WO2016006732A1 - Composition containing epidermal growth factor-derived peptide fragments for wound healing or inhibiting skin wrinkle formation - Google Patents
Composition containing epidermal growth factor-derived peptide fragments for wound healing or inhibiting skin wrinkle formation Download PDFInfo
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- WO2016006732A1 WO2016006732A1 PCT/KR2014/006169 KR2014006169W WO2016006732A1 WO 2016006732 A1 WO2016006732 A1 WO 2016006732A1 KR 2014006169 W KR2014006169 W KR 2014006169W WO 2016006732 A1 WO2016006732 A1 WO 2016006732A1
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Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/06—Tripeptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/07—Tetrapeptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
Definitions
- the present invention relates to a wound healing composition
- a wound healing composition comprising peptide fragments (small peptides or small peptides) derived from epidermal growth factor (EGF); And it relates to a composition for inhibiting skin aging or wrinkle formation.
- the peptide activates the epidermal growth factor receptor and also has activity to promote skin keratinocyte proliferation and angiogenesis.
- Wounds are sometimes referred to as wounds, and their symptoms include pain, bleeding, and dysfunction. Wounds create a unique microenvironment consisting of growth factors, cytokines, neurohormones, and extracellular matrix secreted from surrounding cells, blood derived cells, and sensory neurons. Some factors in the wound microenvironment persist long enough to spread into peripheral blood and then affect stem cells in the bone marrow, causing the bone marrow cells to migrate into peripheral blood, supply to the wound site, and participate in wound healing. It is known.
- Extracellular matrix such as collagen I, III (Type I, III collagens), elastin, and fibronectin present in the skin to maintain its elasticity and strength without breaking the connective tissue of the skin Extracellular matrix (ECM) proteins are important.
- Natural aging or chronic exposure to UV rays reduces the loss of ECM proteins and the elasticity and strength of skin tissues, which are strongly associated with characteristic skin aging such as wrinkles.
- Matrix metalloproteinases (MMPs) are important enzymes in the degradation of dermal ECM. Under stress conditions such as UV irradiation, overexpression of MMPs in keratinocytes and dermal fibroblasts contributes to the degradation of ECM proteins, thereby forming wrinkles on the skin.
- epidermal growth factor is one of growth factors that bind to epidermal growth factor receptor (EGFR) and regulate the proliferation, differentiation and survival of various cells.
- EGFR epidermal growth factor receptor
- EGF is secreted from platelets, macrophages and fibroblasts, and acts as a paracrine fashion to keratinocytes. EGF increases the expression of keratin K6 and K16 and activates cell proliferation signaling.
- epidermal growth factor receptor When the epidermal growth factor receptor is activated, it stimulates the growth of keratinocytes and fibroblasts by inducing the production of growth factors such as VEGF and HGF, and also induces the production of extracellular matrix such as collagen in fibroblasts. Or improve skin wrinkles.
- the present inventors have designed various small peptide fragments that activate epidermal growth factor receptors expressed in keratinocytes and fibroblasts of the skin, and surprisingly, specific peptide fragments or small peptides derived from epidermal growth factor are found to be epidermal growth factor receptors. It has been found that it can promote the re-epithelialization of the epidermis by activating and promoting the proliferation and angiogenesis of keratinocytes.
- an object of the present invention is to provide a pharmaceutical composition for treating wounds or promoting wound treatment comprising a specific peptide fragment derived from epidermal growth factor as an active ingredient.
- an object of the present invention is to provide a cosmetic composition for inhibiting skin aging or inhibiting skin wrinkle formation comprising the specific peptide fragment.
- a pharmaceutical composition for treating wounds or promoting wound healing comprising a peptide selected from the group consisting of the peptides of SEQ ID NOs: 1 to 15 as an active ingredient, and comprising a pharmaceutically acceptable carrier.
- a pharmaceutical composition comprising the peptide of SEQ ID NO: 9 as an active ingredient.
- a cosmetic composition for inhibiting skin aging or inhibiting skin wrinkles comprising a peptide selected from the group consisting of the peptides of SEQ ID NOs: 1 to 15 as an active ingredient.
- a cosmetic composition comprising a peptide of SEQ ID NO: 9 as an active ingredient is provided.
- peptide fragments derived from epidermal growth factor promote epidermal re-epithelialization by activating epidermal growth factor receptors and promoting proliferation and angiogenesis of keratinocytes. Therefore, the peptides may be usefully applied to pharmaceutical compositions for treating wounds or promoting wound healing, and cosmetic compositions for inhibiting skin aging or inhibiting skin wrinkle formation.
- 1 and 2 show the results of evaluating the activation of the epidermal growth factor receptor by the peptide according to the present invention.
- FIG. 3 and 4 show the results of evaluation of phosphorylation of ERK and Akt by peptides according to the present invention in human keratinocytes HaCaT (FIG. 3) and mouse fibroblast NIH3T3 (FIG. 4), respectively.
- Figure 5 shows the results of evaluating the effect of the peptides according to the invention on the proliferation of keratinocytes.
- Figure 6 shows the results of evaluating the angiogenic activity by the peptides according to the present invention.
- wound refers to damage of epithelial and connective tissue caused by intrinsic and external factors, and may preferably be damage to skin.
- skin aging refers to aging of the skin caused by intrinsic and external factors, preferably skin photoaging accompanied with the formation of skin wrinkles, more preferably skin Skin photoaging due to ultraviolet irritation accompanied by wrinkle formation.
- skin wrinkle refers to wrinkle formation on skin.
- the present invention provides a pharmaceutical composition for promoting wound healing or wound treatment comprising a peptide selected from the group consisting of the peptides of SEQ ID NOs: 1 to 15 as an active ingredient, and comprising a pharmaceutically acceptable carrier.
- the present invention provides a cosmetic composition for inhibiting skin aging or skin wrinkle formation comprising a peptide selected from the group consisting of peptides of SEQ ID NO: 1 to 15 as an active ingredient.
- the peptides according to the invention have excellent activity on wound healing and skin regeneration.
- the present invention may be usefully applied to cosmetic compositions for improving skin aging and / or suppressing skin wrinkle formation accompanying skin irritation caused by external stimuli such as ultraviolet rays.
- the peptide fragments are shown in Table 1 below.
- the peptide of the present invention may be a peptide of SEQ ID NO: 9.
- the pharmaceutical composition of the present invention may include excipients such as lactose, corn starch, lubricants such as magnesium stearate, emulsifiers, suspending agents, buffers, tonicity agents, and the like which are well known, and may be used in parenteral dosage forms, preferably It may be formulated in parenteral dosage forms including external dermal preparations.
