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WO2017014480A2 - Composition pour atténuer les rides de la peau et pour traiter les maladies inflammatoires endommageant la peau, contenant comme principe actif un inhibiteur de la sénescence cellulaire - Google Patents

Composition pour atténuer les rides de la peau et pour traiter les maladies inflammatoires endommageant la peau, contenant comme principe actif un inhibiteur de la sénescence cellulaire Download PDF

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Publication number
WO2017014480A2
WO2017014480A2 PCT/KR2016/007581 KR2016007581W WO2017014480A2 WO 2017014480 A2 WO2017014480 A2 WO 2017014480A2 KR 2016007581 W KR2016007581 W KR 2016007581W WO 2017014480 A2 WO2017014480 A2 WO 2017014480A2
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Prior art keywords
composition
skin
present
acid
atm
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English (en)
Korean (ko)
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WO2017014480A3 (fr
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김태국
김정언
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T&k Bioinnovation Inc
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T&k Bioinnovation Inc
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Priority claimed from KR1020160088246A external-priority patent/KR20170009760A/ko
Application filed by T&k Bioinnovation Inc filed Critical T&k Bioinnovation Inc
Priority to CN201680054162.0A priority Critical patent/CN108135815A/zh
Priority to HK18115717.0A priority patent/HK1256597A1/zh
Publication of WO2017014480A2 publication Critical patent/WO2017014480A2/fr
Publication of WO2017014480A3 publication Critical patent/WO2017014480A3/fr
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
    • A61K31/385—Heterocyclic compounds having sulfur as a ring hetero atom having two or more sulfur atoms in the same ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/08—Anti-ageing preparations

Definitions

  • the present invention relates to a composition for improving skin wrinkles and treating skin-damaging inflammatory diseases, which contains a cellular senescence inhibitor which is an ATM / ATR protein kinase inhibitor as an active ingredient.
  • Skin aging is caused by a variety of internal and external factors (Nature Milestones Cutaneous Biology E2-E6, 2013). Increasing elasticity and deep wrinkles are caused by internal factors such as physiological functions that decrease with age. External factors include stress such as ultraviolet rays, reactive oxygen species, and free radicals, which cause rapid aging due to damage to the skin, resulting in rough wrinkles on the surface of the skin and markedly reduced elasticity.
  • retinoid retinoid
  • vitamin A vitamin A or its derivatives.
  • retinoids have problems of stability such as irritation and redness when applied to the skin, and are extremely unstable in heat and light and thus cannot be effective cosmetics. Therefore, it is highly desirable that the absorption of skin and stable low molecular weight compound promote the synthesis of collagen and inhibit the degradation of collagen. Furthermore, it is important for skin beauty and treatment to suppress damage stimulation and inflammatory response caused by external stressors such as ultraviolet rays.
  • compositions for controlling or preventing skin aging by controlling the amount of collagen and at the same time inhibiting or treating pathological stress and damage inflammation on the skin, thereby prolonging the life and regeneration of cells.
  • cellular senescence of various human cells such as skin, for example, replication senescence and premature senescence
  • it prevents aging and further treats diseases that occur frequently according to aging such as cancer.
  • a low-molecular compound invented it is an ATM / ATR protein kinase inhibitor 733 (Korean Patent No. 10-2006-52046; Korean Patent No. 10-2006-0052035; J. of Clinical Investigation 120: 681-693, 2010; International J.
  • An object of the present invention is to provide a composition for improving skin wrinkles and treating inflammatory diseases of skin, comprising ATM / ATR protein kinase inhibitor as an active ingredient.
  • the present invention provides a composition for improving skin wrinkles containing an ATM / ATR protein kinase inhibitor as an active ingredient.
  • the present invention also provides a composition for treating skin damage inflammatory disease containing an ATM / ATR protein kinase inhibitor as an active ingredient.
  • 1 is a measure of the amount of collagen produced when the low-molecular weight compound according to an embodiment of the present invention is treated to human fibroblasts.
  • 2 is a measure of the amount of collagenase that is a collagenase when the low molecular weight compound according to an embodiment of the present invention is treated to human fibroblasts.
