-MSH에 의한 멜라닌 생성을 억제하고, UV-B에 의한 세포사멸, 활성산소종(ROS) 생성, 콜라겐분해 및 염증 관련 유전자 발현을 억제하는 효과를 확인하였으므로, 상기 트라넥사모일 펩타이드는 피부상태 개선용 피부 외용제 조성물로 유용하게 이용될 수 있다.Meanwhile, the present inventors found that the three types of tranexamoyl peptides according to the present invention inhibit melanin production by α-MSH in skin cells, and inhibit UV-B-induced apoptosis, reactive oxygen species (ROS) production, collagen decomposition and Since the effect of suppressing inflammation-related gene expression was confirmed, the tranexamoyl peptide can be usefully used as an external skin composition for improving skin condition.
본 발명의 트라넥사모일 펩타이드를 유효성분으로 함유하는 피부 외용제 조성물을 피부 외용제로 사용하는 경우, 추가로 지방 물질, 유기 용매, 용해제, 농축제 및 겔화제, 연화제, 항산화제, 현탁화제, 안정화제, 발포제(foaming agent), 방향제, 계면활성제, 물, 이온형 또는 비이온형 유화제, 충전제, 금속이온 봉쇄제 및 킬레이트화제, 보존제, 비타민, 차단제, 습윤화제, 필수 오일, 염료, 안료, 친수성 또는 친유성 활성제, 지질 소낭 또는 피부용 외용제에 통상적으로 사용되는 임의의 다른 성분과 같은 피부 과학 분야에서 통상적으로 사용되는 보조제를 함유할 수 있다. 또한, 상기 성분들은 피부 과학 분야에서 일반적으로 사용되는 양으로 도입될 수 있다.When using the skin external composition containing the tranexamoyl peptide of the present invention as an active ingredient as an external skin preparation, fatty substances, organic solvents, solubilizers, thickening and gelling agents, softeners, antioxidants, suspending agents, and stabilizers are added. , foaming agents, fragrances, surfactants, water, ionic or non-ionic emulsifiers, fillers, sequestering agents and chelating agents, preservatives, vitamins, blocking agents, wetting agents, essential oils, dyes, pigments, hydrophilic or It may contain adjuvants commonly used in the field of dermatology, such as lipophilic active agents, lipid vesicles or any other ingredients commonly used in topical preparations for the skin. Additionally, the ingredients may be introduced in amounts commonly used in the field of dermatology.
또한, 본 발명은 트라넥사모일 펩타이드를 유효성분으로 함유하는 멜라닌 색소 과다 침착 질환의 예방 또는 치료용 약학 조성물로서,In addition, the present invention provides a pharmaceutical composition for preventing or treating melanin hyperpigmentation disease containing tranexamoyl peptide as an active ingredient,
상기 트라넥사모일 펩타이드는 트라넥사모일-GS, 트라넥사모일-GA 및 트라넥사모일-GSGA로 이루어진 군에서 선택되는 것인 약학 조성물을 제공한다.The tranexamoyl peptide provides a pharmaceutical composition selected from the group consisting of tranexamoyl-GS, tranexamoyl-GA, and tranexamoyl-GSGA.
본 발명에서, 상기 멜라닌 색소 과다 침착(hyperpigmentation)은 피부 또는 손·발톱의 특정 부위에서 멜라닌의 과도한 증가에 의해 다른 부위에 비해 검게 또는 어둡게 되는 것을 의미한다. 상기 멜라닌 색소 과다 침착 질환은 주근깨, 노인성 반점, 간반, 기미, 갈색 또는 흑점, 일광 색소반, 푸른흑피증(cyanicmelasma), 약물 사용 후의 과다색소침착, 임신성 갈색반(gravidic chloasma), 또는 찰상 및 화상을 비롯한 상처 또는 피부염으로 인한 염증 후 과다 색소 침착 등을 포함하나 이에 제한되지는 않는다.In the present invention, the hyperpigmentation of melanin means that a specific area of the skin or hands or toenails becomes black or dark compared to other areas due to an excessive increase in melanin. The above melanin hyperpigmentation diseases include freckles, senile spots, liver spots, freckles, brown or black spots, solar pigment spots, cyanicmelasma, hyperpigmentation after drug use, gravidic chloasma, or scratches and burns. This includes, but is not limited to, post-inflammatory hyperpigmentation due to wounds or dermatitis.
본 발명의 트라넥사모일 펩타이드는 멜라닌 생성을 억제하여 멜라닌 색소 과다 침착 질환을 예방 또는 치료할 수 있다.The tranexamoyl peptide of the present invention can prevent or treat melanin hyperpigmentation disease by inhibiting melanin production.
본 발명자들은 본 발명에 따른 3종의 트라넥사모일 펩타이드가 피부 세포에서 α-MSH에 의한 멜라닌 생성을 억제하는 효과를 확인하였으므로, 상기 트라넥사모일 펩타이드는 멜라닌 색소 과다 침착 질환 예방 또는 치료용 약학 조성물의 유효성분으로 유용하게 이용될 수 있다.Since the present inventors have confirmed the effect of three types of tranexamoyl peptides according to the present invention on inhibiting melanin production by α-MSH in skin cells, the tranexamoyl peptides can be used as a pharmaceutical composition for preventing or treating melanin hyperpigmentation disease It can be usefully used as an active ingredient.
본 발명의 약학 조성물은 유효성분 이외에 약학적으로 허용되는 담체를 포함할 수 있으며, 이러한 담체는 제제 시에 통상적으로 이용되는 것으로서, 락토스, 덱스트로스, 수크로스, 솔비톨, 만니톨, 전분, 아카시아 고무, 인산 칼슘, 알기네이트, 젤라틴, 규산 칼슘, 미세결정성 셀룰로스, 폴리비닐피롤리돈, 셀룰로스, 물, 시럽, 메틸셀룰로스, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 활석, 스테아르산 마그네슘 및 미네랄 오일 등을 포함하나, 이에 한정되는 것은 아니다. 본 발명의 약학 조성물은 상기 성분들 이외에 윤활제, 습윤제, 감미제, 향미제, 유화제, 현탁제, 보존제 등을 추가로 포함할 수 있다. The pharmaceutical composition of the present invention may contain a pharmaceutically acceptable carrier in addition to the active ingredient, and such carriers are commonly used in formulations, such as lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia gum, Calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methylcellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and minerals. Includes, but is not limited to, oil. In addition to the above components, the pharmaceutical composition of the present invention may further include lubricants, wetting agents, sweeteners, flavoring agents, emulsifiers, suspending agents, preservatives, etc.