- excipients such as lactose, corn starch, lubricants such as magnesium stearate, emulsifiers, suspending agents, buffers, tonicity agents, and the like which are well known, and may be used in parenteral dosage forms, preferably It may be formulated in parenteral dosage forms including external dermal preparations.
- a sterile solution of the active ingredient is usually prepared and may comprise a buffer which can suitably adjust the pH of the solution, and for intravenous administration isotonic in the formulation. May be included to impart this.
- the pharmaceutical composition of the present invention may be in the form of an aqueous solution containing a pharmaceutically acceptable carrier such as saline having a pH of 7.4, and may be locally introduced into the patient's intramuscular blood flow in the form of a solution. have.
- a pharmaceutically acceptable carrier such as saline having a pH of 7.4
- it may be formulated into a transdermal dosage form such as an external preparation, an emulsion, an ointment, a patch and the like according to conventional pharmaceutical methods.
- the pharmaceutical composition of the present invention can be administered to patients with various wounds at a dose of about 1 to 2000 mg / kg per day. Appropriate dosages will generally vary depending on the age, weight and symptoms of the patient.
- the cosmetic composition of the present invention may be in the form of a functional cosmetic composition comprising the peptide as an active ingredient.
- the cosmetic composition may be prepared in various forms according to a conventional cosmetic preparation method.
- the cosmetic composition may be prepared in the form of a cosmetic product containing the peptide, lotion, cream, lotion, etc., which may be diluted with a conventional cleansing liquid, astringent liquid and moisturizing liquid.
- the cosmetic composition may include conventional adjuvants such as stabilizers, solubilizers, vitamins, pigments, and flavorings commonly used in the field of cosmetic compositions.
- the content of the peptide may be contained in an amount effective to achieve an effect of inhibiting skin aging, in particular, skin wrinkle formation, for example, in an amount of 0.001 to 10% by weight based on the total weight of the composition. It may be contained in an amount of about 0.01 to 1% by weight.
- Peptides of SEQ ID NOs: 1 to 15 were synthesized by the FMOC solid-phase method using an automated synthesizer (PeptrEx-R48, Peptron, Daejeon, Korea). The synthesized peptide was purified and analyzed by reverse-phase HPLC using a C18 analytical RP column (Shiseido capcell pak) (Prominence LC-20AB, Shimadzu, Japan), and mass spectrometer (HP 1100 Series). LC / MSD, Hewlett-Packard, Roseville, USA).
- Peptides of SEQ ID NO: 1 to 15 were dissolved in PBS, respectively, to prepare a concentration of 1 M.
- the obtained protein solution was used in the following test example.
- In situ proximity ligation assay was used to confirm whether the peptide of the present invention activates the epidermal growth factor receptor. The test was performed by purchasing Duolink In Situ reagent from Olink Bioscience, Sweden.
- DMEM medium 1 mL was added to a 24-well plate coated with 12 mm glass, and 4.5 ⁇ 10 4 human keratinocyte line HaCaT cells (DKFZ, Heidelberg, Germany) were plated and stabilized for 24 hours.
- Anti-Gab1 Rabbit Polyclonal Antibody (Gab1 Antibody, Cell Signaling Technology, INC., USA) and Anti-Shp2 Mouse Monoclonal Antibody (SH-) to measure the degree of interaction between Gab1 and Shp2 increased by epidermal growth factor receptor activation PTP2 (B-1): sc-7384 mouse mAb, Santa Cruz Biothecnology, INC., USA) was treated with cells at 37 ° C. After 30 minutes, treated with PLA probe solution and incubated at 37 ° C. for 1 hour, then treated with ligation solution and incubated for 30 minutes. Treated with amplication solution and incubated for 100 minutes.
- FIGS. 1 and 2 After the cells treated as described above were washed with washing buffer, the number of red spots was measured using confocal microscopy, and the results are shown in FIGS. 1 and 2.
- Figure 1 when treated with the peptide of SEQ ID NOS: 1 to 7 having 4 amino acids, the interaction between Gab1 and Shp2 increased by about 50 to 100% compared to the control.
- Figure 2 when treated with the peptide of SEQ ID NOS: 8 to 15 having three amino acids, the interaction between Gab1 and Shp2 was increased by about 30 to 170% compared to the control. This indicates that the peptides according to the invention activate the epidermal growth factor receptor, which plays a major role in skin regeneration.
- the peptide of SEQ ID NO. Human keratinocytes HaCaT (DKFZ, Heidelberg, Germany) and mouse fibroblast NIH3T3 (ATCC CRL-1658, USA) were treated with a solution (1 ml) obtained by lysis at a concentration of ⁇ M. After 15 minutes, Western blotting analysis was performed on the cell extracts to measure changes in phosphorylation of ERK and Akt, and the results are shown in FIGS. 3 and 4.
- the phosphorylation degree of ERK and Akt was increased in a concentration-dependent manner by the peptide of SEQ ID NO. Therefore, it can be seen that the peptide according to the present invention activates the epidermal growth factor receptor expressed in keratinocytes and fibroblasts.
- the effect of the peptides according to the invention on angiogenesis was evaluated as follows.
- the interaction between the vascular endothelial component and vascular endothelial cells is an important factor in the formation and maintenance of neovascularization.
- matrigel which is a complex of the bottom membrane component
- a polymerization reaction occurs and a plug .
- Human umbilical vein endothelial cells (HUVECs) were inoculated into a 24 well cell culture plate coated with Matrigel at a density of 8 x 10 4 cells / well, and the peptide of SEQ ID NO: 9 was serum-free M199 medium.
- VEGF Vascular Endothelial Growth Factor
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Abstract
Provided is a composition containing peptide fragments or small peptides derived from epidermal growth factor (EGF) for wound healing and inhibiting aging of the skin or formation of skin wrinkles. The peptides activate EGF receptors and have activities promoting keratinocyte proliferation and angiogenesis in the skin. Accordingly, the peptides can be utilized effectively in wound healing and inhibiting aging of the skin or formation of skin wrinkles.
Description
본 발명은 표피성장인자(epidermal growth factor, EGF)로부터 유래된 펩타이드 단편(peptide fragments 또는 small peptides)을 포함하는 상처 치료용 조성물; 및 피부노화 또는 피부주름 형성 억제용 조성물에 관한 것이다. 상기 펩타이드는 표피성장인자 수용체를 활성화하고, 또한 피부 각질세포 증식 및 혈관신생을 촉진하는 활성을 갖는다.The present invention relates to a wound healing composition comprising peptide fragments (small peptides or small peptides) derived from epidermal growth factor (EGF); And it relates to a composition for inhibiting skin aging or wrinkle formation. The peptide activates the epidermal growth factor receptor and also has activity to promote skin keratinocyte proliferation and angiogenesis.
