KR20200057587A - Peptide AES11-1 for skin regenerating or wound healing and use thereof - Google Patents

Abstract

The present invention relates to peptide AES11-1 for skin regeneration or wound treatment and to a use thereof. The new synthetic peptide (AES11-1) increases collagen synthesis amount by fibroblasts, thereby having excellent regeneration and wound treatment effects on damaged skin, and minimizes side effects caused by the administration of foreign substances due to short residence time in the body and less possibility of hypersensitivity because of being low-molecular and biodegradable as very small-scale peptides composed of 3 amino acids, thereby being used as an effective material which can replace existing skin regeneration agents or existing wound treatment agents.

Description

Peptide AES11-1 for skin regenerating or wound healing and use thereof

The present invention relates to a peptide AES11-1 for skin regeneration or wound treatment and uses thereof.

Acne is a chronic inflammatory skin disease caused by the Propionibacterium acnes (P. acnes) bacteria present in the sebaceous glands, and more than 600 million people worldwide suffer from acne disease and is known as the 8th common disease worldwide (Hagstrom EL) ; Patel S .; Karimkhani C .; Boyers LN; Williams HC; Hay RJ; Weinstock MA; Armstrong AW; Dunnick CA; Margolis DJ; Dellavalle RP Comparing cutaneous research funded by the US National Institutes of Health (NIH) with the US skin disease burden.J. Am. Acad. Dermatol. 2015, 73, 383). The acne-producing P. acnes is a Gram-positive group, anaerobic, and skin symbiosis, and when proliferated in the sebaceous gland, causes extracellular matrix remodeling and skin damage or scarring. In addition, in the case of acne forming cotton, hyperplasia and thickening of the epidermis occurs due to the development of hyperkeratosis of the follicle wall. This process causes skin wounds such as necrotic erosion and serious wounds, and if this process is prolonged, it can cause deep wounds after a second infection or later (Connolly D .; Vu HL; Mariwalla K .; Saedi N. Acne Scarring-Pathogenesis, Evaluation, and Treatment Options.J. Clin.Aesthet.Dermatol. 2017, 10, 12.). Therefore, the rapid recovery of acne-necrotic wounds is important. In actual patients, anti-inflammatory and anti-inflammatory drugs are being used to reduce the level of P. acnes. However, P. acnes does not only show antibiotic resistance and also cause side effects such as homeostatic imbalance of skin-resident microorganisms (Dessinioti C .; Katsambasa A. Propionibacterium acnes and antimicrobial resistance in acne.Clin.Clin.Dermatol. 2017, 35, 163 .), Studies have shown that antibiotics do not have a positive effect on wound healing and rather delay wound healing (Ki V .; Rotstein C. Bacterial skin and soft tissue infections in adults: A review of their epidemiology, pathogenesis , diagnosis, treatment and site of care . Can. J. Infect. Dis. Med. Microbiol. 2008, 19, 173.).

As described above, various side effects have been reported for methods used to heal wounds caused by acne, and there is a need to develop a new therapeutic agent having an effective therapeutic effect while minimizing these side effects.

The present invention has been devised to solve the above problems, and the present inventors prepared a biodegradable peptide composed of 3 amino acids as a result of earnest research on a preparation for skin regeneration or wound healing, and when the peptide was treated , Promoting the activity of fibroblasts, enhancing the amount of collagen synthesis, confirming the effective regenerating effect of damaged skin, and completing the present invention based on this.

Accordingly, an object of the present invention is to provide a peptide for skin regeneration or wound healing, consisting of the amino acid represented by SEQ ID NO: 1.

In addition, another object of the present invention is to provide a pharmaceutical composition for skin regeneration or wound treatment, comprising the peptide or a polynucleotide encoding the same as an active ingredient.

In addition, another object of the present invention is to provide a health functional food / cosmetic composition for skin regeneration or wound improvement, containing the peptide as an active ingredient.

