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WO2018008864A1 - Cosmetic composition for wrinkle relief and anti-aging containing n-acetyl phytospingosine-1-phosphate - Google Patents

Cosmetic composition for wrinkle relief and anti-aging containing n-acetyl phytospingosine-1-phosphate Download PDF

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Publication number
WO2018008864A1
WO2018008864A1 PCT/KR2017/006175 KR2017006175W WO2018008864A1 WO 2018008864 A1 WO2018008864 A1 WO 2018008864A1 KR 2017006175 W KR2017006175 W KR 2017006175W WO 2018008864 A1 WO2018008864 A1 WO 2018008864A1
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Prior art keywords
skin
naps
phosphate
aging
cosmetic composition
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PCT/KR2017/006175
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French (fr)
Korean (ko)
Inventor
최명준
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Phytos Co Ltd
Phytos Co Ltd
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Phytos Co Ltd
Phytos Co Ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/55Phosphorus compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/02Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/11Encapsulated compositions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/02Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/14Liposomes; Vesicles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/68Sphingolipids, e.g. ceramides, cerebrosides, gangliosides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • A61Q19/08Anti-ageing preparations

Definitions

  • the present invention relates to a cosmetic composition for anti-wrinkle and anti-aging, and more particularly to a cosmetic composition for anti-wrinkle and anti-aging containing N-acetyl phytosphingosine-1-phosphate.
  • Skin aging is a phenomenon caused by structural and functional changes in skin cells and tissues. It is classified into intrinsic aging and extrinsic aging.
  • Endogenous aging is an unavoidable aging phenomenon over time, which means skin wrinkles with genetic factors added. Exogenous aging causes skin wrinkles caused by environmental factors such as ultraviolet rays, gravity and polluted air. it means. Representative of exogenous aging is aging phenomenon observed on the skin of the face, back of the hand, neck, etc., which have been exposed to sunlight for a long time due to photoaging.
  • Anti-aging cosmetic research is being conducted by various approaches to improve wrinkles and inhibit aging, which mainly increases collagen production and suppresses degradation, promotes and inhibits elastin production, increases hyaluronic acid production, promotes aging cell regeneration, and activity. Oxygen removal, and the like.
  • anti-aging cosmetics have been developed through the development of cellular signal transduction agents (Son et al (2005) J Invest Dermatol, 124: 1149-1161; Seite et al (2006) J Eur Acad Dermatol Venereol, 20: 980).
  • Sphingolipids are known as representatives of cellular signal transduction. Sphingolipids are a constituent of cell membranes and also a variety of studies are being carried out as active molecules in vivo that regulate biological functions as secondary messengers. Among the sphingolipids, ceramides and sphingosine-1-phosphate (S1P) are known. Ceramide induces cell death, but S1P is a substance that promotes cell survival. In particular, S1P is a lipid metabolized from ceramide and is known to be involved in cell proliferation, differentiation, survival and neovascularization (Chung et al (2000) J Biol Chem, 275: 17229-17232; Spiegel and Milstien (2002) J). Biol Chem, 277: 25851-25854; Spiegel and Milstien (2003) Nat Rev Mol Cell Biol, 4: 397-407; Pyne and Pyne (2000) Biochem J, 349: 385-402).
  • Korean Patent No. 1003532 discloses a hair loss prevention, treatment or hair growth composition comprising N-cyclic phytosphingosine-1-phosphate.
  • Korean Patent Laid-Open No. 10-2014-0096042 relates to a cosmetic preparation comprising N-acyl-phytosphingosine and 1,2-pentanediol, which relates to cosmetic preparations that prevent sagging of skin or increase elasticity. The effect to make it is disclosed.
  • Republic of Korea Patent No. 1514970 discloses a composition for treating and preventing atopic or skin wounds comprising N-acetylphytosphingosine-1-phosphate.
  • the present application is cosmetics for wrinkle improvement and anti-aging including N-acetyl phytosphingosine-1-phosphate (NAPS-1-P) based on phytosphingosine-1-phosphate derivatives To provide a composition for.
  • NAPS-1-P N-acetyl phytosphingosine-1-phosphate
  • an anti-aging cosmetic composition comprising N-acetyl phytosphingosine-1-phosphate (NAPS-1-P) or a cosmetic acceptable salt thereof.
  • NAPS-1-P N-acetyl phytosphingosine-1-phosphate
  • the cosmetic composition according to the present invention has an effect on patent skin aging, and particularly shows an excellent effect on skin wrinkle improvement or skin elasticity enhancement.
  • composition according to the present application may be prepared and applied in various formulations for skin application, and in one embodiment, a liposome formulation is prepared to increase skin absorption.
  • the present application provides a cosmetic composition for promoting collagen production comprising N-acetyl phytosphingosine-1-phosphate (NAPS-1-P) or a cosmetic acceptable salt thereof.
  • NAPS-1-P N-acetyl phytosphingosine-1-phosphate
  • the present application provides an anti-wrinkle or improvement cosmetic composition
  • an anti-wrinkle or improvement cosmetic composition comprising N-acetyl phytosphingosine-1-phosphate (NAPS-1-P) or a cosmetic acceptable salt thereof.
  • NAPS-1-P N-acetyl phytosphingosine-1-phosphate
  • Cosmetic compositions according to the invention can be prepared in various cosmetic forms, for example in the form of lotion, lotion, cream, essence, or ampoule depending on the site or method applied.
  • the N-acetyl phytosphingosine-1-phosphate (NAPS-1-P) or a cosmetic acceptable salt thereof may be included in an amount of 0.01 to 100 ppm.
  • the N-acetyl phytosphingosine-1-phosphate (NAPS-1-P) or a cosmetic acceptable salt thereof may be provided included in the liposome, and the liposome is for example lecithin. It may include ingredients.
  • the liposomes are nanoliposomes with an average diameter of about 100 to 200 nanometers, in particular 150 nanometers.
  • the present disclosure also provides a kit for promoting the proliferation of fibroblasts comprising N-acetyl phytosphingosine-1-phosphate (NAPS-1-P) or salts thereof, the fibroblasts proliferating, proliferating, in particular skin Proliferation of fibroblasts, and through this can be used for various purposes for the purpose of collagen enhancement.
  • NAPS-1-P N-acetyl phytosphingosine-1-phosphate
  • NAPS-1-P N-acetyl phytosphingosine-1-phosphate
  • the present application provides the use of N-acetyl phytosphingosine-1-phosphate (NAPS-1-P) for enhancing collagen synthesis of cells.
  • NAPS-1-P N-acetyl phytosphingosine-1-phosphate
  • the present disclosure provides a method of promoting collagen synthesis in the skin of a subject comprising applying the cosmetic composition according to the present application to the skin of the subject in need of skin condition improvement through collagen synthesis.
  • the present invention provides a method for improving skin conditions, comprising applying the cosmetic composition to a skin of a subject in need of improvement.
  • the present application relates to a cosmetic composition for wrinkle improvement and anti-aging comprising N-acetyl phytosphingosine-1-phosphate (N-acetyl phytosphingosine-1-phosphate, NAPS-1-P), wherein the composition is a fiber Since it promotes the proliferation of blasts, increases collagen synthesis and enhances skin elasticity, it can be usefully used in cosmetics for wrinkle improvement and anti-aging.
  • NAPS-1-P N-acetyl phytosphingosine-1-phosphate
  • composition of the present application is economical because it uses N-acetyl phytosphingosine-1-phosphate, which is a substance to replace expensive sphingosine, which is a precursor of ceramide.
  • NAPS-1-P N-acetyl phytosphingosine-1-phosphate
  • Figure 2 is a result of measuring the effect on the proliferation of fibroblasts according to NAPS-1-P concentration according to an embodiment of the present application.
  • Figure 3 is the result of measuring the collagen production promoting effect of the concentration of NAPS-1-P according to an embodiment of the present application.
  • Figure 4 is a result showing the size distribution of the particles of the nanoliposomes comprising NAPS-1-P prepared according to an embodiment of the present application.
  • the present invention is based on the discovery that N-acetyl phytosphingosine-1-phosphate (NAPS-1-P) promotes proliferation of fibroblasts and increases collagen synthesis.
  • NAPS-1-P N-acetyl phytosphingosine-1-phosphate
  • NAPS-1-P N-acetyl phytosphingosine-1-phosphate
  • the present application is directed to an anti-aging cosmetic composition
  • an anti-aging cosmetic composition comprising N-acetyl phytosphingosine-1-phosphate, a cosmetically acceptable salt or solvate thereof.
  • NAPS-1-P N-acetylphytosphingosine-1-phosphate, Nacetyl-2-amino-3,4-dihydroxyoctadecyl hydrogen phosphate
  • formula (1) NAPS-1-P (N-acetylphytosphingosine-1-phosphate, Nacetyl-2-amino-3,4-dihydroxyoctadecyl hydrogen phosphate) included in the composition according to the present invention is represented by the following formula (1).
  • the compounds according to the invention can be prepared using conventional knowledge known in the field of organic chemistry, for example (S. Li, WK Wilson, GJ Schroepfer, Chemical synthesis of D-ribo-phytosphingosine-1-phosphate, potential modulator of cellular processes.J. Lipid Res. 40: 117-125, 1999). Also refer to the Republic of Korea Patent No. 10-1003532 (composition for the prevention, treatment or hair growth of hair loss) or 10-1514970 (composition for the treatment and prevention of atopic or skin wounds) by the inventor.
  • Acceptable salts of the compounds according to the invention, or solvates thereof, may be appropriately prepared or selected by those skilled in the art of organic chemistry using knowledge known in the art.
  • Salts are physiologically acceptable and do not cause a conventional allergic or similar reaction upon administration to a human.
  • the salts may be organic or inorganic salts, and include, but are not limited to, sodium, calcium and potassium salts. It may be prepared through a method or a process for preparing a salt known in the art.
  • an acid addition salt formed by free acid may be used as the salt.
  • the free acid may be an organic acid or an inorganic acid.
  • the organic acid is not limited thereto, citric acid, acetic acid, lactic acid, tartaric acid, maleic acid, fumaric acid, formic acid, propionic acid, oxalic acid, trifluoroacetic acid, benzoic acid, gluconic acid, metasulfonic acid, glycolic acid, succinic acid, 4-toluenesulfonic acid, Glutaric acid and aspartic acid.
  • the inorganic acid includes, but is not limited to, hydrochloric acid, bromic acid, sulfuric acid and phosphoric acid.
  • the pharmaceutically acceptable salts may be present as acid addition salts in which the compounds of formula (I) form salts with the free acid.
  • the compounds of the formula (I) according to the present application may include not only pharmaceutically acceptable salts, but also all salts, hydrates, and solvates that can be prepared by conventional methods.
  • the compound of formula (I) may be stabilized by an anion paired with an ammonium cation in the compound, the anion may be any anion that is pharmaceutically acceptable and can be paired with an ammonium cation, for example iodide (I -), sulfonate (SO 3 2-), chloride (Cl -), etc., but is not limited to this.
  • the compound according to the present invention or a composition comprising the same can be effectively used for anti-aging, that is, delaying aging, preventing aging through promoting the proliferation and collagen production of fibroblasts.
  • Aging in which the composition according to the present invention is effective refers to skin aging in particular.
  • the aging is a phenomenon caused by structural and functional changes in skin cells and tissues, and is mainly caused by genetic factors such as endogenous aging and ultraviolet rays, This includes extrinsic aging caused by environmental factors such as gravity and polluted air.
  • the aging phenomenon includes, but is not limited to, wrinkles on the skin, elasticity of the skin, and sagging of the skin.
  • Exemplary exogenous aging is the aging phenomenon observed in the skin of the face, back of the hand, neck, etc., due to photoaging when exposed to sunlight for a long time.
  • the compound according to the present application can be usefully used as a cosmetic composition for beauty.
  • the term 'cosmetics' refers to an article used in the human body to brighten the human body to brighten the appearance of the body or to maintain or promote the health of the skin and hair, and refers to a slight action on the human body.
  • it includes all lotions, creams, oils, cleaning products and functional cosmetics.
