Composition containing synergistic quadruple peptide

Abstract

The invention provides a composition containing a synergistic quadruple peptide. The quadruple peptide comprises acetyl dipeptide-1 cetyl ester, palmitoyl tripeptide-8, hexapeptide-3 and / or polytripeptide-6; the quadruple peptide achieves synergistic effects of strengthening cell adhesion, strengthening cell defense, improving moisturizing capacity and / or resisting inflammation and relieving by remarkably promoting phosphorylation of an epidermal growth factor receptor (EGFR), phosphorylation of serine / threonine kinase (Akt) and / or expression of catenin (beta-catenin). The composition containing the synergistic quadruple peptide can give full play to the biological advantages of each functional peptide. By promoting proliferation and differentiation of epidermal cells, the self-healing power of the skin barrier is improved, endogenous root improvement is achieved, the comprehensive synergistic effect of stabilizing the skin barrier, inhibiting inflammation and soothing and soothing muscles is truly achieved, and the composition can be used in cosmetics and beauty products in various forms.

Description

Technical Field

[0001] The present invention relates to a composition comprising peptides, and in particular to a composition comprising synergistic quadruplet peptides. Background Art

[0002] The state of the skin is affected by many factors. From the perspective of external factors such as the current living environment, cold, heat, sun exposure, ionizing radiation, spicy foods, cosmetics, drugs, irregular skin care, as well as pollen, high-protein foods, and dust can cause daily problems such as skin sensitivity and intolerance. Exposure to irritating chemicals, including improperly formulated cosmetics, can also directly cause skin sensitivity. From the perspective of internal factors, factors such as genetics, gender, hormone levels, emotional mental state, and age can also affect the state of the skin. Studies have shown that women are more sensitive to environmental stimuli such as light and humidity, while men are more sensitive to emotional stimuli. The state of the skin can also be affected by some other skin diseases, such as rosacea and atopic dermatitis. In addition, damage to the skin barrier is also an important basic reason, which may increase the sensitivity of the skin to various external factors. At the same time, skin problems are related to the body's immune and inflammatory response. For example, the occurrence of neurogenic inflammation may lead to increased immune and inflammatory responses in the skin, causing skin problems.

[0003] Poor skin condition can cause the skin to be prone to allergies. Slight external stimulation may cause redness, itching, burning, stinging, tightness and other discomforts on the skin, seriously affecting daily life and work. It may also be accompanied by various skin problems, such as rashes, papules, blisters, peeling, etc., which have a certain impact on the patient's appearance and psychology. At the same time, due to the sensitivity of the skin, more skin care products may be needed to maintain skin health, but the selection and use of skin care products may also become a problem, because inappropriate skin care products may cause skin problems to worsen. Sensitive skin can also affect the patient's mental health, because long-term skin problems and constant skin discomfort may lead to psychological problems such as anxiety and depression.

[0004] At present, there are many skin conditioning and repair products on the market, especially some functional peptide beauty products. However, these products are used for problematic skin, especially sensitive skin, and only target a single target to solve specific problems. For example, many products as exogenous ingredients only supplement the missing part of the skin barrier, which is a temporary solution but not a fundamental solution. Skin sensitivity can only be temporarily relieved and is prone to recurrence in the long term. Not only can long-term effects not be achieved, but skin problems are not significantly improved, and the skin cannot maintain a long-term healthy state. The main reasons include: 1) Selectivity and specificity: Different peptide molecules may have different biological activities. If used improperly, only one aspect of the effect is strengthened, which is more likely to cause an imbalance in the skin state and lead to the occurrence of multiple problems. 2) Skin barrier function: Sensitive skin may already have barrier dysfunction, and some peptide molecules may affect the natural barrier of the skin, leading to more severe sensitivity or allergic reactions. 3) Transdermal absorption: The stratum corneum with strong lipophilicity may limit the transdermal absorption of some peptide molecules, especially for peptides with large molecular weight or strong hydrophilicity, the efficiency of transdermal absorption may be reduced, thereby limiting its effectiveness on the skin. 4) Skin inflammatory response and safety and effectiveness of long-term use, etc.

[0005] With the development of molecular biology, the conditioning and repair of skin requires not only attention to the selectivity and specificity of functional peptide products themselves, but also to focus on synergistic effects, using the body's own signal transduction mechanism to effectively improve the skin condition, establish a virtuous cycle mechanism for the skin, and restore the skin to a healthy state. At present, based on the molecular biological mechanism of skin problems, products that give full play to the biological activity advantages of functional peptides and condition and restore the skin to a healthy state are still to be developed, and related problems need to be solved urgently. Summary of the invention

[0006] In order to overcome the defects of the prior art, the present invention provides a composition comprising a synergistic quadrupeptide, which can give full play to the biological advantages of each functional peptide. By promoting the proliferation and differentiation of epidermal cells, the self-healing ability of the skin barrier is improved, and endogenous root improvement is achieved, which truly plays a comprehensive synergistic role in stabilizing the skin barrier, inhibiting inflammation, and soothing the muscles, and can be used in cosmetics and beauty products in various forms.

[0007] The present invention provides a composition comprising a synergistic quadrupeptide, wherein the quadrupeptide includes acetyl dipeptide-1 cetyl ester, palmitoyl tripeptide-8, hexapeptide-3 and / or poly (tripeptide-6); the quadrupeptide significantly promotes epidermal growth factor receptor (EGFR) phosphorylation, serine / threonine kinase (Akt) phosphorylation and / or β-catenin expression, thereby achieving a synergistic effect of strengthening cell adhesion, enhancing cell defense, improving moisturizing ability and / or anti-inflammatory and soothing.

[0008] Epidermal growth factor receptor (EGFR) is a single-chain transmembrane glycoprotein widely distributed on the cell membranes of various tissues in the human body. EGFR combines with epidermal growth factor (EGF) and its family members through the tyrosine kinase pathway. The EGFR signaling pathway is a key regulator in cell proliferation, differentiation, and survival. As a typical receptor tyrosine kinase, EGFR senses extracellular growth signals and transmits signals within cells to regulate a variety of important cellular processes such as cell growth, proliferation, and survival.

[0009] Serine / threonine kinase (Akt) is a proto-oncogene that has become a major focus of medical attention because of its important role in regulating a variety of cellular functions, including metabolism, growth, proliferation, survival, transcription, and protein synthesis. Factors that can activate the Akt signaling cascade include receptor tyrosine kinases, integrins, B-cell and T-cell receptors, cytokine receptors, G protein-coupled receptors, and other stimuli that can induce phosphatidylinositol-3,4,5-triphosphate (PIP3) production through phosphatidylinositol triskinase (PI3K). Akt regulates cell growth by acting on the tuberous sclerosis complex (TSC1 / TSC2) and mammalian target of rapamycin (mTOR) signaling. Akt affects cell proliferation by phosphorylating cyclin inhibitory proteins 21 (p21) and 27 (p27), inhibitors of cyclin-dependent kinases (CDKs).

