WO2016163698A1 - 미세먼지에 의한 피부 손상 진단용 조성물 및 갈랑긴을 유효성분으로 포함하는 조성물 - Google Patents
미세먼지에 의한 피부 손상 진단용 조성물 및 갈랑긴을 유효성분으로 포함하는 조성물 Download PDFInfo
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- WO2016163698A1 WO2016163698A1 PCT/KR2016/003464 KR2016003464W WO2016163698A1 WO 2016163698 A1 WO2016163698 A1 WO 2016163698A1 KR 2016003464 W KR2016003464 W KR 2016003464W WO 2016163698 A1 WO2016163698 A1 WO 2016163698A1
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- gene
- skin
- composition
- fine dust
- galangin
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- 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
- A61Q19/10—Washing or bathing preparations
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/136—Screening for pharmacological compounds
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/158—Expression markers
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2500/00—Screening for compounds of potential therapeutic value
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/20—Dermatological disorders
Definitions
- Disclosed herein is a novel use of a biomarker and a composition comprising the same, a kit comprising the same, and a composition containing galangin as an active ingredient, which can be used to diagnose skin damage caused by fine dust.
- the epidermis of the skin's constituent layers plays an important role in preventing evaporation of moisture inside the human body.
- the epidermis is divided into the stratum corneum, granule layer, polar layer, and basal layer in order from the outside, and the cells of the stratum corneum act as bricks and the intercellular lipids between the stratum corneum act as mortars to form the skin barrier (J Invest.Drmatol. 80 (Suppl.), 44-49.1983.
- the keratinocytes of healthy people have a high concentration of Natural Moisturing Factor (NMF) to help the skin retain moisture.
- NMF Natural Moisturing Factor
- an object of the present invention is to provide a method for diagnosing skin damage caused by fine dust.
- an object of the present invention is to provide a biomarker and a composition containing the same that can be used to diagnose the skin damage caused by fine dust.
- an object of the present invention is to provide a composition containing galangin as an active ingredient.
- an object of the present invention is to provide a composition having a skin moisturizing effect, skin barrier function enhancement or skin keratinocyte differentiation inducing effect.
- an object of the present invention is to prevent or ameliorate skin diseases associated with dry skin or skin barrier dysfunction.
- the present invention silver S100A7 (NM_002963), S100A8 (NM_002964), S100A9 (NM_002965), CYP1A1 (NM_000499), CYP1B1 (NM_000104), PI3 (NM_002638), IL36G (NM_019618), IL000B (NM27) NM_006664), IL8 (NM_000584), PTGS2 (NM_000963), NOX5 (NM_001184779), XDH (NM_000379), CXCL14 (NM_004887), SOD3 (NM_003102), KRT1 (NM_006121), H19 (NR_002196), CAS1014 NM_000421), CASP8 (NM_001080125), KRT15 (NM_002275) and KRT13 (NM_002274) skin cells or skin due to fine dust, including an agent for measuring the expression level of the mRNA or protein of one or
- the present invention provides a kit for diagnosing damage to skin cells or skin barriers by fine dust, comprising the composition.
- the present invention provides a skin moisturizing composition
- a skin moisturizing composition comprising galangin, an isomer thereof, a pharmaceutically acceptable salt thereof, a prodrug thereof, a hydrate thereof, or a solvate thereof as an active ingredient.
- the present invention provides a composition for enhancing skin barrier function comprising galangin, an isomer thereof, a pharmaceutically acceptable salt thereof, a prodrug thereof, a hydrate thereof, or a solvate thereof as an active ingredient.
- the present invention provides a composition for inducing skin keratinocyte differentiation comprising galangin, an isomer thereof, a pharmaceutically acceptable salt thereof, a prodrug thereof, a hydrate thereof, or a solvate thereof as an active ingredient.
- the present invention also provides a composition for improving skin damage by fine dust comprising galangin, an isomer thereof, a pharmaceutically acceptable salt thereof, a prodrug thereof, a hydrate thereof or a solvate thereof as an active ingredient.
- a biomarker for diagnosing skin cell damage by fine dust and a composition containing the same according to whether the damage to the skin cell by the fine dust, the expression of the gene to increase or decrease the expression of the skin It is possible to easily and quickly diagnose whether the cells are damaged, and to check whether the action of the protein encoded by the gene is inhibited or increased, thereby easily screening skin cell damage inhibitors by fine dust.
- composition containing the galangin, the isomer thereof, the pharmaceutically acceptable salt thereof, the prodrug thereof, the hydrate thereof or the solvate thereof as an active ingredient of the present invention promotes the synthesis of filaggrin and keratin, and the skin keratinization.
- promoting the differentiation of the cells to have a skin moisturizing or skin barrier strengthening effect can be used to prevent, treat or improve skin diseases such as atopy, psoriasis. It can also be used to improve damaged skin due to fine dust.
- Figure 1 shows the cell survival rate by the treatment of the fine dust extract, wherein ADSP represents the yellow dust as Asian dust storm particles, PM10 (Particulate matter 10) is fine dust having a particle size of 10 ⁇ m PM2.5 (Particulate matter 2.5) indicates fine dust having a particle size of 2.5 ⁇ m.
- 2A to 2K are diagrams showing that expression levels of genes whose expression levels are increased in skin cells stimulated by microdust are decreased by the treatment of galangin.
- 3A to 3K show that genes whose expression levels are reduced in skin cells stimulated by fine dust increase the expression levels by treatment with galangin.
- 4A to 4E show pilaggrin, keratin 10, keratin 1, keratin 13, and keratin 13 according to the concentration of galangin treated in human normal keratinous skin cells. ), And the relative mRNA expression levels of keratin 15 (Keratin 15).
- Figure 5 shows the degree of differentiation of keratinocytes not treated with fine dust according to the concentration of the treated galangin.
- FIG. 6 confirms the degree of synthesis of filaggrin protein according to the concentration of treated galangin in human normal keratin skin not treated with fine dust.
- fine dust refers to a substance having a particle size of 10 ⁇ m or less as a particulate matter that floats or scatters in the air for a long time as a very small substance which is invisible to the human eye. Particularly, particulate matter having a particle diameter of 2.5 ⁇ m or less is referred to as “ultrafine dust”. In the present invention, “fine dust” is intended to include “ultrafine dust”.
- the present invention relates to a biomarker for diagnosing damage to skin cells or skin barriers due to fine dust, comprising one or more selected from the group consisting of specific genes and proteins encoded from the genes.
- the specific genes are S100A7 (NM_002963), S100A8 (NM_002964), S100A9 (NM_002965), CYP1A1 (NM_000499), CYP1B1 (NM_000104), PI3 (NM_002638), IL36G (NM_019618), IL1B (NM664278) (NM_000584), PTGS2 (NM_000963), NOX5 (NM_001184779), XDH (NM_000379), CXCL14 (NM_004887), SOD3 (NM_003102), KRT1 (NM_006121), H19 (NR_002196), CASP14 (NM_012114), M_000 (NM_001080125), KRT15 (NM_002275) and KRT13 (NM_002274) may be one or more genes selected from the group.
- genes preferably two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, At least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, or at least 22 genes, or all of these genes May be used as a biomarker for diagnosing damage to skin cells or skin barriers due to fine dust.