  • Functional cosmetics herein refers to the control of biological defense rhythms, disease prevention and recovery of cosmetic groups or cosmetic compositions that have added value to act and express the functions of cosmetics by using physical, biochemical and biotechnological techniques. It means cosmetics that are designed and processed to express the function of the gymnastics sufficiently to the living body, and in particular, mean anti-aging cosmetics.
  • Cosmetic compositions according to the invention may be provided as cosmetics, for example, creams, lotions, ampoules, skins, essences, soaps and the like, in other aspects such as basic cosmetic compositions (cosmetics, creams, essences, cleansing foams and cleansing water) Face wash, pack, body oil), color cosmetic composition (foundation, lipstick, mascara, makeup base) or in the form of a mask or pack.
  • the area to which the cosmetic composition according to the present invention can be applied is not limited to a specific part of the body, and may be applied to a wrinkled or wrinkled skin part such as a face, a neck part, a hand, etc. have.
  • Cosmetic compositions according to the invention can be administered at various sites of application, for example by systemic or topical, in particular topical, transdermal, or injection, in particular transdermal routes.
  • the cosmetic composition according to the present application is not particularly limited to other ingredients except for including the compound of the present invention as essential ingredients in the indicated ratios, and in the case of ordinary cosmetics such as cream, vegetable oils, emulsifiers, thickeners, flavorings, water, antioxidants And UV absorbers.
  • the content of the compound included in the composition according to the present application may vary depending on the specific use or formulation of the desired product, but may be included in about 0.001 to about 50% by weight in the total composition, but is not excluded from this range.
  • Cosmetic compositions comprising the compounds herein may include, in addition to the compounds, conventional adjuvants and carriers such as antioxidants, stabilizers, solubilizers, vitamins, pigments, and / or flavors.
  • conventional adjuvants and carriers such as antioxidants, stabilizers, solubilizers, vitamins, pigments, and / or flavors.
  • the cosmetic composition herein may comprise a water soluble base material comprising conjugated linoleic acid, linoleic acid, gamma-linoleic acid, unsaturated fatty acids including alpha-linoleic acid or propylene glycol.
  • Cosmetic compositions herein can also be prepared in any formulation conventionally prepared in the art suitable for administration to the skin for anti-aging, including, for example, solutions, suspensions, emulsions, pastes, gels, creams, lotions, Powders, soaps, surfactant-containing cleansing, oils, powder foundations, emulsion foundations, wax foundations, 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, mask, pack, spray or powder.
  • the formulation of the present composition 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.
  • 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.
  • animal oils vegetable oils, waxes, paraffins, starches, trachants, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicas, talc or zinc oxide
  • cellulose derivatives polyethylene glycols
  • silicones bentonites
  • silicas talc or zinc oxide
  • the formulation of the composition is a powder or a spray
  • lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used, especially in the case of a spray, additionally chlorofluorohydrocarbon, propane Propellant such as butane or dimethyl ether.
  • Cosmetic compositions according to the invention may further comprise a cosmetically / dermatologically acceptable carrier.
  • Cosmetic / dermatologically acceptable means suitable for use in contact with tissue (eg skin or hair) without excessive toxicity, incompatibility, instability, irritation, allergic reactions, and the like.
  • a solvent, solubilizing agent or emulsifying agent 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, glycerol aliphatic ester, polyethylene glycol or sorbitan may be used.
  • the carrier component is water, a liquid diluent such as ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, and microcrystals.
  • a liquid diluent such as ethanol or propylene glycol
  • a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, and microcrystals.
  • Castle cellulose, aluminum metahydroxy, bentonite, agar or tracant and the like can be used.
  • compositions of the present invention may comprise at least one pharmaceutically acceptable excipient, in particular dermatologically acceptable excipients.
  • composition of the present invention has little toxicity and side effects, it can be used with confidence even for prolonged administration for prophylactic purposes.
  • the compound NAPS-1-P according to the present disclosure may be prepared as a nanoliposomal formulation.
  • the nanoliposomes are in the form of conventional liposomes, and the average particle diameter of liposomes, particularly nanoliposomes, of 100-200 nm is 140-160 nm.
  • the liposomes take the form of microcapsules or spheres and may serve to deliver the active ingredients directly to the skin.
  • the NAPS-1-P by containing NAPS-1-P in the nanoliposomes, the NAPS-1-P can be better delivered and absorbed to the skin.
  • Nanoliposomes can be prepared through various methods known in the art. In one embodiment of the present application is manufactured by Sony. Nanoliposomes according to the present invention are in the form of conventional, shelled liposomes. The liposomes take the form of fine capsules or spheres, and may serve to directly transfer the ingredients used in skin care to the skin.
  • NAPS-1-P is provided contained in liposomes formed with lecithin.
  • Lecithin is an amphiphilic phospholipid consisting of fatty acids such as choline, glycerol or glycofatty acid or triglycerides as phosphoric acid and lipid components. Phosphatidylcholine, phosphadidylethanolamine, and / or phosphatidyl inositol, and the like, and are the main constituents of biological membranes, which can be extracted from various animals, plants, yeasts, etc., and are commercially available.
  • the present invention also relates to a kit for promoting proliferation or enhancing collagen synthesis of fibroblasts comprising N-acetyl phytosphingosine-1-phosphate (NAPS-1-P) or salts thereof.
  • NAPS-1-P N-acetyl phytosphingosine-1-phosphate
  • kits according to the present disclosure may refer to the aforementioned, and may further include additional ingredients, usage, etc. for the desired effect in the in vitro.
  • Kits according to the present invention can be used in a variety of ways that promote the growth of fibroblasts or promote collagen production through it.
  • the cosmetic composition comprising the active ingredient according to the present application may improve the condition of the skin such as wrinkle improvement or elasticity through fibroblast proliferation and collagen synthesis.
  • the present invention provides a method for promoting collagen synthesis in the skin of a subject comprising applying the cosmetic composition according to the present application to the skin of a subject in need of improving the skin condition through collagen synthesis or promoting fibroblast proliferation It is about.
  • the present invention provides a method for improving skin condition, comprising applying the cosmetic composition according to another embodiment to the skin of a subject in need of improvement of skin condition.
  • Cosmetic composition used in the method according to the invention can be referred to above.
  • Cosmetic compositions according to the present application can be applied to all or part of the whole body, including various areas that need improvement of the skin, such as the face, neck, hands, arms, legs and the like.
  • Cosmetics according to the present application may be applied in an amount sufficient to produce the desired effect, and those skilled in the art will be able to determine the appropriate amount in view of the disclosure herein and the knowledge in the art.
  • NAPS-1-P N-acetyl phytosphingosine-1-phosphate
  • Human fibroblasts (CCD-9865K, Korea Cell Line Bank) were incubated with DME (Dulbecco's Modified Eagle Medium) medium containing 10% fetal calf serum and 1% penicillin / streptomycin every 3 days with medium. The culture environment was incubated in a 5% CO 2 incubator maintained at 37 ° C. The proliferative effect of fibroblasts was measured using MTT (3- (4,5-dimethylthiazol-2yl) -2,5-diphenyl-2H-tetrazolium bromide) assay (Sigma) according to the manufacturer's method, and the absorbance at 595 nm was measured. The cell proliferation effect was observed.
  • DME Dulbecco's Modified Eagle Medium
  • MTT 3- (4,5-dimethylthiazol-2yl) -2,5-diphenyl-2H-tetrazolium bromide
  • Human fibroblasts were cultured every 3 days in DMEM medium containing 10% fetal calf serum and 1% penicillin / streptomycin to see the effect of promoting collagen synthesis to measure the wrinkle improvement effect of the skin.
  • the culture environment was incubated in a 5% CO 2 incubator maintained at 37 ° C. After incubation for 24 hours, the solution was diluted with culture medium (dissolved in dimethyl sulfoxide (DMSO) at 10000 ppm, diluted with medium, and diluted to 0.1-10 ppm), followed by incubation for 24 hours.
  • DMSO dimethyl sulfoxide
  • the culture medium was taken, and collagen amount was measured using a procollagen type I C-peptide EIA kit (Takara Bio Inc, MK 101) according to the manufacturer's method.
  • the absorbance was measured at 450 nm to calculate the amount of collagen.
  • Nanoliposomes to be applied to the skin was prepared by the sonication method as described below, the composition of the nanoliposomes are shown in Table 1 below. Specifically, lecithin was first dispersed in ethanol or butylene glycol and hexanediol for the preparation of nanoliposomes. NAPS-1-P and arginine were mixed and then dissolved by warming with water. The prepared NAPS-1-P solution was stirred vigorously while slowly added to the lecithin solution. After stirring for 30 minutes, it was sonicated with a bath type sonicator for 60 minutes. The particle size of the prepared nanoliposomes was measured according to the manufacturer's method using laser light scattering (Photal Otsuka Electronics, Japan). The particle size of the nanoliposomes is shown by volume distribution.
  • the nanoliposomes made of the following compositions 1 and 2 were made in a very stable state, and the particle size of the nanoliposomes was measured, and there was no difference in particle size in the two compositions. As shown in FIG. 3, the average particle size of the two compositions was found to be about 150 nm.
  • Skin firmness instrument evaluation was determined using the Cutometer MPA580 (Courage and Khazaka, Germany) measuring equipment according to the manufacturer's method.
  • the measurement method was a non-invasive method of 2mm diameter probe connected to the device in close contact with the skin.
  • the unit of measurement is expressed in arbitrary units AU (arbitary unit).
  • the measurements were taken before and two and four weeks after application to the skin.
  • Skin elasticity improvement rate was calculated as follows.
  • Improvement rate (%) (measured value after applying cosmetics-average value measured before using cosmetics) / average value measured before using cosmetics X 100
  • Human fibroblasts are cells that synthesize collagen, which promotes the proliferation of fibroblasts and can measure the effect of improving wrinkles.
  • Addition of NAPS-1-P in the culture of fibroblasts was shown to promote the proliferation of fibroblasts (FIG. 1).
  • NAPS N-acetyl phytosphingosine
  • NAPS-1-P precursors of NAPS-1-P NAPS does not promote fibroblast proliferation.
  • the result of promoting death was obtained, but NAPS-1-P resulted in promoting fibroblast proliferation (Table 3, FIG. 2). Therefore, NAPS-1-P, unlike NAPS, promotes the proliferation of fibroblasts, indicating that it can be usefully used in anti-aging cosmetics including wrinkle improvement.
  • ampoule cosmetics containing the nanoliposomes of the compositions 1 and 2 were prepared and applied to the skin, and then the change in skin elasticity was measured.
  • Subjects were asked to apply ampoule 1 to the right face and ampoule 2 to the left face twice a day for 4 weeks for 20 people in their 30s to 50s (mean age 43.2) who are concerned about skin aging.
  • Skin elasticity was measured before and 2 weeks and 4 weeks after application and the results are shown in Table 4.
  • the skin elasticity tends to increase with the application time and shows higher skin elasticity than before application.
  • the composition containing NAPS-1-P has the effect of increasing the proliferation of fibroblasts and also increasing collagen synthesis.
  • the application of ampoules comprising the composition according to the present application directly to the skin also showed an increase in skin elasticity. Therefore, the composition containing NAPS-1-P of the present application can be usefully used in anti-aging cosmetics including wrinkle improvement and elasticity improvement.