  • NF-kB is a measure of the DNA binding degree and activity of NF-kB, an inflammatory response measure, when a low molecular weight compound according to an embodiment of the present invention is treated to human fiber cells under stress conditions caused by ultraviolet rays.
  • Figure 4 is a measure of the expression level of inflammatory proteins, such as iNOS and COX2, another measure of the inflammatory response when the low-molecular weight compound according to an embodiment of the present invention to normal human fibroblasts under stress conditions caused by ultraviolet light.
  • inflammatory proteins such as iNOS and COX2
  • the skin by increasing the amount of collagen produced in the natural state where the skin aging occurs, the skin has a multi-modulating ability to improve the wrinkles of the skin, and at the same time have a therapeutic effect on the skin damage inflammatory diseases caused by stress stimulating factors such as ultraviolet rays To develop cosmetic and pharmaceutically beneficial compositions.
  • Patent US2014 / 0243581 et al. Analyzed the effect of aging on the skin wrinkles, and found that ATM / ATR protein kinase inhibitor 733 promotes collagen synthesis and It was confirmed that there is an improvement effect on the skin wrinkles by inhibiting the degradation of the gen and increasing the amount of collagen produced.
  • the present invention relates to a composition for improving skin wrinkles containing an ATM / ATR protein kinase inhibitor as an active ingredient.
  • the ATM / ATR protein kinase inhibitor may be characterized in that it prevents cellular senescence.
  • the inhibitor can be used without limitation as long as it has a function of inhibiting CHK1 / CHK2, p53 protein and the like which are directly activated by ATM / ATR protein kinase and ATM / ATR protein kinase, It may be characterized in that it is selected from the group consisting of low molecular weight compounds defined in 1, their pharmaceutically acceptable salts and hydrates.
  • the compound of Formula 1 may be characterized as defined below:
  • R 1 is one of the structures
  • R2 is any one of the structures
  • X is H, CH 3, CF 3, or CCl 3,
  • Y may be characterized as O or S.
  • the compound of Formula 1 is preferably,
  • R2 is any one of the structures
  • X is CF3, or CCl3
  • Y may be characterized as O or S.
  • the compound of Formula 1 is more preferably,
  • R 1 is one of the following structures:
  • R2 is any one of the structures
  • X is CCl3
  • Y may be characterized as S.
  • the improvement of skin wrinkles of the present invention includes, but is not limited to, for example, improvement of skin wrinkles and improvement of skin tone, improvement of skin elasticity, and lifting by improvement of symptoms exhibited on skin accompanying aging.
  • the pharmaceutically acceptable salt of the low molecular weight compound means a salt made of non-toxic or low acid or base, and salts composed of lithium, sodium, potassium, calcium, ammonium, magnesium or organic amines or Propionic acid, isobutyl acid, oxalic acid, malic acid, malonic acid, benzoic acid, succinic acid, suberic, fumaric acid, manderic acid, phthalic acid, benzenesulfonic acid, p-tolylsulfonic acid, citric acid, tartaric acid, methanesulfonic acid , Salts formed with hydrochloric acid, bromic acid, nitric acid, carbonic acid, monohydrogencarbonic acid, phosphoric acid, monohydrogenphosphate, dihydrogenphosphate, sulfuric acid, monohydrosulfuric acid, hydrogen iodide, phosphorous acid, and the like. It is not limited. It also includes, but is not limited to, salts of amino acids such as argin, arg
  • Topical pharmaceutical or cosmetic pharmaceuticals including, for example, pharmaceutically acceptable carriers or diluents, such as buffered saline, as well as dermatologically or pharmaceutically acceptable carriers, vehicles or mediums. It may include other components typically used in the composition.
  • pharmaceutically acceptable carriers or diluents such as buffered saline
  • dermatologically or pharmaceutically acceptable carriers, vehicles or mediums it may include other components typically used in the composition.
  • dermatologically or pharmaceutically acceptable means that the above-described composition or ingredient does not cause excessive toxicity, incompatibility, allergic reactions, etc. upon skin contact.