- the present invention in another aspect, comprising a preparation for measuring the expression level of the mRNA or protein of one or more genes selected from the group consisting of the gene, the composition for diagnosing damage to the skin cells or skin barrier by fine dust to be.
- the present invention in one aspect, in the preparation of a composition for diagnosing damage to skin cells or skin barriers by fine dust, S100A7 (NM_002963) gene, S100A8 (NM_002964) gene, S100A9 (NM_002965) gene, CYP1A1 (NM_000499) Gene, CYP1B1 (NM_000104) gene, PI3 (NM_002638) gene, IL36G (NM_019618) gene, IL1B (NM_000576) gene, CCL27 (NM_006664) gene, IL8 (NM_000584) gene, PTGS2 (NM_000963) gene, NOX5 (NM_001184779 gene) XDH (NM_000379) gene, CXCL14 (NM_004887) gene, SOD3 (NM_003102) gene, KRT1 (NM_006121) gene, H19 (NR_002196) gene, CASP14 (NM_012114) gene, KRT10 (NM_
- S100A7 (NM_002963) gene, S100A8 (NM_002964) gene, S100A9 (NM_002965) gene, CYP1A1 (NM_000499) gene, CYP1B1 (NM_000104) gene, PI3 (NM_002638) gene, IL36G (NM_019618) gene, IL36 (NM_000576) gene, CCL27 (NM_006664) gene, IL8 (NM_000584) gene, PTGS2 (NM_000963) gene, NOX5 (NM_001184779) gene, XDH (NM_000379) gene, CXCL14 (NM_004887) gene, SOD3 (NM_003102) gene, KRT121 ) MRNA, H19 (NR_002196) gene, CASP14 (NM_012114) gene, KRT10 (NM_000421) gene, CASP8 (NM_001080125) gene, KRT15 (NM_002275
- the agent may be a polynucleotide or fragment thereof complementary to an mRNA of a gene, a primer or probe capable of amplifying the gene, or an antibody that specifically recognizes the protein, such as a monoclonal antibody or polyclonal antibody. Can be.
- the present invention is a kit comprising a composition for diagnosing damage to skin cells or skin barriers due to the fine dust.
- a kit comprising a composition for diagnosing damage to skin cells or skin barriers due to the fine dust.
- CXCL14 (NM_004887) gene, SOD3 (NM_003102) gene, KRT1 (NM_006121) gene, H19 (NR_002196) gene, CASP14 (NM_012114) gene, measured from skin cells of subject , MRNA of one or more genes selected from the group consisting of KRT10 (NM_000421) gene, CASP8 (NM_001080125) gene, KRT15 (NM_002275) gene, KRT13 (NM_002274) gene, and Filaggrin gene or a protein encoded therefrom The degree is lower in the skin cell sample that is not damaged by fine dust, or 2) the S100A7 (NM_002963) gene, the S100A8 (NM_002964) gene, the S100A9 (NM_002965) gene, CYP1A1 (NM_000499), measured from skin cells of the subject.
- the kit is S100A7, S100A8, S100A9, CYP1A1, CYP1B1, PI3, IL36G, IL1B, CCL27, IL8, PTGS2, NOX5, XDH, CXCL14, SOD3, KRT1, H19, CASP14, KRT10, CASP8, KRT15 and KRT15 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, 10 or more, 11 or more selected from the group consisting of KRT13 , At least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, or at least 22 genes or all of these genes It may include one or more antibodies that specifically recognize the protein encoded by the, and by measuring the amount of the antigen bound to the antibody in the skin cells to be diagnosed, it is possible to determine whether the skin damage by the fine dust .
- the present invention is a method for diagnosing damage to skin cells or skin barriers due to fine dust.
- the method comprises: a) S100A7 (NM_002963) gene, S100A8 (NM_002964) gene, S100A9 (NM_002965) gene, CYP1A1 (NM_000499) gene, CYP1B1 (NM_004104) gene, PI3 (NM_002638) gene from a subject's skin cell sample.
- IL36G (NM_019618) gene, IL1B (NM_000576) gene, CCL27 (NM_006664) gene, IL8 (NM_000584) gene, PTGS2 (NM_000963) gene, NOX5 (NM_001184779) gene, XDH (NM_000379) gene, CXCL14 (NM_0043) gene (NM_003102) gene, KRT1 (NM_006121) gene, H19 (NR_002196) gene, CASP14 (NM_012114) gene, KRT10 (NM_000421) gene, CASP8 (NM_001080125) gene, KRT15 (NM_002275) gene and KRT13 (NM_002274) gene Measuring the expression level of mRNA of one or more genes selected or a protein encoded therefrom; And b) comparing the expression level with the expression level of the mRNA of the gene or a protein encoded therein in a skin cell sample which is not damaged by fine dust.
- the method 1) CXCL14 (NM_004887) gene, SOD3 (NM_003102) gene, KRT1 (NM_006121) gene, H19 (NR_002196) gene, CASP14 (NM_012114) gene, measured from the skin cells of the subject,
- the expression level of mRNA of one or more genes selected from the group consisting of KRT10 (NM_000421) gene, CASP8 (NM_001080125) gene, KRT15 (NM_002275) gene, KRT13 (NM_002274) gene, and Filaggrin gene or protein encoded therefrom Is lower in the skin cell sample that is not damaged by fine dust, or 2) the S100A7 (NM_002963) gene, the S100A8 (NM_002964) gene, the S100A9 (NM_002965) gene, the CYP1A1 (NM_000499) gene, measured from skin cells of the subject.
- CYP1B1 (NM_000104) gene, PI3 (NM_002638) gene, IL36G (NM_019618) gene, IL1B (NM_000576) gene, CCL27 (NM_006664) gene, IL8 (NM_000584) gene, PTGS2 (NM_000963) gene, NOX5 (NM_001184779 ) If the expression level of the mRNA of the one or more genes selected from the group consisting of the gene and the XDH (NM_000379) gene or the protein encoded therefrom is lower in the skin cell sample which is not damaged by the fine dust, the skin cells are caused by the fine dust. Or determining that the skin barrier is damaged.
- the method of measuring the expression level of the mRNA or protein of the gene is microarray, PCR, NGS (Nest Generation Sequencing), Western blot, Northern blot, ELISA, radioimmunoassay, radiation It can be selected from the group consisting of immunodiffusion, tissue immunostaining and immunoprecipitation assays.
- normal level such as the amount of gene expression used in the present invention means the amount of gene expression in normal skin cells that are not stimulated by fine dust.
- the present invention by measuring the amount of one or more mRNAs or proteins of the above genes in the skin cells to be diagnosed, and comparing the measured value with the expression level in normal skin cells not stimulated by fine dust, whether the skin cells are damaged Will be evaluated.
- the term “high or low” means that there is a difference compared to the reference amount, and the amount is increased by 1.5 times or more, 2 times or more, preferably 2.2 times or more, compared to the reference amount. Or reduced to show a difference in quantity.
- Tables 1 and 2 a gene whose expression level is increased or decreased by fine dust is shown in Tables 1 and 2 below.
- Table 1 shows genes whose expression level is increased by fine dust
- Table 2 shows genes whose expression level is reduced by fine dust
- Name means genebank accession ID of NCBI
- Gene Symbol is It means official gene symbol
- Gene title means name of each gene.