본 발명에 따른 약학 조성물의 적합한 투여량은 제제화 방법, 투여 방식, 환자의 연령, 체중, 성, 병적 상태, 음식, 투여 시간, 투여 경로, 배설 속도 및 반응 감응성과 같은 요인들에 의해 다양하게 처방될 수 있다. 한편, 본 발명의 약학 조성물의 투여량은 바람직하게는 1일 당 0.0001 내지 100 mg/kg(체중)이다. 본 발명의 약학 조성물은 경구 또는 비경구로 투여할 수 있으며, 비경구 투여의 경우, 피부에 국소적으로 도포, 정맥 내 주입, 피하 주입, 근육 주입, 복강 주입, 경피 투여 등으로 투여할 수 있다. 본 발명의 약학 조성물이 멜라닌 색소 과다 침착 질환을 치료 또는 예방을 위해 적용되는 점을 감안하면, 피부에 국소적으로 도포되어 이루어지는 것이 바람직하다.The appropriate dosage of the pharmaceutical composition according to the present invention is prescribed in various ways depending on factors such as formulation method, administration method, patient's age, weight, sex, pathological condition, food, administration time, administration route, excretion rate, and reaction sensitivity. It can be. Meanwhile, the dosage of the pharmaceutical composition of the present invention is preferably 0.0001 to 100 mg/kg (body weight) per day. The pharmaceutical composition of the present invention can be administered orally or parenterally, and in the case of parenteral administration, it can be administered topically on the skin, intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, transdermal administration, etc. Considering that the pharmaceutical composition of the present invention is applied to treat or prevent melanin hyperpigmentation disease, it is preferably applied topically to the skin.
본 발명의 약학 조성물에 포함되는 유효성분의 농도는 치료 목적, 환자의 상태, 필요기간 등을 고려하여 결정할 수 있으며 특정 범위의 농도로 한정되지 않는다.The concentration of the active ingredient included in the pharmaceutical composition of the present invention can be determined considering the purpose of treatment, patient condition, required period, etc., and is not limited to a specific concentration range.
본 발명의 약학적 조성물은 당해 발명이 속하는 기술분야에서 통상의 지식을 가진 자가 용이하게 실시할 수 있는 방법에 따라, 약학적으로 허용되는 담체 또는 부형제를 이용하여 제제화함으로써 단위 용량 형태로 제조되거나 또는 다용량 용기 내에 내입시켜 제조될 수 있다. 이때 제형은 주사제, 크림, 패취, 분무제, 연고제, 경고제, 로션제, 리니멘트제, 파스타제 및 카타플라스마제 중에서 선택된 어느 하나의 제형으로 제조될 수도 있으며, 분산제 또는 안정화제를 추가적으로 포함할 수 있다.The pharmaceutical composition of the present invention is prepared in unit dosage form by formulating using a pharmaceutically acceptable carrier or excipient according to a method that can be easily performed by a person skilled in the art. It can be manufactured by placing it in a multi-capacity container. At this time, the formulation may be prepared as any one formulation selected from injections, creams, patches, sprays, ointments, warning agents, lotions, liniments, pasta agents, and cataplasmases, and may additionally include a dispersant or stabilizer. there is.
아울러, 본 발명은 트라넥사모일 펩타이드를 유효성분으로 함유하는 멜라닌 색소 과다 침착 질환의 예방 또는 개선용 건강기능식품 조성물로서,In addition, the present invention is a health functional food composition for preventing or improving melanin hyperpigmentation disease containing tranexamoyl peptide as an active ingredient,
상기 트라넥사모일 펩타이드는 트라넥사모일-GS, 트라넥사모일-GA 및 트라넥사모일-GSGA로 이루어진 군에서 선택되는 것인 건강기능식품 조성물을 제공한다.The tranexamoyl peptide provides a health functional food composition selected from the group consisting of tranexamoyl-GS, tranexamoyl-GA, and tranexamoyl-GSGA.
본 발명에서, 상기 트라넥사모일 펩타이드 및 멜라닌 색소 과다 침착 질환에 대해서는 상술한 바와 동일하므로, 구체적인 설명은 상기 내용을 원용하고, 이하에서는 건강기능식품 조성물의 특유한 구성에 대해서만 설명하도록 한다.In the present invention, since the tranexamoyl peptide and the melanin hyperpigmentation disease are the same as described above, the above content will be used for detailed description, and hereinafter, only the unique composition of the health functional food composition will be described.
한편, 본 발명자들은 본 발명에 따른 3종의 트라넥사모일 펩타이드가 피부 세포에서 α-MSH에 의한 멜라닌 생성을 억제하는 효과를 확인하였으므로, 상기 트라넥사모일 펩타이드는 멜라닌 색소 과다 침착 질환 예방 또는 개선용 건강기능식품 조성물의 유효성분으로 유용하게 이용될 수 있다.Meanwhile, the present inventors confirmed the effect of the three types of tranexamoyl peptides according to the present invention on suppressing melanin production by α-MSH in skin cells, so the tranexamoyl peptides are used to prevent or improve melanin hyperpigmentation disease. It can be usefully used as an active ingredient in health functional food compositions.
