WO2017164609A2 - 피부 재생 또는 상처 치료용 펩타이드 및 이의 용도 - Google Patents

피부 재생 또는 상처 치료용 펩타이드 및 이의 용도 Download PDF

Info

Publication number
WO2017164609A2
WO2017164609A2 PCT/KR2017/002998 KR2017002998W WO2017164609A2 WO 2017164609 A2 WO2017164609 A2 WO 2017164609A2 KR 2017002998 W KR2017002998 W KR 2017002998W WO 2017164609 A2 WO2017164609 A2 WO 2017164609A2
Authority
WO
WIPO (PCT)
Prior art keywords
peptide
group
wound
present
skin
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/KR2017/002998
Other languages
English (en)
French (fr)
Korean (ko)
Other versions
WO2017164609A3 (ko
Inventor
조대호
길민찬
이소미
김면수
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Kine Sciences Co Ltd
Original Assignee
Bio Pep Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Bio Pep Co Ltd filed Critical Bio Pep Co Ltd
Priority to JP2018517117A priority Critical patent/JP6573295B2/ja
Priority to US15/739,894 priority patent/US10188694B2/en
Priority to EP17770579.5A priority patent/EP3444265B1/en
Priority to ES17770579T priority patent/ES2835124T3/es
Priority to CN201780002140.4A priority patent/CN109563132B/zh
Publication of WO2017164609A2 publication Critical patent/WO2017164609A2/ko
Publication of WO2017164609A3 publication Critical patent/WO2017164609A3/ko
Anticipated expiration legal-status Critical
Priority to US16/222,808 priority patent/US10995117B2/en
Ceased legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/08—Peptides having 5 to 11 amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/10—Peptides having 12 to 20 amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/08—Anti-ageing preparations
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Definitions