In order to solve the above problems, the present invention provides a peptide (AES11-1) consisting of the amino acid represented by SEQ ID NO: 1.

In addition, the present invention provides a pharmaceutical composition for skin regeneration or wound treatment, which comprises a peptide or a polynucleotide encoding the amino acid represented by SEQ ID NO: 1 as an active ingredient.

At this time, the wound may be due to an imaged acne (acne) or a wound.

In addition, the wound is a non-healing traumatic wound, destruction of tissue by irradiation, abrasion, laceration, appearance, penetrating wound, gunshot wound, burn, burn, frostbite, dry skin, keratosis, cracking, burst, surgical or blood vessel It can be selected from the group consisting of disease wound, bruise, corneal wound, pressure sore, spear wound, postoperative suture, spinal injury wound, gynecological wound, and chemical wound.

In addition, the skin regeneration may be for the treatment of skin ulcers, dermatitis and acne.

In addition, the present invention provides a cosmetic composition for skin regeneration or wound improvement, comprising the peptide as an active ingredient, consisting of the amino acid represented by SEQ ID NO: 1.

At this time, the composition may be in the form of a suspension, emulsion, paste, gel, cream, lotion, powder, wax or spray.

In addition, the present invention provides a method for skin regeneration or wound healing, comprising administering the peptide to an individual.

In addition, the present invention provides a skin rejuvenation or wound treatment use of the peptide.

The novel synthetic peptide (AES11-1) according to the present invention is very excellent in regenerative and wound healing effects of damaged skin by increasing the amount of collagen synthesis by fibroblasts, and is a small-scale peptide composed of 3 amino acids, low molecular weight and biodegradable Because it is sexual, the remaining period in the body is not long, so it is less likely to cause hypersensitivity reactions, thereby minimizing side effects caused by the administration of external substances, and it can be used as an effective substance that can replace existing skin regeneration or wound treatment agents. It is expected.

Figure 1 shows the results of histological comparison of the recovery rate of necrotic skin damage in the acne animal model according to the peptide AES11-1 treatment of the present invention.
Figure 2 shows the results of confirming the collagen synthesis in acne skin tissue according to the peptide AES11-1 treatment of the present invention.
Figure 3 shows the results confirming the degree of activation of fibroblasts according to the peptide AES11-1 treatment of the present invention.
Figure 4 shows the results confirming the expression level of collagen produced from human fibroblasts according to the peptide AES11-1 treatment of the present invention.

Hereinafter, the present invention will be described in more detail.

The present invention provides a peptide (AES11-1) consisting of the amino acid represented by SEQ ID NO: 1.

In the present invention, "peptide (peptide)" means a polymer composed of two or more amino acids linked by amide bonds (or peptide bonds), and for the purposes of the present invention, refers to peptides having skin rejuvenation or wound healing activity. Despite various studies on peptide therapeutics, the peptide itself is too large to effectively enter target tissues or cells, or has a short half-life, which results in the short-term disappearance of the body. The present invention has an effective therapeutic effect. At the same time, there is a technical significance in that a peptide consisting of 3 amino acids was developed.

The peptide of the present invention may be composed of the amino acid represented by SEQ ID NO: 1, and the amino acid sequence represented by SEQ ID NO: 1 and each 75% or more, preferably 80% or more, more preferably 90% or more, most preferably May include an amino acid sequence having 95% or more sequence homology, and may further include an amino acid sequence prepared for a specific purpose to increase targeting sequence, tag, labeled residue, half-life, or peptide stability. .

In addition, functional variants for the peptides of the invention may also be included. The functional variant includes biological equivalents of the peptide sequence (SEQ ID NO: 1) described herein. For example, to further improve the binding affinity and / or other biological properties of the peptide, additional changes may be made to the amino acid or polynucleotide sequence of the peptide. This modification results in deletion of the amino acid sequence residues of the peptide. Insertions, and / or substitutions, and can be made based on the relative similarity of amino acid side chain substituents, such as hydrophobicity, hydrophilicity, charge size, and the like.