본 발명의 건강기능식품 조성물을 식품첨가물로 사용하는 경우, 상기 건강기능식품 조성물을 그대로 첨가하거나 다른 식품 또는 식품성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 유효 성분의 혼합양은 그의 사용 목적(예방 또는 개선)에 따라 적절하게 사용될 수 있다. 일반적으로, 식품 또는 음료의 제조 시 본 발명의 건강기능식품 조성물은 원료에 대하여 15 중량부 이하, 바람직하게는 10 중량부 이하의 양으로 첨가된다. 그러나 건강 및 위생을 목적으로 하거나 또는 건강 조절을 목적으로 하는 장기간의 섭취의 경우에는 상기 양은 상기 범위 이하일 수 있으며, 안전성 면에서 아무런 문제가 없기 때문에 유효성분은 상기 범위 이상의 양으로 사용될 수 있다.When using the health functional food composition of the present invention as a food additive, the health functional food composition may be added as is or used together with other foods or food ingredients, and may be used appropriately according to conventional methods. The mixed amount of active ingredients can be appropriately used depending on the purpose of use (prevention or improvement). Generally, when manufacturing a food or beverage, the health functional food composition of the present invention is added in an amount of 15 parts by weight or less, preferably 10 parts by weight or less, based on the raw materials. However, in the case of long-term intake for the purpose of health and hygiene or health control, the amount may be below the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount above the above range.
상기 건강기능식품의 종류에 특별한 제한은 없다. 상기 건강기능식품 조성물을 첨가할 수 있는 식품의 예로는 육류, 소시지, 빵, 초콜릿, 캔디류, 스낵류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 차 드링크제, 알콜 음료 및 비타민 복합제 등이 있으며, 통상적인 의미에서의 건강식품을 모두 포함한다.There are no particular restrictions on the types of health functional foods. Examples of foods to which the health functional food composition can be added include meat, sausages, bread, chocolate, candies, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, and tea. There are drinks, alcoholic beverages, and vitamin complexes, and it includes all health foods in the conventional sense.
또한, 본 발명의 건강기능식품 조성물은 식품, 특히 기능성 식품으로 제조될 수 있다. 본 발명의 기능성 식품은 식품 제조 시에 통상적으로 첨가되는 성분을 포함하며, 예를 들어, 단백질, 탄수화물, 지방, 영양소 및 조미제를 포함한다. 예컨대, 드링크제로 제조되는 경우에는 유효성분 이외에 천연 탄수화물 또는 향미제를 추가 성분으로서 포함시킬 수 있다. 상기 천연 탄수화물은 모노사카라이드(예컨대, 글루코오스, 프럭토오스 등), 디사카라이드(예컨대, 말토스, 수크로오스 등), 올리고당, 폴리사카라이드(예컨대, 덱스트린, 시클로덱스트린 등), 또는 당알코올(예컨대, 자일리톨, 소르비톨, 에리쓰리톨 등)인 것이 바람직하다. 상기 향미제는 천연 향미제(예컨대, 타우마틴, 스테비아 추출물 등)와 합성 향미제(예컨대, 사카린, 아스파르탐 등)를 이용할 수 있다.Additionally, the health functional food composition of the present invention can be manufactured into food, especially functional food. The functional food of the present invention includes ingredients commonly added during food production, and includes, for example, proteins, carbohydrates, fats, nutrients and seasonings. For example, when manufacturing a drink, natural carbohydrates or flavoring agents may be included as additional ingredients in addition to the active ingredient. The natural carbohydrates include monosaccharides (e.g., glucose, fructose, etc.), disaccharides (e.g., maltose, sucrose, etc.), oligosaccharides, polysaccharides (e.g., dextrins, cyclodextrins, etc.), or sugar alcohols (e.g., For example, xylitol, sorbitol, erythritol, etc.) is preferable. The flavoring agent may be a natural flavoring agent (e.g., thaumatin, stevia extract, etc.) or a synthetic flavoring agent (e.g., saccharin, aspartame, etc.).
상기 건강기능식품 조성물 이외에 여러 가지 영양제, 비타민, 전해질, 풍미제, 착색제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산음료에 사용되는 탄산화제 등을 더 함유할 수 있다. 이러한 상기 첨가되는 성분의 비율은 크게 중요하진 않지만 본 발명의 건강기능식품 조성물 100 중량부에 대하여, 0.01 내지 0.1 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above health functional food composition, various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH regulators, stabilizers, preservatives, glycerin, alcohol, carbonic acid. It may further contain carbonating agents used in beverages. The ratio of the ingredients added is not very important, but is generally selected in the range of 0.01 to 0.1 parts by weight based on 100 parts by weight of the health functional food composition of the present invention.
이하, 본 발명을 실시예 및 실험예에 의해 상세히 설명한다.Hereinafter, the present invention will be described in detail through examples and experimental examples.
단, 하기 실시예 및 실험예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 하기 실시예 및 실험예에 한정되는 것은 아니다.However, the following examples and experimental examples only illustrate the present invention, and the content of the present invention is not limited to the following examples and experimental examples.
<실시예 1> 트라넥사모일 펩타이드(Tranexamoyl-peptide)의 제조<Example 1> Preparation of tranexamoyl peptide (Tranexamoyl-peptide)
하기 표 1과 같이 다이펩타이드(dipeptide) GS(Gly-Ser) 및 GA(Gly-Ala), 테트라펩타이드(tetrapeptide) GSGA(Gly-Ser-Gly-Ala) 각각에 트라넥삼산(Tranexamic acid, Txa)이 결합된 형태의 트라넥사모일 펩타이드(Tranexamoyl-peptide)를 합성하였다. 표 1의 트라넥사모일 펩타이드의 서열이 길지 않기 때문에 대용량으로 획득하기 위한 방법으로 액상에서의 합성법을 이용하였다.As shown in Table 1 below, tranexamic acid (Txa) in dipeptides GS (Gly-Ser) and GA (Gly-Ala), and tetrapeptide GSGA (Gly-Ser-Gly-Ala), respectively. This combined form of tranexamoyl-peptide was synthesized. Since the sequence of the tranexamoyl peptide in Table 1 is not long, a liquid synthesis method was used to obtain it in large quantities.