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Abstract

Disclosed herein is a cosmetic product having anti-aging effects including wrinkle relief and elasticity enhancement, the cosmetic product containing N-acetyl phytosphingosine-1-phosphate (NAPS-1-P). The composition according to the present application can be effectively used in skin anti-aging through wrinkle relief and skin elasticity increase by multiplying fibroblasts and promoting collagen synthesis.

Description

N-아세틸 피토스핑고신-1-포스페이트를 함유하는 주름개선 및 노화방지를 위한 화장품용 조성물Cosmetic composition for wrinkle improvement and anti-aging containing N-acetyl phytosphingosine-1-phosphate

본 발명은 주름개선 및 노화방지를 위한 화장품용 조성물에 관한 것으로, 구체적으로는 N-아세틸 피토스핑고신-1-포스페이트를 함유하는 주름개선 및 노화방지를 위한 화장품용 조성물에 관한 것이다. The present invention relates to a cosmetic composition for anti-wrinkle and anti-aging, and more particularly to a cosmetic composition for anti-wrinkle and anti-aging containing N-acetyl phytosphingosine-1-phosphate.

최근 경제수준과 의학적인 발전으로 인해 평균수명이 늘어나고, 외모에 대한 관심이 향상되면서 자연스럽게 주름개선 및 피부 노화방지에 대한 관심이 증대되고 있는 실정이다. 피부 노화는 피부세포 및 조직의 구조적, 기능적인 변화로 인한 현상으로 내인성 노화(intrinsic aging)와 외인성 노화(extrinsic aging)로 구분된다.Recently, the average life expectancy has increased due to the economic level and medical development, and interest in appearance has improved, and interest in improving wrinkles and preventing skin aging has naturally increased. Skin aging is a phenomenon caused by structural and functional changes in skin cells and tissues. It is classified into intrinsic aging and extrinsic aging.

내인성 노화는 세월이 흐름에 따라 피할 수 없는 노화현상으로 유전적 요인이 가미된 피부주름 발생을 의미하고, 외인성 노화의 경우는 자외선, 중력, 오염된 공기와 같은 환경적 요인에 의한 피부주름 발생을 의미한다. 외인성 노화의 대표적인 것이 광노화로 오랫동안 햇빛에 노출된 얼굴, 손등, 목 등의 피부에서 관찰되는 노화현상을 말한다.Endogenous aging is an unavoidable aging phenomenon over time, which means skin wrinkles with genetic factors added. Exogenous aging causes skin wrinkles caused by environmental factors such as ultraviolet rays, gravity and polluted air. it means. Representative of exogenous aging is aging phenomenon observed on the skin of the face, back of the hand, neck, etc., which have been exposed to sunlight for a long time due to photoaging.

이러한 주름개선 및 노화억제를 위해 다양한 접근 방법으로 항노화 화장품 연구가 진행되고 있으며, 이는 주로 콜라겐 생성의 증가 및 분해의 억제, 엘라스틴의 생성 촉진 및 분해억제, 히아루론산 생성증가, 노화 세포 재생 촉진, 활성산소 제거 등을 포함한다. 또한 최근에는 세포신호 전달 조절 물질 개발을 통해 항노화 화장품을 개발하고 있다 (Son et al (2005) J Invest Dermatol, 124: 1149-1161; Seite et al (2006) J Eur Acad Dermatol Venereol, 20: 980-987; Ghersetich et al (1994) Int J Dermatol, 33: 661; Petropoules and Friguet (2005) Biochimica Biophtsica Acta, 1703: 261-266; Hazane et al (2005) J Photochem Photobiol, 79: 171-190). Anti-aging cosmetic research is being conducted by various approaches to improve wrinkles and inhibit aging, which mainly increases collagen production and suppresses degradation, promotes and inhibits elastin production, increases hyaluronic acid production, promotes aging cell regeneration, and activity. Oxygen removal, and the like. Recently, anti-aging cosmetics have been developed through the development of cellular signal transduction agents (Son et al (2005) J Invest Dermatol, 124: 1149-1161; Seite et al (2006) J Eur Acad Dermatol Venereol, 20: 980). -987; Ghersetich et al (1994) Int J Dermatol, 33: 661; Petropoules and Friguet (2005) Biochimica Biophtsica Acta, 1703: 261-266; Hazane et al (2005) J Photochem Photobiol, 79: 171-190).

세포 신호 전달의 대표적인 물질로 알려진 것이 스핑고지질이다. 스핑고지질은 세포막의 구성 성분이면서 또한 2차 전령물질로써 생체 기능을 조절하는 생체내 활성분자로 다양한 연구가 진행되고 있다. 스핑고지질 중에 대표적인 것으로 세라마이드와 스핑고신-1-포스페이트(sphingosine-1-phosphate, S1P)가 알려져 있다. 세라마이드는 세포사멸을 유도하지만 S1P는 세포생존을 촉진하는 물질이다. 특히 S1P는 세라마이드로부터 대사된 지질로 세포의 번식, 분화, 생존 및 신생혈관생성 등에 관여하는 것으로 알려져 있다 (Chung et al (2000) J Biol Chem, 275: 17229-17232; Spiegel and Milstien (2002) J Biol Chem, 277: 25851-25854; Spiegel and Milstien (2003) Nat Rev Mol Cell Biol, 4: 397-407; Pyne and Pyne (2000) Biochem J, 349: 385-402).Sphingolipids are known as representatives of cellular signal transduction. Sphingolipids are a constituent of cell membranes and also a variety of studies are being carried out as active molecules in vivo that regulate biological functions as secondary messengers. Among the sphingolipids, ceramides and sphingosine-1-phosphate (S1P) are known. Ceramide induces cell death, but S1P is a substance that promotes cell survival. In particular, S1P is a lipid metabolized from ceramide and is known to be involved in cell proliferation, differentiation, survival and neovascularization (Chung et al (2000) J Biol Chem, 275: 17229-17232; Spiegel and Milstien (2002) J). Biol Chem, 277: 25851-25854; Spiegel and Milstien (2003) Nat Rev Mol Cell Biol, 4: 397-407; Pyne and Pyne (2000) Biochem J, 349: 385-402).

대한민국 등록특허 제1003532호는 N-시클릭 피토스핑고신-1-포스페이트를 포함하는 탈모 예방, 치료 또는 육모용 조성물을 개시하고 있다. Korean Patent No. 1003532 discloses a hair loss prevention, treatment or hair growth composition comprising N-cyclic phytosphingosine-1-phosphate.

대한민국 공개특허 제10-2014-0096042호는 N-아실-피토스핑고신 및 1,2-펜탄디올을 포함하는 화장품 제제에 관한 것으로 유하는 화장품제제에 관한 것으로 피부의 처짐을 방지하거나 탄력을 증가시키는 효과를 개시하고 있다. Korean Patent Laid-Open No. 10-2014-0096042 relates to a cosmetic preparation comprising N-acyl-phytosphingosine and 1,2-pentanediol, which relates to cosmetic preparations that prevent sagging of skin or increase elasticity. The effect to make it is disclosed.

대한민국 등록특허 제1514970호는 N-아세틸피토스핑고신-1-포스페이트를 포함하는 아토피 또는 피부상처 치료 및 예방용 조성물을 개시한다. Republic of Korea Patent No. 1514970 discloses a composition for treating and preventing atopic or skin wounds comprising N-acetylphytosphingosine-1-phosphate.

하지만 상기 어떤 특허도 N-아세틸 피토스핑고신-1-포스페이트의 섬유아세포 증식 효과 및 콜라겐 생성 촉진 효과에 기반한 주름을 포함하는 피부노화, 피부 탄력 증가와 같은 효과에 대하여는 전혀 개시하고 있지 않다. However, none of the above patents discloses any effects such as skin aging including wrinkles based on fibroblast proliferation and collagen production promoting effects of N-acetyl phytosphingosine-1-phosphate and increased skin elasticity.

본원은 피토스핑고신-1-포스페이트 유도체 기반 N-아세틸 피토스핑고신-1-포스페이트(N-acetyl phytosphingosine-1-phosphate, NAPS-1-P)를 포함하는 주름개선 및 노화방지를 위한 화장품용 조성물을 제공하고자 한다.The present application is cosmetics for wrinkle improvement and anti-aging including N-acetyl phytosphingosine-1-phosphate (NAPS-1-P) based on phytosphingosine-1-phosphate derivatives To provide a composition for.

한 양태에서 본원은 N-아세틸 피토스핑고신-1-포스페이트(NAPS-1-P) 또는 그 화장품용로 허용가능한 염을 포함하는 항노화 화장품 조성물을 제공한다. In one aspect the present disclosure provides an anti-aging cosmetic composition comprising N-acetyl phytosphingosine-1-phosphate (NAPS-1-P) or a cosmetic acceptable salt thereof.

본원에 따른 화장품 조성물은 특허 피부 노화에 효과가 있으며, 특히 피부 주름개선 또는 피부 탄력 증진에 우수한 효과를 나타낸다. The cosmetic composition according to the present invention has an effect on patent skin aging, and particularly shows an excellent effect on skin wrinkle improvement or skin elasticity enhancement.

본원에 따른 조성물을 피부도포를 위해 다양한 제형으로 제조되어 적용될 수 있으며, 일 구현예에서는 리포좀 제형으로 제조되어 피부 흡수율이 높아진다. The composition according to the present application may be prepared and applied in various formulations for skin application, and in one embodiment, a liposome formulation is prepared to increase skin absorption.