  • Cosmetic compositions may include, for example, conventional adjuvants and carriers such as antioxidants, stabilizers, solubilizers, vitamins, pigments and / or flavors.
  • the low molecular weight compounds may exist in unsolvated form as well as in solvated forms (eg, hydrates), including hydrate forms depending on the compound.
  • the compounds of the present invention may exist in crystalline or amorphous form, and all such physical forms are included within the scope of the present invention, and the low molecular weight compounds may have asymmetric carbon atoms or double bonds, which are optical centers, depending on the compound, resulting in racemic Sieves, enantiomers, diastereomers, geometric isomers and the like may be present and these are also within the scope of the present invention.
  • composition for improving skin wrinkles of the present invention can be prepared in the form of pharmaceuticals and cosmetics.
  • Such pharmaceuticals and cosmetics may include pharmaceutically acceptable excipients or additives.
  • the composition for improving skin wrinkles of the present invention may be administered alone or in admixture with any convenient carrier, excipient, etc., and such dosage forms may be single or repeated dose formulations.
  • Medicines and cosmetics comprising the composition for improving skin wrinkles of the present invention may be a solid preparation, a liquid preparation or a semi-solid preparation.
  • Solid preparations include, but are not limited to, powders, granules, tablets, capsules, suppositories, and the like.
  • Solid form preparations may include, but are not limited to, excipients, flavors, binders, preservatives, disintegrants, lubricants, fillers and the like.
  • Liquid formulations include, but are not limited to, solutions such as water, propylene glycol solutions, suspensions, emulsions, and the like, and may be prepared by adding suitable colorants, flavors, stabilizers, viscosity agents, and the like.
  • Semi-solid preparations include, but are not limited to, creams, lotions, emulsifiers, lining agents, and the like, and may be prepared by adding suitable colorants, flavoring agents, stabilizers, viscosity agents, surfactants, and the like.
  • powders may be prepared by simple mixing of the inhibitor of the present invention with suitable pharmaceutically acceptable excipients such as lactose, starch, microcrystalline cellulose.
  • Granules are inhibitors of the invention; Pharmaceutically acceptable excipients; And a pharmaceutically acceptable binder such as polyvinylpyrrolidone and hydroxypropyl cellulose, and then prepared by using a wet granulation method using a solvent such as water, ethanol, isopropanol, or a dry granulation method using a compressive force.
  • Tablets may also be prepared by mixing the granules with a suitable pharmaceutically acceptable glidant such as magnesium stearate and then tableting using a tableting machine.
  • compositions of the present invention are preferably applied topically to the skin and are therefore preferably prepared in conventional skin application cosmetic formulations. That is, the composition for improving skin wrinkles according to the present invention may be prepared and used in the formulation of cosmetics or makeup products such as lotion, essence, makeup oil, cream, powder, pack, foundation, makeup base, makeup stick, etc. Can be. It can be applied in various forms such as liquid, cream, paste, solid, and can be prepared by a cosmetic preparation method commonly known in the art.
  • the cosmetic preparation after stirring and dispersing the carbomer in purified water, butylene glycol, glycerin, Fiji-1500 and the like are added, and polyoxyethylene-cured castor oil, triethanol, preservative, inhibitor according to the present invention, and the like It can manufacture by dissolving in a suitable solvent, such as ethanol, and mixing.
  • the lotion formulation may contain cetearyl alcohol, glyceryl stearate / pG-100 stearate, polysorbate 60, sorbitan sesquioleate, cetyloctanoate, squalene and the like at about 70 ° C.
  • butylene glycol, magnesium aluminum silicate, xanthan gum, and preservatives are dissolved and dispersed in purified water and emulsified in heated to 70 ° C., the emulsion is cooled, and the present invention is dissolved in a suitable solvent or component. It can be prepared by adding an inhibitor of the mixture and stirring the mixture, followed by cooling to room temperature.
  • the cosmetic composition of the present disclosure may include a water-soluble base material comprising conjugated linoleic acid, linoleic acid, gamma-linoleic acid, unsaturated fatty acid including alpha-linoleic acid or propylene glycol.