[0010] The Wnt / β-catenin pathway is called the canonical Wnt pathway. The conserved Wnt / β-Catenin pathway regulates stem cell pluripotency and determines cell proliferation, differentiation, and apoptosis during development. This developmental cascade integrates signals from other pathways, including retinoic acid, fibroblast growth factor (FGF), transforming growth factor β (TGF-β), and bone morphogenetic protein (BMP), and is present in a variety of different cell types and tissues.

[0011] EGFR, Akt and β-catenin protein expression are three major signaling pathways that influence each other and play a synergistic regulatory role in the health of human skin.

[0012] After many experiments, the inventors found that the quadrupeptide simultaneously works on the above three signal pathways, exerts a synergistic effect, and activates signal pathways such as cell proliferation, differentiation, survival and migration. For example, the inventors used ultraviolet irradiation to establish a cell damage model. The experiment showed that compared with the control group: the experimental groups given different concentrations of quadrupeptide can promote the improvement of EGFR phosphorylation, such as the experimental group containing 2μg / mL of a specific ratio of quadrupeptide in the composition, which increased by 601%; promote the improvement of Akt phosphorylation, such as the experimental group containing 2μg / mL of a specific ratio of quadrupeptide in the composition, which increased by 730%; promote the improvement of β-catenin expression, such as the experimental group containing 2μg / mL of a specific ratio of quadrupeptide in the composition, which increased by 175%.

[0013] From the perspective of mechanism of action, the quadrupeptide fully activates the proliferation, migration, adhesion and differentiation of epidermal cells by promoting the transduction of the three signal pathways of EGFR, P13K / Akt, and Wnt / β-catenin, thereby endogenously renewing and strengthening the skin barrier, repairing sensitivity from the root and solving the problem of repeated sensitivity. Furthermore, palmitoyl tripeptide-8 and acetyl dipeptide-1 cetyl ester can block the release of neurotransmitters substance P and calcitonin gene-related peptide (CGRP), thereby inhibiting the activation of mast cells and transient receptor potential vanilloid subtype 1 (TRPV1) from the source, and relieving redness, itching, swelling and pain; palmitoyl tripeptide-8, mimics α-MSH and activates two signal pathways at the same time, promoting the expression of anti-inflammatory factors and inhibiting the release of pro-inflammatory factors, and has a two-way anti-inflammatory effect; poly (tripeptide-6) and hexapeptide-3 can resist external stimuli, promote the proliferation and adhesion of epidermal cells, increase the expression of barrier-related proteins, enhance the integrity of the skin barrier structure and improve resistance to external stimuli. Therefore, experiments have shown that the quadrupeptide provided by the present invention can simultaneously promote EGFR phosphorylation, Akt phosphorylation and / or β-catenin expression, thereby achieving a synergistic effect of strengthening cell adhesion, enhancing cell defense, improving moisturizing ability and / or anti-inflammatory and soothing effects.

[0014] Preferably, in the composition provided by the present invention, strengthening cell adhesion is achieved by enhancing the gene expression of tight junction protein (Claudin-1) and / or the gene expression of tight junction plaque protein (ZO-1); strengthening cell defense is achieved by enhancing the gene expression of involucrin (IVL) and / or the gene expression of filaggrin (FLG); improving moisturizing ability is achieved by enhancing the gene expression of barrier protease - mouse cysteine ​​protease 14 (Caspase-14) and / or the gene expression of aquaporin (APQ-3); anti-inflammatory and soothing effects are achieved by reducing the gene expression of key inflammatory factors interleukin 1β (IL-1β), interleukin 6 (IL-6), reducing the gene expression of secondary inflammatory mediators interleukin 8 (IL-8) and / or cyclooxygenase-2 (COX-2).

[0015] At the genetic level, the inventors found through many experiments, such as using ultraviolet irradiation to establish a cell damage model. The experiments showed that compared with the model group, the experimental groups given different single peptides and different concentrations of quadrupeptides respectively: the quadrupeptide enhanced the gene expression of tight junction transmembrane protein (Claudin-l), for example, the experimental group whose composition contained 2μg / mL of quadrupeptide with a specific ratio increased by 37%; enhanced the gene expression of tight junction plaque protein (ZO-1), for example, the experimental group whose composition contained 2μg / mL of quadrupeptide with a specific ratio increased by 32%, which was significantly higher than the single peptide and model groups at the same concentration, and played a role in strengthening cell adhesion.

[0016] The quadrupeptide enhanced the gene expression of involucrin (IVL), for example, the experimental group whose composition contained 2μg / mL of the quadrupeptide in a specific ratio increased by 142%; and enhanced the gene expression of filaggrin (FLG), for example, the experimental group whose composition contained 2μg / mL of the quadrupeptide in a specific ratio increased by 25%, which was significantly higher than the single peptide and model groups at the same concentration, and played a role in strengthening cell defense.

[0017] The quadrupeptide enhanced the gene expression of barrier protease (Caspase-14), for example, the experimental group whose composition contained 2μg / mL of the quadrupeptide in a specific ratio increased by 165%; and enhanced the gene expression of aquaporin (APQ-3), for example, the experimental group whose composition contained 2μg / mL of the quadrupeptide in a specific ratio increased by 109%, which was significantly higher than the single peptide and model groups at the same concentration, and played a role in improving the moisturizing ability.

[0018] It reduces the gene expression of key inflammatory factors IL-1β (for example, the experimental group whose composition contains 2μg / mL of a tetrapeptide with a specific ratio has a 60% reduction), IL-6 gene expression (for example, the experimental group whose composition contains 2μg / mL of a tetrapeptide with a specific ratio has a 50% reduction), reduces the gene expression of secondary inflammatory mediators IL-8 (for example, the experimental group whose composition contains 2μg / mL of a tetrapeptide with a specific ratio has a 51% reduction), and COX-2 gene expression (for example, the experimental group whose composition contains 2μg / mL of a tetrapeptide with a specific ratio has a 59% reduction), which are significantly lower than those of single peptide and model groups at the same concentration, and play an anti-inflammatory and soothing role.

[0019] It can be seen that the quadrupeptide provided by the present invention has a synergistic effect at the gene expression level, further achieving the beneficial effects of strengthening cell adhesion, enhancing cell defense, improving moisturizing ability and / or anti-inflammatory and soothing.