구체적으로, 도 1의 모식도와 같이 Txa-GS 및 Txa-GA를 합성하기 위해 트라넥삼산(Txa)의 N-말단을 보호기인 Boc-으로 치환하여 Boc-트라넥삼산(Boc-Txa-OH, 2)을 생성하였다. Boc-Txa-OH의 C-말단을 커플링 시약인 DCC(N,N'-Dicyclohexylcarbodiimide) 및 NHS(N-Hydroxysuccinimide)를 처리하여 활성품인 Boc-Txa-OSu(2)를 생성한 후에 글라이신(Glycine, Gly)을 물에 녹여 첨가함으로써 Boc-Txa-Gly(4)을 생성하였다. 그 다음, 유기용매를 제거 후 산을 첨가하고 여과하여 결정체로 정제하였다. 정제한 Boc-Txa-Gly에 DCC/NHS를 첨가하여 활성 형태의 화합물인 Boc-Txa-Gly-OSu(5)을 생성한 후 O-삼차부틸화된 세린(O-tertbutylated Serine, Ser(tBu))을 처리하여 Boc-Txa-GS(tBu)-OH(6)을 생성하였고, Boc-Txa-Gly-OSu(5)에 알라닌(Alanine, Ala)을 처리하여 Boc-Txa-GA(8)를 생성하였다. 이후 보호기인 Boc-과 tBu-을 TFA로 처리하여 탈보호하여 Txa-Gly-Ser(Txa-GS, 7) 및 Txa-Gly-Ala(Txa-GA, 9)을 획득하였다. Txa-GSGA를 합성하기 위해 Boc-Txa-GS(tBu)-OH(6)에 커플링 시약인 DCC(N,N'-Dicyclohexylcarbodiimide) 및 NHS(N-Hydroxysuccinimide)를 처리하여 활성품인 Boc-Txa-GS(tBu)OSu(10)을 생성한 후 다이펩타이드 Gly-Ala(GA)를 첨가함으로써 Boc-Txa-GS(tBu)GA(11)을 생성하였다. 이후 보호기인 Boc-과 tBu-을 TFA로 처리하여 탈보호하여 Txa-GSGA(12)를 획득하였다. Specifically, to synthesize Txa-GS and Txa-GA as shown in the schematic diagram of Figure 1, the N-terminus of tranexamic acid (Txa) is replaced with the protecting group Boc- to produce Boc-tranexamic acid (Boc-Txa-OH, 2) was created. The C-terminus of Boc-Txa-OH is treated with coupling reagents DCC (N,N'-Dicyclohexylcarbodiimide) and NHS (N-Hydroxysuccinimide) to generate the active product Boc-Txa-OSu(2), followed by glycine ( Boc-Txa-Gly (4) was produced by dissolving and adding Glycine, Gly) in water. Next, the organic solvent was removed, acid was added, filtered, and purified into crystals. DCC/NHS was added to purified Boc-Txa-Gly to generate the active compound Boc-Txa-Gly-OSu(5), and then O-tertbutylated Serine (Ser(tBu)) ) was treated to produce Boc-Txa-GS(tBu)-OH (6), and Boc-Txa-Gly-OSu (5) was treated with alanine (Ala) to produce Boc-Txa-GA (8). created. Afterwards, the protecting groups Boc- and tBu- were deprotected by treatment with TFA to obtain Txa-Gly-Ser (Txa-GS, 7) and Txa-Gly-Ala (Txa-GA, 9). To synthesize Txa-GSGA, Boc-Txa-GS(tBu)-OH(6) was treated with the coupling reagents DCC (N,N'-Dicyclohexylcarbodiimide) and NHS (N-Hydroxysuccinimide) to form the active product, Boc-Txa. After generating -GS(tBu)OSu(10), Boc-Txa-GS(tBu)GA(11) was generated by adding the dipeptide Gly-Ala(GA). Afterwards, the protecting groups Boc- and tBu- were deprotected by treatment with TFA to obtain Txa-GSGA (12).
<실험예 1> 트라넥사모일 펩타이드 피부상태 개선 효과 확인<Experimental Example 1> Confirmation of tranexamoyl peptide skin condition improvement effect
<1-1> α-MSH에 의한 멜라닌 생성 억제 효과 확인<1-1> Confirmation of melanin production inhibition effect by α-MSH
<실시예 1>에서 제조한 트라넥사모일 펩타이드의 피부상태 개선 효과를 알아보기 위하여, 상기 <실시예 1>에서 제조한 트라넥사모일 펩타이드를 처리한 흑색종 세포에서 α-MSH에 의한 멜라닌 생성 억제를 확인하였다. In order to determine the effect of the tranexamoyl peptide prepared in <Example 1> on improving skin condition, inhibition of melanin production by α-MSH in melanoma cells treated with the tranexamoyl peptide prepared in <Example 1> was confirmed.
구체적으로, 마우스 흑색종 세포주인 B16F1 세포를 10% 우태아혈청(fetal bovine serum, Sigma)이 포함된 DMEM 배지(Dulbecco's modified Eagle's media, Sigma)로 37℃, 5% CO2 조건에서 배양하였다. 24-웰 플레이트에 1 × 105 cells/웰의 농도로 세포를 배양하고 세포의 부착을 확인한 뒤, 대조군(Con)에는 아무것도 처리하지 않고 DMSO만 처리였다. 양성대조군(DMSO)은 멜라닌 합성을 촉진시키는 α-MSH 20 μM과 DMSO를 처리하였다. 실험군(Txa-GS, Txa-GA, Txa-GSGA)은 a-MSH 20 μM과 상기 <실시예 1>에서 제조한 트라넥사모일 펩타이드 100 μM을 처리하였다. 비교군(Txa, GS, GA, GSGA)은 a-MSH 20 μM과 트라넥삼산(Txa), 다이펩타이드 GS, GA, 테트라펩타이드 GSGA 각각을 100 μM로 처리하였다. 시험물질을 가한 뒤 3일 동안 배양한 후, 원심분리를 통해 배양액을 제거하고 세포 내 멜라닌 생성량을 측정하기 위하여 세포를 용해하여 세포 내 멜라닌을 수집하여 490 nm에서 관찰하였다. Specifically, B16F1 cells, a mouse melanoma cell line, were cultured in DMEM medium (Dulbecco's modified Eagle's media, Sigma) containing 10% fetal bovine serum (Sigma) at 37°C and 5% CO 2 conditions. Cells were cultured in a 24-well plate at a concentration of 1 × 10 5 cells/well and cell adhesion was confirmed. The control group (Con) was treated with only DMSO without any treatment. The positive control group (DMSO) was treated with 20 μM of α-MSH, which promotes melanin synthesis, and DMSO. The experimental group (Txa-GS, Txa-GA, Txa-GSGA) was treated with 20 μM of a-MSH and 100 μM of the tranexamoyl peptide prepared in <Example 1>. The comparison group (Txa, GS, GA, GSGA) was treated with 20 μM of a-MSH and 100 μM each of tranexamic acid (Txa), dipeptides GS, GA, and tetrapeptide GSGA. After adding the test substance and culturing for 3 days, the culture medium was removed through centrifugation. To measure the amount of melanin produced within the cells, the cells were lysed and the melanin within the cells was collected and observed at 490 nm.