- the polynucleotide used as a probe in the kit of the present invention includes a full length or a fragment thereof of a marker gene whose expression level is increased or decreased by stimulation by microdust.
- the length of the fragment preferably includes 10 or more contiguous nucleotides, since non-specifically bound probes of 10 bps or less.
- the polynucleotide used as a primer in the kit of the present invention is not limited in length, but it is advantageous to use a primer of 18 to 22 preferably.
- Monoclonal antibodies to the polypeptides encoded by the marker gene, included in the kit of the present invention can be prepared by a general monoclonal antibody production method.
- the present invention provides a composition for inhibiting or ameliorating damage of skin cells caused by fine dust by controlling the expression level of a specific gene in the skin cells damaged by fine dust to a normal level.
- the genes in the skin cells affected by the fine dust are S100A7, S100A8, S100A9, CYP1A1, CYP1B1, PI3, IL36G, IL1B, CCL27, IL8, PTGS2, NOX5, XDH, CXCL14, SOD3, KRT1, H19, CASP14, KRT10, CASP8, KRT15, KRT13 and the like.
- S100A7, S100A8, S100A9, CYP1A1, CYP1B1, PI3, IL36G, IL1B, CCL27, IL8, PTGS2, NOX5 and XDH are genes whose expression levels are increased by fine dust, skin cells by reducing the expression level of these genes to normal levels Suppresses damage.
- CXCL14, SOD3, KRT1, H19, CASP14, KRT10, CASP8, KRT15, and KRT13 are genes with reduced expression levels, damage to skin cells is suppressed by increasing the expression levels of these genes to normal levels.
- the invention in one aspect, the step of treating the fine dust on the skin cells; Treating the test substance on the skin cells treated with the fine dust; And in the skin cells treated with the test substance, S100A7 (NM_002963) gene, S100A8 (NM_002964) gene, S100A9 (NM_002965) gene, CYP1A1 (NM_000499) gene, CYP1B1 (NM_004104) gene, PI3 (NM_002638) before and after test substance treatment.
- IL36G (NM_019618) Gene, IL1B (NM_000576) Gene, CCL27 (NM_006664) Gene, IL8 (NM_000584) Gene, PTGS2 (NM_000963) Gene, NOX5 (NM_001184779) Gene, XDH (NM_000379) Gene, CXCL14 (NM_004887) Consisting of SOD3 (NM_003102) gene, KRT1 (NM_006121) gene, H19 (NR_002196) gene, CASP14 (NM_012114) gene, KRT10 (NM_000421) gene, CASP8 (NM_001080125) gene, KRT15 (NM_002275) gene, and KRT13 (NM_002274) gene Identifying the level of one or more expressions selected from the group consisting of mRNA of one or more genes selected from the group or proteins encoded from said genes, skin damage by fine dust Improved material screening method.
- the method after the test material treatment compared to before the test material treatment 1) CXCL14 (NM_004887) gene, SOD3 (NM_003102) gene, KRT1 (NM_006121) gene, H19 (NR_002196) gene, CASP14 (NM_012114) gene , MRNA of at least one gene selected from the group consisting of KRT10 (NM_000421) gene, CASP8 (NM_001080125) gene, KRT15 (NM_002275) gene, KRT13 (NM_002274) gene, and Filaggrin gene or a protein encoded from the genes 2) S100A7 (NM_002963) gene, S100A8 (NM_002964) gene, S100A9 (NM_002965) gene, CYP1A1 (NM_000499) gene, CYP1B1 (NM_004104) gene, PI3 (NM_002638) Gene, IL36G (NM_019618) gene, IL1B (
- the skin cells may be keratinocytes.
- Materials that inhibit or ameliorate damage to skin cells or skin barriers by fine dust, screened by the methods as described above, include but are not limited to galangin.
- the present invention is a composition for moisturizing the skin comprising galangin, an isomer thereof, a pharmaceutically acceptable salt thereof, a prodrug thereof, a hydrate thereof, or a solvate thereof as an active ingredient.
- the present invention is, in one aspect, a method of moisturizing skin, comprising administering to a subject in need galangin, an isomer thereof, a pharmaceutically acceptable salt thereof, a prodrug thereof, a hydrate thereof, or a solvate thereof.
- the present invention is the use in the skin moisturization of galangin, isomer thereof, pharmaceutically acceptable salt thereof, prodrug thereof, hydrate thereof or solvate thereof.
- the present invention is the use of galangin, isomer thereof, pharmaceutically acceptable salt thereof, prodrug thereof, hydrate thereof or solvate thereof in preparing a skin moisturizing composition.
- Galangin is a yellow needle-shaped crystal, which is a kind of flavonoid. Chemical formula is C 15 H 10 O 5 , molecular weight is 270, and melting point is 214 ⁇ 215 ° C. Propolis, Helichrysum aureonitens, Alpinia officinarum , and galangal roots. Galangin is known to have anti-microbial, antiviral and breast cancer cell growth inhibitory effects. The structure of galangin is shown in the following formula (1).
- the galangin may have a derivative such as triacetyl galangin (C 15 H 7 O 2 (OCOCH 3 ) 3 ) or trimethyl galangin (C 15 H 7 O 2 (OCH 3 ) 3 ), but It is not limited.
- isomers in particular are not only optical isomers (eg, essentially pure enantiomers, essentially pure diastereomers or mixtures thereof), but also form isomers ( conformation isomers (ie, isomers that differ only by their angles of one or more chemical bonds), position isomers (especially tautomers) or geometric isomers (eg, cis-trans isomers) do.
- essentially pure means, when used in connection with, for example, an enantiomer or diastereomer, about 90% or more, specifically about 95% or more, of specific compounds, for example enantiomers or diastereomers, More specifically at least about 97% or at least about 98%, even more specifically at least about 99%, even more specifically at least about 99.5% (w / w).
- pharmaceutically acceptable means the approval of a government or equivalent regulatory body to use in animals, more specifically in humans, by avoiding significant toxic effects when used in conventional medicinal dosages. It can be received or approved, or listed in a pharmacopoeia or recognized as another general pharmacopeia.
- salts means salts according to one aspect of the invention that are pharmaceutically acceptable and have the desired pharmacological activity of the parent compound.
- the salt is formed from (1) an inorganic acid such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, or the like; Or acetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, 3- (4-hydroxybenzoyl) Benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethane-disulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenes
- prodrug refers to a drug that modulates physical and chemical properties by chemically changing a drug, which itself does not exhibit physiological activity, but is originally produced by the action of a chemical or enzyme in the body after administration. The drug can be turned into a drug.
- hydrate refers to a compound to which water is bound, and is a broad concept including an inclusion compound having no chemical bonding force between water and the compound.
- solvate means a higher order compound produced between molecules or ions of a solute and molecules or ions of a solvent.
- the present invention is a composition for enhancing skin barrier function comprising galangin, an isomer thereof, a pharmaceutically acceptable salt thereof, a prodrug thereof, a hydrate thereof, or a solvate thereof as an active ingredient.
- the present invention in one aspect, a method of enhancing skin barrier function, comprising administering to a subject in need galangin, an isomer thereof, a pharmaceutically acceptable salt thereof, a prodrug thereof, a hydrate thereof or a solvate thereof. to be.