상처는 창상이라고 칭해지기도 하며, 그 따른 증세로는 통증, 출혈, 기능장애 등이 있다. 상처는 주변 세포, 혈액 유래 세포 및 감각 뉴우런으로부터 분비되는 성장인자, 사이토카인, 신경호르몬, 및 세포 외 기질로 이루어지는 특이한 미세환경(microenvironment)을 창출한다. 상처 미세환경의 일부 인자는 충분히 오랜 기간 지속하여 말초혈액으로 확산된 후, 골수의 줄기세포에 영향을 미쳐 골수 세포의 말초혈액으로의 이동, 상처 부위로의 공급, 및 상처 치유에의 참여를 유발하는 것으로 알려져 있다.Wounds are sometimes referred to as wounds, and their symptoms include pain, bleeding, and dysfunction. Wounds create a unique microenvironment consisting of growth factors, cytokines, neurohormones, and extracellular matrix secreted from surrounding cells, blood derived cells, and sensory neurons. Some factors in the wound microenvironment persist long enough to spread into peripheral blood and then affect stem cells in the bone marrow, causing the bone marrow cells to migrate into peripheral blood, supply to the wound site, and participate in wound healing. It is known.
피부의 결합조직이 파괴되지 않고 온전히 그 탄성과 강도를 유지하기 위해서는, 피부에 존재하는 콜라겐 I, III (Type I, III collagens), 엘라스틴(elastin), 파이브로넥틴(fibronectin)과 같은 세포외 기질(ECM: Extracellular matrix) 단백질이 중요하다. 자연 노화 또는 자외선에 대한 만성적인 노출은 ECM 단백질의 손실과 피부조직의 탄성과 강도를 감소시키며, 이러한 현상들은 주름형성과 같은 특징적인 피부 노화와 강하게 연관되어 있다. 기저막 단백질 분해 효소(MMPs: matrix metalloproteinases)는 진피 ECM을 분해하는데 있어서 중요한 효소로 작용한다. 자외선 조사 등과 같은 스트레스 조건하에서 각질형성세포(keratinocytes) 및 진피 섬유아세포에서의 MMPs의 과발현은 ECM 단백질을 분해하는데 기여함으로써, 피부에 주름을 형성하게 된다.Extracellular matrix such as collagen I, III (Type I, III collagens), elastin, and fibronectin present in the skin to maintain its elasticity and strength without breaking the connective tissue of the skin Extracellular matrix (ECM) proteins are important. Natural aging or chronic exposure to UV rays reduces the loss of ECM proteins and the elasticity and strength of skin tissues, which are strongly associated with characteristic skin aging such as wrinkles. Matrix metalloproteinases (MMPs) are important enzymes in the degradation of dermal ECM. Under stress conditions such as UV irradiation, overexpression of MMPs in keratinocytes and dermal fibroblasts contributes to the degradation of ECM proteins, thereby forming wrinkles on the skin.
한편, 표피성장인자는 표피성장인자 수용체(EGFR)에 결합하여 다양한 세포의 증식, 분화 및 생존을 조절하는 성장인자 중 하나이다. 특히, 각질세포의 증식과 세포이동을 촉진하여 재상피화에 주요한 역할을 담당함으로써, 상처치료에 탁월한 기능하는 것으로 알려져 있다. EGF는 혈소판, 대식세포, 섬유모세포 등에서 분비되며 각질세포에는 주변분비 형식(paracrine fashion)으로 작용한다. EGF는 케라틴 K6와 K16의 발현을 증가시키며, 세포증식 신호전달과정을 활성화한다. 임상적으로 조직이식부위, 당뇨성 족부괴양과 같은 만성 창상에 외용 표피성장인자를 도포할 경우 상피화가 촉진되어 상처회복 속도가 단축되는 것으로 알려져 있다 (Barrientos S, Stojadinovic O, Golinko M, Brem H, Vinay Tomic-Canic M. 2008. Growth factors and cytokines in wound healing. Wound Rep Reg. 16:585). 표피성장인자 수용체가 활성화되면, VEGF와 HGF와 같은 성장인자의 생성을 유도하여 각질세포와 섬유모세포의 성장을 촉진하며, 또한 섬유모세포에서 콜라겐과 같은 세포외기질의 생성을 유도함으로써, 피부노화 및/또는 피부주름을 개선한다.Meanwhile, epidermal growth factor is one of growth factors that bind to epidermal growth factor receptor (EGFR) and regulate the proliferation, differentiation and survival of various cells. In particular, by promoting the proliferation and cell migration of keratinocytes plays a major role in re-epithelialization, it is known to function excellent in wound healing. EGF is secreted from platelets, macrophages and fibroblasts, and acts as a paracrine fashion to keratinocytes. EGF increases the expression of keratin K6 and K16 and activates cell proliferation signaling. Clinically, the application of external epidermal growth factors to chronic wounds such as tissue grafts and diabetic foot ulcers is known to promote epithelialization and reduce the rate of wound healing (Barrientos S, Stojadinovic O, Golinko M, Brem H, Vinay Tomic-Canic M. 2008. Growth factors and cytokines in wound healing.Wound Rep Reg. 16: 585). When the epidermal growth factor receptor is activated, it stimulates the growth of keratinocytes and fibroblasts by inducing the production of growth factors such as VEGF and HGF, and also induces the production of extracellular matrix such as collagen in fibroblasts. Or improve skin wrinkles.
본 발명자들은 피부의 각질세포와 섬유모세포에서 발현되는 표피성장인자 수용체를 활성화하는 다양한 작은 펩타이드 단편을 설계하였으며, 놀랍게도 표피성장인자로부터 유래된 특정 펩타이드 단편(peptide fragments 또는 small peptides)이 표피성장인자 수용체를 활성화하고, 각질세포의 증식 및 혈관신생을 촉진함으로써 표피의 재상피화를 촉진할 수 있음을 발견하였다.The present inventors have designed various small peptide fragments that activate epidermal growth factor receptors expressed in keratinocytes and fibroblasts of the skin, and surprisingly, specific peptide fragments or small peptides derived from epidermal growth factor are found to be epidermal growth factor receptors. It has been found that it can promote the re-epithelialization of the epidermis by activating and promoting the proliferation and angiogenesis of keratinocytes.