In addition, the peptide of the present invention can be obtained by various methods well known in the art. As an example, it may be prepared using polynucleotide recombination and a protein expression system or synthesized in vitro through chemical synthesis such as peptide synthesis, and cell-free protein synthesis.

In addition, to obtain better chemical stability, enhanced pharmacological properties (half-life, absorbency, potency, efficacy, etc.), altered specificity (e.g., broad biological activity spectrum), reduced antigenicity, N- or C of the peptide -A protecting group may be attached to the terminal. Preferably, the protecting group may be an acetyl group, a fluorenyl methoxy carbonyl group, a formyl group, a palmitoyl group, a myristyl group, a stearyl group or polyethylene glycol (PEG), but the modification of the peptide, particularly to improve the stability of the peptide If it is a possible ingredient, it can be included without limitation. As used herein, the term “stability” means not only the in vivo stability that protects the peptides of the present invention from attack by protein cleavage enzymes in vivo, but also storage stability (eg, storage stability at room temperature). In the present invention, "polynucleotide (polynucleotide)" is a nucleotide-coupled polymer, and serves to transfer genetic information. For the purposes of the present invention, the peptide of SEQ ID NO: 1 is encoded, and the polynucleotide sequence encoding the peptide is 75% or more, preferably 85% or more, more preferably 90% or more, and most preferably 95% It may include a sequence having abnormal sequence homology. The "homology" is intended to indicate a similar degree to a wild-type amino acid sequence or a polynucleotide sequence, and comparison of the homology can be performed using a comparison program well known in the art, and homology between two or more sequences Can be calculated as a percentage (%).

As another aspect of the present invention, the present invention is composed of an amino acid represented by SEQ ID NO: 1, a peptide or a polynucleotide encoding the same, as an active ingredient, skin regeneration or wound treatment pharmaceutical composition; Use of the peptides for skin regeneration or wound healing; And administering a therapeutically effective amount of the peptide to an individual.

As used in the present invention, the term "treatment" refers to all actions in which symptoms of wounds are improved or beneficially changed by administration of a pharmaceutical composition according to the present invention.

In the present invention, "individual" refers to a subject in need of treatment of wounds, and more specifically, human or non-human primates, mice, mammals such as dogs, cats, horses, and cattle.

As used in the present invention, the term “skin regeneration” refers to a series of reactions in which skin tissue is reconstituted in response to overall skin aging and external stimuli caused by the skin, and as one embodiment, treatment of skin ulcers, dermatitis and acne, It has the effect of skin whitening, skin elasticity enhancement and wrinkle improvement. The "skin whitening" refers to improving skin hyperpigmentation such as freckles or freckles caused by ultraviolet rays, hormones or genetics, as well as brightening the skin tone by inhibiting the synthesis of melanin pigments.

The term used in the present invention, a wound (wound) refers to a phenomenon in which tissue is damaged by external stimulation, and healing of a general wound is usually degeneration and death of cells, flow of blast cells, tissue fluid from surrounding tissues, and Processes such as the deposition of fibrin and the formation of granulation tissue. For the purpose of the present invention, the wound treatment refers to assisting the reconstitution to normal skin tissue by promoting the process as described above, while the wound may be caused by vulgar acne (acne) or wound, but is not limited thereto. It does not work. In addition, the wound is a non-healing traumatic wound, destruction of tissue by irradiation, abrasion, laceration, appearance, penetrating wound, gunshot wound, burn, burn, frostbite, dry skin, keratosis, cracking, burst, surgical or blood vessel It can be selected from the group consisting of disease wound, bruise, corneal wound, pressure sore, spear wound, postoperative suture, spinal injury wound, gynecological wound, and chemical wound.