- the present invention is a use in strengthening the skin barrier function of galangin, an isomer thereof, a pharmaceutically acceptable salt thereof, a prodrug thereof, a hydrate thereof or a solvate thereof.
- the present invention is the use of galangin, isomer thereof, pharmaceutically acceptable salt thereof, prodrug thereof, hydrate thereof or solvate thereof in preparing a composition for enhancing skin barrier function.
- the present invention is a composition for inducing skin keratinocyte differentiation comprising galangin, an isomer thereof, a pharmaceutically acceptable salt thereof, a prodrug thereof, a hydrate thereof, or a solvate thereof as an active ingredient.
- the invention in one aspect, comprises keratinocyte differentiation comprising administering to a subject in need of galangin, an isomer thereof, a pharmaceutically acceptable salt thereof, a prodrug thereof, a hydrate thereof or a solvate thereof. Way.
- the present invention is the use in inducing cutaneous keratinocyte differentiation of galangin, an isomer thereof, a pharmaceutically acceptable salt thereof, a prodrug thereof, a hydrate thereof or a solvate thereof.
- the present invention is the use of galangin, isomer thereof, pharmaceutically acceptable salt thereof, prodrug thereof, hydrate thereof or solvate thereof in preparing a composition for inducing skin keratinocyte differentiation. .
- the present invention is a composition for improving skin damage by fine dust comprising galangin, an isomer thereof, a pharmaceutically acceptable salt thereof, a prodrug thereof, a hydrate thereof, or a solvate thereof as an active ingredient.
- skin damage is a broad concept that includes a decrease or weakening of skin function.
- it may include a decrease in skin barrier function, a decrease in skin moisturizing power, or a decrease in skin elasticity.
- the present invention in one aspect, impaired by fine dust, comprising administering to a subject in need galangin, an isomer thereof, a pharmaceutically acceptable salt thereof, a prodrug thereof, a hydrate thereof, or a solvate thereof How to improve skin condition.
- the present invention is a use for improving skin damage by fine dust of galangin, an isomer thereof, a pharmaceutically acceptable salt thereof, a prodrug thereof, a hydrate thereof or a solvate thereof.
- the present invention the use of galangin, isomers thereof, pharmaceutically acceptable salts thereof, prodrugs thereof, hydrates or solvates thereof in the preparation of a composition for improving skin damage by fine dust. to be.
- the composition comprises, in an amount of 0.000001 to 30 weights of galangin, an isomer thereof, a pharmaceutically acceptable salt thereof, a prodrug thereof, a hydrate thereof, or a solvate thereof based on the total weight of the composition. May contain%.
- the content is 0.000001 to 30% by weight, the skin moisturizing effect, skin barrier function strengthening effect, and skin keratinocyte differentiation induction effect by the above components were excellent.
- the concentration of galangin, isomer thereof, pharmaceutically acceptable salt thereof, prodrug thereof, hydrate thereof or solvate thereof may be 0.1 to 5 ⁇ M relative to the total composition volume.
- the composition is CXCL14 (NM_004887) gene, SOD3 (NM_003102) gene, KRT1 (NM_006121) gene, H19 (NR_002196) gene, CASP14 (NM_012114) gene, KRT10 (NM_000421) gene, CASP8 (NM_001080125) gene , KRT15 (NM_002275) gene, KRT13 (NM_002274) gene and Filaggrin gene, can promote the expression of one or more selected from the group consisting of.
- the composition may promote the synthesis of filaggrin protein or keratin protein.
- composition S100A7 (NM_002963) gene, S100A8 (NM_002964) gene, S100A9 (NM_002965) gene, CYP1A1 (NM_000499) gene, CYP1B1 (NM_000104) gene, PI3 (NM_002638) gene, IL36G (NM_019618) gene, IL36 One or more expressions selected from the group consisting of NM_000576) gene, CCL27 (NM_006664) gene, IL8 (NM_000584) gene, PTGS2 (NM_000963) gene, NOX5 (NM_001184779) gene and XDH (NM_000379) gene.
- composition which is one aspect of this invention shows the outstanding effect in the prevention, improvement, or treatment of atopic dermatitis, psoriasis, and dry dermatitis.
- the composition may be a cosmetic composition, may be a pharmaceutical composition, may be a dietary supplement composition.
- Cosmetic compositions include cosmetics such as various creams, lotions, various creams, lotions, skins, and the like, cleansing agents, face washes, soaps, and essences.
- the cosmetic to which the composition containing the galangin of this invention was added can take the form of a solution, an emulsion, a viscous mixture, etc.
- the cosmetic of the present invention is not particularly limited in the formulation, for example, latex, cream, lotion, essence, pack, gel, powder, makeup base, foundation, lotion, ointment, patch, beauty liquid, cleansing foam, cleansing Formulations such as creams, cleansing water, body lotions, body creams, body oils, body essences, shampoos, rinses, body cleansers, soaps, hair dyes, sprays and the like.
- the above-mentioned preparations may contain a skin absorption promoting substance to increase skin moisturizing effect, skin barrier function enhancing effect, and skin keratinocyte differentiation inducing effect.
- the cosmetic of the present invention may include a composition selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, polymer peptides, polymer polysaccharides, sphingolipids and seaweed extract.
- Other components that may be added include fats and oils, moisturizers, emollients, surfactants, organic and inorganic pigments, organic powders, ultraviolet absorbers, preservatives, fungicides, antioxidants, plant extracts, pH adjusters, alcohols, pigments, flavorings, Blood circulation accelerators, cooling agents, restriction agents, purified water and the like.
- the compounding component which may be added other than this is not limited to this, Moreover, any of the above components can be mix
- the pharmaceutical composition comprising the galangin of the present invention may further include suitable carriers, excipients and diluents commonly used in the manufacture of pharmaceutical compositions.
- the pharmaceutical composition comprising the galangin according to the present invention may be used in any form suitable for pharmaceutical preparations, including external preparations such as ointments, gels, creams, patches or sprays, respectively, according to a conventional method. have.
- the dosage of the preparation is different depending on the subject's age, sex, weight, symptoms, and method of administration, but it is preferable to apply it at 1.0 to 3.0 ml per day and apply it 1 to 5 times a day for more than one month.
- health foods are manufactured using nutrients or ingredients (functional ingredients) having useful functions for the human body, which are often lacking in daily meals, and maintaining health through maintaining normal functions of the human body or activating physiological functions. It may mean a food to improve, but is not limited thereto.
- the health food may be manufactured and processed in the form of tablets, capsules, powders, granules, liquids, pills, and the like, but is not limited thereto and may be manufactured and processed in any form according to the law.
- the health beverage composition is not particularly limited to other ingredients except for containing the compound as an essential ingredient in the indicated ratio, and may contain various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks.
- natural carbohydrates are conventional sugars such as monosaccharide polysaccharides, cyclodextrins, and the like, and sugar alcohols such as xylitol, sorbitol, and erythritol.
- natural flavoring agents tacumatin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be used.
- the effective amount administered by the health food composition may range from 0.0001 mg / kg / day to approximately 1000 mg / kg / day. More preferred dosages may be from 0.02 mg / kg / day to 6 mg / kg /. Administration may be administered once a day or may be divided several times.