또 다른 양태에서 본원은 N-아세틸 피토스핑고신-1-포스페이트(NAPS-1-P) 또는 그 화장품용으로 허용가능한 염을 포함하는 콜라겐 생성 촉진용 화장품 조성물을 제공한다. In another aspect the present application provides a cosmetic composition for promoting collagen production comprising N-acetyl phytosphingosine-1-phosphate (NAPS-1-P) or a cosmetic acceptable salt thereof.

또 다른 양태에서 본원은 N-아세틸 피토스핑고신-1-포스페이트(NAPS-1-P) 또는 그 화장품용으로 허용가능한 염을 포함하는 주름억제 또는 개선용 화장품 조성물을 제공한다. In another aspect, the present application provides an anti-wrinkle or improvement cosmetic composition comprising N-acetyl phytosphingosine-1-phosphate (NAPS-1-P) or a cosmetic acceptable salt thereof.

본원에 따른 화장품 조성물은 다양한 화장품 형태 예를 들면 적용되는 부위 또는 방법에 따라 화장수, 로션, 크림, 에센스, 또는 앰플 형태로 제조될 수 있다. Cosmetic compositions according to the invention can be prepared in various cosmetic forms, for example in the form of lotion, lotion, cream, essence, or ampoule depending on the site or method applied.

본원에 따른 화장품 조성물에서, 상기 N-아세틸 피토스핑고신-1-포스페이트(NAPS-1-P) 또는 그 화장품용으로 허용가능한 염은 0.01 내지 100ppm으로 포함될 수 있다. In the cosmetic composition according to the present application, the N-acetyl phytosphingosine-1-phosphate (NAPS-1-P) or a cosmetic acceptable salt thereof may be included in an amount of 0.01 to 100 ppm.

본원에 따른 화장품 조성물에서, 상기 N-아세틸 피토스핑고신-1-포스페이트(NAPS-1-P) 또는 그 화장품용으로 허용가능한 염은 리포좀에 포함되어 제공될 수 있으며, 리포좀은 예를 들면 레시틴 성분을 포함할 수 있다. In the cosmetic composition according to the present invention, the N-acetyl phytosphingosine-1-phosphate (NAPS-1-P) or a cosmetic acceptable salt thereof may be provided included in the liposome, and the liposome is for example lecithin. It may include ingredients.

본원에 따른 화장품 조성물에서, 리포좀은 나노리포좀으로 평균 직경은 약 100 내지 200나노미터, 특히 150 나노미터이다. In the cosmetic composition according to the invention, the liposomes are nanoliposomes with an average diameter of about 100 to 200 nanometers, in particular 150 nanometers.

또 다른 양태에서 본원은 또한 N-아세틸 피토스핑고신-1-포스페이트(NAPS-1-P) 또는 그 염을 포함하는 섬유아세포의 증식 촉진용 키트를 제공하며, 섬유아세포의 증식, 증식 특히 피부의 섬유아세포의 증식, 및 이를 통해 콜라겐 증진 등의 목적을 위해 다양한 목적으로 사용될 수 있다.In another aspect the present disclosure also provides a kit for promoting the proliferation of fibroblasts comprising N-acetyl phytosphingosine-1-phosphate (NAPS-1-P) or salts thereof, the fibroblasts proliferating, proliferating, in particular skin Proliferation of fibroblasts, and through this can be used for various purposes for the purpose of collagen enhancement.

또 다른 양태에서 본원은 N-아세틸 피토스핑고신-1-포스페이트(NAPS-1-P)의 섬유아세포의 증식 촉진용 용도를 제공한다. In another aspect the present application provides the use of N-acetyl phytosphingosine-1-phosphate (NAPS-1-P) for promoting the proliferation of fibroblasts.

또 다른 양태에서 본원은 N-아세틸 피토스핑고신-1-포스페이트(NAPS-1-P)의 세포의 콜라겐 합성 증진용 용도를 제공한다. In another aspect, the present application provides the use of N-acetyl phytosphingosine-1-phosphate (NAPS-1-P) for enhancing collagen synthesis of cells.

또 다른 양태에서 본원은 본원에 따른 화장품 조성물을 콜라겐 합성을 통해 피부 상태 개선이 필요한 대상체의 피부에 도포하는 단계를 포함하는, 상기 대상체의 피부에서 콜라겐 합성을 촉진하는 방법을 제공한다. In another aspect the present disclosure provides a method of promoting collagen synthesis in the skin of a subject comprising applying the cosmetic composition according to the present application to the skin of the subject in need of skin condition improvement through collagen synthesis.

또 다른 양태에서 따른 화장품 조성물을 피부상태의 개선이 필요한 대상체의 피부에 도포하는 단계를 포함하는, 피부상태 개선 방법을 제공한다. In another aspect, the present invention provides a method for improving skin conditions, comprising applying the cosmetic composition to a skin of a subject in need of improvement.

본원은 N-아세틸 피토스핑고신-1-포스페이트(N-acetyl phytosphingosine-1-phosphate, NAPS-1-P)를 포함하는 주름개선 및 노화방지를 위한 화장품용 조성물에 관한 것으로, 상기 조성물은 섬유아세포의 증식을 촉진하고, 콜라겐 합성을 증가시키고 피부 탄력을 증진시키므로, 주름개선 및 노화방지용 화장품에 유용하게 사용될 수 있다.The present application relates to a cosmetic composition for wrinkle improvement and anti-aging comprising N-acetyl phytosphingosine-1-phosphate (N-acetyl phytosphingosine-1-phosphate, NAPS-1-P), wherein the composition is a fiber Since it promotes the proliferation of blasts, increases collagen synthesis and enhances skin elasticity, it can be usefully used in cosmetics for wrinkle improvement and anti-aging.

또한 본원의 조성물은 세라미이드의 전구체인 고가의 스핑고신을 대체할 물질인 N-아세틸 피토스핑고신-1-포스페이트를 사용하므로 경제적이다.In addition, the composition of the present application is economical because it uses N-acetyl phytosphingosine-1-phosphate, which is a substance to replace expensive sphingosine, which is a precursor of ceramide.

도 1은 본원의 일 구현예에 따른 NAPS-1-P(N-acetyl phytosphingosine-1-phosphate) 처리군과 대조군의 섬유아세포 증식에 대한 효과를 측정한 결과이다. 1 is a result of measuring the effect on the fibroblast proliferation of NAPS-1-P (N-acetyl phytosphingosine-1-phosphate) treatment group and the control group according to an embodiment of the present application.

도 2는 본원의 일 구현예에 따른 NAPS-1-P 농도에 따른 섬유아세포의 증식에 대한 효과를 측정한 결과이다. Figure 2 is a result of measuring the effect on the proliferation of fibroblasts according to NAPS-1-P concentration according to an embodiment of the present application.

도 3은 본원의 일 구현예에 따른 NAPS-1-P의 농도에 따른 콜라겐 생성 촉진 효과를 측정한 결과이다.Figure 3 is the result of measuring the collagen production promoting effect of the concentration of NAPS-1-P according to an embodiment of the present application.

도 4는 본원의 일 구현예에 따라 제조된 NAPS-1-P를 포함하는 나노리포좀의 입자의 크기 분포를 나타낸 결과이다. Figure 4 is a result showing the size distribution of the particles of the nanoliposomes comprising NAPS-1-P prepared according to an embodiment of the present application.

본 발명은 N-아세틸 피토스핑고신-1-포스페이트(N-acetyl phytosphingosine-1-phosphate, NAPS-1-P)가 섬유아세포의 증식을 촉진하고, 콜라겐 합성을 증가시킨다는 발견에 근거한 것이다. The present invention is based on the discovery that N-acetyl phytosphingosine-1-phosphate (NAPS-1-P) promotes proliferation of fibroblasts and increases collagen synthesis.

이에 본원은 N-아세틸 피토스핑고신-1-포스페이트(NAPS-1-P)의 섬유아세포의 증식 촉진용 또는 콜라겐 합성 증진용 용도 또는 피부상태 개선 용도에 관한 것이다. Therefore, the present application relates to the use of N-acetyl phytosphingosine-1-phosphate (NAPS-1-P) for promoting the proliferation of fibroblasts or for enhancing collagen synthesis or for improving skin condition.

한 양태에서 본원은 N-아세틸 피토스핑고신-1-포스페이트, 그 화장품적으로 허용가능한 염 또는 용매화물을 포함하는 항노화 화장품 조성물에 관한 것이다. In one embodiment the present application is directed to an anti-aging cosmetic composition comprising N-acetyl phytosphingosine-1-phosphate, a cosmetically acceptable salt or solvate thereof.

본원에 따른 조성물에 포함되는 NAPS-1-P(N-아세틸피토스핑고신-1-포스페이트, Nacetyl-2-amino-3,4-dihydroxyoctadecyl hydrogen phosphate)하기 화학식 1로 표시된다.NAPS-1-P (N-acetylphytosphingosine-1-phosphate, Nacetyl-2-amino-3,4-dihydroxyoctadecyl hydrogen phosphate) included in the composition according to the present invention is represented by the following formula (1).

[화학식 I][Formula I]

Figure PCTKR2017006175-appb-I000001
Figure PCTKR2017006175-appb-I000001

본원에 따른 화합물은 유기화학 분야에 공지되어 있는 통상의 지식을 이용하여 제조할 수 있으며, 예를 들어 (S. Li, W.K. Wilson, G.J. Schroepfer, Chemical synthesis of D-ribo-phytosphingosine-1-phosphate, potential modulator of cellular processes. J. Lipid Res. 40: 117-125, 1999)에 개시되어 있는 방법을 참조하여 제조할 수 있다. 또한 본 발명자에 의한 대한민국 등록특허 제10-1003532호(탈모의 예방, 치료 또는 육모용 조성물) 또는 제10-1514970호(아토피 또는 피부상처 치료 및 예방용 조성물)를 참조할 수 있다. The compounds according to the invention can be prepared using conventional knowledge known in the field of organic chemistry, for example (S. Li, WK Wilson, GJ Schroepfer, Chemical synthesis of D-ribo-phytosphingosine-1-phosphate, potential modulator of cellular processes.J. Lipid Res. 40: 117-125, 1999). Also refer to the Republic of Korea Patent No. 10-1003532 (composition for the prevention, treatment or hair growth of hair loss) or 10-1514970 (composition for the treatment and prevention of atopic or skin wounds) by the inventor.

본원에 따른 화합물의 혀용가능한 염, 또는 그 용매화물은 유기화학분야에서 통상의 지식을 가진 자가 당해 기술 분야에 공지된 지식을 이용하여 적절히 제조하거나 선택할 수 있다. Acceptable salts of the compounds according to the invention, or solvates thereof, may be appropriately prepared or selected by those skilled in the art of organic chemistry using knowledge known in the art.