On the other hand, the peptide of the present invention or a polynucleotide encoding the same may be carried in a pharmaceutically acceptable carrier such as colloidal suspension, powder, saline, lipid, liposome, microsphere microspheres), or nano spherical particles. These can be complexed or associated with transport vehicles, and can be used in the art, such as lipids, liposomes, microparticles, gold, nanoparticles, polymers, condensation reagents, polysaccharides, polyamino acids, dendrimers, saponins, adsorption enhancing substances or fatty acids. It can be transported in vivo using known transport systems.

In addition to this, pharmaceutically acceptable carriers include lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia, rubber, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, Polyvinyl pyridone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate, and mineral oil, and the like, but is not limited thereto. In addition, lubricants, wetting agents, sweetening agents, flavoring agents, emulsifying agents, suspending agents, preservatives, etc. may be further included in addition to the above components.

In addition, for the purposes of the present invention, the pharmaceutical composition of the present invention may preferably contain the peptide of the present invention at a concentration of 1 to 10000 ng / ml for the skin regeneration effect, but can expect an effective therapeutic effect without cytotoxicity. If it is a concentration, it is not limited to this.

The pharmaceutical composition of the present invention may be administered orally or parenterally (eg, applied intramuscularly, intravenously, intraperitoneally, subcutaneously, subcutaneously, or topically) according to a desired method, and the dosage is It depends on the condition and weight, the degree of disease, the type of drug, the route of administration and time, but can be appropriately selected by those skilled in the art.

In particular, when the pharmaceutical composition of the present invention is used as an external preparation for skin, fatty substances, organic solvents, solubilizers, thickening agents and gelling agents, emollients, antioxidants, suspending agents, stabilizers, foaming agents, fragrances , Surfactant, water, ionic emulsifier, nonionic emulsifier, filler, metal ion blocker, chelating agent, preservative, vitamin, blocker, wetting agent, essential oil, dye, pigment, hydrophilic active agent, lipophilic active agent or lipid vesicle It may contain adjuvants commonly used in the skin science field, such as any other ingredients commonly used in external preparations for skin. In addition, the ingredients may be introduced in an amount commonly used in the field of skin science. In addition, when the pharmaceutical composition is provided as an external preparation for skin, it is not limited thereto, and may be a formulation such as ointment, patch, gel, cream or spray.

The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. In the present invention, "a pharmaceutically effective amount" means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level is the type of patient's disease, severity, activity of the drug, Sensitivity to the drug, time of administration, route of administration and rate of excretion, duration of treatment, factors including co-drugs and other factors well known in the medical arts may be determined. The pharmaceutical composition according to the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered simultaneously, separately, or sequentially with a conventional therapeutic agent, and may be administered single or multiple. Considering all of the above factors, it is important to administer an amount that can achieve the maximum effect in a minimal amount without side effects, which can be easily determined by those skilled in the art.

Specifically, the effective amount of the pharmaceutical composition of the present invention may vary depending on the patient's age, sex, condition, weight, absorption of active ingredients in the body, inactivation rate, excretion rate, disease type, and drugs used in combination, Obesity may increase or decrease depending on the severity, sex, weight, and age.

In addition, as another aspect of the present invention, the present invention provides a health functional food / cosmetic composition for skin regeneration or wound improvement, comprising an amino acid represented by SEQ ID NO: 1, a peptide or a polynucleotide encoding the same as an active ingredient. do.

As used herein, the term "improvement" refers to any action that at least reduces the extent of symptoms associated with the condition being treated, such as symptoms. At this time, the health functional food / cosmetic composition may be used at the same time or separately as a drug for treatment, before or after the onset stage of the related disease, for the prevention or improvement of skin regeneration, skin aging or wounds.

In the dietary supplement composition of the present invention, the active ingredient may be added to the food as it is or used with other foods or food ingredients, and may be suitably used according to conventional methods. The mixing amount of the active ingredient can be appropriately determined depending on the purpose of use (for prevention or improvement). In general, the composition of the present invention in the manufacture of food or beverage may be added in an amount of preferably 15% by weight or less, preferably 10% by weight or less with respect to the raw materials. However, in the case of long-term intake for health and hygiene purposes or for health control purposes, the amount may be below the above range.