- the fine dust was collected using a low volume air sampler (Sensidyne, Gillian, Low Volume Air Sampler, FL, USA), and the filter pack was replaced by the filter and the denude at around 10 am every measurement day for about 24 hours. Was taken. Fine dust was collected every day from February 1, 2014 to February 28, 2014 at Pung Ha Station in Seoul (6 floors of the dormitory of the Hankuk University of Foreign Studies, Cheoin-gu, Yongin-si, Gyeonggi-do). The timer was recorded when the timer was turned on and the vacuum pump was turned off.
- the sampling flow rate was 16.7 L / min, and the flow rate was measured using a flow meter (Model 4143, TSI Inc.) at the start of the measurement, and the flow rate was measured again at the end of the measurement.
- the Teflon filter in the filter pack was weighed before and after sampling. Before weighing the Teflon filter, weigh it in a desiccator (NIKKO, Japan) with a relative humidity of 40% for 24 hours, and then weigh twice on an electronic scale (DVG215CD, Ohaus) with 5 decimal places. Recorded. Even after the sample was taken, the weight was measured in a desiccator for 24 hours before weighing, and then the weight was measured twice and compared with the weight measured before sampling to calculate the mass concentration.
- Extraction of fine dust was performed by soaking the Teflon filter in 1 mL of ethanol and then adding 14 mL of DW so that the aerosol collecting surface of the filter was in contact with the water, and then applying ultrasonic waves for 30 minutes with an ultrasonic cleaner.
- the filter is completely removed from the desiccator for 48 hours, and then weighed on the filter using a Mettler Toledo Company that can measure up to 0.1 mg. And weighed before and after extraction of the filter.
- Human normal keratinocytes skin cells Human epidermal neonatal keratinocyte cells
- Ron its Liptonza, Inc. Walkersville, Maryland material
- CO 2 incubator a CO 2 incubator after subculture purchased from, 5% CO 2 Incubated under conditions.
- Cell cultures were in accordance with Lonza's guidelines.
- KBM-2 KBM TM -2, CC-3103 media in KGM-2 bullet kit CC-4152 (KGM TM -2 Bullet kit, CC-4152 (component: Bovine pituitary extract), human epidermal growth factor (hEGF), insulin, hydrocortisone, transferrin, KGM-2 Bullet Kit CC-3107 (KGM) with Epinephrine, and Gentamicin Sulfate + Amphofericin-B (Gentamycin Suflate + Amphofericin-B: GA-1000) TM- 2 Bullet Kit, CC-3107).
- KGM TM -2 Bullet kit, CC-4152 component: Bovine pituitary extract
- human epidermal growth factor (hEGF) human epidermal growth factor
- insulin hydrocortisone
- transferrin KGM-2 Bullet Kit CC-3107
- KGM KGM-2 Bullet Kit CC-3107
- Gentamicin Sulfate + Amphofericin-B Genetamycin Suflate + Amphofericin
- MTT experiment using (normal human) keratinocyte line was performed by the method of Mossman et al. (J. Immunol. Methods, 65, 55-63, 1983).
- a fine dust dispersion was prepared by dispersing fine dust having a diameter of 10 ⁇ m and fine particles having a diameter of 2.5 ⁇ m in purified water using a 24-well plate, respectively, in Example 2, followed by Example 2
- MTT 3-4,5-dimethylthiazol-2,5-diphenyltetra zolium bromide
- 5 mg / ml were mixed and further incubated at 37 ° C. for 3 hours. Thereafter, the medium was removed and the formed formazan crystal was dissolved in 500 ⁇ l of DMSO. The lysate was transferred to a 96-well plate and aliquoted and the OD value was measured at absorbance 540 nm. The measurement result is shown in FIG.
- the concentration (IC20) value of 80% survival rate against the cytotoxicity caused by the dispersion in which the fine particles were dispersed at 2.5 micrometers and 10 micrometers or less in the cell line was 2.5 micrometers and 10 micrometers or less.
- the dust-soluble extract all were 12.5 ⁇ g / ml.
- RNA-sequence data processing and analysis reference was made to general analysis steps developed by Trapnell et al. (2012). RNA-seq data quality was confirmed using FastQC (http://www.bioinformatics.babraham.ac.uk/projects/fastqc/) and FASTX (http://hannonlab.cshl.edu/fastx_toolkit/) This eliminated inferior base and adapter sequences. The alignment was then performed using Tophat (Trapnell et al., 2009) and the human genome (hg19), and the amount of data in each sample was confirmed using EVER-seq, renamed RSeQC (Wang et al., 2012). ).
- transcripts were quantified using Cufflinks, and transcription levels were compared between two microdust dispersion treated samples and normal samples (Trapnell et al., 2010).
- FDR adjusted p-value ⁇ 0.05, applying a strict cutoff of ⁇ 2.0 fold-change, genes exhibiting significant expression differences in the treatment of dispersions of fine dust with a diameter of 2.5 ⁇ m and dispersions of fine dust with a diameter of 10 ⁇ m Decided. The measurement results are shown in Tables 3 and 4 below.
- Example 1 The fine dust having a diameter of 2.5 ⁇ m extracted in Example 1 was treated in human cultured keratinous skin cells cultured in Example 2 in an amount of 12.5 ⁇ g in 1 ml of cell culture medium, and the primers of genes shown in Tables 5 and 6 Relative mRNA expression was measured using applied biosystems TaqMan® Primers).
- PBS phosphate buffered saline
- CDNA was synthesized from the RNA using Invitrogen's reverse transcriptase kit (Superscript Reverse Transcriptase (RT) kit, Invitrogen, Carlsbad, Calif.), And the real-time reverse transcription polymerase chain reaction using the primers of Tables 5 and 6 (Q) -RT-PCR: Quantitative analysis was performed by real time-reverse transcription polymerase chain reaction. Changes in the expression patterns of the genes were evaluated by real-time PCR using the TaqMan gene expression assay kit (Applied Biosystems, Applied Biosystems, Foster City, CA). 3 is shown. Both Q-RT-PCR and real-time PCR were performed according to the standard protocol distributed by Life Technology. Specifically, the process was performed at 95 ° C. for 20 seconds, followed by 3 seconds at 95 ° C. and 30 seconds at 60 ° C. 40 cycles were carried out.
- RT Superscript Reverse Transcriptase
- Galangin was treated to human normal keratinous skin cells cultured in Example 2 at different concentrations (0 ⁇ M, 0.5 ⁇ M, 1 ⁇ M, 2 ⁇ M), filaggrin (Filaggrin), keratin 10 (Keratin 10, keratin 1 (Keratin 1, keratin) Relative mRNA expression levels of 13 (Keratin 13) and keratin 15 (Keratin 15) were measured.
- RNA in cells After 24 hours of treatment with each galangin concentration in the medium, the culture medium was removed, the cells were washed with 2 ml of phosphate buffered saline (PBS), and then trizol reagent (Trizol reagent, Invitrogen, Carlsbad) , CA, USA) was used to isolate RNA in cells.
- PBS phosphate buffered saline
- Trizol reagent Trizol reagent, Invitrogen, Carlsbad
- Filaggrin Filaggrin
- keratin 10 Keratin 10
- keratin 1 Keratin 1
- keratin 13 Keratin 13
- keratin 15 Keratin 15
- Galangin was treated to human normal keratinous skin cells cultured in Example 2 at different concentrations (0 ⁇ M, 1 ⁇ M, 2 ⁇ M), and after 24 hours, the culture medium was removed, and the degree of differentiation of keratinocytes was measured under an optical microscope (Olympus IX71). Model) (40-fold, 200-fold). As a result, as shown in Figure 5, it was found that with the increase in the concentration of galangin, the differentiation of human normal keratinous skin cells not treated with fine dust is active.