염은 생리학적으로 허용되고 인간에게 투여시 통상적인 알레르기 반응 또는 이와 유사한 반응을 일으키지 않는 것을 말한다. 상기 염으로는 유기 또는 무기염이 가능하며, 나트륨, 칼슘 및 칼륨 염 등이 있으나 이에 제한되는 것은 아니다. 당해 기술분야에서 알려진 염의 제조방법이나 제조과정을 통하여 제조될 수 있다. 또한 상기 염으로는 유리산(free acid)에 의하여 형성된 산 부가염이 사용될 수 있다. 상기 유리산은 유기산과 무기산을 사용할 수 있다. 상기 유기산은 이에 제한되는 것은 아니나, 구연산, 초산, 젖산, 주석산, 말레인산, 푸마르산, 포름산, 프로피온산, 옥살산, 트리플로오로아세트산, 벤조산, 글루콘산, 메타술폰산, 글리콜산, 숙신산, 4-톨루엔술폰산, 글루탄산 및 아스파르트산을 포함한다. 또한, 상기 무기산은 이에 제한되는 것은 아니나 염산, 브롬산, 황산 및 인산을 포함한다. Salts are physiologically acceptable and do not cause a conventional allergic or similar reaction upon administration to a human. The salts may be organic or inorganic salts, and include, but are not limited to, sodium, calcium and potassium salts. It may be prepared through a method or a process for preparing a salt known in the art. In addition, as the salt, an acid addition salt formed by free acid may be used. The free acid may be an organic acid or an inorganic acid. The organic acid is not limited thereto, citric acid, acetic acid, lactic acid, tartaric acid, maleic acid, fumaric acid, formic acid, propionic acid, oxalic acid, trifluoroacetic acid, benzoic acid, gluconic acid, metasulfonic acid, glycolic acid, succinic acid, 4-toluenesulfonic acid, Glutaric acid and aspartic acid. In addition, the inorganic acid includes, but is not limited to, hydrochloric acid, bromic acid, sulfuric acid and phosphoric acid.

본원에 따른 일 구현예에서 약학적으로 허용 가능한 염은 상기 화학식 I의 화합물이 유리산과 함께 염을 형성하는 산부가염으로 존재할 수 있다. 또한, 본원에 따른 상기 화학식 I의 화합물은 약학적으로 허용 가능한 염뿐만 아니라, 통상의 방법에 의해 제조될 수 있는 모든 염, 수화물, 용매화물을 모두 포함할 수 있다.In one embodiment according to the invention the pharmaceutically acceptable salts may be present as acid addition salts in which the compounds of formula (I) form salts with the free acid. In addition, the compounds of the formula (I) according to the present application may include not only pharmaceutically acceptable salts, but also all salts, hydrates, and solvates that can be prepared by conventional methods.

상기 화학식 I의 화합물은 화합물 내의 암모늄 양이온과 짝을 이루는 음이온에 의해 안정화 될 수 있으며, 상기 음이온은 약제학적으로 허용되면서 암모늄 양이온과 함께 짝을 이룰 수 있는 임의의 음이온일 수 있으며, 예를 들어 요오다이드(I-), 설포네이트(SO3 2-), 클로라이드(Cl-) 등이 있으나 이에 한정되는 것은 아니다.The compound of formula (I) may be stabilized by an anion paired with an ammonium cation in the compound, the anion may be any anion that is pharmaceutically acceptable and can be paired with an ammonium cation, for example iodide (I -), sulfonate (SO 3 2-), chloride (Cl -), etc., but is not limited to this.

본원에 따른 화합물 또는 이를 포함하는 조성물은 섬유아세포의 증식 및 콜라겐 생성 촉진을 통해 항노화, 즉 노화지연, 노화예방 등에 효과적으로 사용될 수 있다. The compound according to the present invention or a composition comprising the same can be effectively used for anti-aging, that is, delaying aging, preventing aging through promoting the proliferation and collagen production of fibroblasts.

본원에 따른 조성물이 효과를 나타내는 노화란 특히 피부노화를 일컫는 것으로 이러한 노화는 피부세포 및 조직의 구조적, 기능적인 변화로 인한 현상으로, 주로 유전적 요인에 기인하는 내인성 노화(intrinsic aging)와 자외선, 중력, 오염된 공기와 같은 환경적 요인에 의한 외인성 노화(extrinsic aging)를 포함하는 것이다. 노화의 결과, 즉 노화현상은 피부에 주름이 발생하고, 피부의 탄력성이 감소되어 피부가 처지는 현상을 포함하나 이로 제한하는 것은 아니다. 외인성 노화의 대표적인 것으로 광노화로 햇빛에 오랫동안 노출된 경우 광노화로 인해 얼굴, 손등, 목 등의 피부에서 관찰되는 노화현상을 들 수 있다. Aging in which the composition according to the present invention is effective refers to skin aging in particular. The aging is a phenomenon caused by structural and functional changes in skin cells and tissues, and is mainly caused by genetic factors such as endogenous aging and ultraviolet rays, This includes extrinsic aging caused by environmental factors such as gravity and polluted air. As a result of aging, that is, the aging phenomenon includes, but is not limited to, wrinkles on the skin, elasticity of the skin, and sagging of the skin. Exemplary exogenous aging is the aging phenomenon observed in the skin of the face, back of the hand, neck, etc., due to photoaging when exposed to sunlight for a long time.

따라서 본원에 따른 화합물은 미용을 위한 화장품 조성물로 유용하게 사용될 수 있다. Therefore, the compound according to the present application can be usefully used as a cosmetic composition for beauty.

본원에서 사용된 용어 ‘화장품’은 인체를 청결 미화하여 용모를 밝게 변화시키거나 피부, 모발의 건강을 유지 또는 증진하기 위하여 인체에 사용되는 물품을 의미하며, 인체에 대한 작용이 경미한 것을 말한다. 통상적인 의미로서, 로션, 크림, 오일, 세정용 제품 및 기능성 화장품을 모두 포함한다. As used herein, the term 'cosmetics' refers to an article used in the human body to brighten the human body to brighten the appearance of the body or to maintain or promote the health of the skin and hair, and refers to a slight action on the human body. By conventional meaning, it includes all lotions, creams, oils, cleaning products and functional cosmetics.

본원에서 기능성 화장품이란 물리적, 생화학적, 생물공학적 수법 등을 이용하여 해당 화장품의 기능을 특정 목적에 작용, 발현하도록 부가가치를 부여한 화장품군이나 화장품 조성이 갖는 생체방어리듬조절, 질병방지와 회복 등에 관한 체조절기능을 생체에 대하여 충분히 발현하도록 설계하여 가공한 화장품을 의미하며, 특히 항노화 화장품을 의미한다.Functional cosmetics herein refers to the control of biological defense rhythms, disease prevention and recovery of cosmetic groups or cosmetic compositions that have added value to act and express the functions of cosmetics by using physical, biochemical and biotechnological techniques. It means cosmetics that are designed and processed to express the function of the gymnastics sufficiently to the living body, and in particular, mean anti-aging cosmetics.

본원에 따른 화장품 조성물은 화장품, 예를 들면, 크림, 로션, 앰플, 스킨, 에센스, 비누 등으로 제공될 수 있으며, 다른 측면에서 기초 화장품 조성물(화장수, 크림, 에센스, 클렌징 폼 및 클렌징 워터와 같은 세안제, 팩, 보디오일), 색조 화장품 조성물(화운데이션, 립스틱, 마스카라, 메이크업 베이스) 또는 마스크 또는 팩의 형태로 제조될 수 있다.Cosmetic compositions according to the invention may be provided as cosmetics, for example, creams, lotions, ampoules, skins, essences, soaps and the like, in other aspects such as basic cosmetic compositions (cosmetics, creams, essences, cleansing foams and cleansing water) Face wash, pack, body oil), color cosmetic composition (foundation, lipstick, mascara, makeup base) or in the form of a mask or pack.

본원에 따른 화장품 조성물이 적용될 수 있는 부위는 신체의 특정 부위에 한정되는 것은 아니며, 주 예를 들면 안면, 목 부위, 손등과 같은 주름이 있거나 주름지기 쉬운 피부 부위, 탄력의 증가 필요한 부위에 적용될 수 있다. The area to which the cosmetic composition according to the present invention can be applied is not limited to a specific part of the body, and may be applied to a wrinkled or wrinkled skin part such as a face, a neck part, a hand, etc. have.

본원에 따른 화장품 조성물은 적용되는 부위에 다양한 투여 경로, 예를 들면 전신 또는 국소, 특히 국소 투여, 경피, 또는 주사, 특히 경피 경로로 투여될 수 있다. Cosmetic compositions according to the invention can be administered at various sites of application, for example by systemic or topical, in particular topical, transdermal, or injection, in particular transdermal routes.

본원에 따른 화장품 조성물은 지시된 비율로 필수 성분으로서 본원의 화합물을 포함하는 외에는 다른 성분에는 특별한 제한이 없으며 통상의 화장품, 예를 들면 크림의 경우 식물성 오일, 유화제, 증점제, 향료, 물, 산화방지제, 및 UV 흡수제를 포함할 수 있다.The cosmetic composition according to the present application is not particularly limited to other ingredients except for including the compound of the present invention as essential ingredients in the indicated ratios, and in the case of ordinary cosmetics such as cream, vegetable oils, emulsifiers, thickeners, flavorings, water, antioxidants And UV absorbers.

본원에 따른 조성물에 포함되는 화합물의 함량은 목적하는 제품의 구체적 용도 또는 제형 등에 따라 달라질 수 있으나, 전체 조성물 중에 약 0.001 내지 약 50 중량%로 포함될 수 있으나, 이 범위를 벗어나는 것을 제외하는 것은 아니다. The content of the compound included in the composition according to the present application may vary depending on the specific use or formulation of the desired product, but may be included in about 0.001 to about 50% by weight in the total composition, but is not excluded from this range.

본원의 화합물을 포함하는 화장품 조성물은 상기 화합물 이외에 항산화제, 안정화제, 용해화제, 비타민, 안료 및/또는 향료와 같은 통상적인 보조제 및 담체를 포함할 수 있다. Cosmetic compositions comprising the compounds herein may include, in addition to the compounds, conventional adjuvants and carriers such as antioxidants, stabilizers, solubilizers, vitamins, pigments, and / or flavors.

본원의 화장품 조성물은 공액리놀레산, 리놀레산, 감마-리놀레산, 알파-리놀레산을 포함하는 불포화지방산 또는 프로필렌 글리콜을 포함하는 수용성 기제 물질을 포함할 수 있다. The cosmetic composition herein may comprise a water soluble base material comprising conjugated linoleic acid, linoleic acid, gamma-linoleic acid, unsaturated fatty acids including alpha-linoleic acid or propylene glycol.