The health functional food composition of the present invention may contain other ingredients as essential ingredients without particular limitations other than those containing the active ingredient. For example, it can contain various flavoring agents, natural carbohydrates, and the like as additional components, such as ordinary beverages. Examples of the natural carbohydrates described above include monosaccharides, such as glucose, fructose, and the like; Disaccharides such as maltose, sucrose, etc .; And polysaccharides, for example, conventional sugars such as dextrin, cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. Natural flavoring agents (such as taumatin and stevia extracts (e.g., rebaudioside A, glycyrrhizine)) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used as flavoring agents other than those described above. Can be. The proportion of the natural carbohydrate can be appropriately determined by the choice of those skilled in the art.

In addition to the above, the health functional food composition of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic flavoring agents and natural flavoring agents, coloring agents and neutralizing agents (cheese, chocolate, etc.), pectic acid and salts thereof, Alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonic acid used in carbonated beverages, and the like. These ingredients may be used independently or in combination, and the proportion of these additives may also be appropriately selected by those skilled in the art.

The cosmetic composition of the present invention may be prepared in any formulation conventionally prepared in the art, for example, solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, surfactant-containing cleaning , May be formulated as an oil, powder foundation, emulsion foundation, wax foundation and spray, but is not limited thereto. More specifically, it can be prepared in the form of flexible lotion, nutrition lotion, nutrition cream, massage cream, essence, eye cream, cleansing cream, cleansing foam, cleansing water, pack, spray or powder.

As an effective carrier contained in the cosmetic composition of the present invention, depending on the formulation, a carrier commonly used in the art may be used. When the formulation of the present invention is a paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, trakant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide, etc. may be used as a carrier component. Can be.

When the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component, and in the case of a spray, additionally chlorofluorohydrocarbon, propane / Propellant such as butane or dimethyl ether.

When the formulation of the present invention is a solution or emulsion, a solvent, solubilizer or emulsifier is used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 , 3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan fatty acid ester.

When the formulation of the present invention is a suspension, liquid diluents such as water, ethanol or propylene glycol as carrier components, ethoxylated isostearyl alcohol, suspensions such as polyoxyethylene sorbitol esters and polyoxyethylene sorbitan esters, microcrystals Sex cellulose, aluminum metahydroxide, bentonite, agar or trakant, etc. can be used.

When the formulation of the present invention is a surfactant-containing cleansing, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivatives, methyltaurate, sarcosinate, fatty acid amide as a carrier component Ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives or ethoxylated glycerol fatty acid esters and the like can be used.

The ingredients included in the cosmetic composition of the present invention include ingredients commonly used in cosmetic compositions in addition to the active ingredients and carrier ingredients, such as antioxidants, stabilizers, solubilizers, vitamins, pigments and fragrances. It can contain.

[Example]

Hereinafter, the present invention will be described in more detail through examples. These examples are only for illustrating the present invention, it will be apparent to those skilled in the art that the scope of the present invention is not to be construed as limited by these examples. Therefore, the substantial scope of the present invention will be defined by the appended claims and their equivalents.

Peptide AES11 -1 Preparation

First, a peptide AES11-1 consisting of the amino acid sequence represented by SEQ ID NO: 1 was prepared. Subsequently, the synthesized peptide was purified using high performance liquid chromatography (SHIMADZU Prominence HPLC), and the column was a Shiseido capcell pak C18 Column (4.6 x 50 mm). In addition, the mass of the synthesized peptide was confirmed using a mass spectrometer (HP 1100 series LC / MSD).

Acne  Preparations

As an acne fungus, P. acnes was purchased from the Korea Research Institute of Bioscience and Biotechnology (BRC) at the Korea Research Institute of Bioscience and Biotechnology (KCTC). Bacteria were collected at a number of 5 X 10 ⁹ colony forming units (CFU) / mL, and 100 μl, 5 X 10 ⁸ CFU, was injected into the dorsal central endothelium of the mouse, and treated with human fibroblast at 95 ° C. for 5 minutes. It was used after heat treatment.