따라서, 본 발명은 표피성장인자로부터 유래된 특정 펩타이드 단편을 유효성분으로 포함하는 상처 치료 또는 상처 치료 촉진용 약학 조성물을 제공하는 것을 목적으로 한다.Accordingly, an object of the present invention is to provide a pharmaceutical composition for treating wounds or promoting wound treatment comprising a specific peptide fragment derived from epidermal growth factor as an active ingredient.
또한, 본 발명은 상기 특정 펩타이드 단편을 포함하는 피부노화 억제 또는 피부 주름형성 억제용 화장료 조성물을 제공하는 것을 목적으로 한다.In addition, an object of the present invention is to provide a cosmetic composition for inhibiting skin aging or inhibiting skin wrinkle formation comprising the specific peptide fragment.
본 발명의 일 태양에 따라, 서열번호 1 내지 15의 펩타이드로 이루어진 군으로부터 선택된 펩타이드를 유효성분으로 포함하고, 약학적으로 허용가능한 담체를 포함하는 상처 치료 또는 상처 치료 촉진용 약학 조성물이 제공된다. 일 구현예에서, 유효성분으로서 서열번호 9의 펩타이드를 포함하는 약학 조성물이 제공된다.According to one aspect of the present invention, there is provided a pharmaceutical composition for treating wounds or promoting wound healing, comprising a peptide selected from the group consisting of the peptides of SEQ ID NOs: 1 to 15 as an active ingredient, and comprising a pharmaceutically acceptable carrier. In one embodiment, provided is a pharmaceutical composition comprising the peptide of SEQ ID NO: 9 as an active ingredient.
본 발명의 다른 태양에 따라, 서열번호 1 내지 15의 펩타이드로 이루어진 군으로부터 선택된 펩타이드를 유효성분으로 포함하는, 피부노화 억제 또는 피부 주름형성 억제용 화장료 조성물이 제공된다. 일 구현예에서, 유효성분으로서 서열번호 9의 펩타이드를 포함하는 화장료 조성물이 제공된다.According to another aspect of the present invention, there is provided a cosmetic composition for inhibiting skin aging or inhibiting skin wrinkles, comprising a peptide selected from the group consisting of the peptides of SEQ ID NOs: 1 to 15 as an active ingredient. In one embodiment, a cosmetic composition comprising a peptide of SEQ ID NO: 9 as an active ingredient is provided.
본 발명에 따라 표피성장인자로부터 유래된 특정 펩타이드 단편이 표피성장인자 수용체를 활성화하고, 각질세포의 증식 및 혈관신생을 촉진함으로써 표피의 재상피화를 촉진한다는 것이 밝혀졌다. 따라서, 상기 펩타이드는 상처 치료 또는 상처 치료 촉진용 약학 조성물 및 피부노화 억제 또는 피부 주름형성 억제용 화장료 조성물에 유용하게 적용될 수 있다.It has been found in accordance with the present invention that certain peptide fragments derived from epidermal growth factor promote epidermal re-epithelialization by activating epidermal growth factor receptors and promoting proliferation and angiogenesis of keratinocytes. Therefore, the peptides may be usefully applied to pharmaceutical compositions for treating wounds or promoting wound healing, and cosmetic compositions for inhibiting skin aging or inhibiting skin wrinkle formation.
도 1 및 도 2는 본 발명에 따른 펩타이드에 의한 표피성장인자 수용체의 활성화를 평가한 결과를 나타낸다.1 and 2 show the results of evaluating the activation of the epidermal growth factor receptor by the peptide according to the present invention.
도 3 및 도 4는 각각 사람 각질세포 HaCaT(도 3) 및 생쥐 섬유모세포 NIH3T3(도 4)에서 본 발명에 따른 펩타이드에 의한 ERK와 Akt의 인산화를 평가한 결과를 나타낸다.3 and 4 show the results of evaluation of phosphorylation of ERK and Akt by peptides according to the present invention in human keratinocytes HaCaT (FIG. 3) and mouse fibroblast NIH3T3 (FIG. 4), respectively.
도 5는 본 발명에 따른 펩타이드가 각질세포의 증식에 미치는 영향을 평가한 결과를 나타낸다.Figure 5 shows the results of evaluating the effect of the peptides according to the invention on the proliferation of keratinocytes.
도 6은 본 발명에 따른 펩타이드에 의한 혈관신생 촉진 활성을 평가한 결과를 나타낸다.Figure 6 shows the results of evaluating the angiogenic activity by the peptides according to the present invention.
본 명세서에서, "상처(wound)"라 함은 내재적 및 외부요인에 의해 발생하는 상피조직과 결합조직의 손상을 말하며, 바람직하게는 피부의 손상일 수 있다.As used herein, the term "wound" refers to damage of epithelial and connective tissue caused by intrinsic and external factors, and may preferably be damage to skin.
또한, "피부노화(skin aging)"이라 함은 내재적 및 외부요인에 의해 발생하는 피부의 노화를 말하며, 바람직하게는 피부주름 형성을 동반하는 피부 광노화(photoaging)일 수 있으며, 더욱 바람직하게는 피부주름 형성을 동반하는 자외선 자극에 의한 피부 광노화를 포함한다.In addition, "skin aging" refers to aging of the skin caused by intrinsic and external factors, preferably skin photoaging accompanied with the formation of skin wrinkles, more preferably skin Skin photoaging due to ultraviolet irritation accompanied by wrinkle formation.
또한, "피부 주름(skin wrinkle)"이라 함은 피부상에 형성된 주름(wrinkle formation on skin)을 말한다.In addition, the term "skin wrinkle" refers to wrinkle formation on skin.
본 발명은 서열번호 1 내지 15의 펩타이드로 이루어진 군으로부터 선택된 펩타이드를 유효성분으로 포함하고, 약학적으로 허용가능한 담체를 포함하는 상처 치료 또는 상처 치료 촉진용 약학 조성물을 제공한다.The present invention provides a pharmaceutical composition for promoting wound healing or wound treatment comprising a peptide selected from the group consisting of the peptides of SEQ ID NOs: 1 to 15 as an active ingredient, and comprising a pharmaceutically acceptable carrier.
또한, 본 발명은 서열번호 1 내지 15의 펩타이드로 이루어진 군으로부터 선택된 펩타이드를 유효성분으로 포함하는, 피부노화 억제 또는 피부 주름형성 억제용 화장료 조성물을 제공한다.In another aspect, the present invention provides a cosmetic composition for inhibiting skin aging or skin wrinkle formation comprising a peptide selected from the group consisting of peptides of SEQ ID NO: 1 to 15 as an active ingredient.