[0020] Preferably, the composition provided by the present invention, wherein the quadrupeptide is dispersed in the composition in a separated or mixed form, including one or more of a solution, a powder, a microcapsule, a suspension, a liposome and / or other coated forms; when the quadrupeptide is dispersed in the composition, the process temperature is lower than 60 ºC, and it is not in direct contact with aldehyde-containing compounds, metal ions, strong acids, strong bases and / or active enzymes; wherein the process temperature is preferably below 40 ºC. The quadrupeptide avoids being compatible with aldehyde-containing compounds, metal ions, strong acids, strong bases and active enzymes.

[0021] Preferably, in the composition provided by the present invention, the proportion of acetyl dipeptide-1 cetyl ester, palmitoyl tripeptide-8, hexapeptide-3 and / or poly (tripeptide-6) in the quadrupeptide is between 0.05 and 0.85, respectively, to achieve a synergistic effect. The quadrupeptide adopts the above ratio to meet the purpose of acetyl dipeptide-1 cetyl ester, palmitoyl tripeptide-8, hexapeptide-3 and / or poly (tripeptide-6) to act on specific skin receptors and gene levels during use. The inventor has verified through multiple experiments that it has an obvious effect of improving skin condition.

[0022] Preferably, in the composition provided by the present invention, the proportion of acetyl dipeptide-1 cetyl ester, palmitoyl tripeptide-8, hexapeptide-3 and / or poly (tripeptide-6) in the tetrapeptide is between 0.1 and 0.7, respectively. After in-depth research by the inventors, the use of the tetrapeptide with this ratio has a more significant effect of improving skin condition.

[0023] Preferably, the composition provided by the present invention, wherein the quadrupeptide can be used to repair skin barrier damage, inhibit immune and inflammatory responses and / or inhibit neurovascular hyperreactivity. The quadrupeptide provided by the present invention targets and inhibits neurovascular hyperreactivity, blocks the expression of inflammatory factors and inflammatory cascades at the source, and promotes epidermal cell proliferation and barrier repair, thereby achieving multi-target, full-link sensitive skin repair.

[0024] The inventor's research shows that acetyl dipeptide-1 cetyl ester is a small molecule dipeptide designed to mimic β-endorphin, a natural peptide substance produced in the human body with morphine-like analgesic effects. Acetyl dipeptide-1 cetyl ester can mimic endorphin, bind to opioid receptors on nerve endings, block the release of neurotransmitters (such as substance P, CGRP, etc.), inhibit skin vasodilation, relieve redness; and relieve sensitive discomfort symptoms such as tingling and burning by inhibiting the activation of TRPV1.

[0025] Palmitoyl tripeptide-8 can block the release of neurotransmitter substance P, inhibit mast cell degranulation and release of histamine, reduce vasodilation, edema, skin itching, and prevent and alleviate neurosensitivity; in addition, palmitoyl tripeptide-8 can activate melanocortin receptor 1 (MC1R), on the one hand, promote the expression of anti-inflammatory factors through the mitogen-activated protein kinase (MAPK) pathway, and actively fight inflammation; on the other hand, inhibit the release of pro-inflammatory factors through the tyrosine protein kinase / signal transducer and activator of transcription pathway (JAK / STAT) pathway, and passively fight inflammation.

[0026] Poly (tripeptide-6) can promote the proliferation and differentiation of keratinocytes, and promote the de novo synthesis of ceramide by activating the activity of serine palmitoyltransferase (SPT); in addition, it can promote the expression of barrier-related proteins such as IVL, AQP3 and Caspase-14, thereby enhancing the integrity of the skin barrier.

[0027] Hexapeptide-3 is a small molecule peptide with a sequence of 6 amino acid fragments in the type III unit of the fibronectin molecule. It can simulate the role of fibronectin in the skin extracellular matrix (ECM), promote the expression of laminin-5 and ꞵ1 integrin, enhance cell adhesion, and thus promote tissue remodeling and skin repair.

[0028] The targeted protein receptors in human skin are interrelated, forming a microenvironment for signal transmission. On the one hand, the synergistic quadrupeptide repairs the damaged barrier from the root, improves the resistance of the skin barrier, blocks external stimuli, and avoids aggravation and recurrence of sensitivity; at the same time, it inhibits immune inflammatory response, avoids damage to healthy cells and skin tissue caused by inflammatory cascades and excessive immunity, and relieves redness; and quickly inhibits the high response of nerves and blood vessels, soothes and calms, reduces symptoms such as itching, stinging, and burning of the skin, and increases the threshold of skin sensitivity. In response to the above three problems, through the signal transduction mechanism, a synergistic effect is exerted to repair the skin, allowing the skin to enter a virtuous cycle and restore to a healthy state.

[0029] Preferably, the composition provided by the present invention, wherein the quadrupeptide is used for sensitive skin repair. The occurrence mechanism of sensitive skin can be summarized as impaired skin barrier function, increased neurovascular reactivity, and immune and inflammatory response. The three are not independent, but influence each other and are causally related, which is also the reason why sensitive skin problems are prone to recurrence and long-term non-healing. The synergistic quadrupeptide can simultaneously target the three problems of impaired skin barrier function, increased neurovascular reactivity, and immune and inflammatory response, improve skin dryness, tightness, susceptibility to irritation; redness, erythema, edema, tingling; itching, burning, tightness, tingling, red bloodshot and other problems, and is used for sensitive skin repair.

[0030] Preferably, the composition provided by the present invention, wherein the composition is used as a makeup and / or beauty, care product, including essence water / toner, lotion, face cream, beauty cream, foundation, concealer, isolation, setting makeup, eye shadow, contouring, blush, lipstick, single-use stock solution, freeze-dried powder / freeze-dried liquid, facial mask liquid / mask powder / frozen mask, and / or functional medical beauty products.