  • the cosmetic compositions herein can also be prepared in any formulations commonly prepared in the art, including, for example, solutions, suspensions, emulsions, pastes, gels, creams, lotions, powders, soaps, surfactant-containing It may be formulated as a cleansing, oil, powder foundation, emulsion foundation, wax foundation and spray, but is 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, hair tonic, shampoo, rinse, cleansing cream, cleansing foam, cleansing water, pack, spray or powder. .
  • the formulation of the present composition is a paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, trakant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as a carrier component.
  • animal oil, vegetable oil, wax, paraffin, starch, trakant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as a carrier component.
  • animal oil vegetable oil, wax, paraffin, starch, trakant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, 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.
  • 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 esters, polyethyleneglycol or sorbitan can 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 composition may comprise at least one pharmaceutically acceptable excipient.
  • compositions according to the present disclosure may also include at least one adjuvant selected from thickeners, preservatives, flavoring agents, colorants, chemical or inorganic salt filters, humectants, thermal spring water, and the like, which are known pharmaceutical agents.
  • preservatives commonly used in cosmetics are molecules having antimicrobial activity, such as capryl derivatives (capryloylglycine and glyceryl caprylate), for example hexanediol and sodium levulinate, zinc and copper derivatives.
  • Gluconate and PCA phytosphingosine and derivatives thereof, benzoyl peroxide, pyroxtonolamine, zinc pyrithione and selenium sulfides, econazole, ketoconazole, or topical antibiotics such as erythromycin and clindamycin Can be.
  • composition may further comprise any ingredient conventionally used for cosmetic purposes, such as improving skin aging, such as wrinkles.
  • compositions may comprise solutions, emulsions, suspensions, creams, lotions, gels, powders or other solid compositions or liquid compositions typical for use with the skin in which the compositions can be employed.
  • composition for improving skin wrinkles of the present invention may be oral, injectable (eg, intramuscular injection, intraperitoneal injection, intravenous injection, infusion, subcutaneous injection, implant), inhalant, depending on the condition to be treated and the condition of the individual.
  • Nasal, vaginal, rectal, sublingual, transdermal, topical, etc. may be administered, but is not limited thereto.
  • It may be formulated into a suitable dosage unit dosage form comprising a pharmaceutically acceptable carrier, excipient, vehicle, conventionally used and nontoxic, depending on the route of administration. Depot formulations capable of continually releasing the drug for a period of time are also within the scope of the present invention.
  • topical formulations applied directly to the skin are most preferred for the purposes of the present invention of improving skin wrinkles.
  • the present invention also promotes collagen synthesis and inhibits the breakdown of collagen to increase the amount of collagen produced, thereby improving skin wrinkles, and at the same time, the low molecular weight compound 733, which is an ATM / ATR protein kinase inhibitor, is characterized by The purpose of this study was to determine whether it is effective in treating inflammatory diseases of skin damage caused by stress factors.
  • the present invention relates to a composition for treating skin damage inflammatory disease containing an ATM / ATR protein kinase inhibitor as an active ingredient.
  • the ATM / ATR protein kinase inhibitor may be characterized in that it prevents cellular senescence.
  • the inhibitor can be used without limitation as long as it has a function of inhibiting CHK1 / CHK2, p53 protein and the like which are directly activated by ATM / ATR protein kinase and ATM / ATR protein kinase, It may be characterized in that it is selected from the group consisting of low molecular weight compounds defined in 1, pharmaceutically acceptable salts and hydrates thereof.
  • the compound of Formula 1 may be characterized as defined below:
  • R 1 is one of the structures
  • R2 is any one of the structures
  • X is H, CH 3, CF 3, or CCl 3,
  • Y may be characterized as O or S.
  • the compound of Formula 1 is preferably,
  • R2 is any one of the structures
  • X is CF3, or CCl3
  • Y may be characterized as O or S.
  • the compound of Formula 1 is more preferably,
  • R 1 is one of the following structures:
  • R2 is any one of the structures
  • X is CCl3
  • Y may be characterized as S.