그 결과, 도 2에 나타낸 바와 같이, 양성대조군(DMSO)은 대조군(Con)에 비해 멜라닌 생성이 증가하는 반면, 실험군(Txa-GS, Txa-GA, Txa-GSGA)은 멜라닌 생성이 억제되었다. 특히, 실험군(Txa-GS, Txa-GA, Txa-GSGA)은 비교군 Txa에 비해 멜라닌 생성 억제 효과가 우수함을 확인하였다. 또한, 실험군 Txa-GS, Txa-GA, Txa-GSGA 각각은 Txa가 결합되지 않은 펩타이드 처리군인 비교군 GS, GA, GSGA 각각에 비해서도 멜라닌 생성 억제 효과가 우수함을 확인하였다.As a result, as shown in Figure 2, melanin production increased in the positive control group (DMSO) compared to the control group (Con), while melanin production was suppressed in the experimental groups (Txa-GS, Txa-GA, Txa-GSGA). In particular, the experimental group (Txa-GS, Txa-GA, Txa-GSGA) was confirmed to have a superior melanin production inhibition effect compared to the comparison group Txa. In addition, it was confirmed that the experimental groups Txa-GS, Txa-GA, and Txa-GSGA each had a superior melanin production inhibition effect compared to the comparison groups GS, GA, and GSGA, which were the peptide treatment groups to which Txa was not bound.
상기의 결과를 통해 본 발명의 트라넥사모일 펩타이드 Txa-GS, Txa-GA, Txa-GSGA는 멜라닌 생성 억제에 따른 피부 미백 효과가 있음을 알 수 있다.From the above results, it can be seen that the tranexamoyl peptides Txa-GS, Txa-GA, and Txa-GSGA of the present invention have a skin whitening effect by inhibiting melanin production.
<1-2> 세포독성 평가<1-2> Cytotoxicity evaluation
<실시예 1>에서 제조한 트라넥사모일 펩타이드의 세포독성을 알아보기 위하여, MTT assay를 수행하였다.In order to determine the cytotoxicity of the tranexamoyl peptide prepared in <Example 1>, MTT assay was performed.
구체적으로, 인간 각질세포주인 HaCaT 세포를 24-웰 플레이트에 4 × 104 cells/웰로 분주한 후 24시간 동안 37℃, 5% CO2 조건으로 항온배양하였다. 배양 후 PBS로 2회 세척 후 상기 <실시예 1>에서 제조한 트라넥사모일 펩타이드를 농도별(25, 50, 100, 200 μM)로 처리하고 24시간 동안 항온배양하였다. 배양 후 0.5% MTT(3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazoliumbromide, SIGMA, USA)를 포함하는 DPBS를 배양배지와 1 : 9(v/v)로 혼합하여 첨가한 후 2시간 동안 배양한 후 생성된 포마잔(formazan)을 DMSO에 녹여 ELISA를 이용하여 570 nm에서 측정하였다.Specifically, HaCaT cells, a human keratinocyte cell line, were distributed at 4 × 10 4 cells/well in a 24-well plate and incubated at 37°C and 5% CO 2 for 24 hours. After incubation and washing twice with PBS, the tranexamoyl peptide prepared in <Example 1> was treated with different concentrations (25, 50, 100, 200 μM) and incubated for 24 hours. After culturing, DPBS containing 0.5% MTT (3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazoliumbromide, SIGMA, USA) was mixed with the culture medium at a ratio of 1:9 (v/v) and added. After culturing for 2 hours, the produced formazan was dissolved in DMSO and measured at 570 nm using ELISA.
그 결과, 도 3에 나타낸 바와 같이, 저농도에서 고농도로 Txa-GS, Txa-GA, Txa-GSGA 각각을 처리한 세포군 모두 세포수의 감소는 관찰되지 않았고, 현미경 관찰에서도 별다른 변화가 관찰되지 않았다. As a result, as shown in Figure 3, no decrease in cell number was observed in any of the cell groups treated with Txa-GS, Txa-GA, and Txa-GSGA from low to high concentrations, and no significant changes were observed in microscopic observation.
상기의 결과를 통해 본 발명의 트라넥사모일 펩타이드 Txa-GS, Txa-GA, Txa-GSGA는 세포독성이 없음을 알 수 있다.From the above results, it can be seen that the tranexamoyl peptides Txa-GS, Txa-GA, and Txa-GSGA of the present invention have no cytotoxicity.
<1-3> UV-B에 의한 세포사멸 억제효과 확인<1-3> Confirmation of apoptosis inhibition effect by UV-B
<실시예 1>에서 제조한 트라넥사모일 펩타이드의 피부상태 개선 효과를 알아보기 위하여, 상기 <실시예 1>에서 제조한 트라넥사모일 펩타이드를 처리한 각질세포에서 UV-B에 의한 세포사멸 억제를 확인하였다. In order to determine the effect of the tranexamoyl peptide prepared in <Example 1> on improving skin condition, the inhibition of apoptosis by UV-B was examined in keratinocytes treated with the tranexamoyl peptide prepared in <Example 1>. Confirmed.