[0031] The present invention provides a composition comprising a synergistic quadrupeptide. Through creative research by the inventor, acetyl dipeptide-1 cetyl ester, palmitoyl tripeptide-8, hexapeptide-3 and / or poly (tripeptide-6) are used in combination. Whether from the receptor level, the gene level, or even from the process and product adaptability, including the special use of the product, compared with single peptides or other products, the composition has substantial progress far beyond the existing products. It not only starts from a single target, but also gives full play to the functional synergistic effect of peptides, thereby scientifically solving the skin problems brought about by modern life. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required for use in the description of the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0033] Figure 1 Schematic diagram of the internal signal transduction mechanism of skin problems; FIG2 is the data of the effect of the quadruple peptide provided by the present invention on promoting EGFR phosphorylation; FIG3 : The effect data of the quadruple peptide provided by the present invention on promoting Akt phosphorylation; FIG4 is the effect data of the quadruple peptide provided by the present invention on promoting the expression of β-catenin; FIG5 is the data of the effect of the quadruple peptide provided by the present invention on enhancing the gene expression of tight junction transmembrane protein (Claudin-1); FIG6 is the data of the effect of the quadruple peptide provided by the present invention on enhancing the expression of the tight junction plaque protein (ZO-1) gene; FIG7 shows the effect data of the tetrapeptide provided by the present invention on enhancing the expression of the involucrin (IVL) gene; FIG8 shows the effect data of the tetrapeptide provided by the present invention on enhancing the expression of the filaggrin (FLG) gene; FIG9 shows the effect data of the quadruple peptide provided by the present invention on enhancing the gene expression of barrier protease (Caspase-14); FIG10 is the data of the effect of the quadruple peptide provided by the present invention on enhancing the gene expression of aquaporin (APQ-3); FIG11 is the effect data of the quadruple peptide provided by the present invention on reducing the gene expression of inflammatory factors IL-1β and IL-6; FIG12 is the data of the effect of the quadruple peptide provided by the present invention on reducing the gene expression of chemokine IL-8 and COX-2; DETAILED DESCRIPTION

[0034] In order to further illustrate the present invention, examples are given below. It should be noted that these examples are purely illustrative. The purpose of providing these examples is to fully illustrate the meaning and content of the present invention, but the present invention is not limited to the scope of the examples. Example 1 Western blot detection of the effect of the tetrapeptide on the expression of phosphorylated epidermal growth factor receptor (p-EGFR), β-catenin and phosphorylated serine / threonine kinase (p-Akt) proteins in human immortalized keratinocytes (HaCaT)

[0035] The causes of skin problems include impaired skin barrier function, inflammatory state of the epidermis, abnormalities of the skin's sensory nervous system, etc., and these causes often promote and interfere with each other, such as Figure 1 As shown, sensitive skin problems will fall into a vicious cycle and will not easily turn into normal skin. At the same time, the three major signaling pathways expressed by EGFR, Akt and β-catenin proteins affect each other and play a synergistic regulatory role in the health of human skin: Activation of the EGFR signaling pathway can promote cell proliferation and differentiation, promote DNA and RNA synthesis, and play an important role in epithelial cell proliferation, differentiation and migration. Under the stimulation of EGF, the rate of cell proliferation and differentiation is accelerated, and the activity of hyaluronidase will also be significantly enhanced, thereby promoting the increase of hyaluronic acid synthesis. In addition, EGFR activation participates in the skin wound healing process, not only promoting the division of epithelial cells and mesenchymal cells in various tissues, but also promoting the migration of fibroblasts, endothelial cells and epithelial cells. In the process of wound repair, the migration of the above cells plays a very critical role. Receptor dimerization is a key step in tyrosine phosphorylation activation, activating its intrinsic tyrosine kinase activity, so that RAS / Raf / MEK / ERK activates JAK / STAT, PI3K / AKT / mTOR signaling and PLCγ / PKC signaling pathways, affecting downstream signals, regulating cell proliferation, cell differentiation and apoptosis, and thus regulating many physiological processes.

[0036] AkT is a serine / threonine protein kinase with a relative molecular weight of about 56kDa. It is also a related kinase of protein kinase A (PKA) and protein kinase C (PKC). It plays an important role in cell metabolism such as cell proliferation, cell survival and apoptosis. AkT is an important component of the PI3K / AKT / mTOR pathway and is the downstream region of PI3K. PI3K activates downstream signaling pathways by activating AkT's phosphokinase and phosphorylating AkT. AkT regulates the cell cycle by phosphorylating glycogen synthase kinase-3 (GSK3) and regulating mTOR. EGF is downstream of the PI3K / AKT pathway. Activating the PI3K / AKT pathway can upregulate the expression of EGF. At the same time, the increased expression of EGF can also feedback to the PI3K / AKT signaling pathway through binding to EGFR. Activation of the PI3K / AKT pathway can also reduce the expression of matrix metalloproteinase 2 (MMP-2), thereby promoting wound repair.

[0037] When the Wnt signaling pathway is activated, the Wnt protein, which plays a role in signal release, binds to the frizzled protein (FZD) receptor and low-density lipoprotein receptor-related protein 5 / 6 (LRP5 / 6) to form a complex, and then binds to the scaffold protein (DVL) and the axis inhibitor protein (Axin), which inactivates GSK-3β phosphorylation, and β-catenin cannot be phosphorylated and cannot be degraded. More and more free β-catenin enters the cell nucleus, binds to the lymphocyte enhancer factor (TCF), and activates the expression of downstream target genes such as Cyclin D1 and C-myc, thereby promoting cell proliferation and differentiation. The Wnt pathway plays an important role in regulating the growth of the epidermis and appendages, promoting the formation of epidermal tissue, and accelerating the blood vessel generation and epithelial reconstruction of the wound. When the skin is damaged, the Wnt signaling pathway is activated and participates in every step of the wound healing process from inflammation control to tissue remodeling. Increased expression of Wnt and β-catenin can enhance the proliferation, differentiation and migration ability of skin cells, thereby promoting wound repair. In addition, β-catenin can inhibit the activation of nuclear factor κB (NF-κB). It has been confirmed in fibroblasts, epithelial cells and other cells that β-catenin can inhibit the NF-κB pathway, thereby reducing inflammatory responses and promoting the repair of skin and other tissues. GSK-3β is both a downstream molecule of the PI3K / AKT signaling pathway and a key factor in the regulation of the Wnt / β-catenin pathway. Both DVL in the Wnt / β-catenin pathway and AKT in the PI3K / AKT pathway have the function of inhibiting the activity of GSK-3β.

[0038] Therefore, the three major signal pathways are interrelated and have a synergistic chain reaction. The inventors conducted experiments to verify the synergistic effect of the four peptides on the three major signal pathways of p-EGFR, β-catenin and p-Akt protein expression in HaCaT cells.

[0039] Experimental preparation: A tetrapeptide with acetyl dipeptide-1 cetyl ester, palmitoyl tripeptide-8, hexapeptide-3, and poly (tripeptide-6) in the proportions of 0.7, 0.1, 0.1, and 0.1, respectively, is mixed in the form of a solution at a process temperature below 40ºC to prepare a composition containing different concentrations of tetrapeptides (e.g., 0.5μg / mL, 1.0μg / mL, 2.0μg / mL), without direct contact with aldehyde-containing compounds, metal ions, strong acids, strong bases, and / or active enzymes during the process.

[0040] Experimental process: Skin injury modeling: Prepare HaCaT cells, cause cell damage through ultraviolet irradiation, and establish a cell damage model.