  • the pharmaceutically acceptable salt of the low molecular weight compound means a salt made of non-toxic or low acid or base, and salts composed of lithium, sodium, potassium, calcium, ammonium, magnesium or organic amines or Propionic acid, isobutyl acid, oxalic acid, malic acid, malonic acid, benzoic acid, succinic acid, suberic, fumaric acid, manderic acid, phthalic acid, benzenesulfonic acid, p-tolylsulfonic acid, citric acid, tartaric acid, methanesulfonic acid , Salts formed with hydrochloric acid, bromic acid, nitric acid, carbonic acid, monohydrogencarbonic acid, phosphoric acid, monohydrogenphosphate, dihydrogenphosphate, sulfuric acid, monohydrosulfuric acid, hydrogen iodide, phosphorous acid, and the like. It is not limited. It also includes, but is not limited to, salts of amino acids such as argin, arg
  • the low molecular weight compounds may exist in unsolvated form as well as in solvated forms (eg, hydrates), including hydrate forms depending on the compound.
  • the compounds of the present invention may exist in crystalline or amorphous form, and all such physical forms are included within the scope of the present invention, and the low molecular weight compounds may have asymmetric carbon atoms or double bonds, which are optical centers, depending on the compound, resulting in racemic Sieves, enantiomers, diastereomers, geometric isomers and the like may be present and these are also within the scope of the present invention.
  • composition for treating skin injury inflammatory disease comprising the inhibitor of the present invention may further include a pharmaceutically acceptable carrier, and may be formulated with the carrier.
  • the term "pharmaceutically acceptable carrier” refers to a carrier or diluent that does not stimulate the organism and does not inhibit the biological activity and properties of the administered compound.
  • Acceptable pharmaceutical carriers in compositions formulated as liquid solutions are sterile and physiologically compatible, including saline, sterile water, Ringer's solution, buffered saline, albumin injectable solutions, dextrose solution, maltodextrin solution, glycerol, ethanol and One or more of these components may be mixed and used, and other conventional additives such as antioxidants, buffers and bacteriostatic agents may be added as necessary.
  • Diluents, dispersants, surfactants, binders and lubricants may also be added in addition to formulate into injectable formulations, pills, capsules, granules or tablets such as aqueous solutions, suspensions, emulsions and the like.
  • composition for treating skin injury inflammatory disease comprising the inhibitor of the present invention and a pharmaceutically acceptable carrier is applicable to any formulation containing it as an active ingredient, it can be prepared in oral or parenteral formulations.
  • Pharmaceutical formulations of the invention may be oral, rectal, nasal, topical (including the cheek and sublingual), subcutaneous, vaginal or parenteral (intramuscular, subcutaneous). And forms suitable for administration by inhalation or insufflation.
  • Oral dosage forms containing the composition of the present invention as an active ingredient include, for example, tablets, troches, lozenges, water-soluble or oily suspensions, preparation powders or granules, emulsions, hard or soft capsules, syrups or elixirs. can do.
  • lactose For formulation into tablets and capsules, lactose, saccharose, sorbitol, mannitol, starch, amylopectin, binders such as cellulose or gelatin, excipients such as dicalcium phosphate, disintegrants such as corn starch or sweet potato starch, stearic acid masne It may include a lubricating oil such as calcium, calcium stearate, sodium stearyl fumarate or polyethylene glycol wax, and in the case of a capsule, it may further contain a liquid carrier such as fatty oil in addition to the above-mentioned materials.
  • a lubricating oil such as calcium, calcium stearate, sodium stearyl fumarate or polyethylene glycol wax
  • a liquid carrier such as fatty oil in addition to the above-mentioned materials.
  • Formulations for parenteral administration comprising the composition of the present invention as an active ingredient, for injection, such as subcutaneous injection, intravenous injection or intramuscular injection, a suppository injection method or aerosol for spraying by inhalation through the respiratory system It can be formulated as.
  • the compositions of the present invention may be mixed in water with stabilizers or buffers to prepare solutions or suspensions, which may be formulated for unit administration of ampoules or vials.