또한 본원의 화장품 조성물은 항노화를 위해 피부에 투여하기에 적합한 당업계에서 통상적으로 제조되는 어떠한 제형으로도 제조될 수 있으며, 예를 들어 용액, 현탁액, 유탁액, 페이스트, 겔, 크림, 로션, 파우더, 비누, 계면활성제-함유 클렌징, 오일, 분말 파운데이션, 유탁액 파운데이션, 왁스 파운데이션 및 스프레이 등으로 제형화될 수 있으나, 이에 한정되는 것은 아니다. 보다 상세하게는, 유연 화장수, 영양 화장수, 영양 크림, 마사지 크림, 에센스, 아이 크림, 클렌징 크림, 클렌징 폼, 클렌징 워터, 마스크, 팩, 스프레이 또는 파우더의 제형으로 제조될 수 있다.Cosmetic compositions herein can also be prepared in any formulation conventionally prepared in the art suitable for administration to the skin for anti-aging, including, for example, solutions, suspensions, emulsions, pastes, gels, creams, lotions, Powders, soaps, surfactant-containing cleansing, oils, powder foundations, emulsion foundations, wax foundations, 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, mask, pack, spray or powder.

본원 조성물의 제형이 페이스트, 크림 또는 겔인 경우에는 담체 성분으로서 동물성유, 식물성유, 왁스, 파라핀, 전분, 트라칸트, 셀룰로오스 유도체, 폴리에틸렌 글리콜, 실리콘, 벤토나이트, 실리카, 탈크 또는 산화아연 등이 이용될 수 있다.When the formulation of the present composition 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. Can be.

본원 조성물의 제형이 파우더 또는 스프레이인 경우에는 담체 성분으로서 락토스, 탈크, 실리카, 알루미늄 히드록시드, 칼슘 실리케이트 또는 폴리아미드 파우더가 이용될 수 있고, 특히 스프레이인 경우에는 추가적으로 클로로플루오로히드로카본, 프로판/부탄 또는 디메틸 에테르와 같은 추진체를 포함할 수 있다.If the formulation of the composition is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used, especially in the case of a spray, additionally chlorofluorohydrocarbon, propane Propellant such as butane or dimethyl ether.

본원에 따른 화장품 조성물은 화장품용으로/피부학적으로 허용가능한 담체를 추가로 포함할 수 있다. “화장품용으로/피부학적으로 허용가능한”은 지나친 독성, 불상용성, 불안정성, 자극, 알러지 반응 등이 없이 조직(예를 들어, 피부 또는 모발)과 접촉하여 사용하기에 적합함을 의미한다.Cosmetic compositions according to the invention may further comprise a cosmetically / dermatologically acceptable carrier. “Cosmetic / dermatologically acceptable” means suitable for use in contact with tissue (eg skin or hair) without excessive toxicity, incompatibility, instability, irritation, allergic reactions, and the like.

본원 조성물의 제형이 용액 또는 유탁액인 경우에는 담체 성분으로서 용매, 용해화제 또는 유탁화제가 이용되고, 예컨대 물, 에탄올, 이소프로판올, 에틸 카보네이트, 에틸 아세테이트, 벤질 알코올, 벤질 벤조에이트, 프로필렌글리콜, 1,3-부틸글리콜, 글리세롤 지방족 에스테르, 폴리에틸렌 글리콜 또는 소르비탄의 지방산 에스테르가 사용될 수 있다. When the formulation of the composition is a solution or emulsion, a solvent, solubilizing agent or emulsifying agent 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, glycerol aliphatic ester, polyethylene glycol or sorbitan may be used.

본원 조성물의 제형이 현탁액인 경우에는 담체 성분으로서 물, 에탄올 또는 프로필렌글리콜과 같은 액상의 희석제, 에톡실화 이소스테아릴 알코올, 폴리옥시에틸렌 소르비톨 에스테르 및 폴리옥시에틸렌 소르비탄 에스테르와 같은 현탁제, 미소 결정성 셀룰로오스, 알루미늄 메타히드록시드, 벤토나이트, 아가 또는 트라칸트 등이 사용될 수 있다.When the formulation of the composition is a suspension, the carrier component is water, a liquid diluent such as ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, and microcrystals. Castle cellulose, aluminum metahydroxy, bentonite, agar or tracant and the like can be used.

본원 조성물의 제형이 계면-활성제 함유 클렌징인 경우에는 담체 성분으로서 지방족 알코올 설페이트, 지방족 알코올 에테르설페이트, 설포숙신산 모노에스테르, 이세티오네이트, 이미다졸리움 유도체, 메틸타우레이트, 사르코시네이트, 지방산 아미드 에테르 설페이트, 알킬아미도베타인, 지방족 알코올, 지방산 글리세리드, 지방산 디에탄올아미드, 식물성유, 라놀린 유도체 또는 에톡실화 글리세롤 지방산 에스테르 등이 이용될 수 있다. 바람직한 투여 유형에 따르면, 본 발명의 조성물은 최소한 하나의 약학적으로 허용되는 부형제, 특히 피부학적으로 허용 가능한 부형제를 포함할 수 있다. When the formulation of the present composition is a surfactant-containing cleansing, as a carrier component, an aliphatic alcohol sulfate, an aliphatic alcohol ether sulfate, a sulfosuccinic acid monoester, isethionate, an imidazolium 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. According to a preferred dosage type, the compositions of the present invention may comprise at least one pharmaceutically acceptable excipient, in particular dermatologically acceptable excipients.

또한, 상기 각 제형의 피부용 화장품 조성물에 있어서, 상기한 필수 성분 이외의 다른 성분들은 기타 피부용 조성물 또는 사용목적 등에 따라 당업자가 어려움 없이 선정하여 배합할 수 있다.In addition, in the cosmetic composition for skin of each formulation, other components than the above essential ingredients can be selected and blended by those skilled in the art without difficulty according to other skin compositions or purposes of use.

본 발명의 조성물은 독성 및 부작용은 거의 없으므로 예방 목적으로 장기간 투여 시에도 안심하고 사용할 수 있다. Since the composition of the present invention has little toxicity and side effects, it can be used with confidence even for prolonged administration for prophylactic purposes.

본원에 따른 일 구현예에서 본원에 따른 화합물 NAPS-1-P는 나노리포좀 제형으로 제조될 수 있다. 상기 나노리포좀은 통상적인 리포좀의 형태를 갖는 것으로서 평균 입자 지름이 100 내지 200nm인 리포좀, 특히 나노리포좀의 평균 입자 지름은 140 내지 160nm이다. 상기 리포좀은 미세한 캡슐이나 구의 형태를 띠고 있으며, 유효 성분을 피부에 직접 전달하는 역할을 수행할 수 있다. 본 발명에서는 상기 나노리포좀에 NAPS-1-P이 함유됨으로써, 상기 NAPS-1-P를 피부에 더욱 잘 전달, 흡수되도록 할 수 있다.In one embodiment according to the present disclosure the compound NAPS-1-P according to the present disclosure may be prepared as a nanoliposomal formulation. The nanoliposomes are in the form of conventional liposomes, and the average particle diameter of liposomes, particularly nanoliposomes, of 100-200 nm is 140-160 nm. The liposomes take the form of microcapsules or spheres and may serve to deliver the active ingredients directly to the skin. In the present invention, by containing NAPS-1-P in the nanoliposomes, the NAPS-1-P can be better delivered and absorbed to the skin.

상기 나노리포좀은 당업계에 공지된 다양한 방법을 통해 제조될 수 있다. 본원의 일 구현예에서 소니케이션으로 제조된다. 본 발명에 따른 나노리포좀은 통상적인, 쉘을 갖는 리포좀의 형태이다. 상기 리포좀은 미세한 캡슐이나 구의 형태를 띠고 있으며, 스킨케어에 사용되는 성분을 피부에 직접 전달하는 역할을 수행할 수 있다.The nanoliposomes can be prepared through various methods known in the art. In one embodiment of the present application is manufactured by Sony. Nanoliposomes according to the present invention are in the form of conventional, shelled liposomes. The liposomes take the form of fine capsules or spheres, and may serve to directly transfer the ingredients used in skin care to the skin.

일 구현예에서 본원에 따른 NAPS-1-P은 레시틴으로 형성된 리포좀에 함유되어 제공된다. 레시틴은 양친매성의 인지질로서 인산 및 지질성분으로 콜린, 글리세롤 또는 글리코지방산 또는 트리글리세라이드와 같은 지방산으로 구성된다. 포스파티딜콜린, 포스파디딜에탄올아민, 및/또는 포스파티딜이노시톨 등을 포함하며, 생체막의 주요 구성 성분으로, 다양한 동물, 식물, 효모 등에서 추출할 수 있으며, 시중에서 구입할 수 있다. In one embodiment NAPS-1-P according to the present application is provided contained in liposomes formed with lecithin. Lecithin is an amphiphilic phospholipid consisting of fatty acids such as choline, glycerol or glycofatty acid or triglycerides as phosphoric acid and lipid components. Phosphatidylcholine, phosphadidylethanolamine, and / or phosphatidyl inositol, and the like, and are the main constituents of biological membranes, which can be extracted from various animals, plants, yeasts, etc., and are commercially available.

다른 측면에서 본원은 또한 N-아세틸 피토스핑고신-1-포스페이트(NAPS-1-P) 또는 그 염을 포함하는 섬유아세포의 증식 촉진용 또는 콜라겐 합성 증진용 키트에 관한 것이다. In another aspect, the present invention also relates to a kit for promoting proliferation or enhancing collagen synthesis of fibroblasts comprising N-acetyl phytosphingosine-1-phosphate (NAPS-1-P) or salts thereof.

본원에 따른 키트에 포함되는 유효성분은 앞서 언급한 바를 참조할 수 있으며 인비트로에서 상기 목적하는 효과를 위한 추가의 성분 및 사용법 등을 추가로 포함할 수 있다. 본원에 따른 키트는 섬유아세포의 증식 촉진 또는 이를 통한 콜라겐 생성 촉진이 필요한 다양한 방식으로 사용될 수 있다.The active ingredient included in the kit according to the present disclosure may refer to the aforementioned, and may further include additional ingredients, usage, etc. for the desired effect in the in vitro. Kits according to the present invention can be used in a variety of ways that promote the growth of fibroblasts or promote collagen production through it.

앞서 언급한 바와 같이 본원에 따른 유효성분을 포함하는 화장품 조성물은 섬유아세포 증식 및 콜라겐 합성을 통해 주름개선 또는 탄력증진과 같이 피부의 상태를 개선할 수 있다. As mentioned above, the cosmetic composition comprising the active ingredient according to the present application may improve the condition of the skin such as wrinkle improvement or elasticity through fibroblast proliferation and collagen synthesis.

이에, 다른 양태에서 본원은 본원에 따른 화장품 조성물을 콜라겐 합성 또는 섬유아세포 증식 촉진을 통해 피부 상태 개선이 필요한 대상체의 피부에 도포하는 단계를 포함하는, 상기 대상체의 피부에서 콜라겐 합성을 촉진하는 방법에 관한 것이다. Thus, in another aspect, the present invention provides a method for promoting collagen synthesis in the skin of a subject comprising applying the cosmetic composition according to the present application to the skin of a subject in need of improving the skin condition through collagen synthesis or promoting fibroblast proliferation It is about.

아울러 또 다른 양태에서 따른 화장품 조성물을 피부 상태의 개선이 필요한 대상체의 피부에 도포하는 단계를 포함하는, 피부상태 개선 방법을 제공한다. In addition, the present invention provides a method for improving skin condition, comprising applying the cosmetic composition according to another embodiment to the skin of a subject in need of improvement of skin condition.