- Galangin was treated to human normal keratin skin cells pretreated in Example 2 by concentration (0 ⁇ M, 0.5 ⁇ M, 1 ⁇ M, 2 ⁇ M), and after 24 hours, the culture medium was removed, and 2 ml of phosphate buffered saline (Phosphate Buffered Saline). After washing the cells with PBS), the cell lysis solution was added and vortexed to obtain a supernatant, followed by protein quantification. Proteins of normal and dry skin epidermis were loaded onto SDS-Gel and blotted using filaggrin antibodies (filaggrin, Covance, france). Relative quantitative values were corrected for betaactin ( ⁇ -actin, Sigma, USA). As a result, as shown in Figure 6, it was confirmed that the filaggrin protein increases as the concentration of galangin increases.
- Vitamin A Acetate 70 ⁇ g Vitamin E 1.0mg Vitamin B1 0.13mg Vitamin B2 0.15mg Vitamin B6 0.5mg Vitamin B12 0.2 ⁇ g Vitamin c 10mg Biotin 10 ⁇ g Nicotinic acid amide 1.7mg Folic acid 50 ⁇ g Calcium Pantothenate 0.5mg Ferrous sulfate 1.75mg Zinc oxide 0.82 mg Magnesium carbonate 25.3 mg Potassium phosphate monobasic 15 mg Dicalcium Phosphate 55 mg Potassium citrate 90 mg Calcium carbonate 100mg Magnesium chloride 24.8 mg
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Abstract
Description
증가유전자 | ||
Name | GeneSymbol | Gene title |
NM_002963 | S100A7 | S100 calcium binding protein A7 |
NM_002964 | S100A8 | S100 calcium binding protein A8 |
NM_002965 | S100A9 | S100 calcium binding protein A9 |
NM_000499 | CYP1A1 | cytochrome P450, family 1, subfamily A, polypeptide 1 |
NM_000104 | CYP1B1 | cytochrome P450, family 1, subfamily B, polypeptide 1 |
NM_002638 | PI3 | peptidase inhibitor 3, skin-derived |
NM_019618 | IL36G | interleukin 36, gamma |
NM_000576 | IL1B | interleukin 1, beta |
NM_006664 | CCL27 | chemokine (C-C motif) ligand 27 |
NM_000584 | IL8 | interleukin 8 |
NM_000963 | PTGS2 | Cyclooxygenase-2 (COX-2) |
NM_001184779 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 |
NM_000379 | XDH | xanthine dehydrogenase |
감소유전자 | ||
Name | GeneSymbol | Gene title |
NM_004887 | CXCL14 | chemokine (C-X-C motif) ligand 14 |
NM_003102 | SOD3 | superoxide dismutase 3, extracellular |
NM_006121 | KRT1 | keratin 1 |
NR_002196 | H19 | H19, imprinted maternally expressed transcript |
NM_012114 | CASP14 | caspase 14, apoptosis-related cysteine peptidase |
NM_000421 | KRT10 | keratin 10 |
NM_001080125 | CASP8 | caspase 8, apoptosis-related cysteine peptidase |
NM_002275 | KRT15 | keratin 15 |
NM_002274 | KRT13 | keratin 13 |
증가유전자 | ||
Name | GeneSymbol | 배수 변화량 |
NM_002963 | S100A7 | 9.515833375 |
NM_002964 | S100A8 | 3.766981583 |
NM_002965 | S100A9 | 5.179254242 |
NM_000499 | CYP1A1 | 48.06825714 |
NM_000104 | CYP1B1 | 34.49696749 |
NM_002638 | PI3 | 6.738762497 |
NM_019618 | IL36G | 6.742761413 |
NM_000576 | IL1B | 11.31259177 |
NM_006664 | CCL27 | 2.97282529 |
NM_000584 | IL8 | 2.258148839 |
NM_000963 | PTGS2 | 2.284968542 |
NM_001184779 | NOX5 | 3.303502622 |
NM_000379 | XDH | 2.57463302 |
감소유전자 | ||
Name | GeneSymbol | 배수 변화량 |
NM_004887 | CXCL14 | -12.19511071 |
NM_003102 | SOD3 | -4.341912612 |
NM_006121 | KRT1 | -3.259468923 |
NR_002196 | H19 | -4.151100642 |
NM_012114 | CASP14 | -2.396041041 |
NM_000421 | KRT10 | -2.269122522 |
NM_001080125 | CASP8 | -2.25127321 |
NM_002275 | KRT15 | -4.343467673 |
NM_002274 | KRT13 | -3.269661942 |
증가유전자 | ||
Name | GeneSymbol | TaqMan® 프라이머 |
NM_002963 | S100A7 | Hs00161488_m1 |
NM_002964 | S100A8 | Hs00374263_m1 |
NM_002965 | S100A9 | Hs00268204_m1 |
NM_000499 | CYP1A1 | Hs00153120_m1 |
NM_000104 | CYP1B1 | Hs00164383_m1 |
NM_002638 | PI3 | Hs00160066_m1 |
NM_019618 | IL36G | Hs00219742_m1 |
NM_000576 | IL1B | Hs01555410_m1 |
NM_006664 | CCL27 | Hs00171157_m1 |
NM_000584 | IL8 | Hs00174103_m1 |
NM_000963 | PTGS2 | Hs00153133_m1 |
NM_001184779 | NOX5 | Hs00225846_m1 |
NM_000379 | XDH | Hs00166010_m1 |
감소유전자 | ||
Name | GeneSymbol | TaqMan® 프라이머 |
NM_004887 | CXCL14 | Hs01557413_m1 |