본 발명자들은 표피성장인자로부터 다양한 길이의 단편을 제조하여, 그 활성을 검색하였다. 놀랍게도, 표피성장인자로부터 유래한 펩타이드로서, 3개 또는 4개의 아미노산으로 구성된 짧은 길이를 갖는 특정 펩타이드 단편들이 표피성장인자 수용체를 활성화하고, 각질세포의 증식 및 혈관신생을 촉진함으로써 표피의 재상피화를 촉진한다는 것을 발견하였다. 따라서, 본 발명에 따른 펩타이드는 상처 치유 및 피부 재생에 대한 우수한 활성을 갖는다. 또한, 자외선과 같은 외부자극에 의해 유발되는 피부염증반응에 동반되는 피부노화의 개선 및/또는 피부주름 형성의 억제를 위한 화장료 조성물에 유용하게 적용될 수 있다. 상기 펩타이드 단편들은 다음 표 1과 같다. 일 구현예에서, 본 발명의 펩타이드는 서열번호 9의 펩타이드일 수 있다.We prepared fragments of various lengths from epidermal growth factor and searched for their activity. Surprisingly, as peptides derived from epidermal growth factor, specific peptide fragments of short length consisting of three or four amino acids activate epidermal growth factor receptors and promote epidermal re-epithelialization by promoting keratinocyte proliferation and angiogenesis. Found to promote. Thus, the peptides according to the invention have excellent activity on wound healing and skin regeneration. In addition, the present invention may be usefully applied to cosmetic compositions for improving skin aging and / or suppressing skin wrinkle formation accompanying skin irritation caused by external stimuli such as ultraviolet rays. The peptide fragments are shown in Table 1 below. In one embodiment, the peptide of the present invention may be a peptide of SEQ ID NO: 9.
표 1
Table 1
| 펩타이드명칭 | 서열번호 | 아미노산 서열 |
| SE208 A | 서열번호 1 | VCMY |
| SE208 B | 서열번호 2 | YACN |
| SE208 C | 서열번호 3 | ACNC |
| SE208 D | 서열번호 4 | CNCV |
| SE208 E | 서열번호 5 | NCVV |
| SE208 F | 서열번호 6 | CVVG |
| SE208 G | 서열번호 7 | VVGY |
| SE208 H | 서열번호 8 | VCM |
| SE208 I | 서열번호 9 | YAC |
| SE208 J | 서열번호 10 | ACN |
| SE208 K | 서열번호 11 | CNC |
| SE208 L | 서열번호 12 | NCV |
| SE208 M | 서열번호 13 | CVV |
| SE208 N | 서열번호 14 | VVG |
| SE208 O | 서열번호 15 | VGY |
| Peptide Name | SEQ ID NO: | Amino acid sequence |
| SE208 A | SEQ ID NO: 1 | VCMY |
| SE208 B | SEQ ID NO: 2 | YACN |
| SE208 C | SEQ ID NO: 3 | ACNC |
| SE208 D | SEQ ID NO: 4 | CNCV |
| SE208 E | SEQ ID NO: 5 | NCVV |
| SE208 F | SEQ ID NO: 6 | CVVG |
| SE208 G | SEQ ID NO: 7 | VVGY |
| SE208 H | SEQ ID NO: 8 | VCM |
| SE208 I | SEQ ID NO: 9 | YAC |
| SE208 J | SEQ ID NO: 10 | ACN |
| SE208 K | SEQ ID NO: 11 | CNC |
| SE208 L | SEQ ID NO: 12 | NCV |
| SE208 M | SEQ ID NO: 13 | CVV |
| SE208 N | SEQ ID NO: 14 | VVG |
| SE208 O | SEQ ID NO: 15 | VGY |
본 발명의 약학 조성물은 락토즈, 옥수수전분 등의 부형제, 마그네슘 스테아레이트 등의 윤활제, 공지되어 사용가능한 유화제, 현탁제, 완충제, 등장화제 등을 포함할 수 있으며, 비경구 투여 형태, 바람직하게는 피부 외용제를 포함한 비경구 투여형태로 제제화될 수 있다. 근육내, 복강내, 피하 및 정맥 내 투여 형태의 경우, 통상 활성 성분의 멸균 용액을 제조하고, 용액의 pH를 적합하게 조절할 수 있는 완충제를 포함할 수 있으며, 정맥내 투여의 경우 제제에 등장성이 부여되도록 등장화제를 포함할 수 있다. 또한, 본 발명의 약학 조성물은 pH가 7.4인 염수와 같은 약학적으로 허용되는 담체를 포함하는 수용액제의 형태가 될 수 있으며, 용액제의 형태로 국소적으로 환자의 근육내 혈류에 도입할 수 있다. 또한, 통상의 제제학적 방법에 따라 외용액제, 에멀젼, 연고제, 패치 등의 경피투여용 제형으로 제제화될 수 있다. 본 발명의 약학 조성물은 다양한 상처를 갖는 환자에게 1일 약 1 내지 2000 mg/kg의 용량으로 투여될 수 있다. 적절한 투여량은 환자의 연령, 체중 및 증상에 따라 일반적으로 변경될 수 있다. The pharmaceutical composition of the present invention may include excipients such as lactose, corn starch, lubricants such as magnesium stearate, emulsifiers, suspending agents, buffers, tonicity agents, and the like which are well known, and may be used in parenteral dosage forms, preferably It may be formulated in parenteral dosage forms including external dermal preparations. For intramuscular, intraperitoneal, subcutaneous and intravenous dosage forms, a sterile solution of the active ingredient is usually prepared and may comprise a buffer which can suitably adjust the pH of the solution, and for intravenous administration isotonic in the formulation. May be included to impart this. In addition, the pharmaceutical composition of the present invention may be in the form of an aqueous solution containing a pharmaceutically acceptable carrier such as saline having a pH of 7.4, and may be locally introduced into the patient's intramuscular blood flow in the form of a solution. have. In addition, it may be formulated into a transdermal dosage form such as an external preparation, an emulsion, an ointment, a patch and the like according to conventional pharmaceutical methods. The pharmaceutical composition of the present invention can be administered to patients with various wounds at a dose of about 1 to 2000 mg / kg per day. Appropriate dosages will generally vary depending on the age, weight and symptoms of the patient.