Acne animal model establishment and skin regeneration, collagen Synthetic sheep  Measure

To establish an animal model of acne disease, 6-week-old Hairless-1 mice were used. The 6 week old Hairless-1 rat had a stabilization period of about a week before the experiment. For the generation of acne, P. acnes was injected into the endothelium of the rat's central back.

From the next day after the fungus injection, the peptide AES11-1 synthesized according to the present invention was injected subcutaneously for 1 week every 2 days at a concentration of 10 μg / kg, and the necrotic wound site caused by acne was photographed daily and observed. Along with this, Hyaluronic acid (HA, 24 mg / kg) was injected as a positive experimental group for collagen synthesis (Quan T .; Wang F .; Shao Y .; Rittie L .; Xia W .; Orringer JS; Voorhees JJ; Fisher GJ Enhancing structural support of the dermal microenvironment activates fibroblasts, endothelial cells, and keratinocytes in aged human skin in vivo.J. Invest.Dermatol. 2013, 133 , 658.), injected with phospho-buffered saline (PBS) as a negative control Did.

Histological examination

To observe the area of the wound size histologically, 7 days after the injection of the peptide, the acne-necrotic wound was cut and fixed, and then the skin tissue observation data was made and stained and observed. Specifically, after fixing the skin tissue to 4% paraformaldehyde, and then thinly incised, the histological pattern was tested through hematoxyne & eosin staining, and the amount of collagen was stained and confirmed using Picro-Sirius Red solution, fibronectin Was confirmed by performing immunostaining.

Cell culture

Primary human dermal fibroblast cells were purchased from the International Center for Biologics (ATCC) and cultured in fibroblast basal medium (FBM). Cells were cultured in 6-well plates at 1 × 10 ⁵ / ml. TGF-β was treated with 10 ng / ml as a positive control (Das F .; Bera A .; Ghosh-Choudhury N .; Abboud HE; Kasinath BS; Choudhury GG TGFb-induced deptor suppression recruits mTORC1 and not mTORC2 to enhance collagen I (a2) gene expression. PLoS One . 2014, 9, e109608.). β-actin protein was used for quantitative comparison.

Western Blot

After culture, the treated cells broke the cell wall and extracted only proteins. 20 μg of the extracted protein was denatured with a sodium dodecyl sulfate (SDS) sample buffer, electrophoresis separated on 10% SDS-polyacrylamide gel electrophoresis (PAGE) gels, and then attached to a polyvinylidene fluoride (PVDF) membrane. The membrane was placed in 5% skim milk for 1 hour to prevent non-specific binding. The amount of collagen protein was immunostained using anti-goat collagen type I antibody. β-actin protein was used for quantitative comparison.

Statistical analysis

The difference between the control group and the experimental group was evaluated by paired Student's t- test, and was considered as a significant difference when P -values <0.05.

Example  1. Synthesis Peptide AES11 Acne damage skin regeneration effect caused by -1

Figure 1 shows the results of histological comparison of the recovery rate of necrotic skin damage in the acne animal model according to the peptide AES11-1 treatment of the present invention. As shown in Figure 1, the synthetic peptide AES11-1 according to the present invention can be confirmed that the acne skin injected at a concentration of 10 μg / kg has a faster rate of closing necrotic skin damage than the negative control group, and the initial stage of skin regeneration. It can be seen that the rate of cell migration in the recovery site, which is a step, is also active. In addition, it can be seen that the size of the necrotic skin damage site is significantly reduced, and the size between the wounds is also reduced in histological analysis through hematoxylin & eosin staining. In addition, the cell migration site, which is the initial stage of cell regeneration, was observed with a dotted line at the enlarged area of the box indicated in FIG. 1, thereby confirming that the pattern of cell migration in the recovery site, which is the initial stage of skin regeneration, increases. It was confirmed that the synthetic peptide AES11-1 according to the present invention has the ability to effectively regenerate skin damaged by acne.