구체적으로, 인간 각질세포주인 HaCaT 세포를 96-웰 플레이트에 4 × 105 cells/웰이 되도록 분주하고, 37℃, 5% CO2 조건에서 24시간 동안 배양하였다. 24시간 뒤 DMEM 배지를 제거한 후, 5% BSA(SIGMA, USA)가 첨가된 무혈청 저농도 포도당(free serum low glucose) DMEM(Gibco, USA)배지에 대조군(UV(-)_DMSO) 및 양성대조군(UV(+)_DMSO)은 DMSO를 첨가하고, 실험군(UV(+)_Txa-GS, UV(+)_Txa-GA, UV(+)_Txa-GSGA)은 상기 <실시예 1>에서 제조한 트라넥사모일 펩타이드를 농도별(3, 6, 13, 25, 50, 100, 200 μM)로 첨가하여 세포에 처리한 다음 10시간 동안 37℃, 5% CO2 조건에서 반응하였다. 10시간이 지난 뒤 양성대조군 및 실험군은 UVB를 조사하고 12시간 CO2 배양기에 방치하였다. 12시간 후 배지를 제거한 뒤 MTT를 넣고 3시간 동안 37℃, 5% CO2 배양기에서 배양한 다음 각 웰에 들어있는 배지를 제거하고 DMSO(Dimethyl sulfoxide, SIGMA, USA) 100 μL를 넣어 녹을 수 있도록 10분간 방치 뒤 ELISA를 이용하여 490 nm에서 흡광도를 측정하였다. 흡광도는 MTT가 세포에 의해서 환원된 양을 나타내며, 따라서 각 웰에 존재하는 생존 세포수와 비례한다. 측정시 공시료는 DMSO로 하였고 생존율(%)은 (시료처리군의 흡광도/대조군의 흡광도)×100으로 계산하였다.Specifically, HaCaT cells, a human keratinocyte cell line, were distributed in a 96-well plate at 4 × 10 5 cells/well and cultured for 24 hours at 37°C and 5% CO 2 conditions. After removing the DMEM medium after 24 hours, the control group (UV(-)_DMSO) and the positive control group were added to free serum low glucose DMEM (Gibco, USA) medium supplemented with 5% BSA (SIGMA, USA). UV(+)_DMSO) added DMSO, and the experimental group (UV(+)_Txa-GS, UV(+)_Txa-GA, UV(+)_Txa-GSGA) was prepared with tranexamo prepared in <Example 1> above. Each peptide was added at various concentrations (3, 6, 13, 25, 50, 100, 200 μM) to treat the cells, and then reacted at 37°C and 5% CO 2 for 10 hours. After 10 hours, the positive control and experimental groups were irradiated with UVB and left in a CO 2 incubator for 12 hours. After 12 hours, remove the medium, add MTT, and culture in an incubator at 37°C, 5% CO 2 for 3 hours. Then, remove the medium in each well and add 100 μL of DMSO (Dimethyl sulfoxide, SIGMA, USA) to dissolve it. After leaving for 10 minutes, absorbance was measured at 490 nm using ELISA. Absorbance represents the amount of MTT reduced by cells and is therefore proportional to the number of viable cells present in each well. When measuring, the blank sample was DMSO, and the survival rate (%) was calculated as (absorbance of sample treatment group/absorbance of control group) × 100.
그 결과, 도 4에 나타낸 바와 같이, 대조군(UV(-)_DMSO)에 비해 양성대조군(UV(+)_DMSO)에서 UV-B 조사에 의해 세포사멸이 증가하는 반면, 실험군(UV(+)_Txa-GS, UV(+)_Txa-GA, UV(+)_Txa-GSGA)에서는 UV-B 조사에 의해 세포사멸이 유의적으로 감소하였다.As a result, as shown in Figure 4, cell death increased by UV-B irradiation in the positive control group (UV(+)_DMSO) compared to the control group (UV(-)_DMSO), while the experimental group (UV(+)_Txa -GS, UV(+)_Txa-GA, UV(+)_Txa-GSGA), cell death was significantly reduced by UV-B irradiation.
상기의 결과를 통해 본 발명의 트라넥사모일 펩타이드 Txa-GS, Txa-GA, Txa-GSGA는 광노화에 의한 세포사멸을 억제하는 것을 알 수 있다.From the above results, it can be seen that the tranexamoyl peptides Txa-GS, Txa-GA, and Txa-GSGA of the present invention inhibit cell death caused by photoaging.
<1-4> UV-B에 의한 활성산소종(ROS) 생성 억제효과 확인<1-4> Confirmation of the inhibitory effect of UV-B on the production of reactive oxygen species (ROS)
<실시예 1>에서 제조한 트라넥사모일 펩타이드의 피부상태 개선 효과를 알아보기 위하여, 상기 <실시예 1>에서 제조한 트라넥사모일 펩타이드를 처리한 각질세포에서 UV-B에 의한 활성산소종(ROS) 생성 억제를 확인하였다. In order to determine the effect of the tranexamoyl peptide prepared in <Example 1> on improving skin condition, reactive oxygen species ( Suppression of ROS) production was confirmed.
구체적으로, 인간 각질세포주인 HaCaT 세포를 24-웰 플레이트에 1 × 105 cells/웰이 되도록 분주하고, 37℃, 5% CO2 조건에서 24시간 동안 배양하였다. 24시간 뒤 DMEM 배지는 제거한 후, 5% BSA(SIGMA, USA)가 첨가된 무혈청 저농도 포도당(free serum lowglucose) DMEM(Gibco, USA) 배지에 대조군(DMSO)은 DMSO를 첨가하고, 실험군(Txa-GS, Txa-GA, Txa-GSGA)은 상기 <실시예 1>에서 제조한 트라넥사모일 펩타이드를 농도별(50, 100 μM)로 첨가하여 세포에 처리한 다음 10시간 동안 37℃, 5% CO2 배양기에서 반응시켰다. 10시간 뒤 UVB를 조사하고 12시간 동안 방치하였다. 그 다음, 멸균된 PBS(pH 7.4)로 2회 세척하고, 0.2% NBT 용액 0.2 mL를 첨가하여 5% CO2 배양기에서 90분간 반응시켰다. 반응 완료 후, 100% 아세트산(acetic acid) 50 μL를 첨가하고 30분 동안 방치하여 생성된 짙은 파란색 포르마잔(formazan)을 ELSIA를 이용하여 570 nm에서 흡광도를 측정하였다. ROS는 짙은 파란색 포르마잔(formazan)으로 측정하고 이것을 대조군에 퍼센트(%)로 계산하였다. Specifically, HaCaT cells, a human keratinocyte cell line, were distributed in a 24-well plate at 1 × 10 5 cells/well and cultured for 24 hours at 37°C and 5% CO 2 conditions. After 24 hours, the DMEM medium was removed, and then DMSO was added to the control group (DMSO) and the experimental group (Txa) was added to free serum low glucose DMEM (Gibco, USA) medium supplemented with 5% BSA (SIGMA, USA). -GS, Txa-GA, Txa-GSGA) was treated with cells by adding the tranexamoyl peptide prepared in <Example 1> at different concentrations (50, 100 μM), and then incubated at 37°C, 5% CO for 10 hours. The reaction was performed in a CO 2 incubator. After 10 hours, UVB was irradiated and left for 12 hours. Next, it was washed twice with sterilized PBS (pH 7.4), 0.2 mL of 0.2% NBT solution was added, and reaction was performed in a 5% CO 2 incubator for 90 minutes. After completion of the reaction, 50 μL of 100% acetic acid was added and left for 30 minutes. The absorbance of the dark blue formazan produced was measured at 570 nm using ELSIA. ROS was measured as dark blue formazan and calculated as a percentage of the control.