[0041] Set up control group and experimental group: Control group: observe the self-repair of the damaged cell model at 48 hours, and use Western blot to detect the expression of p-EGFR, β-catenin and p-Akt proteins in the cells; Experimental group: The above-mentioned composition containing different concentrations of the quadrupeptide (such as 0.5μg / mL, 1.0μg / mL, and 2.0μg / mL) was added to the cell damage model, and the self-repair of the cell damage model was observed after 48 hours. The expression levels of cell p-EGFR, p-Akt, and β-catenin proteins were detected by Western blot.

[0042] Experimental results: like Figure 2 , Figure 3 , Figure 4 As shown, compared with the model group, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001. Compared with the control group, #P<0.05, ##P<0.01, ###P<0.001, ####P<0.0001.

[0043] It can be seen that the composition containing the quadruplet peptide at concentrations of 0.5 μg / mL, 1.0 μg / mL, and 2.0 μg / mL, respectively, increased the expression of EGFR phosphorylated protein in HaCaT cells by 150% (P < 0.001), 510% (P < 0.0001), and 601% (P < 0.0001) in the experimental group (+) compared with the control group (-); For the expression of Akt receptor phosphorylation protein in HaCaT cells, the experimental group (+) increased by 98% (P < 0.01), 261% (P < 0.0001), and 730% (P < 0.0001) compared with the control group (-); The expression of β-catenin in HaCaT cells was increased by 26%, 156% (P<0.001), and 175% (P<0.0001) in the experimental group (+) compared with the control group (-).

[0044] It can be seen that different concentrations of quadrupeptides can promote the phosphorylation of EGFR and Akt in UVB-damaged HaCaT cells, and promote the expression of β-catenin protein, and are concentration-dependent, that is, there is a trend of further improvement with the increase of concentration. The simultaneous detection of three signal pathways can fully demonstrate that the repair peptide can activate multiple signal pathways in the skin after compounding, thereby promoting the proliferation and migration of skin cells through different pathways at the same time, and exerting repair and anti-inflammatory effects, rather than just through a single signal pathway. This also explains why the combined use of quadrupeptides can show synergistic effects in promoting multiple skin barrier-related genes and inhibiting the expression of inflammation-related genes.

[0045] At the same time, studies have shown that the quadrupeptides provided by the present invention, such as palmitoyl tripeptide-8 and acetyl dipeptide-1 cetyl ester, can block the release of neurotransmitters substance P and CGRP, thereby inhibiting the activation of mast cells and TRPV1 at the source, and relieving redness, itching, swelling and pain; palmitoyl tripeptide-8 simulates α-MSH and simultaneously activates two signal pathways, promotes the expression of anti-inflammatory factors and inhibits the release of pro-inflammatory factors, and has a bidirectional anti-inflammatory effect; poly (tripeptide-6) and hexapeptide-3 can resist external stimuli, promote the proliferation and adhesion of epidermal cells, increase the expression of barrier-related proteins, enhance the integrity of the skin barrier structure and improve resistance to external stimuli.

[0046] Based on the significant effects of the quadrupeptide on the three signaling pathways, its regulatory mechanism on human skin and related clinical observations, the quadrupeptide provided by the present invention achieves a synergistic effect of strengthening cell adhesion, enhancing cell defense, improving moisturizing ability and / or anti-inflammatory and soothing by significantly promoting EGFR phosphorylation, Akt phosphorylation and / or β-catenin expression. Example 2 The tetrapeptide significantly enhances the tight junction transmembrane protein (Claudin-1) gene expression and / or the tight junction plaque protein (ZO-1) gene expression

[0047] Studies have shown that poly (tripeptide-6) and hexapeptide-3 can resist external stimuli, promote the proliferation and adhesion of epidermal cells, increase the expression of barrier-related proteins, enhance the integrity of the skin barrier structure and improve resistance to external stimuli. The inventors used single peptides of poly (tripeptide-6) and hexapeptide-3 to compare the strong cell adhesion effect of the quadrupeptide, fully verifying the synergistic effect and effect of the quadrupeptide.

[0048] Experimental preparation: A tetrapeptide with acetyl dipeptide-1 cetyl ester, palmitoyl tripeptide-8, hexapeptide-3, and poly (tripeptide-6) in the proportions of 0.85, 0.05, 0.05, and 0.05, respectively, is mixed in the form of a solution at a process temperature below 60ºC to prepare a composition containing different concentrations of tetrapeptides (e.g., 0.5μg / mL, 1.0μg / mL, 2.0μg / mL), without direct contact with aldehyde-containing compounds, metal ions, strong acids, strong bases, and / or active enzymes during the process.

[0049] Experimental process: Skin injury modeling: Prepare HaCaT cells, cause cell damage through ultraviolet irradiation, and establish a cell damage model.

[0050] Set up control group, model group and experimental group: Control group: PCR method was used to detect the Claudin-1 gene expression and ZO-1 gene expression of normal HaCaT cells at 48 hours; Model group: observed the self-repair of the damaged cell model after 48 hours, and used PCR to detect the expression of Claudin-1 gene and ZO-1 gene; Experimental group: Hexapeptide-3 (single peptide 2 μg / mL), poly (tripeptide-6) (single peptide 2 μg / mL), and the above-mentioned combination containing different concentrations of quadrupeptides (such as 0.5μg / mL, 1.0μg / mL, 2.0μg / mL) were added to the cell damage model, and the self-repair of the cell damage model was observed after 48 hours. The expression levels of Claudin-1 gene and ZO-1 gene were detected by PCR.

[0051] Experimental results: like Figure 5 , Figure 6 As shown, compared with the model group, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001. Compared with the control group, #P<0.05, ##P<0.01, ###P<0.001, ####P<0.0001.

[0052] Under UVB conditions, the expression of Claudin-1 gene in the model group cells was significantly reduced (P < 0.001), and the relative expression of the 2 μg / mL hexapeptide-3 and poly (tripeptide-6) single peptide experimental groups increased by 15% (P < 0.05) and 4%, respectively; the relative expression of the experimental groups containing different concentrations of quadrupeptides (such as 0.5μg / mL, 1.0μg / mL, 2.0μg / mL) increased by 10%, 12% and 37% (P < 0.0001). It can be seen that the same concentration of quadrupeptides significantly increased the expression of Claudin-1 gene compared with single peptides.

[0053] Under UVB conditions, the expression of ZO-1 gene in the model group cells was significantly reduced (P < 0.01), and the relative expression of the 2 μg / mL hexapeptide-3 and poly (tripeptide-6) single peptide experimental groups increased by 19% (P < 0.05) and 12% (P < 0.001), respectively; the relative expression of the experimental groups containing different concentrations of quadrupeptides (such as 1.0μg / mL and 2.0μg / mL) increased by 21% (P < 0.01) and 32% (P < 0.0001), respectively. It can be seen that 1.0μg / mL and the same concentration of quadrupeptides significantly increased the expression of ZO-1 gene compared with single peptides.