Example  2. Evaluation of collagen synthesis of damaged skin regeneration sites

The synthetic amount of collagen in the acne skin tissue according to the peptide AES11-1 treatment of the present invention was confirmed, and the results are shown in FIG. 2 below. At this time, the amount of dyed collagen was quantified and verified with an image J program (error bar, mean ± SD. *** P -values <0.005, performed for a negative control).

Through this, it was confirmed that collagen synthesis was significantly increased at the skin wound site compared to the control group when the peptide AES11-1 of the present invention was treated.

Example  3. Evaluation of fibroblast activation at damaged skin regeneration sites

The degree of activation of fibroblasts according to the peptide AES11-1 treatment of the present invention was confirmed, and the results are shown in FIG. 3 below. Specifically, in order to confirm the activation of the fibroblasts leading to collagen synthesis near the regeneration site of acne skin in which the synthetic peptide AES11-1 of the present invention was injected at a concentration of 10 μg / kg, immunostained fibronectin The number of was verified by digitizing with the image J program (error bar, mean ± SD., ** P -values <0.05, performed for the negative comparison group).

Through this, it was confirmed that when the peptide AES11-1 of the present invention is treated, the amount of fibronectin, a cognitive protein of fibroblasts, increases, and thus, the activity of fibroblasts for collagen synthesis is significantly improved.

Example  4. Evaluation of collagen synthesis amount produced by human fibroblasts

The synthetic peptide AES11-1 of the present invention was treated with human fibroblasts for 10 ng / ml and cultured for 24 hours, and then the cells were collected and the collagen synthesis ability was evaluated by confirming the expression level of collagen by western blotting assay. It is shown in 4. At this time, TGF-β was treated as 10ng / ml as a positive control, and β-actin protein was used for comparison of quantitative.

Through this, it was confirmed that when the synthetic peptide AES11-1 of the present invention is treated on human fibroblasts infected with acne bacteria, the synthesis ability of collagen is significantly improved.

Since the specific parts of the present invention have been described in detail above, it is obvious that for those skilled in the art, this specific technique is only a preferred embodiment, and the scope of the present invention is not limited thereby. something to do. Accordingly, the substantial scope of the present invention will be defined by the appended claims and their equivalents.

<110> Korea University Research and Business Foundation <120> Peptide AES11-1 for skin regenerating or wound healing and use          thereof <130> JKP-1161R1 <150> KR 10-2018-0141722 <151> 2018-11-16 <160> 1 <170> KoPatentIn 3.0 <210> 1 <211> 3 <212> PRT <213> Artificial Sequence <220> <223> Peptide sequence for AES11-1 <400> 1 Ser Asp Gly   One

Claims (7)

A peptide consisting of the amino acid represented by SEQ ID NO: 1. A pharmaceutical composition for skin rejuvenation or wound treatment, comprising a peptide or a polynucleotide encoding the amino acid represented by SEQ ID NO: 1 as an active ingredient. According to claim 2,
The wound is characterized by the wounded acne (acne) or wound, pharmaceutical composition. According to claim 3,
The wounds are non-healing traumatic wounds, tissue destruction by irradiation, abrasions, lacerations, appendages, through wounds, cuts, burns, burns, frostbite, dry skin, keratosis, cracks, bursts, surgical or vascular disease wounds , Bruises, corneal wounds, bedsores, lancets, postoperative sutures, spinal injury wounds, gynecological wounds, and chemical wounds. According to claim 2,
The skin regeneration is characterized in that for the treatment of skin ulcers, dermatitis and acne, pharmaceutical composition. Cosmetic composition for skin regeneration or wound improvement, comprising a peptide consisting of the amino acid represented by SEQ ID NO: 1 as an active ingredient. The method of claim 6,
The composition is characterized in that the suspension, emulsion, paste, gel, cream, lotion, powder, wax or spray form, cosmetic composition.

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