본원에 따른 방법에 사용되는 화장품 조성물은 앞서 언급한 바를 참조할 수 있다. 본원에 따른 화장품 조성물은 피부의 개선이 필요한 다양한 부위, 예를 들면 얼굴, 목, 손, 팔, 및 다리 등을 포함하는 전신의 전부 또는 일부에 적용될 수 있다. 본원에 따른 화장품은 목적하는 효과를 가져오기에 충분한 양으로 도포될 수 있으며, 당업자라면 본원에 개시된 사항 및 당업계의 지식을 고려하여 적절한 양을 판단할 수 있을 것이다. The cosmetic composition used in the method according to the invention can be referred to above. Cosmetic compositions according to the present application can be applied to all or part of the whole body, including various areas that need improvement of the skin, such as the face, neck, hands, arms, legs and the like. Cosmetics according to the present application may be applied in an amount sufficient to produce the desired effect, and those skilled in the art will be able to determine the appropriate amount in view of the disclosure herein and the knowledge in the art.

이하, 본 발명의 이해를 돕기 위해서 실시예를 제시한다. 그러나 하기의 실시예는 본 발명을 보다 쉽게 이해하기 위하여 제공되는 것일 뿐 본 발명이 하기의 실시예에 한정되는 것은 아니다.Hereinafter, examples are provided to help understand the present invention. However, the following examples are provided only to more easily understand the present invention, and the present invention is not limited to the following examples.

실 시 예 Example

실험재료 및 방법Experimental Materials and Methods

NAPS-1-P의 제조Preparation of NAPS-1-P

NAPS-1-P(N-아세틸 피토스핑고신-1-포스페이트)는 대한민국 등록특허 제1003532호에 기재된 방법에 따라 제조하여 사용하였다.NAPS-1-P (N-acetyl phytosphingosine-1-phosphate) was prepared and used according to the method described in Korean Patent No. 1003532.

섬유아세포의 증식 측정Proliferation of Fibroblasts

인간 섬유아세포(CCD-9865K, 한국세포주은행)를 10% 우태아혈청과 1% 페니실린/스트렙토마이신이 함유된 DMEM(Dulbecco's Modified Eagle Medium) 배지에서 3일마다 배양액을 교환하면서 배양하였다. 배양 환경은 37℃로 유지되는 5% CO2 배양기에서 배양하였다. 섬유아세포의 증식 효과는 MTT (3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-2H-tetrazolium bromide) assay (Sigma)를 제조자의 방법대로 사용하여 측정하였으며, 595nm에서 흡광도를 측정하여 세포증식 효과를 관찰하였다.Human fibroblasts (CCD-9865K, Korea Cell Line Bank) were incubated with DME (Dulbecco's Modified Eagle Medium) medium containing 10% fetal calf serum and 1% penicillin / streptomycin every 3 days with medium. The culture environment was incubated in a 5% CO 2 incubator maintained at 37 ° C. The proliferative effect of fibroblasts was measured using MTT (3- (4,5-dimethylthiazol-2yl) -2,5-diphenyl-2H-tetrazolium bromide) assay (Sigma) according to the manufacturer's method, and the absorbance at 595 nm was measured. The cell proliferation effect was observed.

콜라겐 합성 효과 측정Collagen Synthesis Effect Measurement

피부의 주름 개선효과를 측정하는 콜라겐 합성 촉진 효과를 보기 위하여 인간 섬유아세포를 10% 우태아혈청과 1% 페니실린/스트렙토마이신이 함유된 DMEM 배지에서 3일마다 배양액을 교환하면서 배양하였다. 배양 환경은 37℃로 유지되는 5% CO2 배양기에서 배양하였다. 24시간 배양 후에 배양배지로 희석(디메칠설폭사이드 (DMSO)에 10000ppm으로 녹인 후 배지로 희석하여 0.1-10ppm으로 희석)한 NAPS-1-P를 첨가한 후에 24시간 동안 배양하였다. 이어 배양액을 취하여, 프로콜라겐 타입 I(procollagen type I) C-peptide EIA kit (Takara Bio Inc, MK 101)을 제조자의 방법대로 이용하여 콜라겐 양을 측정하였다. 450nm에서 흡광도를 측정하여 콜라겐 양을 계산하였다.Human fibroblasts were cultured every 3 days in DMEM medium containing 10% fetal calf serum and 1% penicillin / streptomycin to see the effect of promoting collagen synthesis to measure the wrinkle improvement effect of the skin. The culture environment was incubated in a 5% CO 2 incubator maintained at 37 ° C. After incubation for 24 hours, the solution was diluted with culture medium (dissolved in dimethyl sulfoxide (DMSO) at 10000 ppm, diluted with medium, and diluted to 0.1-10 ppm), followed by incubation for 24 hours. Subsequently, the culture medium was taken, and collagen amount was measured using a procollagen type I C-peptide EIA kit (Takara Bio Inc, MK 101) according to the manufacturer's method. The absorbance was measured at 450 nm to calculate the amount of collagen.

NAPS-1-P 함유 나노리포좀 제조 Preparation of NAPS-1-P-containing Nanoliposomes

피부에 도포할 나노리포좀은 하기에 기재한 바와 같이 소니케이션 방법으로 제조하였으며, 나노리포좀의 조성은 하기 표 1에 나타낸 바와 같다. 구체적으로 나노리포좀의 제조를 위해 레시틴은 에탄올 혹은 부틸렌글리콜과 헥산디올 용액에 먼저 분산시켰다. NAPS-1-P과 아르기닌을 혼합한 후 물을 첨가하여 가온하여 용해시켰다. 상기 제조한 NAPS-1-P 용액을 레시틴 용액에 천천히 첨가하면서 강하게 교반해 주었다. 30분간 교반한 후에 60분간 배스 타입(bath type) 소니케이터로 초음파 처리하였다. 제조된 나노리포좀의 입자 크기는 레이저 광산란(laser light scattering)을 이용하여 제조자의 방법대로 측정하였다 (Photal Otsuka Electronics, Japan). 나노리포좀의 입자 크기는 부피 분포(volume distribution)로 나타내었다.Nanoliposomes to be applied to the skin was prepared by the sonication method as described below, the composition of the nanoliposomes are shown in Table 1 below. Specifically, lecithin was first dispersed in ethanol or butylene glycol and hexanediol for the preparation of nanoliposomes. NAPS-1-P and arginine were mixed and then dissolved by warming with water. The prepared NAPS-1-P solution was stirred vigorously while slowly added to the lecithin solution. After stirring for 30 minutes, it was sonicated with a bath type sonicator for 60 minutes. The particle size of the prepared nanoliposomes was measured according to the manufacturer's method using laser light scattering (Photal Otsuka Electronics, Japan). The particle size of the nanoliposomes is shown by volume distribution.

하기 조성 1과 조성 2로 만들어진 나노리포좀은 매우 안정한 상태로 만들어졌으며, 나노리포좀의 입자 크기를 측정한 결과, 두 조성에서 입자 크기 차이는 없었다. 도 3에서 보는 것처럼, 두 조성에서 평균 입자의 크기가 150nm 정도인 것으로 나타났다.The nanoliposomes made of the following compositions 1 and 2 were made in a very stable state, and the particle size of the nanoliposomes was measured, and there was no difference in particle size in the two compositions. As shown in FIG. 3, the average particle size of the two compositions was found to be about 150 nm.

[표 1] NAPS-1-P를 함유한 나노리포좀의 조성Table 1 Composition of Nanoliposomes Containing NAPS-1-P

Figure PCTKR2017006175-appb-I000002
Figure PCTKR2017006175-appb-I000002

피부 탄력 측정Skin elasticity measurement

피부 탄력 기기 평가는 Cutometer MPA580 (Courage and Khazaka, Germany) 측정 장비를 제조자의 방법대로 이용하여 측정하였다. 측정방법은 기기에 연결된 2mm 직경의 probe를 피부에 밀착시키고 비침습적인 방법으로 측정하였다. 측정단위는 임의의 단위 AU(arbitary unit)로 표시된다. 측정은 피부에 적용하기 전과 적용 후 2주 및 4주 후에 측정하였다. 피부탄력 개선율은 다음과 같이 계산하였다. Skin firmness instrument evaluation was determined using the Cutometer MPA580 (Courage and Khazaka, Germany) measuring equipment according to the manufacturer's method. The measurement method was a non-invasive method of 2mm diameter probe connected to the device in close contact with the skin. The unit of measurement is expressed in arbitrary units AU (arbitary unit). The measurements were taken before and two and four weeks after application to the skin. Skin elasticity improvement rate was calculated as follows.

개선율 (%) = (화장품 도포후 측정값 평균 - 화장품 사용전 측정 값 평균) / 화장품 사용전 측정 값 평균 X 100Improvement rate (%) = (measured value after applying cosmetics-average value measured before using cosmetics) / average value measured before using cosmetics X 100

피부탄력을 측정하기 위한 NAPS-1-P 나노리포좀을 함유하는 화장품(앰플)을 제조하였다. 앰플 화장품의 조성은 아래의 표 2와 같다.Cosmetics (ampoules) containing NAPS-1-P nanoliposomes for measuring skin elasticity were prepared. The composition of the ampoule cosmetics is shown in Table 2 below.

[표 2] 조성1과 2를 함유한 앰플 화장품의 조성Table 2 Composition of ampoule cosmetics containing compositions 1 and 2

Figure PCTKR2017006175-appb-I000003
Figure PCTKR2017006175-appb-I000003

실시예 1. NAPS-1-P에 의한 섬유아세포 증식 촉진효과Example 1 Fibroblast Proliferation Promoting Effect by NAPS-1-P

사람 섬유아세포는 콜라겐을 합성하는 세포로 섬유아세포의 증식을 촉진시키는 것으로 주름개선 효과를 측정할 수 있다. NAPS-1-P를 섬유아세포에 배양시 첨가하면 섬유아세포의 증식이 촉진되는 것으로 나타났다 (도 1). NAPS-1-P의 전구물질인 N-아세틸 피토스핑고신(N-acetyl phytosphingosine, NAPS)과 NAPS-1-P의 섬유아세포 증식효과를 측정한 결과 NAPS는 섬유아세포의 증식을 촉진하는 것이 아니라 반대로 사멸을 촉진하는 결과를 얻었지만, NAPS-1-P는 섬유아세포 증식을 촉진하는 결과를 얻었다 (표 3, 도 2). 따라서 NAPS-1-P는 NAPS와는 달리 섬유아세포의 증식을 촉진하므로, 주름개선을 포함하는 항노화 화장품에 유용하게 사용될 수 있음을 나타내는 것이다. Human fibroblasts are cells that synthesize collagen, which promotes the proliferation of fibroblasts and can measure the effect of improving wrinkles. Addition of NAPS-1-P in the culture of fibroblasts was shown to promote the proliferation of fibroblasts (FIG. 1). As a result of measuring the fibroblast proliferation effect of N-acetyl phytosphingosine (NAPS) and NAPS-1-P precursors of NAPS-1-P, NAPS does not promote fibroblast proliferation. On the contrary, the result of promoting death was obtained, but NAPS-1-P resulted in promoting fibroblast proliferation (Table 3, FIG. 2). Therefore, NAPS-1-P, unlike NAPS, promotes the proliferation of fibroblasts, indicating that it can be usefully used in anti-aging cosmetics including wrinkle improvement.