[0054] Therefore, the quadrupeptide provided by the present invention can significantly increase the expression of Claudin-1 gene and ZO-1 gene at the same concentration or even at a lower concentration. According to the action principle of related gene expression and experimental observation, the unique synergistic effect between the quadrupeptides can achieve the effect of significantly strengthening cell adhesion. Example 3 The tetrapeptide significantly enhances the expression of involucrin (IVL) gene and / or filaggrin (FLG) gene

[0055] Studies have shown that poly (tripeptide-6) and hexapeptide-3 can resist external stimuli, promote the proliferation and adhesion of epidermal cells, increase the expression of barrier-related proteins, enhance the integrity of the skin barrier structure and improve resistance to external stimuli. The inventors used single peptides of poly (tripeptide-6) and hexapeptide-3 to compare the effects of tetrapeptide on strengthening cell defense, fully verifying the synergistic effect and effect of tetrapeptide.

[0056] Experimental preparation: A tetrapeptide with acetyl dipeptide-1 cetyl ester, palmitoyl tripeptide-8, hexapeptide-3, and poly (tripeptide-6) in the proportions of 0.60, 0.13, 0.13, and 0.14, respectively, is mixed in the form of a solution at a process temperature below 40ºC to prepare a composition containing different concentrations of tetrapeptides (e.g., 0.5μg / mL, 1.0μg / mL, 2.0μg / mL), without direct contact with aldehyde-containing compounds, metal ions, strong acids, strong bases, and / or active enzymes during the process.

[0057] Experimental process: Skin injury modeling: Prepare HaCaT cells, cause cell damage through ultraviolet irradiation, and establish a cell damage model.

[0058] Set up control group, model group and experimental group: Control group: PCR method was used to detect the IVL gene expression and FLG gene expression of normal HaCaT cells at 48 hours; Model group: observe the self-repair of the damaged cell model after 48 hours, and use PCR to detect the expression of IVL gene and FLG gene; Experimental group: Hexapeptide-3 (single peptide 2 μg / mL), poly (tripeptide-6) (single peptide 2 μg / mL), and the above-mentioned combination containing different concentrations of quadrupeptides (such as 0.5μg / mL, 1.0μg / mL, 2.0μg / mL) were added to the cell damage model, and the self-repair of the cell damage model was observed after 48 hours. The expression levels of IVL gene and FLG gene were detected by PCR.

[0059] Experimental results: like Figure 7 , Figure 8 As shown, compared with the model group, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001. Compared with the control group, #P<0.05, ##P<0.01, ###P<0.001, ####P<0.0001.

[0060] Under UVB conditions, the expression of IVL gene in the model group cells was significantly reduced (P < 0.0001), and the relative expression of the 2 μg / mL hexapeptide-3 and poly (tripeptide-6) single peptide experimental groups increased by 63% (P < 0.0001) and 44% (P < 0.001), respectively; the relative expression of the experimental groups containing different concentrations of quadrupeptides (such as 0.5μg / mL, 1.0μg / mL, 2.0μg / mL) increased by 82% (P < 0.0001), 88% (P < 0.0001) and 142% (P < 0.0001), respectively. It can be seen that 0.5μg / mL, 1.0μg / mL and the same concentration of quadrupeptides significantly increased the expression of IVL gene compared with single peptides.

[0061] Under UVB conditions, the relative expression levels of the 2 μg / mL hexapeptide-3 and poly (tripeptide-6) single peptide experimental groups increased by 3% and 18% (P < 0.01) compared with the control group; the relative expression levels of the experimental groups containing different concentrations of quadrupeptides (such as 1.0 μg / mL and 2.0 μg / mL) increased by 22% (P < 0.01) and 25% (P < 0.0001), respectively. It can be seen that 1.0 μg / mL and the same concentration of quadrupeptides significantly increased the expression of FLG genes compared with single peptides.

[0062] Therefore, the quadrupeptide provided by the present invention can significantly increase the expression of IVL gene and FLG gene at the same concentration or even at a lower concentration. According to the action principle of related gene expression and experimental observation, the unique synergistic effect between the quadrupeptides can achieve the effect of significantly enhancing cell defense. Example 4 The tetrapeptide significantly enhances the gene expression of barrier protease (Caspase-14) and / or the gene expression of aquaporin (APQ-3)

[0063] Studies have shown that poly (tripeptide-6) and hexapeptide-3 can resist external stimuli, promote the proliferation and adhesion of epidermal cells, increase the expression of barrier-related proteins, enhance the integrity of the skin barrier structure and improve resistance to external stimuli. The inventors used single peptides of poly (tripeptide-6) and hexapeptide-3 to compare the moisturizing effect of quadrupeptides, fully verifying the synergistic effect and effect of quadrupeptides.

[0064] Experimental preparation: A tetrapeptide with acetyl dipeptide-1 cetyl ester, palmitoyl tripeptide-8, hexapeptide-3, and poly (tripeptide-6) in the proportions of 0.45, 0.15, 0.20, and 0.20, respectively, is mixed in the form of a solution at a process temperature below 40ºC to prepare a composition containing different concentrations of tetrapeptides (e.g., 0.5μg / mL, 1.0μg / mL, 2.0μg / mL), without direct contact with aldehyde-containing compounds, metal ions, strong acids, strong bases, and / or active enzymes during the process.

[0065] Experimental process: Skin injury modeling: Prepare HaCaT cells, cause cell damage through ultraviolet irradiation, and establish a cell damage model.

[0066] Set up control group, model group and experimental group: Control group: PCR method was used to detect the expression of Caspase-14 gene and APQ-3 gene in normal HaCaT cells at 48 hours; Model group: observed the self-repair of the damaged cell model after 48 hours, and used PCR to detect the expression of Caspase-14 gene and APQ-3 gene; Experimental group: Hexapeptide-3 (single peptide 2 μg / mL), poly (tripeptide-6) (single peptide 2 μg / mL), and the above-mentioned combination containing different concentrations of quadrupeptides (such as 0.5μg / mL, 1.0μg / mL, 2.0μg / mL) were added to the cell damage model, and the self-repair of the cell damage model was observed after 48 hours. The expression levels of Caspase-14 gene and APQ-3 gene were detected by PCR.

[0067] Experimental results: like Fig. 9 , Fig.10 As shown, compared with the model group, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001. Compared with the control group, #P<0.05, ##P<0.01, ###P<0.001, ####P<0.0001.