  • the present invention relates to peptides and their use for skin regeneration or wound treatment.
  • the present invention was made by the task number 1711030975 under the support of the Ministry of Republic of Korea, the research management specialized agency of the project is the Korea Research Foundation, the research project name is the creative material discovery project, the research title is the development of biodegradable skin regeneration material based on functional immune body technology, The period of research is from 2015.12.04 to 2016.04.30.
  • Skin is the body's primary protective film that protects organs in the body from stimuli caused by temperature, humidity changes, ultraviolet rays, pollutants, and other environmental conditions, and plays an important role in maintaining homeostasis.
  • the outermost keratin that exists on the outside of the skin is a tissue formed by changes in skin cells, and is composed of completely dead cells.
  • the cell layer formed coarse in the dermal connective tissue of the dermis becomes the epidermal layer and loses the vitality of the cell and becomes a firm and regular cell layer.
  • This kind of skin acts as a defensive line to protect the body's moisture from the outside and to defend various substances coming in from the outside. That is, when a wound occurs on the surface of the skin, the rapid regeneration of the epidermis may promote recovery of the wound, thereby preventing further infection through the wound, and may serve to reduce scarring on the surface of the skin.
  • the wound healing process is a very complex reaction involving various cells and factors.
  • platelet aggregates in the wound area and various cell proliferation factors such as transforming growth factor, platelet-derived growth factor, and epithelial cell growth factor are released. It stimulates vascular endothelial cells, phagocytic cells, fibroblasts and epithelial cells to promote cell proliferation. At the same time, these cells themselves produce and release fibroblast proliferation, transforming proliferation factor, and interleukin. Wound healing mechanism is in progress.
  • EGF Extracellular growth factor
  • the present invention has been made to solve the above problems, the present inventors made a thorough study on the preparation for skin regeneration or wound treatment, and produced a peptide consisting of up to 15 amino acids, when the peptide is treated Increasing the amount of collagen production of fibroblasts, the amount of melanin production of melanoma cells, and the inhibitory effect of tyrosinase activity were confirmed.
  • an object of the present invention to provide a peptide for skin regeneration or wound treatment, consisting of amino acids represented by SEQ ID NO: 1 or 2.
  • Another object of the present invention is to provide a pharmaceutical composition for treating skin regeneration or wound, comprising the peptide or polynucleotide encoding the same as an active ingredient.
  • Another object of the present invention to provide a health functional food / cosmetic composition for skin aging or wound improvement, comprising the peptide as an active ingredient.
  • the present invention provides a peptide consisting of the amino acid represented by SEQ ID NO: 1 or 2.
  • the N- or C- terminal of the peptide is an acetyl group, fluorenyl methoxy carbonyl group, formyl group, palmitoyl group, myristyl group, stearyl group, and polyethylene glycol (PEG) It may be combined with a protecting group selected from the group consisting of.
  • the present invention also provides a pharmaceutical composition for skin regeneration or wound treatment comprising the peptide or polynucleotide encoding the same as an active ingredient.
  • the peptide may be contained in a concentration of 1 to 500ng / ml.
  • the wound may be due to a wound.
  • the composition may further comprise a pharmaceutically acceptable carrier.
  • the present invention provides a cosmetic composition for skin aging or wound improvement comprising the peptide as an active ingredient.
  • the composition may be in the form of a suspension, emulsion, paste, gel, cream, lotion, powder, wax or spray.
  • it may have a skin lightening activity.
  • the present invention provides a method for treating skin regeneration or wound, comprising administering the peptide to a subject.
  • the present invention provides a skin regeneration or wound treatment of the peptide.
  • novel peptide according to the present invention enhances collagen production of fibroblasts, promotes wound healing, inhibits melanin production and tyrosinase activity of melanoma cells, and shows excellent whitening effect. Since the side effects of the administration of the substance can be minimized, it is expected that it can be used as an effective substance that can replace the existing preparations for skin regeneration or wound treatment.
  • Figure 6 shows the results of confirming the effect of wound healing in vitro wound model according to the peptide 2 treatment of the present invention.
  • 11 is a result of confirming the change of the skin tissue in the acute wound animal model according to the peptide 1 or 2 treatment of the present invention through H & E staining.
  • the present invention provides a peptide consisting of the amino acid represented by SEQ ID NO: 1 or 2.
  • peptide refers to a polymer consisting of two or more amino acids linked by an amide bond (or peptide bond), and for the purposes of the present invention, means a peptide having skin regeneration or wound healing activity.
  • amide bond or peptide bond
  • the peptide of the present invention may be composed of amino acids represented by SEQ ID NO: 1 or 2, and at least 75%, preferably 80% or more, and more preferably 90% or more of the amino acid sequence represented by SEQ ID NO: 1 or 2, respectively. And, most preferably, amino acid sequences having at least 95% sequence homology, and additionally amino acid sequences prepared for specific purposes to increase targeting stability, tags, labeled residues, half-life or peptide stability. It may include.
  • Such functional variants include biological equivalents of the peptide sequences (SEQ ID NO: 1 or 2) described herein.
  • further changes can be made to the amino acid or polynucleotide sequence of the peptide to further improve the binding affinity and / or other biological properties of the peptide.