본 발명의 화장료 조성물은 상기한 펩타이드를 유효성분으로 포함하는 기능성 화장료 조성물 형태일 수 있다. 상기 화장료 조성물은 통상의 화장료 제조방법에 따라, 다양한 형태로 제조될 수 있다. 예를 들어, 상기 화장료 조성물은 상기 펩타이드를 함유하는 향장 제품, 화장수, 크림, 로오숀 등의 형태로 제조될 수 있으며, 이는 통상의 클렌징액, 수렴액 및 보습액으로 희석하여 사용될 수 있다. 또한, 상기 화장료 조성물은 화장료 조성물 분야에서 통상적으로 사용되는 안정화제, 용해화제, 비타민, 안료, 및 향료와 같은 통상적인 보조제를 포함할 수 있다. 상기 화장료 조성물에 있어서, 상기 펩타이드의 함량은 피부노화 억제, 특히 피부주름 형성 억제 효과를 달성하기에 유효한 양, 예를 들면 조성물 총 중량에 대하여 0.001 ∼ 10 중량%의 함량으로 함유될 수 있고, 바람직하게는 약 0.01 ∼ 1 중량%의 함량으로 함유될 수 있다.The cosmetic composition of the present invention may be in the form of a functional cosmetic composition comprising the peptide as an active ingredient. The cosmetic composition may be prepared in various forms according to a conventional cosmetic preparation method. For example, the cosmetic composition may be prepared in the form of a cosmetic product containing the peptide, lotion, cream, lotion, etc., which may be diluted with a conventional cleansing liquid, astringent liquid and moisturizing liquid. In addition, the cosmetic composition may include conventional adjuvants such as stabilizers, solubilizers, vitamins, pigments, and flavorings commonly used in the field of cosmetic compositions. In the cosmetic composition, the content of the peptide may be contained in an amount effective to achieve an effect of inhibiting skin aging, in particular, skin wrinkle formation, for example, in an amount of 0.001 to 10% by weight based on the total weight of the composition. It may be contained in an amount of about 0.01 to 1% by weight.
이하, 본 발명을 실시예 및 시험예를 통하여 더욱 상세히 설명한다. 그러나, 이들 실시예 및 시험예는 본 발명을 예시하기 위한 것으로, 본 발명이 이들 실시예 및 시험예에 한정되는 것은 아니다.Hereinafter, the present invention will be described in more detail through Examples and Test Examples. However, these Examples and Test Examples are for illustrating the present invention, and the present invention is not limited to these Examples and Test Examples.
실시예 1. 펩타이드의 합성Example 1 Synthesis of Peptides
서열번호 1 내지 15의 펩타이드는 자동화합성기(PeptrEx-R48, 펩트론사, 대전, 대한민국)를 이용하여 FMOC 고체-상 방법(FMOC solid-phase method)으로 합성하였다. 합성된 펩타이드는 C18 분석용 RP 컬럼(Shiseido capcell pak)을 사용한 역상 고속액체크로마토그래피(reverse-phase HPLC) (Prominence LC-20AB, Shimadzu사, 일본)로 정제 및 분석하였으며, 질량분석기(HP 1100 Series LC/MSD, Hewlett-Packard사, Roseville, 미국)를 이용하여 동정하였다.Peptides of SEQ ID NOs: 1 to 15 were synthesized by the FMOC solid-phase method using an automated synthesizer (PeptrEx-R48, Peptron, Daejeon, Korea). The synthesized peptide was purified and analyzed by reverse-phase HPLC using a C18 analytical RP column (Shiseido capcell pak) (Prominence LC-20AB, Shimadzu, Japan), and mass spectrometer (HP 1100 Series). LC / MSD, Hewlett-Packard, Roseville, USA).
실시예 2. 펩타이드를 포함하는 조성물의 제조Example 2. Preparation of a Composition Comprising a Peptide
서열번호 1 내지 15의 펩타이드를 PBS에 각각 용해시켜, 1 M의 농도가 되도록 제조하였다. 얻어진 단백질 용액을 하기 시험예에서 사용하였다.Peptides of SEQ ID NO: 1 to 15 were dissolved in PBS, respectively, to prepare a concentration of 1 M. The obtained protein solution was used in the following test example.
시험예 1. 표피성장인자 수용체의 활성화 평가Test Example 1 Evaluation of Activation of Epidermal Growth Factor Receptor
본 발명의 펩타이드가 표피성장인자 수용체를 활성화하는지 확인하기 위하여 in situ proximity ligation assay 방법을 사용하였다. 상기 시험은 스웨덴 오링크 바이오사이언스(Olink Bioscience, Sweden)로부터 Duolink In Situ 시약을 구입하여 수행하였다.In situ proximity ligation assay was used to confirm whether the peptide of the present invention activates the epidermal growth factor receptor. The test was performed by purchasing Duolink In Situ reagent from Olink Bioscience, Sweden.