[0068] Under UVB conditions, the gene expression of Caspase-14 in the model group cells was significantly reduced (P < 0.0001), and the relative expression of the 2 μg / mL hexapeptide-3 and poly (tripeptide-6) single peptide experimental groups increased by 38% (P < 0.05) and 0%, respectively; the relative expression of the experimental groups containing different concentrations of tetrapeptides (such as 0.5μg / mL, 1.0μg / mL, 2.0μg / mL) increased by 80% (P < 0.0001), 133% (P < 0.0001) and 165% (P < 0.0001), respectively. It can be seen that 0.5μg / mL, 1.0μg / mL and the same concentration of tetrapeptides significantly increased the gene expression of Caspase-14 compared with single peptides.

[0069] Under UVB conditions, the expression of APQ-3 gene in the model group cells was significantly reduced (P < 0.0001), and the relative expression of the 2 μg / mL hexapeptide-3 and poly (tripeptide-6) single peptide experimental groups increased by 59% (P < 0.0001) and 47% (P < 0.0001), respectively; the relative expression of the experimental groups containing different concentrations of quadrupeptides (such as 0.5μg / mL, 1.0μg / mL, 2.0μg / mL) increased by 38% (P < 0.0001), 98% (P < 0.0001) and 109% (P < 0.0001), respectively. It can be seen that 1.0μg / mL and the same concentration of quadrupeptides significantly increased the expression of APQ-3 gene compared with single peptides.

[0070] Therefore, the quadrupeptide provided by the present invention can significantly increase the expression of Caspase-14 gene and APQ-3 gene at the same concentration or even at a lower concentration. According to the action principle of related gene expression and experimental observation, the unique synergistic effect between the quadrupeptides can achieve the effect of significantly improving the moisturizing ability. Example 5 The tetrapeptide significantly reduces the gene expression of key inflammatory factors IL-1β and IL-6, and reduces the gene expression of secondary inflammatory mediators IL-8 and / or COX-2

[0071] Studies have shown that palmitoyl tripeptide-8 and acetyl dipeptide-1 cetyl ester can block the release of neurotransmitters substance P and CGRP, thereby inhibiting the activation of mast cells and TRPV1 at the source and relieving redness, itching, swelling and pain; and palmitoyl tripeptide-8, mimics α-MSH and activates two signaling pathways at the same time, promoting the expression of anti-inflammatory factors and inhibiting the release of pro-inflammatory factors, and has a two-way anti-inflammatory effect. The inventors used single peptides of palmitoyl tripeptide-8 and acetyl dipeptide-1 cetyl ester to compare the anti-inflammatory and soothing effects of the quadrupeptide, fully verifying the synergistic effect and effect of the quadrupeptide.

[0072] Experimental preparation: A tetrapeptide with acetyl dipeptide-1 cetyl ester, palmitoyl tripeptide-8, hexapeptide-3, and poly (tripeptide-6) in the proportions of 0.40, 0.20, 0.20, and 0.20, respectively, is mixed in the form of a solution at a process temperature below 40ºC to prepare a composition containing different concentrations of tetrapeptides (e.g., 0.5μg / mL, 1.0μg / mL, 2.0μg / mL), without direct contact with aldehyde-containing compounds, metal ions, strong acids, strong bases, and / or active enzymes during the process.

[0073] Experimental process: Skin injury modeling: Prepare HaCaT cells, cause cell damage through ultraviolet irradiation, and establish a cell damage model.

[0074] Set up control group, model group and experimental group: Control group: PCR method was used to detect the IL-1β gene expression, IL-6 gene expression, IL-8 gene expression and / or COX-2 gene expression of normal HaCaT cells at 48 hours; Model group: observe the self-repair of the damaged cell model at 48 hours, and use PCR to detect the expression of IL-1β gene, IL-6 gene, IL-8 gene and / or COX-2 gene; Experimental group: Palmitoyl tripeptide-8 (single peptide 2 μg / mL), acetyl dipeptide-1 cetyl ester (single peptide 2 μg / mL), and the above-mentioned composition containing different concentrations of quadrupeptides (such as 0.5μg / mL, 1.0μg / mL, 2.0μg / mL) were added to the cell damage model, and the self-repair of the cell damage model was observed after 48 hours. The PCR method was used to detect the expression of IL-1β gene, IL-6 gene, IL-8 gene and / or COX-2 gene.

[0075] Experimental results: like Fig.11 , Fig.12 As shown, compared with the model group, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001. Compared with the control group, #P<0.05, ##P<0.01, ###P<0.001, ####P<0.0001.

[0076] Under UVB conditions, the expression of IL-1β gene in the model group cells was significantly increased (P<0.0001), and the expression of 2 μg / mL palmitoyl tripeptide-8 and acetyl dipeptide-1 cetyl ester single peptide experimental groups was reduced by 45% (P<0.0001) and 67% (P<0.0001) respectively compared with the model group; the relative expression of the experimental groups containing different concentrations of tetrapeptides (such as 0.5μg / mL, 1.0μg / mL, 2.0μg / mL) was reduced by 47% (P<0.0001), 55% (P<0.0001) and 60% (P<0.0001) respectively. It can be seen that the expression of IL-1β gene in different concentrations of tetrapeptides was significantly reduced compared with palmitoyl tripeptide-8 and the model group.

[0077] Under UVB conditions, the expression of IL-6 gene in the model group cells was significantly increased (P < 0.0001), and the expression of 2 μg / mL palmitoyl tripeptide-8 and acetyl dipeptide-1 cetyl ester single peptide experimental groups was reduced by 16% (P < 0.001) and 48% (P < 0.0001) respectively compared with the model group; the relative expression of the experimental groups containing different concentrations of quadrupeptides (such as 0.5μg / mL, 1.0μg / mL, 2.0μg / mL) was reduced by 42% (P < 0.0001), 46% (P < 0.0001) and 50% (P < 0.0001) respectively. It can be seen that the same concentration of quadrupeptides reduced the expression of IL-6 gene compared with the two single peptides and the model group.

[0078] Under UVB conditions, the expression of IL-8 gene in the model group cells was significantly increased (P < 0.0001), and the expression of 2 μg / mL palmitoyl tripeptide-8 and acetyl dipeptide-1 cetyl ester in the experimental groups was reduced by 76% (P < 0.0001) and 26% (P < 0.0001) respectively compared with the model group; the relative expression of the experimental groups containing different concentrations of tetrapeptides (such as 0.5μg / mL, 1.0μg / mL, 2.0μg / mL) was reduced by 35% (P < 0.0001), 42% (P < 0.0001) and 51% (P < 0.0001) respectively. It can be seen that 0.5μg / mL, 1.0μg / mL and the same concentration of tetrapeptides significantly reduced the expression of IL-8 gene compared with acetyl dipeptide-1 cetyl ester and the model group.