그 결과, 도 5에 나타낸 바와 같이, 실험군(Txa-GS, Txa-GA, Txa-GSGA)은 대조군(DMSO)에 비해 ROS 함량이 낮은 것으로 나타났다.As a result, as shown in Figure 5, the experimental groups (Txa-GS, Txa-GA, Txa-GSGA) showed lower ROS content than the control group (DMSO).
상기의 결과를 통해 본 발명의 트라넥사모일 펩타이드 Txa-GS, Txa-GA, Txa-GSGA는 피부에서 ROS 생성을 억제하는 항산화 효과가 있는 것을 알 수 있다.From the above results, it can be seen that the tranexamoyl peptides Txa-GS, Txa-GA, and Txa-GSGA of the present invention have an antioxidant effect that inhibits ROS production in the skin.
<1-5> 콜라겐 합성 촉진 및 항염증 효과 확인<1-5> Promotion of collagen synthesis and confirmation of anti-inflammatory effect
자외선에 장기간 노출된 피부는 콜라겐을 합성하는 속도가 떨어지고 콜라겐이 쉽게 분해된다, 특히, 콜라겐이 감소한 피부는 주름이 늘어나고 탄력성을 잃게 되며, 피부노화가 촉진된다. 또한, 자외선은 피부의 염증반응을 야기한다. 이에, <실시예 1>에서 제조한 트라넥사모일 펩타이드의 피부상태 개선 효과를 알아보기 위하여, 상기 <실시예 1>에서 제조한 트라넥사모일 펩타이드를 처리한 각질세포에서 UV-B에 의한 콜라겐분해 억제를 확인하였고, 염증 관련 유전자의 발현 억제를 확인하였다.Skin exposed to ultraviolet rays for a long period of time slows down the synthesis of collagen and the collagen is easily decomposed. In particular, skin with reduced collagen has increased wrinkles and loss of elasticity, and skin aging is accelerated. Additionally, ultraviolet rays cause an inflammatory response in the skin. Therefore, in order to determine the effect of the tranexamoyl peptide prepared in <Example 1> on improving skin condition, collagen decomposition by UV-B was performed in keratinocytes treated with the tranexamoyl peptide prepared in <Example 1>. Inhibition was confirmed, and inhibition of expression of inflammation-related genes was confirmed.
구체적으로, 인간 각질세포주인 HaCaT 세포를 10% FBS가 첨가된 고농도 포도당 DMEM 배지를 이용하여 페트리 접시(petri dish)에 1 × 106 cells/웰이 되도록 분주하고, 37℃, 5% CO2 조건에서 24시간 동안 배양하였다. 24시간 뒤 DMEM 배지는 제거한 후, 5% BSA가 첨가된 무혈청 저포도당(free serum low glucose) DMEM(Gibco, USA) 배지에서 1시간 동안 방치하였다. 그 다음, 대조군(DMSA)은 DMSO를 첨가하고, 실험군(Txa-GS, Txa-GA, Txa-GSGA)은 상기 <실시예 1>에서 제조한 트라넥사모일 펩타이드를 100 μM을 첨가한 후 10시간 동안 37℃, 5% CO2 배양기에서 반응시켰다. 10시간 뒤 UVB를 조사 후 12 시간 동안 방치하였다. 그 다음, 멸균된 PBS(pH 7.4)로 2회 세척하고 트리졸 시약(TRIzol reagent, Life Technologies, Rockville, MD, USA)으로 제조사의 절차에 따라 전체 RNA를 추출하였다. RNA를 정량한 후, 역전사효소키트를 사용하여 1 μg의 RNA로부터 cDNA를 합성하였다. 합성된 cDNA를 이용하여 실시간 PCR을 수행하였다. 콜라겐 합성 및 콜라겐분해효소 억제를 확인하기 위해, 실시간 PCR 시 콜라겐으로 타입 I 콜라겐(Collagen-1)를, 콜라겐분해효소로 타입 I 콜라겐 분해효소인 MMP-1(Matrix metalloproteinase-1)에 대한 프라이머를 이용하였다. 또한, 염증 관련 유전자의 발현 억제를 확인하기 위해 실시간 PCR 시 염증 관련 유전자 TNF-α 및 iNOS에 대한 프라이머를 이용하였다.Specifically, HaCaT cells, a human keratinocyte cell line, were distributed at 1 × 10 6 cells/well in a Petri dish using high-concentration glucose DMEM medium supplemented with 10% FBS, and incubated at 37°C and 5% CO 2 conditions. was cultured for 24 hours. After 24 hours, the DMEM medium was removed, and the cells were left in serum-free, low glucose DMEM (Gibco, USA) medium supplemented with 5% BSA for 1 hour. Next, DMSO was added to the control group (DMSA), and 100 μM of the tranexamoyl peptide prepared in <Example 1> was added to the experimental groups (Txa-GS, Txa-GA, Txa-GSGA) for 10 hours. The reaction was performed in an incubator at 37°C and 5% CO 2 . After 10 hours, UVB was irradiated and left for 12 hours. Next, the cells were washed twice with sterilized PBS (pH 7.4), and total RNA was extracted with TRIzol reagent (Life Technologies, Rockville, MD, USA) according to the manufacturer's procedure. After quantifying RNA, cDNA was synthesized from 1 μg of RNA using a reverse transcriptase kit. Real-time PCR was performed using the synthesized cDNA. To confirm collagen synthesis and collagenase inhibition, primers for type I collagen (Collagen-1) were used as collagen and primers for MMP-1 (Matrix metalloproteinase-1), a type I collagenase, were used as collagen during real-time PCR. used. Additionally, to confirm the inhibition of expression of inflammation-related genes, primers for inflammation-related genes TNF-α and iNOS were used during real-time PCR.