  • Such modifications result in deletion of amino acid sequence residues of the peptide. Insertions, and / or substitutions, and are made based on the relative similarity of amino acid side chain substituents such as hydrophobicity, hydrophilicity, charge size, and the like.
  • arginine, lysine and histidine are all positively charged residues; Alanine, glycine and serine have similar sizes; It can be seen that phenylalanine, tryptophan and tyrosine have a similar shape.
  • arginine, lysine and histidine; Alanine, glycine and serine; Phenylalanine, tryptophan, tyrosine, and the like are biologically equivalent functionalities.
  • the peptides 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 protein expression systems or by in vitro synthesis through chemical synthesis such as peptide synthesis, cell-free protein synthesis, and the like.
  • the protector may be connected at the end.
  • the protecting group may be an acetyl group, fluorenyl methoxy carbonyl group, formyl group, palmitoyl group, myristyl group, stearyl group or polyethylene glycol (PEG), but the modification of the peptide, in particular to enhance the stability of the peptide If it can be contained, it can include without limitation.
  • the term "stability" refers to in vivo stability, as well as storage stability (eg, room temperature storage stability), which protects the peptides of the invention from the attack of protein cleavage enzymes in vivo.
  • a "polynucleotide” is a polymer in which nucleotides are bound, and serves to transmit genetic information.
  • at least 75%, preferably at least 85%, more preferably at least 90%, most preferably at least 75% of the polynucleotide sequence encoding the peptide of SEQ ID NO: 1 or 2, respectively; May comprise a sequence having at least 95% sequence homology.
  • the "homology” is intended to indicate a similar degree to the wild-type amino acid sequence or polynucleotide sequence, the comparison of the homology can be carried out using a comparison program well known in the art, homology between two or more sequences Can be calculated as a percentage (%).
  • the present invention comprises the peptide or a polynucleotide encoding the same as an active ingredient, comprising as an active ingredient, therapeutic pharmaceutical composition for skin regeneration or wound treatment; The use of said peptides for skin regeneration or wound healing; And administering a therapeutically effective amount of the peptide to the subject.
  • treatment means any action that improves or advantageously alters the symptoms of a wound by administration of a pharmaceutical composition according to the present invention.
  • “individual” means a subject in need of treatment of a wound, and more specifically, a mammal, such as a primate, mouse, dog, cat, horse, and cow, which is human or non-human.
  • skin regeneration refers to a series of reactions in which skin tissue is reconstituted in response to overall skin aging and external stimuli induced by the skin, and in one embodiment, skin whitening, skin elasticity enhancement, wrinkle improvement Effect.
  • skin whitening refers to improving skin hyperpigmentation such as blemishes and freckles due to ultraviolet rays, hormones or heredity, as well as brightening skin tone by inhibiting the synthesis of melanin pigment.
  • wound refers to a phenomenon in which tissue is damaged by an external stimulus.
  • wound healing is usually performed by degeneration and death of cells, flow of tissue cells, tissue fluid from surrounding tissues, and It will go through the process of precipitation of fiber and formation of granulation tissue.
  • the wound treatment refers to promoting the process as described above to assist in reconstitution into normal skin tissue, while the wound may be preferably wound, but is not limited thereto.
  • two kinds of peptides (peptide 1 and peptide 2) were prepared (see Example 1), and by treating the peptides, it was possible to promote wound healing by promoting collagen production and B16F10. By inhibiting melanin production and tyrosinase activity of melanoma cell line was confirmed excellent whitening effect (see Examples 2 to 4).
  • a scratch assay to evaluate the mobility of HaCaT cells, and an acute wound animal model, it was possible to confirm the excellent wound healing effect (wound reduction) of the peptide (see Examples 5 and 6). It may be widely used as an active substance and a skin whitening agent that can replace a preparation for skin regeneration or wound treatment.
  • the peptide of the present invention or a polynucleotide encoding the same may be carried in a pharmaceutically acceptable carrier such as colloidal suspensions, powders, saline, lipids, liposomes, microspheres), or nano spherical particles. They may be complexed with or related to the vehicle and are known 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 delivered in vivo using known delivery systems.
  • a pharmaceutically acceptable carrier such as colloidal suspensions, powders, saline, lipids, liposomes, microspheres), or nano spherical particles. They may be complexed with or related to the vehicle and are known in the art such as lipids, liposomes, microparticles, gold, nanoparticles, polymers
  • pharmaceutically acceptable carriers include lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia, rubber, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, Polyvinyl pyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate and mineral oil, and the like, but are not limited thereto.
  • it may further include a lubricant, a humectant, a sweetener, a flavoring agent, an emulsifier, a suspending agent, a preservative, and the like.
  • the pharmaceutical composition of the present invention may preferably contain a peptide of the present invention in a concentration of 1 to 500ng / ml for the skin regeneration effect, can be expected effective therapeutic effect without cytotoxicity If it is a concentration, it is not limited to this.
  • compositions of the present invention can be administered orally or parenterally (eg, applied intramuscularly, intravenously, intraperitoneally, subcutaneously, intradermal, or topically) according to the desired method, and the dosage is determined by the patient.
  • parenterally eg, applied intramuscularly, intravenously, intraperitoneally, subcutaneously, intradermal, or topically