[0079] Under UVB conditions, the expression of COX-2 gene in the model group cells was significantly increased (P < 0.0001), and the expression of 2 μg / mL palmitoyl tripeptide-8 and acetyl dipeptide-1 cetyl ester single peptide experimental groups was reduced by 42% (P < 0.0001) and 58% (P < 0.0001) respectively compared with the model group; the relative expression of the experimental groups containing different concentrations of quadrupeptides (such as 0.5μg / mL, 1.0μg / mL, 2.0μg / mL) was reduced by 40% (P < 0.0001), 45% (P < 0.0001) and 59% (P < 0.0001) respectively. It can be seen that the same concentration of quadrupeptides reduced the expression of COX-2 gene compared with the two single peptides and the model group.

[0080] Therefore, the quadrupeptide provided by the present invention can significantly reduce the key inflammatory factor IL-1β gene expression and IL-6 gene expression at the same concentration or even at a lower concentration, and can significantly reduce the secondary inflammatory mediator IL-8 gene expression and / or COX-2 gene expression. According to the action principle of related gene expression and experimental observation, the unique synergistic effect between the quadrupeptides can achieve a significant improvement in the anti-inflammatory and soothing effect.

[0081] In summary, the tetrapeptide provided by the present invention promotes EGFR phosphorylation, Akt phosphorylation and activation of the Wnt / β-catenin pathway, which is beneficial to promoting the proliferation, survival and migration of epidermal keratinocytes. At the same concentration, the tetrapeptide has a better effect on increasing the expression of HaCaT cell skin barrier-related genes than the use of hexapeptide-3 or poly (tripeptide-6) alone, and has a better inhibitory effect on the expression of inflammatory factor-related genes than the use of acetyl dipeptide-1 cetyl ester or palmitoyl tripeptide-8 alone, showing that the tetrapeptide has more significant effects in promoting skin barrier repair and toughness, inhibiting inflammation, and soothing and calming. Example 6 Application of a tetrapeptide and a composition containing the synergistic tetrapeptide

[0082] Based on the above research, the quadrupeptide can be used to repair damaged skin barrier, inhibit immune and inflammatory responses and / or inhibit neurovascular hyperreactivity, especially for sensitive skin repair.

[0083] Before use, the tetrapeptide is dispersed in the composition in a separated or mixed form, including one or more of a solution, powder, microcapsule, suspension, liposome and / or other encapsulated forms. The composition can be used for makeup and / or beauty and care products, including essence water / toner, lotion, face cream, beauty cream, base makeup, concealer, isolation, setting makeup, eye shadow, contouring, blush, lipstick, disposable stock solution, freeze-dried powder / freeze-dried liquid, mask liquid / mask powder / frozen mask, and / or functional medical beauty products.

[0084] When used, the composition can be a stock solution, or added at a ratio of 1% to 50% as a cosmetic and / or beauty care product. For example, it can be added in the final stage of the processing of cosmetic and / or beauty care products, with a processing temperature below 60°C, preferably below 40°C, and is not compatible with aldehyde-containing compounds, metal ions, strong acids, strong bases and / or active enzymes.

[0085] The finished product should be stored at 2~8℃ in a dry and cool place.

[0086] The above is only a specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Any person skilled in the art can easily think of changes or substitutions within the technical scope disclosed by the present invention, which should be included in the protection scope of the present invention. Therefore, the protection scope of the present invention should be based on the protection scope of the claims.

Claims

1. A composition comprising a synergistic quadrupeptide, characterized in that The quadrupeptide comprises acetyl dipeptide-1 cetyl ester, palmitoyl tripeptide-8, hexapeptide-3 and / or polytripeptide-6; the quadrupeptide significantly promotes epidermal growth factor receptor (EGFR) phosphorylation, serine / threonine kinase (Akt) phosphorylation and / or β-catenin expression, thereby achieving a synergistic effect of strengthening cell adhesion, enhancing cell defense, improving moisturizing ability and / or anti-inflammatory and soothing.

2. The composition according to claim 1, characterized in that The strengthening of cell adhesion is achieved by enhancing the expression of tight junction transmembrane protein (Claudin-1) gene and / or tight junction plaque protein (ZO-1) gene expression; the strengthening of cell defense is achieved by enhancing the expression of involucrin (IVL) gene and / or filaggrin (FLG) gene expression; the improvement of moisturizing ability is achieved by enhancing the expression of barrier protease (Caspase-14) gene and / or aquaporin (APQ-3) gene expression; the anti-inflammatory and soothing effect is achieved by reducing the expression of key inflammatory factors interleukin 1β (IL-1β) gene expression, interleukin 6 (IL-6) gene expression, and reducing the expression of secondary inflammatory mediator interleukin 8 (IL-8) gene expression and / or cyclooxygenase-2 (COX-2) gene expression.

3. The composition according to claim 1, characterized in that The quadrupeptide is dispersed in the composition in a separated or mixed form, including one or more of a solution, a powder, a microcapsule, a suspension, a liposome and / or other encapsulated forms; when the quadrupeptide is dispersed in the composition, the process temperature is lower than 60°C.

4. The composition according to claim 3, characterized in that When the quadrupeptide is dispersed in the composition, the process temperature is below 40°C and it does not come into direct contact with aldehyde-containing compounds, metal ions, strong acids, strong bases and / or active enzymes.

5. The composition according to claim 1, characterized in that The proportions of acetyl dipeptide-1 cetyl ester, palmitoyl tripeptide-8, hexapeptide-3 and / or tripeptide-6 in the quadrupeptide are respectively between 0.05 and 0.85 to achieve a synergistic effect.

6. The composition according to claim 5, characterized in that The proportions of acetyl dipeptide-1 cetyl ester, palmitoyl tripeptide-8, hexapeptide-3 and / or tripeptide-6 in the tetrapeptide are respectively between 0.1 and 0.

7.

7. The composition according to claim 1, characterized in that The quadrupeptide can be used to repair skin barrier damage, inhibit immune and inflammatory responses and / or inhibit neurovascular hyperreactivity.

8. The composition according to claim 1, characterized in that The quadrupeptide is used for repairing sensitive skin.

9. The composition according to claim 1, characterized in that The composition is used as a makeup and / or beauty and care product, including essence water / toner, lotion, face cream, beauty cream, base makeup, concealer, isolation, setting makeup, eye shadow, contouring, blush, lipstick, single-use stock solution, freeze-dried powder / freeze-dried liquid, facial mask liquid / facial mask powder / frozen mask, and / or functional medical beauty products.

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