그 결과, 도 6에 나타낸 바와 같이, 실험군(Txa-GS, Txa-GA, Txa-GSGA)은 대조군(DMSO)에 비해 MMP-1 발현이 50% 이상 감소하고, 타입 I 콜라겐 발현이 감소하는 것으로 나타났다. As a result, as shown in Figure 6, the experimental group (Txa-GS, Txa-GA, Txa-GSGA) showed a decrease in MMP-1 expression by more than 50% and a decrease in type I collagen expression compared to the control group (DMSO). appear.
또한, 도 7에 나타낸 바와 같이, 실험군(Txa-GS, Txa-GA, Txa-GSGA)은 대조군(DMSO)에 비해 TNF-α 및 iNOS 발현이 현저히 감소하는 것으로 나타났다. 특히, Txa-GS 및 Txa-GSGA 처리군은 iNOS 발현이 현저히 감소하여 극히 미비한 수준으로 발현되는 것으로 나타났다. Additionally, as shown in Figure 7, the experimental groups (Txa-GS, Txa-GA, Txa-GSGA) showed a significant decrease in TNF-α and iNOS expression compared to the control group (DMSO). In particular, in the Txa-GS and Txa-GSGA treatment groups, iNOS expression was significantly reduced and expressed at an extremely low level.
상기의 결과를 통해 본 발명의 트라넥사모일 펩타이드 Txa-GS, Txa-GA, Txa-GSGA는 피부에서 콜라겐 분해 및 염증반응을 억제하는 것을 알 수 있다. From the above results, it can be seen that the tranexamoyl peptides Txa-GS, Txa-GA, and Txa-GSGA of the present invention inhibit collagen decomposition and inflammatory response in the skin.
Claims (7)
상기 트라넥사모일 펩타이드는 트라넥사모일-GS, 트라넥사모일-GA 및 트라넥사모일-GSGA로 이루어진 군에서 선택되는 것인 화장료 조성물.
A cosmetic composition for improving skin condition containing tranexamoyl-peptide as an active ingredient,
A cosmetic composition wherein the tranexamoyl peptide is selected from the group consisting of tranexamoyl-GS, tranexamoyl-GA, and tranexamoyl-GSGA.
The cosmetic composition of claim 1, wherein the skin condition improvement is one or more selected from the group consisting of skin whitening, anti-aging, skin protection by ultraviolet rays, antioxidant, skin wrinkle improvement, skin elasticity improvement, and anti-inflammation.
The cosmetic composition of claim 2, wherein the improvement in skin condition is achieved by inhibiting melanin synthesis, inhibiting apoptosis caused by ultraviolet rays, inhibiting the production of active oxygen, promoting collagen synthesis, inhibiting the expression of collagenase, or inhibiting the expression of inflammation-related factors. .
상기 트라넥사모일 펩타이드는 트라넥사모일-GS, 트라넥사모일-GA 및 트라넥사모일-GSGA로 이루어진 군에서 선택되는 것인 피부 외용제 조성물.
An external skin composition for improving skin condition containing tranexamoyl peptide as an active ingredient,
A composition for external application for skin, wherein the tranexamoyl peptide is selected from the group consisting of tranexamoyl-GS, tranexamoyl-GA, and tranexamoyl-GSGA.
상기 트라넥사모일 펩타이드는 트라넥사모일-GS, 트라넥사모일-GA 및 트라넥사모일-GSGA로 이루어진 군에서 선택되는 것인 약학 조성물.
A pharmaceutical composition for preventing or treating melanin hyperpigmentation disease containing tranexamoyl peptide as an active ingredient,
A pharmaceutical composition wherein the tranexamoyl peptide is selected from the group consisting of tranexamoyl-GS, tranexamoyl-GA, and tranexamoyl-GSGA.
The method of claim 5, wherein the melanin hyperpigmentation disease includes freckles, senile spots, liver spots, melasma, brown or dark spots, solar pigmentation spots, cyanic melasma, hyperpigmentation after drug use, and pregnancy brown spots (gravidic spots). A pharmaceutical composition selected from the group consisting of post-injury hyperpigmentation, including chloasma, abrasions and burns, and post-inflammatory hyperpigmentation due to dermatitis.
상기 트라넥사모일 펩타이드는 트라넥사모일-GS, 트라넥사모일-GA 및 트라넥사모일-GSGA로 이루어진 군에서 선택되는 것인 건강기능식품 조성물.
A health functional food composition for preventing or improving melanin hyperpigmentation disease containing tranexamoyl peptide as an active ingredient,
A health functional food composition wherein the tranexamoyl peptide is selected from the group consisting of tranexamoyl-GS, tranexamoyl-GA, and tranexamoyl-GSGA.
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Citations (3)
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KR100921947B1 (en) | 2003-11-19 | 2009-10-15 | (주)아모레퍼시픽 | Skin whitening cosmetic composition |
KR100923141B1 (en) | 2007-12-26 | 2009-10-23 | 부산대학교 산학협력단 | Skin whitening composition comprising arbutin ?-derivative |
KR101342485B1 (en) | 2012-02-29 | 2013-12-17 | 미원상사주식회사 | Anti-aging, anti-wrinkle, whitening and anti-inflammatory tripeptide and cosmetic composition containing the same |
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Publication number | Priority date | Publication date | Assignee | Title |
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KR100921947B1 (en) | 2003-11-19 | 2009-10-15 | (주)아모레퍼시픽 | Skin whitening cosmetic composition |
KR100923141B1 (en) | 2007-12-26 | 2009-10-23 | 부산대학교 산학협력단 | Skin whitening composition comprising arbutin ?-derivative |
KR101342485B1 (en) | 2012-02-29 | 2013-12-17 | 미원상사주식회사 | Anti-aging, anti-wrinkle, whitening and anti-inflammatory tripeptide and cosmetic composition containing the same |
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