  • the dosage is determined by the patient.
  • it may be appropriately selected by those skilled in the art.
  • the pharmaceutical composition of the present invention when used as an external preparation for skin, it may further contain fatty substances, organic solvents, solubilizers, thickening and gelling agents, emollients, antioxidants, suspending agents, stabilizers, foaming agents, fragrances.
  • the pharmaceutical composition when provided as an external preparation for skin, it may be a formulation such as, but not limited to, ointment, patch, gel, cream or spray.
  • the pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount.
  • 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 disease, severity, activity of the drug, The sensitivity to the drug, time of administration, route of administration and rate of release, duration of treatment, factors including concurrent use of the drug, and other factors well known in the medical art can be determined.
  • the pharmaceutical compositions according to the present invention may be administered as individual therapeutic agents or in combination with other therapeutic agents, and may be administered simultaneously, separately, or sequentially with conventional therapeutic agents, and may be single or multiple administrations. Taking all of the above factors into consideration, it is important to administer an amount that can achieve the maximum effect with a minimum amount without side effects, which can be readily determined by one skilled in the art.
  • the effective amount of the pharmaceutical composition of the present invention may vary depending on the age, sex, condition, weight of the patient, the absorbency of the active ingredient in the body, the inactivation rate, the rate of excretion, the type of disease, the drug used in combination, the route of administration, It may increase or decrease depending on the severity of obesity, sex, weight, age, and the like.
  • the present invention provides a health functional food / cosmetic composition for skin aging or wound improvement comprising the peptide or a polynucleotide encoding the same as an active ingredient.
  • the term " improvement" means any action that at least reduces the parameters associated with the condition being treated, eg, the degree of symptoms.
  • the nutraceutical / cosmetic composition may be used simultaneously or separately with a medicament for treatment before or after the onset of related diseases, for the prevention or improvement of skin aging or wound.
  • the active ingredient may be added to the food as it is or used with other foods or food ingredients, and may be appropriately used according to a conventional method.
  • the mixing amount of the active ingredient can be suitably determined according to the purpose of use (prevention or improvement).
  • the compositions of the invention may be added in an amount of preferably up to 15% by weight, preferably up to 10% by weight relative to the raw materials.
  • the amount may be below the above range.
  • the health functional food composition of the present invention may contain other ingredients as essential ingredients in addition to the above-mentioned active ingredient without particular limitation.
  • various flavors, natural carbohydrates, and the like may be contained as additional ingredients, as in normal beverages.
  • natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And conventional sugars such as polysaccharides such as dextrin, cyclodextrin, and sugar alcohols such as xylitol, sorbitol, erythritol.
  • natural flavoring agents such as tauumatin, stevia extract (e.g., rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used.
  • the proportion of the natural carbohydrate can be appropriately determined by the choice of those skilled in the art.
  • the nutraceutical composition of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic and natural flavors, coloring and neutralizing agents (such as cheese, chocolate), pectic acid and salts thereof, Alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated drinks and the like.
  • these components may be used independently or in combination, and the ratio of these additives may also be appropriately selected by those skilled in the art.
  • Cosmetic compositions of the present invention may be prepared in any formulation conventionally prepared in the art, for example, solutions, suspensions, emulsions, pastes, gels, creams, lotions, powders, soaps, surfactant-containing cleansing , Oils, powder foundations, emulsion foundations, wax foundations and sprays, and the like, but are not limited thereto. More specifically, it may be prepared in the form of a flexible lotion, nutrition lotion, nutrition cream, massage cream, essence, eye cream, cleansing cream, cleansing foam, cleansing water, pack, spray or powder.
  • a carrier commonly used in the art may be used, depending on the dosage form.
  • the formulation of the present invention is a paste, cream or gel, animal oils, vegetable oils, waxes, paraffins, starches, trachants, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicas, talc or zinc oxide may be used as carrier components.
  • lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used, in particular, in the case of spray, additionally chloro fluorohydrocarbon, propane Propellant such as butane or dimethyl ether.
  • a solvent, solubilizer or emulsifier is used as the carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 Fatty acid esters of, 3-butylglycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan.
  • liquid carrier diluents such as water, ethanol or propylene glycol
  • suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, microcrystals Soluble cellulose, aluminum metahydroxy, bentonite, agar or tracant and the like can be used.
  • the carrier component is an aliphatic alcohol sulfate, an aliphatic alcohol ether sulfate, a sulfosuccinic acid monoester, an isethionate, an imidazolinium derivative, a methyltaurate, a sarcosinate, a fatty acid amide.
  • 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 conventionally used in cosmetic compositions, and include, for example, conventional auxiliaries such as antioxidants, stabilizers, solubilizers, vitamins, pigments and flavorings. It may include.