  • solutions or suspensions which may be formulated for unit administration of ampoules or vials.
  • solutions or suspensions which may be formulated for unit administration of ampoules or vials.
  • a rectal composition such as suppositories or enema, including conventional suppository bases such as cocoa butter or other glycerides.
  • a propellant or the like may be combined with the additives to disperse the dispersed dispersion or wet powder.
  • compositions of the present invention are preferably applied topically to the skin and are therefore preferably prepared in conventional skin application cosmetic formulations. That is, the composition for treating skin damage inflammatory diseases according to the present invention is prepared in the form of a cosmetic or make-up products such as lotion, essence, cosmetic oil, cream, powder, pack, foundation, makeup base, makeup stick, etc. Can be used. It can be applied in various forms such as liquid, cream, paste, solid, and can be prepared by a cosmetic preparation method commonly known in the art.
  • a cosmetic or make-up products such as lotion, essence, cosmetic oil, cream, powder, pack, foundation, makeup base, makeup stick, etc.
  • Cosmetic preparation method commonly known in the art.
  • the cosmetic preparation after stirring and dispersing the carbomer in purified water, butylene glycol, glycerin, Fiji-1500 and the like are added, and polyoxyethylene-cured castor oil, triethanol, preservative, inhibitor according to the present invention, and the like It can manufacture by dissolving in a suitable solvent, such as ethanol, and mixing.
  • the lotion formulation may contain cetearyl alcohol, glyceryl stearate / pG-100 stearate, polysorbate 60, sorbitan sesquioleate, cetyloctanoate, squalene and the like at about 70 ° C.
  • butylene glycol, magnesium aluminum silicate, xanthan gum, and preservatives are dissolved and dispersed in purified water and emulsified in heated to 70 ° C., the emulsion is cooled, and the present invention is dissolved in a suitable solvent or component. It can be prepared by adding an inhibitor of the mixture and stirring the mixture, followed by cooling to room temperature.
  • the cosmetic composition of the present disclosure may include a water-soluble base material comprising conjugated linoleic acid, linoleic acid, gamma-linoleic acid, unsaturated fatty acid including alpha-linoleic acid or propylene glycol.
  • the cosmetic compositions herein can also be prepared in any formulations commonly prepared in the art, including, for example, solutions, suspensions, emulsions, pastes, gels, creams, lotions, powders, soaps, surfactant-containing It may be formulated as a cleansing, oil, powder foundation, emulsion foundation, wax foundation and spray, but is 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, hair tonic, shampoo, rinse, cleansing cream, cleansing foam, cleansing water, pack, spray or powder. .
  • the formulation of the present composition is a paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, trakant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as a carrier component.
  • animal oil, vegetable oil, wax, paraffin, starch, trakant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as a carrier component.
  • animal oil vegetable oil, wax, paraffin, starch, trakant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, 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.
  • 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 esters, polyethyleneglycol or sorbitan can 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 composition may comprise at least one pharmaceutically acceptable excipient.
  • the composition according to the present invention has good and stable skin absorption and contains an ATM / ATR protein kinase inhibitor, thereby promoting collagen production in the natural state where skin aging occurs and at the same time inhibiting the activity of collagen degrading enzymes. By preventing degradation, the amount of collagen produced is increased, thereby improving skin wrinkles. Furthermore, it is useful for treating skin inflammatory diseases caused by stress damaging factors such as ultraviolet rays as well as skin wrinkle improvement function of functional cosmetics. Therefore, in addition to improving skin wrinkles of general functional cosmetics, it also prevents senescence of cells and prolongs their life, thereby fundamentally preventing aging, and prevents and treats diseases such as skin inflammation and damage caused by stress factors. It is useful as a material for multi-functional cosmetics that has both various cosmetics and pharmaceutical functions.
  • the present invention relates to a method for treating skin wrinkle improvement or skin damage inflammatory disease using an ATM / ATR protein kinase inhibitor.
  • the present invention relates to the use of an ATM / ATR protein kinase inhibitor to improve skin wrinkles or treat skin damage inflammatory diseases.