NM_003102 | SOD3 | Hs00162090_m1 |
NM_006121 | KRT1 | Hs00196158_m1 |
NR_002196 | H19 | Hs00262142_g1 |
NM_012114 | CASP14 | Hs00201637_m1 |
NM_000421 | KRT10 | Hs00166289_m1 |
NM_001080125 | CASP8 | Hs01018151_m1 |
NM_002275 | KRT15 | Hs00267035_m1 |
NM_002274 | KRT13 | Hs02558881_s1 |
배합성분 | 함량(%) |
갈랑긴 | 5.00 |
유지 | 적량 |
수산화나트륨 | 적량 |
염화나트륨 | 적량 |
향료 | 적량 |
정제수 | 잔량 |
배합성분 | 함량(%) |
갈랑긴 | 5.00 |
L-아스코르빈산-2-인산마그네슘염 | 1.00 |
수용성 콜라겐 (1 % 수용액) | 1.00 |
시트르산나트륨 | 0.10 |
시트르산 | 0.05 |
감초 엑기스 | 0.20 |
1,3-부틸렌글리콜 | 3.00 |
정제수 | 잔량 |
배합성분 | 함량(%) |
갈랑긴 | 3.00 |
폴리에틸렌글리콜모노스테알레이트 | 2.00 |
자기유화형모노스테아르산글리세린 | 5.00 |
세틸알코올 | 4.00 |
스쿠알렌 | 6.00 |
트리2-에틸헥산산글리세릴 | 6.00 |
스핑고당지질 | 1.00 |
1.3-부틸렌글리콜 | 7.00 |
정제수 | 잔량 |
배합성분 | 함량(%) |
갈랑긴 | 5.00 |
폴리비닐알코올 | 13.00 |
L-아스코르빈산-2-인산마그네슘염 | 1.00 |
라우로일히드록시프롤린 | 1.00 |
수용성 콜라겐 (1 % 수용액) | 2.00 |
1,3-부틸렌글리콜 | 3.00 |
에탄올 | 5.00 |
정제수 | 잔량 |
배합성분 | 함량(%) |
갈랑긴 | 3.00 |
히드록시에틸렌셀룰로오스(2 % 수용액) | 12.00 |
크산탄검(2 % 수용액) | 2.00 |
1,3-부틸렌글리콜 | 6.00 |
진한 글리세린 | 4.00 |
히알루론산나트륨 (1 % 수용액) | 2.00 |
정제수 | 잔량 |
배합 성분 | 함량 |
갈랑긴 | 2mg |
비타민 A 아세테이트 | 70μg |
비타민 E | 1.0mg |
비타민 B1 | 0.13mg |
비타민 B2 | 0.15mg |
비타민 B6 | 0.5mg |
비타민 B12 | 0.2μg |
비타민 C | 10mg |
비오틴 | 10μg |
니코틴산아미드 | 1.7mg |
엽산 | 50μg |
판토텐산 칼슘 | 0.5mg |
황산 제1철 | 1.75mg |
산화아연 | 0.82mg |
탄산마그네슘 | 25.3mg |
제1인산칼륨 | 15mg |
제2인산칼슘 | 55mg |
구연산칼륨 | 90mg |
탄산칼슘 | 100mg |
염화마그네슘 | 24.8mg |
배합성분 | 함량 |
갈랑긴 | 50mg |
구연산 | 1000mg |
올리고당 | 100 g |
타우린 | 1g |
정제수 | 잔량 |
Claims (20)
- S100A7(NM_002963) 유전자, S100A8(NM_002964) 유전자, S100A9(NM_002965) 유전자, CYP1A1(NM_000499) 유전자, CYP1B1(NM_000104) 유전자, PI3(NM_002638) 유전자, IL36G(NM_019618) 유전자, IL1B(NM_000576) 유전자, CCL27(NM_006664) 유전자, IL8(NM_000584) 유전자, PTGS2(NM_000963) 유전자, NOX5(NM_001184779) 유전자, XDH(NM_000379) 유전자, CXCL14(NM_004887) 유전자, SOD3(NM_003102) 유전자, KRT1(NM_006121) 유전자, H19(NR_002196) 유전자, CASP14(NM_012114) 유전자, KRT10(NM_000421) 유전자, CASP8(NM_001080125) 유전자, KRT15(NM_002275) 유전자, KRT13(NM_002274) 유전자로 이루어진 군에서 선택되는 하나 이상의 유전자의 mRNA 또는 이의 단백질의 발현 정도를 측정하는 제제를 포함하는, 미세먼지에 의한 피부 세포 또는 피부 장벽의 손상 여부 진단용 조성물.
- 제1항에 있어서, 상기 단백질의 발현 정도를 측정하는 제제는 상기 유전자의 mRNA에 상보적인 폴리뉴클레오티드 또는 이의 단편, 상기 유전자를 증폭시킬 수 있는 프라이머 또는 프로브인 것을 특징으로 하는 조성물.
- 제1항에 있어서, 상기 단백질의 발현 정도를 측정하는 제제는 상기 단백질을 특이적으로 인식하는 항체인 것을 특징으로 하는 조성물.
- 제1항 내지 제3항 중 어느 한 항의 조성물을 포함하는, 미세먼지에 의한 피부 세포 또는 피부 장벽의 손상 여부 진단용 키트.
- 미세먼지에 의한 피부 세포 또는 피부 장벽의 손상 여부를 진단하는 방법으로서,상기 방법은,a) 피험자의 피부 세포 시료로부터,S100A7(NM_002963) 유전자, S100A8(NM_002964) 유전자, S100A9(NM_002965) 유전자, CYP1A1(NM_000499) 유전자, CYP1B1(NM_000104) 유전자, PI3(NM_002638) 유전자, IL36G(NM_019618) 유전자, IL1B(NM_000576) 유전자, CCL27(NM_006664) 유전자, IL8(NM_000584) 유전자, PTGS2(NM_000963) 유전자, NOX5(NM_001184779) 유전자, XDH(NM_000379) 유전자, CXCL14(NM_004887) 유전자, SOD3(NM_003102) 유전자, KRT1(NM_006121) 유전자, H19(NR_002196) 유전자, CASP14(NM_012114) 유전자, KRT10(NM_000421) 유전자, CASP8(NM_001080125) 유전자, KRT15(NM_002275) 유전자 및 KRT13(NM_002274) 유전자로 이루어진 군으로부터 선택된 하나 이상의 유전자의 mRNA 또는 이로부터 암호화되는 단백질의 발현 정도를 측정하는 단계; 및b) 상기 발현 정도를, 미세먼지에 의해 손상되지 않은 피부 세포 시료 내에서의 상기 유전자의 mRNA 또는 이로부터 암호화되는 단백질의 발현 정도와 비교하는 단계를 포함하는, 미세먼지에 의한 피부 세포 또는 피부 장벽의 손상 여부를 진단하는 방법.
- 제 5항에 있어서,상기 방법은,1) 피험자의 피부세포로부터 측정된, CXCL14(NM_004887) 유전자, SOD3(NM_003102) 유전자, KRT1(NM_006121) 유전자, H19(NR_002196) 유전자, CASP14(NM_012114) 유전자, KRT10(NM_000421) 유전자, CASP8(NM_001080125) 유전자, KRT15(NM_002275) 유전자, KRT13(NM_002274) 유전자,및 필라그린(Filaggrin) 유전자로 이루어진 군으로부터 선택된 하나 이상의 유전자의 mRNA 또는 이들로부터 암호화되는 단백질의 발현정도가 미세먼지에 의해 손상되지 않은 피부 세포 시료 내에서 보다 낮거나,2) 피험자의 피부세포로부터 측정된, S100A7(NM_002963) 유전자, S100A8(NM_002964) 유전자, S100A9(NM_002965) 유전자, CYP1A1(NM_000499) 유전자, CYP1B1(NM_000104) 유전자, PI3(NM_002638) 유전자, IL36G(NM_019618) 유전자, IL1B(NM_000576) 유전자, CCL27(NM_006664) 유전자, IL8(NM_000584) 유전자, PTGS2(NM_000963) 유전자, NOX5(NM_001184779) 유전자 및 XDH(NM_000379) 유전자로 이루어진 군으로부터 선택된 하나 이상의 유전자의 mRNA 또는 이들로부터 암호화되는 단백질의 발현정도가 미세먼지에 의해 손상되지 않은 피부 세포 시료 내에서 보다 높은 경우, 미세먼지에 의해 피부 세포 또는 피부 장벽이 손상된 것으로 판정하는 단계를 더 포함하는, 미세먼지에 의한 피부 세포 또는 피부 장벽의 손상 여부를 진단하는 방법.