12 mm glass가 깔린 24 웰 플레이트에 1 mL의 DMEM 배지를 첨가하고, 4.5 × 104 개의 사람 각질세포주 HaCaT 세포(DKFZ, Heidelberg, Germany)를 도말한 후, 24시간 동안 안정화하였다. 서열번호 1 내지 15의 펩타이드를 무혈청 DMEM 배지에 각각 용해시켜 얻어진 용액을 10 μM이 되도록 첨가하고, 15분 후 4% 포름알데히드로 고정하였다. 대조군은 미처리군을 의미한다. 한 방울의 blocking solution을 각 웰의 세포에 떨어뜨리고, 37℃에서 30 분간 인큐베이션하였다. 표피성장인자 수용체 활성화에 의해 증가하는 Gab1과 Shp2간의 상호작용 정도를 측정하기 위해 항-Gab1 토끼다클론항체(Gab1 Antibody, Cell Signaling Technology, INC., USA)와 항-Shp2 생쥐단클론항체(SH-PTP2(B-1):sc-7384 mouse mAb, Santa Cruz Biothecnology, INC., USA)를 37℃에서 세포에 처리하였다. 30분 후, PLA probe solution으로 처리하고 37℃에서 1시간 동안 인큐베이션한 후, ligation solution으로 처리하고 30분간 인큐베이션한 다음. amplication solution으로 처리하고 100분간 인큐베이션하였다. 상기와 같이 처리된 세포를 washing buffer로 세척한 후, confocal microscopy를 이용하여 붉은점의 수를 측정하였으며, 그 결과는 도 1 및 도 2와 같다. 도 1에서 알 수 있는 바와 같이, 4개 아미노산을 갖는 서열번호 1 내지 7의 펩타이드를 처리한 경우, Gab1과 Shp2 간의 상호작용이 대조군에 비하여 약 50∼100 % 정도로 증가하였다. 또한, 도 2에서 알 수 있는 바와 같이, 3개 아미노산을 갖는 서열번호 8 내지 15의 펩타이드를 처리한 경우, Gab1과 Shp2간의 상호작용이 대조군에 비하여 약 30∼170 % 정도로 증가되었다. 이는 본 발명에 따른 펩타이드가 피부재생에서 주요한 역할을 하는 표피성장인자 수용체를 활성화한다는 것을 나타낸다. 1 mL of DMEM medium was added to a 24-well plate coated with 12 mm glass, and 4.5 × 10 4 human keratinocyte line HaCaT cells (DKFZ, Heidelberg, Germany) were plated and stabilized for 24 hours. The solutions obtained by dissolving the peptides of SEQ ID NOs: 1 to 15 in serum-free DMEM medium, respectively, were added to 10 μM, and after 15 minutes, 4% formaldehyde was fixed. Control means untreated group. A drop of blocking solution was dropped on the cells of each well and incubated at 37 ° C. for 30 minutes. Anti-Gab1 Rabbit Polyclonal Antibody (Gab1 Antibody, Cell Signaling Technology, INC., USA) and Anti-Shp2 Mouse Monoclonal Antibody (SH-) to measure the degree of interaction between Gab1 and Shp2 increased by epidermal growth factor receptor activation PTP2 (B-1): sc-7384 mouse mAb, Santa Cruz Biothecnology, INC., USA) was treated with cells at 37 ° C. After 30 minutes, treated with PLA probe solution and incubated at 37 ° C. for 1 hour, then treated with ligation solution and incubated for 30 minutes. Treated with amplication solution and incubated for 100 minutes. After the cells treated as described above were washed with washing buffer, the number of red spots was measured using confocal microscopy, and the results are shown in FIGS. 1 and 2. As can be seen in Figure 1, when treated with the peptide of SEQ ID NOS: 1 to 7 having 4 amino acids, the interaction between Gab1 and Shp2 increased by about 50 to 100% compared to the control. In addition, as can be seen in Figure 2, when treated with the peptide of SEQ ID NOS: 8 to 15 having three amino acids, the interaction between Gab1 and Shp2 was increased by about 30 to 170% compared to the control. This indicates that the peptides according to the invention activate the epidermal growth factor receptor, which plays a major role in skin regeneration.
시험예 2. ERK와 Akt 활성화 평가 Test Example 2 Evaluation of ERK and Akt Activation
본 발명의 펩타이드의 처리에 의하여 각질세포와 섬유모세포에서 표피성장인자 수용체 신호전달경로가 활성화되는지를 평가하기 위하여 서열번호 9의 펩타이드를 무혈청 DMEM 배지에 0.05, 0.1, 0.5, 1, 5, 10 μM 농도로 용해시켜 얻어진 용액(1 ml)로 사람 각질세포 HaCaT(DKFZ, Heidelberg, Germany)과 생쥐 섬유모세포 NIH3T3(ATCC CRL-1658, USA)를 처리하였다. 15분 후, 세포추출물을 대상으로 웨스턴 블롯팅 분석을 실시하여 ERK와 Akt의 인산화의 변화를 측정하였으며, 그 결과는 도 3 및 도 4와 같다. 도 3 및 도 4에서 확인할 수 있는 바와 같이, ERK와 Akt의 인산화 정도는 서열번호 9의 펩타이드에 의하여 농도의존적으로 증가하였다. 따라서, 본 발명에 따른 펩타이드는 각질세포와 섬유모세포에서 발현되는 표피성장인자 수용체를 활성화한다는 것을 확인할 수 있다.In order to evaluate whether the epidermal growth factor receptor signaling pathway is activated in keratinocytes and fibroblasts by treatment of the peptide of the present invention, the peptide of SEQ ID NO. Human keratinocytes HaCaT (DKFZ, Heidelberg, Germany) and mouse fibroblast NIH3T3 (ATCC CRL-1658, USA) were treated with a solution (1 ml) obtained by lysis at a concentration of μM. After 15 minutes, Western blotting analysis was performed on the cell extracts to measure changes in phosphorylation of ERK and Akt, and the results are shown in FIGS. 3 and 4. As can be seen in Figures 3 and 4, the phosphorylation degree of ERK and Akt was increased in a concentration-dependent manner by the peptide of SEQ ID NO. Therefore, it can be seen that the peptide according to the present invention activates the epidermal growth factor receptor expressed in keratinocytes and fibroblasts.
시험예 3. 사람 각질세포주 HaCaT의 증식 촉진 시험Experimental Example 3. Proliferation promoting test of human keratinocyte line HaCaT
96-웰 마이크로플레이트의 각 웰에 5X103 개의 HaCaT 세포(DKFZ, Heidelberg, Germany)를 100 μL의 DMEM 배지에 분주하고 37℃, 5% CO2 인큐베이터에서 24시간 배양한 후, 서열번호 9의 펩타이드를 무혈청 DMEM 배지에 0.01, 0.1, 또는 1 μM의 농도로 용해시켜 얻어진 용액(100 μL)을 첨가하였다. 대조군은 미처리군을 의미한다. 이 후 24, 48, 72시간 동안 배양하고, 각 웰 당 10 μL의 CCK-8 (Dojindo Laboratories, Japan)으로 2 시간 처리하고, Spectramax plus 190 plate reader(Molecular Devices, USA)로 450 nm에서 흡광도를 측정하였다. 그 결과는 도 5와 같다. 도 5에서 확인할 수 있는 바와 같이, 서열번호 9의 펩타이드를 처리한 경우, HaCaT 세포의 증식이 펩타이드의 처리 농도에 따라 농도 의존적으로 증가되었다. 이는 본 발명에 따른 펩타이드가 각질세포의 증식을 촉진한다는 것을 나타낸다.In each well of a 96-well microplate, 5 × 10 3 HaCaT cells (DKFZ, Heidelberg, Germany) were dispensed in 100 μL of DMEM medium and incubated for 24 hours in a 37 ° C., 5% CO 2 incubator, followed by peptide of SEQ ID NO: 9 Was dissolved in serum free DMEM medium at a concentration of 0.01, 0.1, or 1 μM (100 μL) was added. Control means untreated group. Then incubate for 24, 48 and 72 hours, treat for 2 hours with 10 μL of CCK-8 (Dojindo Laboratories, Japan) per well and absorbance at 450 nm with Spectramax plus 190 plate reader (Molecular Devices, USA). Measured. The result is shown in FIG. As can be seen in Figure 5, when the peptide of SEQ ID NO: 9, the proliferation of HaCaT cells increased concentration-dependently depending on the concentration of the peptide. This indicates that the peptide according to the present invention promotes the proliferation of keratinocytes.