  • Example 1 Determination of the amount of collagen by 733
  • Example 2 Determination of the amount of collagenase that is a collagen degrading enzyme by 733
  • NF-kB The activity of NF-kB was used as a representative measure of the inflammatory response caused by various stresses.
  • Human skin cells foreskin primary cell line
  • FBS / DMEM medium Gibco
  • 733 (20uM) After pretreatment with 733 (20uM), etc., cells were treated with 150 mJ / cm2 UV light using a crosslinker 800 series (GEX-800, UVP). Binding DNA fragments of enhancers were synthesized and measured for their relative strength by EMSA (Molecular & Cellular Biology 12: 4412-4421, 1992).
  • Example 4 Determination of the expression level of a representative protein that is an inflammatory response measure by 733
  • the composition according to the present invention is good and stable skin absorption, while promoting the production of collagen in the natural state of skin aging and at the same time inhibit the activity of collagen degrading enzymes to prevent the breakdown of collagen to increase the amount of collagen produced by the skin Improves wrinkles. Furthermore, in addition to the general skin wrinkle improvement function of functional cosmetics, it is useful for treating skin inflammatory diseases caused by stress damaging factors such as ultraviolet rays. Therefore, in addition to improving skin wrinkles of general functional cosmetics, it prevents cellular senescence and prolongs life, thereby fundamentally preventing aging and prevents and treats diseases such as skin inflammation and damage caused by stress factors. It is useful as a material for multi-functional cosmetics with various cosmetics and pharmaceutical functions.

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  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La présente invention concerne une composition visant à atténuer les rides de la peau ou à traiter les maladies inflammatoire endommageant la peau, contenant, comme principe actif un inhibiteur de la sénescence cellulaire, qui est un inhibiteur de la protéine kinase ATM/ATR. La composition selon la présente invention augmente la quantité de production de collagène, ayant ainsi pour effet d'atténuer les rides de la peau et, simultanément, étant utiles dans le traitement des maladies inflammatoires endommageant la peau provoquées par des facteurs de stress tels que des rayons ultraviolets.
PCT/KR2016/007581 2015-07-17 2016-07-13 Composition pour atténuer les rides de la peau et pour traiter les maladies inflammatoires endommageant la peau, contenant comme principe actif un inhibiteur de la sénescence cellulaire Ceased WO2017014480A2 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
CN201680054162.0A CN108135815A (zh) 2015-07-17 2016-07-13 含有细胞老化抑制剂作为有效成分的皮肤皱纹改善用及皮肤损伤炎症疾病治疗用组合物
HK18115717.0A HK1256597A1 (zh) 2015-07-17 2016-07-13 含有细胞老化抑制剂作为有效成分的皮肤皱纹改善用及皮肤损伤炎症疾病治疗用组合物

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
KR10-2015-0101514 2015-07-17
KR20150101514 2015-07-17
KR1020160088246A KR20170009760A (ko) 2015-07-17 2016-07-12 세포 노화 저해제를 유효성분으로 함유하는 피부 주름 개선용 및 피부 손상 염증 질환 치료용 조성물
KR10-2016-0088246 2016-07-12

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WO2017014480A2 true WO2017014480A2 (fr) 2017-01-26
WO2017014480A3 WO2017014480A3 (fr) 2017-05-11

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PCT/KR2016/007581 Ceased WO2017014480A2 (fr) 2015-07-17 2016-07-13 Composition pour atténuer les rides de la peau et pour traiter les maladies inflammatoires endommageant la peau, contenant comme principe actif un inhibiteur de la sénescence cellulaire

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050276765A1 (en) * 2004-06-10 2005-12-15 Paul Nghiem Preventing skin damage
WO2007015632A1 (fr) * 2005-08-04 2007-02-08 Cgk Co., Ltd. Inhibiteur d’atm et d’atr
KR100792587B1 (ko) * 2006-06-09 2008-01-09 씨지케이 주식회사 유레아 화합물을 유효성분으로 함유하는 포유동물세포의노화방지제

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