  • the peptides of Table 1 were prepared. Subsequently, the synthesized peptide was purified purely using high performance liquid chromatography (SHIMADZU Prominence HPLC), and the column was prepared using Shiseido capcell pak C18 Column (4.6 x 50 mm). In addition, the mass of the synthesized peptide was confirmed by using a mass spectrometer (HP 1100 series LC / MSD).
  • Collagen is a main component of skin connective tissue, and it is essential to increase the expression of collagen in the treatment of wounds such as wounds or skin regeneration.
  • human fibroblasts Human dermal fibroblast, HDF
  • FBS Fetal Bovine Albumin
  • the peptide (100, 10, 1 ng / ml) of the present invention was treated and cultured again for 24 hours, and then secreted into culture medium using Procollagen Type I C-peptide (PIP) EIA Kit.
  • PIP Procollagen Type I C-peptide
  • the amount of procollagen was measured, RNA was extracted with Trizol reagent, and the expression of Col1A1 (collagen type I, alpha 1) mRNA of human fibroblasts was confirmed by real-time PCR.
  • the control group was not added to the treatment (Control), the positive control group was used TGF- treated group (TGF-).
  • the group treated with the peptide of the present invention increased the secretion amount of procollagen compared to the control and TGF- ⁇ treated group, the expression level of Col1A1 at a concentration of 10ng / ml or more Significantly increased. From the above results, it can be seen that the peptide of the present invention induces collagen production and contributes to the promotion of skin regeneration or wound healing.
  • the color of the skin is determined by the amount of melanin pigment produced by the macranine cells, and much research has been conducted to improve pigmentation of abnormal skin. In particular, excessive pigmentation that occurs in chronic wounds has been treated as an important medical problem, but there is no reliable treatment method yet.
  • the melanin production capacity of melanoma cell line according to the treatment of the peptide (peptide 1) prepared in Example 1 is known (Life Sci. 2013 Aug 14; 93 (5-6): 226-32 Evaluation was carried out through the experimental method disclosed in).
  • Melanoma cell line B16F10 cells were cultured in DMEM medium with 10% Fetal Bovine Albumin, and the cultured cells were divided into 12 well-plates at 1 ⁇ 10 5 cell / well concentrations.
  • the cells were treated with ⁇ -MSH (10 uM) that promotes melanin synthesis and the peptide of the present invention (1, 10, 100 ng / ml) and incubated for 24 hours again. 200 ⁇ l of 1N NaOH solution was added and dissolved at 100 ° C. for 30 minutes. Then, by measuring the absorbance at 405nm with an ELISA reader to determine the amount of melanin generated from the melanoma cell line. On the other hand, the group that was not added to the treatment as a control, the group treated with ⁇ -MSH only as a positive control was used.
  • Tyrosinase is a rate-regulating enzyme that catalyzes the reaction in melanin biosynthesis and is known to play a critical role in regulating the amount of melanin in cells.
  • tyrosinase activity of melanoma cell line according to the treatment of the peptide (peptide 1) prepared in Example 1 is described in J. Dermatol. Sci. Vol. 57 (2010) 170-177. Evaluation was made through the disclosed test method.
  • melanoma cell line B16F10 cells After dispensing melanoma cell line B16F10 cells in 12 well-plate at a concentration of 1 ⁇ 10 5 cell / well and incubating for 24 hours, ⁇ -MSH (1M) and the peptide of the present invention (1, 10, 100ng / ml) The cells were incubated for 24 hours, and each well was washed with PBS and suspended in 50 mM Phosphate buffer (pH 6.8) containing 1% Triton X-100. After Vortexing, the mixture was frozen at ⁇ 80 ° C. for 30 minutes, and then melted at room temperature.
  • the wound treatment effect of the treatment of the peptides (peptides 1 and 2) prepared in Example 1 was confirmed through a scratch assay.
  • Mitomycin C (10 ug / ml) was added to serum free medium to incubate HaCaT cells, a human epithelial cell line for 2 hours, to induce scratches.
  • Example 1 the wound healing effect of the peptides (peptides 1 and 2) prepared in Example 1 was confirmed in vivo using an acute wound animal model.
  • mice After 8-week-old Balb / c nude mice were anesthetized with Avertin (2.5%), a 10 mm diameter round punch was used to incise the skin at the back of the animal to induce acute wounds. A total of 5 peptides were treated at the extraction site at 24 hour intervals (500 ng / 1 time), and the decrease in wound area over time was measured for 14 days, and EGF was used as a positive control (10 ug / 1 time). . At this time, the peptide was treated with a mixture of 20% pluronic F-127 (PBS), and the wound size was measured and quantified over time using a digital camera and an ImageJ program.
  • PBS pluronic F-127
  • Acute wounds were induced in the same manner as in Example 6-1, and the tissue sections were prepared by dissecting the skin tissue on the 5th day of causing the acute wounds. Then, by performing the H & E staining and observing the microscope, the histological change according to the peptite treatment was observed. On the other hand, EGF was used as a positive control.
  • the tissue treated with peptide 1 and peptide 2 the thickness of the epidermis (derider) layer, dermis (dermis) layer was thicker than the PBS negative control group, as in the positive control group, epithelialization (epithelialization) ) was also actively progressing, confirming histological findings related to the healing or repair of the wound.
  • the peptides of the present invention were able to significantly accelerate the wound healing rate, it can be seen that it can be used as an effective material for the treatment of wounds.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Organic Chemistry (AREA)
  • Dermatology (AREA)
  • Engineering & Computer Science (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Immunology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Birds (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Gerontology & Geriatric Medicine (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Cosmetics (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Peptides Or Proteins (AREA)
PCT/KR2017/002998 2016-03-23 2017-03-21 피부 재생 또는 상처 치료용 펩타이드 및 이의 용도 Ceased WO2017164609A2 (ko)