시험예 4. 시험관 내(in vitro) 혈관신생 촉진 시험Test Example 4 In vitro Angiogenesis Promoting Test
본 발명에 따른 펩타이드가 혈관신생에 미치는 영향을 하기와 같이 평가하였다. 일반적으로, 혈관의 바닥막 성분과 혈관내피 세포의 상호작용은 신생혈관의 형성과 유지에 중요한 요소이며, 바닥막 성분의 복합체인 매트리겔(Matrigel)을 24-웰 플레이트에 넣으면 중합반응을 일으켜 플러그(plug)를 형성하게 된다. 인간 제정맥 내피 세포(human umbilical vein endothelial cells, HUVECs)을 8 x 104 cells/well의 밀도로 매트리겔이 도포된 24 well 세포배양판에 접종한 후, 서열번호 9의 펩타이드를 무혈청 M199 배지에 1, 10, 또는 100 μM의 농도로 용해시켜 얻어진 용액((1 mL)을 첨가하고 배양하였다. 대조군으로는 펩타이드 용액을 첨가하지 않은 세포배양판에 혈관내피성장인자(Vascular Endothelial Growth Factor; VEGF, 10 ng/ml)를 첨가한 것과 첨가하지 않은 것을 사용하였다. 24시간 후 도립현미경하에서 x50 배율로 확대하여 신생혈관 형성여부를 관찰하고 정량화하여 그 결과를 도 6에 나타내었다. 도 6에서 확인할 수 있는 바와 같이, 본 발명의 펩타이드를 함유한 용액으로 처리한 경우, 혈관신생이 현저하게 촉진되는 것을 알 수 있다. The effect of the peptides according to the invention on angiogenesis was evaluated as follows. In general, the interaction between the vascular endothelial component and vascular endothelial cells is an important factor in the formation and maintenance of neovascularization. When the matrigel, which is a complex of the bottom membrane component, is put into a 24-well plate, a polymerization reaction occurs and a plug ). Human umbilical vein endothelial cells (HUVECs) were inoculated into a 24 well cell culture plate coated with Matrigel at a density of 8 x 10 4 cells / well, and the peptide of SEQ ID NO: 9 was serum-free M199 medium. A solution obtained by dissolving at a concentration of 1, 10, or 100 μM ((1 mL) was added and incubated. As a control, Vascular Endothelial Growth Factor (VEGF) was added to a cell culture plate without adding a peptide solution. , 10 ng / ml) was added and not added, after 24 hours, magnified at x50 magnification under an inverted microscope to observe the formation of neovascularization and quantified the results are shown in Fig. 6. As can be seen, when treated with a solution containing the peptide of the present invention, it can be seen that angiogenesis is significantly promoted.
Claims (4)
- 서열번호 1 내지 15의 펩타이드로 이루어진 군으로부터 선택된 펩타이드를 유효성분으로 포함하고, 약학적으로 허용가능한 담체를 포함하는 상처 치료 또는 상처 치료 촉진용 약학 조성물.A pharmaceutical composition for treating wounds or promoting wound care, comprising a peptide selected from the group consisting of the peptides of SEQ ID NOs: 1 to 15 as an active ingredient, and comprising a pharmaceutically acceptable carrier.
- 제1항에 있어서, 서열번호 9의 펩타이드를 유효성분으로 포함하는 것을 특징으로 하는 약학 조성물.The pharmaceutical composition according to claim 1, comprising the peptide of SEQ ID NO: 9 as an active ingredient.
- 서열번호 1 내지 15의 펩타이드로 이루어진 군으로부터 선택된 펩타이드를 유효성분으로 포함하는, 피부노화 억제 또는 피부 주름형성 억제용 화장료 조성물.Cosmetic composition for inhibiting skin aging or skin wrinkle formation comprising a peptide selected from the group consisting of peptides of SEQ ID NO: 1 to 15 as an active ingredient.
- 제3항에 있어서, 서열번호 9의 펩타이드를 유효성분으로 포함하는 것을 특징으로 하는 화장료 조성물.According to claim 3, Cosmetic composition characterized in that it comprises a peptide of SEQ ID NO: 9 as an active ingredient.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/KR2014/006169 WO2016006732A1 (en) | 2014-07-09 | 2014-07-09 | Composition containing epidermal growth factor-derived peptide fragments for wound healing or inhibiting skin wrinkle formation |
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| Application Number | Priority Date | Filing Date | Title |
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| PCT/KR2014/006169 WO2016006732A1 (en) | 2014-07-09 | 2014-07-09 | Composition containing epidermal growth factor-derived peptide fragments for wound healing or inhibiting skin wrinkle formation |
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5492894A (en) * | 1991-03-21 | 1996-02-20 | The Procter & Gamble Company | Compositions for treating wrinkles comprising a peptide |
| US20060148706A1 (en) * | 2005-01-03 | 2006-07-06 | Blue Blood Biotech Corp. | Composition for wound healing and use thereof |
| WO2008044846A1 (en) * | 2006-10-10 | 2008-04-17 | Caregen Co., Ltd | Peptides having activities of epidermal growth factor and its uses |
| KR20100092150A (en) * | 2009-02-12 | 2010-08-20 | 주식회사 웰스킨 | Composition for skin whitening containing dipeptide |
| WO2012121428A1 (en) * | 2011-03-07 | 2012-09-13 | 주식회사 웰스킨 | Fibroblast growth composition comprising a dipeptide as an active ingredient, and a product comprising the composition |
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2014
- 2014-07-09 WO PCT/KR2014/006169 patent/WO2016006732A1/en active Application Filing
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5492894A (en) * | 1991-03-21 | 1996-02-20 | The Procter & Gamble Company | Compositions for treating wrinkles comprising a peptide |
| US20060148706A1 (en) * | 2005-01-03 | 2006-07-06 | Blue Blood Biotech Corp. | Composition for wound healing and use thereof |
| WO2008044846A1 (en) * | 2006-10-10 | 2008-04-17 | Caregen Co., Ltd | Peptides having activities of epidermal growth factor and its uses |
| KR20100092150A (en) * | 2009-02-12 | 2010-08-20 | 주식회사 웰스킨 | Composition for skin whitening containing dipeptide |
| WO2012121428A1 (en) * | 2011-03-07 | 2012-09-13 | 주식회사 웰스킨 | Fibroblast growth composition comprising a dipeptide as an active ingredient, and a product comprising the composition |
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