[표 3] NAPS-1-P와 NAPS의 섬유아세포 생존율 비교[Table 3] Fibroblast Survival Comparison of NAPS-1-P and NAPS

Figure PCTKR2017006175-appb-I000004
Figure PCTKR2017006175-appb-I000004

실시예 2. NAPS-1-P에 의한 콜라겐 생성 촉진 효과Example 2 Collagen Production Promoting Effect by NAPS-1-P

주름개선, 탄력 증진을 위해서는 콜라겐의 합성 촉진과 분해 억제가 중요하다. 따라서 주름개선, 탄력 증진을 포함하는 항노화 화장품을 위해서는 콜라겐 합성 증가와 콜라겐의 분해 억제 효과를 측정하였다. NAPS-1-P를 섬유아세포 배양시 첨가하였을 때, 섬유아세포의 증식과 더불어, 섬유아세포에서 합성하는 콜라겐의 양이 증가를 측정하였다. NAPS-1-P의 농도가 증가하면서 섬유아세포의 증식 뿐 아니라 콜라겐의 생성도 증가하는 것으로 나타났다(도 3). 상기 결과는 NAPS-1-P에 의해 콜라겐의 합성이 촉진되어 콜라겐 생성이 증가되는 것을 알 수 있고, 이로써 NAPS-1-P에 의해 주름개선, 탄력증가의 효과가 있으므로, NAPS-1-P는 주름개선 및 탄력증가를 포함하는 항노화 화장품에 유용하다.In order to improve wrinkles and improve elasticity, it is important to promote collagen synthesis and inhibit degradation. Therefore, for anti-aging cosmetics including wrinkle improvement and elasticity enhancement, collagen synthesis and collagen degradation inhibitory effects were measured. When NAPS-1-P was added in the culture of fibroblasts, the growth of fibroblasts and the amount of collagen synthesized in the fibroblasts were measured. Increasing the concentration of NAPS-1-P was shown to increase the production of collagen as well as the proliferation of fibroblasts (Fig. 3). The results indicate that the synthesis of collagen is promoted by NAPS-1-P, which increases collagen production. As a result, NAPS-1-P has an effect of improving wrinkles and increasing elasticity. It is useful for anti-aging cosmetics including wrinkle improvement and elasticity.

실시예 3. 피부탄력 증진 효과Example 3. Skin elasticity enhancing effect

상기 실험방법에 기재된 바와 같이 조성 1과 2의 나노리포좀을 함유한 앰플 화장품을 제조하여 피부에 도포한 후 피부 탄력 변화를 측정하였다. 피험자는 피부노화를 고민하는 30대에서 50대 (평균나이 43.2) 20명을 대상으로 앰플 1은 오른쪽 얼굴에, 앰플 2는 왼쪽 얼굴에 1일 2회씩 4주간 도포하도록 하였다. 피부탄력은 도포 전 및 도포 후 2주 및 4주째 측정하였고 그 결과를 표 4에 나타내었다. 그 결과 피부 탄력은 도포 시간 경과에 따라 증가하는 경향을 보이고 있으며, 바르기 전보다 높은 피부 탄력을 보여주고 있다. 상이한 조성의 두 종류 앰플 화장품 사이에서는 피부 탄력도는 차이가 없었다. 이러한 결과는, NAPS-1-P는 주름개선 및 탄력증가 개선을 포함하는 항노화 화장품에 유용하게 사용될 수 있는 물질임을 나타낸다. As described in the above experimental method, ampoule cosmetics containing the nanoliposomes of the compositions 1 and 2 were prepared and applied to the skin, and then the change in skin elasticity was measured. Subjects were asked to apply ampoule 1 to the right face and ampoule 2 to the left face twice a day for 4 weeks for 20 people in their 30s to 50s (mean age 43.2) who are concerned about skin aging. Skin elasticity was measured before and 2 weeks and 4 weeks after application and the results are shown in Table 4. As a result, the skin elasticity tends to increase with the application time and shows higher skin elasticity than before application. There was no difference in skin elasticity between the two ampoule cosmetics of different compositions. These results indicate that NAPS-1-P is a material that can be usefully used in anti-aging cosmetics including wrinkle improvement and elasticity improvement.

[표 4] NAPS-1-P를 함유한 앰플 화장품 피부 탄력도 변화[Table 4] Change of skin elasticity of ampoule cosmetics containing NAPS-1-P

Figure PCTKR2017006175-appb-I000005
Figure PCTKR2017006175-appb-I000005

상기한 바와 같이 NAPS-1-P를 함유하는 조성물은 섬유아세포의 증식을 증가시키고, 콜라겐 합성도 증가시키는 효과를 가진다. 피부에 직접 본원에 따른 조성물을 포함하는 앰플을 도포한 결과 피부탄력도 증가하는 것으로 나타났다. 따라서 본원의 NAPS-1-P를 함유하는 조성물은 주름개선 및 탄력증가 개선을 포함하는 항노화 화장품에 유용하게 사용될 수 있다.As described above, the composition containing NAPS-1-P has the effect of increasing the proliferation of fibroblasts and also increasing collagen synthesis. The application of ampoules comprising the composition according to the present application directly to the skin also showed an increase in skin elasticity. Therefore, the composition containing NAPS-1-P of the present application can be usefully used in anti-aging cosmetics including wrinkle improvement and elasticity improvement.

이상에서 본원의 예시적인 실시예에 대하여 상세하게 설명하였지만 본원의 권리범위는 이에 한정되는 것은 아니고 다음의 청구범위에서 정의하고 있는 본원의 기본 개념을 이용한 당업자의 여러 변형 및 개량 형태 또한 본원의 권리범위에 속하는 것이다.Although the exemplary embodiments of the present application have been described in detail above, the scope of the present application is not limited thereto, and various modifications and improvements of those skilled in the art using the basic concepts of the present invention defined in the following claims are also provided. It belongs to.

본 발명에서 사용되는 모든 기술용어는, 달리 정의되지 않는 이상, 본 발명의 관련 분야에서 통상의 당업자가 일반적으로 이해하는 바와 같은 의미로 사용된다. 본 명세서에 참고문헌으로 기재되는 모든 간행물의 내용은 본 발명에 도입된다.All technical terms used in the present invention, unless defined otherwise, are used in the meaning as commonly understood by those skilled in the art in the related field of the present invention. The contents of all publications described herein by reference are incorporated into the present invention.

Claims (12)

N-아세틸 피토스핑고신-1-포스페이트(NAPS-1-P) 또는 그 화장품용으로 허용가능한 염 및 화장품용으로 허용가능한 담체를 포함하는 항노화용 화장품 조성물. An anti-aging cosmetic composition comprising N-acetyl phytosphingosine-1-phosphate (NAPS-1-P) or a cosmetic acceptable salt thereof and a cosmetically acceptable carrier. 제 1 항에 있어서, 상기 항노화는 피부 주름개선 또는 피부 탄력 증가인, 항노화 화장품 조성물. The anti-aging cosmetic composition of claim 1, wherein the anti-aging is skin wrinkle improvement or skin elasticity increase. 제 1 항에 있어서, 상기 조성물은 피부 도포를 위한 리포좀 제형인, 항노화 화장품 조성물. The anti-aging cosmetic composition of claim 1, wherein the composition is a liposome formulation for skin application. 제 3 항에 있어서, 상기 리포좀의 쉘은 레시틴을 포함하며, 상기 리포좀의 평균 직경은 약 100 내지 200 나노미터인, 항노화 화장품 조성물. The anti-aging cosmetic composition of claim 3, wherein the shell of the liposome comprises lecithin, and the average diameter of the liposome is about 100 to 200 nanometers. N-아세틸 피토스핑고신-1-포스페이트(NAPS-1-P) 또는 그 화장품용으로 허용가능한 염 및 화장품용으로 허용가능한 담체를 포함하는 콜라겐 생성 촉진용 화장품 조성물. Cosmetic composition for promoting collagen production comprising N-acetyl phytosphingosine-1-phosphate (NAPS-1-P) or an acceptable salt for cosmetics and an acceptable carrier for cosmetics. N-아세틸 피토스핑고신-1-포스페이트(NAPS-1-P) 또는 그 화장품용으로 허용가능한 염 및 화장품용으로 허용가능한 담체를 포함하는 주름억제 또는 개선용 화장품 조성물.N-acetyl phytosphingosine-1-phosphate (NAPS-1-P) or a cosmetic composition for inhibiting or improving wrinkles comprising a salt acceptable for cosmetics and an acceptable carrier for cosmetics. 제 1 항 내지 제 6 항 중 어느 한 항에 있어서, 상기 화장품 조성물이 화장수, 로션, 크림, 에센스, 또는 앰플 형태인, 조성물. The composition of claim 1, wherein the cosmetic composition is in the form of a lotion, lotion, cream, essence, or ampoule. 제 1 항 내지 제 6 항 중 어느 한 항에 있어서, 상기 N-아세틸 피토스핑고신-1-포스페이트(NAPS-1-P) 또는 그 화장품용으로 허용가능한 염은 0.01 내지 100ppm으로 포함되는 것인, 조성물. The method according to any one of claims 1 to 6, wherein the N-acetyl phytosphingosine-1-phosphate (NAPS-1-P) or a cosmetically acceptable salt thereof is included in an amount of 0.01 to 100 ppm. , Composition. N-아세틸 피토스핑고신-1-포스페이트(NAPS-1-P)의 섬유아세포의 증식 촉진용 용도. Use for promoting the proliferation of fibroblasts of N-acetyl phytosphingosine-1-phosphate (NAPS-1-P). N-아세틸 피토스핑고신-1-포스페이트(NAPS-1-P)의 세포의 콜라겐 합성 증진용 용도. Use of N-acetyl phytosphingosine-1-phosphate (NAPS-1-P) for enhancing collagen synthesis of cells. 제 1 항에 따른 화장품 조성물을 대상체의 피부에 도포하는 단계를 포함하는, 상기 대상체의 피부에서 콜라겐 합성을 촉진하는 방법. A method of promoting collagen synthesis in the skin of a subject, comprising applying the cosmetic composition of claim 1 to the skin of the subject. 제 1 항에 따른 화장품 조성물을 피부상태의 개선이 필요한 대상체의 피부에 도포하는 단계를 포함하는, 주름개선 또는 탄력증진을 포함하는 피부상태 개선 방법. A method for improving skin conditions, including wrinkle improvement or elasticity enhancement, comprising applying the cosmetic composition of claim 1 to the skin of a subject in need of improvement of skin condition.
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