Priority Applications (6)

Application Number Priority Date Filing Date Title
JP2018517117A JP6573295B2 (ja) 2016-03-23 2017-03-21 肌再生または傷治療用ペプチド及びこの用途
US15/739,894 US10188694B2 (en) 2016-03-23 2017-03-21 Peptide for skin regeneration or wound treatment and use thereof
EP17770579.5A EP3444265B1 (en) 2016-03-23 2017-03-21 Peptide for skin regeneration or wound treatment and use thereof
ES17770579T ES2835124T3 (es) 2016-03-23 2017-03-21 Péptido para la regeneración de la piel o el tratamiento de heridas y utilización del mismo
CN201780002140.4A CN109563132B (zh) 2016-03-23 2017-03-21 皮肤再生或伤口治疗用的肽及其用途
US16/222,808 US10995117B2 (en) 2016-03-23 2018-12-17 Peptide for skin regeneration or wound treatment and use thereof

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR10-2016-0034327 2016-03-23
KR20160034327 2016-03-23

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US15/739,894 A-371-Of-International US10188694B2 (en) 2016-03-23 2017-03-21 Peptide for skin regeneration or wound treatment and use thereof
US16/222,808 Continuation-In-Part US10995117B2 (en) 2016-03-23 2018-12-17 Peptide for skin regeneration or wound treatment and use thereof

Publications (2)

Publication Number Publication Date
WO2017164609A2 true WO2017164609A2 (ko) 2017-09-28
WO2017164609A3 WO2017164609A3 (ko) 2018-07-12

Family

ID=59899599

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2017/002998 Ceased WO2017164609A2 (ko) 2016-03-23 2017-03-21 피부 재생 또는 상처 치료용 펩타이드 및 이의 용도

Country Status (7)