- 제5항에 있어서, 상기 유전자의 mRNA 또는 단백질의 발현 정도를 측정하는 방법은 마이크로어레이, PCR, NGS(Nest Generation Sequencing; 차세대 염기서열분석), 웨스턴 블럿, 노던 블럿, ELISA, 방사선 면역 분석, 방사 면역 확산법, 조직면역 염색 및 면역침전 분석법으로 이루어진 군에서 선택되는 것임을 특징으로 하는, 방법.
- 피부세포에 미세먼지를 처리하는 단계;미세먼지를 처리한 피부세포에 시험 물질을 처리하는 단계; 및상기 시험 물질을 처리한 피부세포에서, 시험 물질 처리 전후의 S100A7(NM_002963) 유전자, S100A8(NM_002964) 유전자, S100A9(NM_002965) 유전자, CYP1A1(NM_000499) 유전자, CYP1B1(NM_000104) 유전자, PI3(NM_002638) 유전자, IL36G(NM_019618) 유전자, IL1B(NM_000576) 유전자, CCL27(NM_006664) 유전자, IL8(NM_000584) 유전자, PTGS2(NM_000963) 유전자, NOX5(NM_001184779) 유전자, XDH(NM_000379) 유전자, CXCL14(NM_004887) 유전자, SOD3(NM_003102) 유전자, KRT1(NM_006121) 유전자, H19(NR_002196) 유전자, CASP14(NM_012114) 유전자, KRT10(NM_000421) 유전자, CASP8(NM_001080125) 유전자, KRT15(NM_002275) 유전자 및 KRT13(NM_002274) 유전자로 이루어진 군에서 선택되는 하나 이상의 유전자의 mRNA 또는 상기 유전자들로부터 암호화되는 단백질의 발현 정도를 확인하는 단계를 포함하는, 미세먼지에 의한 피부 손상 개선 물질 스크리닝 방법.
- 제8항에 있어서,상기 방법은,시험물질 처리 전에 비하여 시험물질 처리 후에1) CXCL14(NM_004887) 유전자, SOD3(NM_003102) 유전자, KRT1(NM_006121) 유전자, H19(NR_002196) 유전자, CASP14(NM_012114) 유전자, KRT10(NM_000421) 유전자, CASP8(NM_001080125) 유전자, KRT15(NM_002275) 유전자, KRT13(NM_002274) 유전자 및 필라그린(Filaggrin) 유전자로 이루어지는 군으로부터 선택된 하나 이상의 유전자의 mRNA 또는 상기 유전자들로부터 암호화되는 단백질로 이루어진 군으로부터 선택되는 하나 이상의 발현정도가 증가하거나,2) S100A7(NM_002963) 유전자, S100A8(NM_002964) 유전자, S100A9(NM_002965) 유전자, CYP1A1(NM_000499) 유전자, CYP1B1(NM_000104) 유전자, PI3(NM_002638) 유전자, IL36G(NM_019618) 유전자, IL1B(NM_000576) 유전자, CCL27(NM_006664) 유전자, IL8(NM_000584) 유전자, PTGS2(NM_000963) 유전자, NOX5(NM_001184779) 유전자 및 XDH(NM_000379) 유전자로 이루어지는 군으로부터 선택된 하나 이상의 유전자의 mRNA 또는 상기 유전자들로부터 암호화되는 단백질로 이루어진 군으로부터 선택되는 하나 이상의 발현정도가 감소하는 경우, 미세먼지에 의한 피부 손상 개선 물질로 판단하는 단계를 더 포함하는, 미세먼지에 의한 피부 손상 개선 물질 스크리닝 방법.
- 제8항에 있어서,상기 피부세포는, 각질형성세포인, 미세먼지에 의한 피부 손상 개선 물질 스크리닝 방법.
- 갈랑긴, 이의 이성질체, 이의 약학적으로 허용 가능한 염, 이의 프로드럭, 이의 수화물 또는 이의 용매화물을 유효성분으로 포함하는 피부 보습용 조성물.
- 갈랑긴, 이의 이성질체, 이의 약학적으로 허용 가능한 염, 이의 프로드럭, 이의 수화물 또는 이의 용매화물을 유효성분으로 포함하는 피부 장벽기능 강화용 조성물.
- 갈랑긴, 이의 이성질체, 이의 약학적으로 허용 가능한 염, 이의 프로드럭, 이의 수화물 또는 이의 용매화물을 유효성분으로 포함하는 피부 각질형성 세포 분화 유도용 조성물.
- 갈랑긴, 이의 이성질체, 이의 약학적으로 허용 가능한 염, 이의 프로드럭, 이의 수화물 또는 이의 용매화물을 유효성분으로 포함하는 미세먼지에 의한 피부 손상 개선용 조성물.
- 제11항 내지 제14항 중 어느 한 항에 있어서,상기 조성물은,갈랑긴, 이의 이성질체, 이의 약학적으로 허용 가능한 염, 이의 프로드럭, 이의 수화물 또는 이의 용매화물을, 조성물 총 중량을 기준으로 0.000001 내지 30중량%로 포함하는 조성물.
- 제11항 내지 제14항 중 어느 한 항에 있어서,갈랑긴, 이의 이성질체, 이의 약학적으로 허용 가능한 염, 이의 프로드럭, 이의 수화물 또는 이의 용매화물의 농도는,조성물 총 부피에 대해, 0.1 내지 5μM인 조성물.
- 제11항 내지 제14항 중 어느 한 항에 있어서,상기 조성물은,CXCL14(NM_004887) 유전자, SOD3(NM_003102) 유전자, KRT1(NM_006121) 유전자, H19(NR_002196) 유전자, CASP14(NM_012114) 유전자, KRT10(NM_000421) 유전자, CASP8(NM_001080125) 유전자, KRT15(NM_002275) 유전자, KRT13(NM_002274) 유전자 및 필라그린(Filaggrin) 유전자로 이루어진 군으로부터 선택된 하나 이상의 발현을 촉진하는 것인 조성물.
- 제11항 내지 제14항 중 어느 한 항에 있어서,상기 조성물은,S100A7(NM_002963) 유전자, S100A8(NM_002964) 유전자, S100A9(NM_002965) 유전자, CYP1A1(NM_000499) 유전자, CYP1B1(NM_000104) 유전자, PI3(NM_002638) 유전자, IL36G(NM_019618) 유전자, IL1B(NM_000576) 유전자, CCL27(NM_006664) 유전자, IL8(NM_000584) 유전자, PTGS2(NM_000963) 유전자, NOX5(NM_001184779) 유전자 및 XDH(NM_000379) 유전자로 이루어진 군으로부터 선택된 하나 이상의 발현을 감소시키는 것인, 조성물.
- 제11항 내지 제14항 중 어느 한 항에 있어서,상기 조성물은, 필라그린 단백질 또는 케라틴 단백질의 합성을 촉진하는 것인 조성물.
- 제11항 내지 제14항 중 어느 한 항에 있어서,상기 조성물은, 화장료 조성물, 약학적 조성물 또는 건강식품 조성물인 조성물.
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WO2007046087A2 (en) * | 2005-10-16 | 2007-04-26 | Yeda Research And Development Co.Ltd. | Pharmaceutical compositions and diagnostic methods for inflammatory skin disesaes, disorders or conditions |
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