Country Link
US (1) US10188694B2 (enExample)
EP (1) EP3444265B1 (enExample)
JP (1) JP6573295B2 (enExample)
KR (1) KR101969904B1 (enExample)
CN (1) CN109563132B (enExample)
ES (1) ES2835124T3 (enExample)
WO (1) WO2017164609A2 (enExample)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN117304263A (zh) * 2019-08-20 2023-12-29 凯尔格恩有限公司 具有皮肤美白活性的肽以及其用途

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10995117B2 (en) * 2016-03-23 2021-05-04 Kine Sciences Co., Ltd. Peptide for skin regeneration or wound treatment and use thereof
KR102233646B1 (ko) * 2018-11-16 2021-03-30 고려대학교 산학협력단 피부 재생 또는 상처 치료용 펩타이드 aes11-1 및 이의 용도
KR102261105B1 (ko) * 2018-11-16 2021-06-04 고려대학교 산학협력단 피부 재생 또는 상처 치료용 펩타이드 aesis-1p3 및 이의 용도
KR102233647B1 (ko) * 2018-11-16 2021-03-30 고려대학교 산학협력단 피부 재생 또는 상처 치료용 펩타이드 aec1d 및 이의 용도
KR102265435B1 (ko) * 2019-08-20 2021-06-15 주식회사 케어젠 피부 미백 활성을 갖는 펩타이드 및 이의 용도
KR102506020B1 (ko) * 2020-11-27 2023-03-06 웰펩 주식회사 항산화 활성 및 티로시나제 저해활성을 갖는 펩타이드 및 이를 포함하는 조성물
KR20240086794A (ko) * 2022-12-07 2024-06-19 (주)케어젠 피부 상태 개선 활성을 갖는 펩타이드 및 이의 용도

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20150135743A (ko) 2014-05-22 2015-12-03 제주대학교 산학협력단 해조류 추출물을 포함하는 상처 치료 및 피부 재생용 조성물
KR20160034327A (ko) 2013-07-18 2016-03-29 캐터필러 에스에이알엘 건설 기계용 캣워크

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2002344519A1 (en) * 2002-10-21 2004-05-04 Shanghai Yizhong Biotechnology Co., Ltd Activity of osteogenic growth peptide (ogp) for promoting proliferation of hemopoietic progenitor cell in erythron and its use
US20060234210A1 (en) * 2004-04-14 2006-10-19 Affinergy, Inc. Filtration device and method for removing selected materials from biological fluids
KR101020658B1 (ko) * 2006-01-23 2011-03-09 주식회사 이매진 신규한 펩타이드 및 이의 용도
KR101092915B1 (ko) * 2009-07-10 2011-12-12 (주)케어젠 성장인자―유래 펩타이드 및 이의 용도
EP4012714A1 (en) * 2010-03-23 2022-06-15 Iogenetics, LLC. Bioinformatic processes for determination of peptide binding
WO2013040142A2 (en) * 2011-09-16 2013-03-21 Iogenetics, Llc Bioinformatic processes for determination of peptide binding
EP2944305B1 (en) * 2013-01-08 2018-04-11 Novacell Technology Inc. Novel peptide having collagen synthesizing abiliity and use thereof
KR101355385B1 (ko) * 2013-09-10 2014-02-06 주식회사 위노바 피부재생용 펩타이드, 이를 포함하는 화장품 조성물 및 이를 이용한 피부재생 방법
KR20150029498A (ko) * 2013-11-14 2015-03-18 우리들휴브레인 주식회사 피부재생용 펩타이드, 이를 포함하는 화장품 조성물 및 이를 이용한 피부재생 방법
KR20150130614A (ko) * 2014-05-13 2015-11-24 (주)케어젠 성장인자 활성을 나타내는 펩타이드 및 그의 용도
KR101772045B1 (ko) * 2014-07-10 2017-08-28 강원대학교산학협력단 표피성장인자 유래의 펩타이드 단편을 포함하는 상처 치료 또는 피부 주름형성 억제용 조성물

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20160034327A (ko) 2013-07-18 2016-03-29 캐터필러 에스에이알엘 건설 기계용 캣워크
KR20150135743A (ko) 2014-05-22 2015-12-03 제주대학교 산학협력단 해조류 추출물을 포함하는 상처 치료 및 피부 재생용 조성물

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
J. BIOL.CHEM., vol. 268, no. 14, 1993, pages 9941 - 9944
J. DERMATOL. SCI., vol. 57, 2010, pages 170 - 177
LIFE SCI., vol. 93, no. 5-6, 14 August 2013 (2013-08-14), pages 226 - 32
See also references of EP3444265A4

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN117304263A (zh) * 2019-08-20 2023-12-29 凯尔格恩有限公司 具有皮肤美白活性的肽以及其用途

Also Published As

Publication number Publication date
EP3444265B1 (en) 2020-09-02
WO2017164609A3 (ko) 2018-07-12
JP2018528978A (ja) 2018-10-04
KR20170113156A (ko) 2017-10-12
CN109563132B (zh) 2022-03-29
EP3444265A2 (en) 2019-02-20
CN109563132A (zh) 2019-04-02
ES2835124T3 (es) 2021-06-21
KR101969904B1 (ko) 2019-04-18
EP3444265A4 (en) 2019-08-21
JP6573295B2 (ja) 2019-09-11
US10188694B2 (en) 2019-01-29
US20180193406A1 (en) 2018-07-12

Similar Documents

Publication Publication Date Title
WO2017164609A2 (ko) 피부 재생 또는 상처 치료용 펩타이드 및 이의 용도
KR101988675B1 (ko) 피부 및/또는 점막의 치료 및/또는 관리에 유용한 펩티드 및 화장품학적 또는 약제학적 조성물에 있어서의 이의 용도
JP7010823B2 (ja) 皮膚、毛髪、爪および／または粘膜の処置および／またはケアにおいて有用な化合物
KR101842521B1 (ko) 부화액 효소 및 그 용도
WO2021033829A1 (ko) 피부 상태 개선 활성을 갖는 펩타이드 및 이의 용도
US20170112737A1 (en) Cosmetics and pharmaceutical applications of gallic acid and gallic acid derivatives
US20240352069A1 (en) Synthetic peptide, and cosmetic composition or pharmaceutical composition and application thereof
KR102132274B1 (ko) 근육 이완용 조성물
US10532018B2 (en) Method of whitening skin using tranexamic acid-peptide having skin whitening activity
WO2021033833A1 (ko) 피부 미백 활성을 갖는 펩타이드 및 이의 용도
US8450456B2 (en) Activating peptide of the synthesis of aquaporins and cosmetic and/or pharmaceutical composition containing it
US10995117B2 (en) Peptide for skin regeneration or wound treatment and use thereof
WO2022240243A1 (ko) 나노베지클을 포함하는 피부 미백용 조성물
KR102261105B1 (ko) 피부 재생 또는 상처 치료용 펩타이드 aesis-1p3 및 이의 용도
WO2018034453A1 (ko) 미녹시딜과 펩타이드의 결합체
WO2023127986A1 (ko) 피부 상태 개선 활성을 갖는 펩타이드 및 이의 용도
CN116801857A (zh) 一种六肽衍生物及其美容组合物或药用组合物和用途
KR101868058B1 (ko) 피부 재생 또는 상처 치료를 위한 적혈구 분화 조절인자 1의 신규한 용도
TW201730204A (zh) 刺激黑色素生成的胜肽、方法及組合物
KR102775224B1 (ko) 항산화, 미백, 항염증, 피부보호 등의 기능을 갖는 락토페린 유도체 제조방법 및 이를 포함하는 피부 치료용 연고 및 화장품 조성물
CN116528825B (zh) 一种四肽衍生物及其组合物和用途
KR20190085413A (ko) 창상 치료제로서의 sis-1 펩타이드의 용도
WO2023127987A1 (ko) 피부 상태 개선 활성을 갖는 펩타이드 및 이의 용도
WO2024106587A1 (ko) 피부 상태 개선 활성을 갖는 펩타이드 및 이의 용도
WO2024210459A1 (ko) 피부 상태 개선 활성을 갖는 펩타이드 및 이의 용도

Legal Events

Date Code Title Description
ENP Entry into the national phase

Ref document number: 2018517117

Country of ref document: JP

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 17770579

Country of ref document: EP

Kind code of ref document: A2