WO2013143855A2 - Préparations cosmétiques et dermatologiques contenant une ou plusieurs substances qui modulent le gène du facteur de type krüppel 9 ("krüppel-like factor 9" (klf9)) - Google Patents

Préparations cosmétiques et dermatologiques contenant une ou plusieurs substances qui modulent le gène du facteur de type krüppel 9 ("krüppel-like factor 9" (klf9)) Download PDF

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Publication number
WO2013143855A2
WO2013143855A2 PCT/EP2013/055146 EP2013055146W WO2013143855A2 WO 2013143855 A2 WO2013143855 A2 WO 2013143855A2 EP 2013055146 W EP2013055146 W EP 2013055146W WO 2013143855 A2 WO2013143855 A2 WO 2013143855A2
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WO
WIPO (PCT)
Prior art keywords
skin
klf9
cosmetic
circadian
weight
Prior art date
Application number
PCT/EP2013/055146
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German (de)
English (en)
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WO2013143855A3 (fr
Inventor
Helga Biergiesser
Florian Spoerl
Judit MEYER-KOVAC
Sandra KORGE
Original Assignee
Beiersdorf Ag
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Publication date
Application filed by Beiersdorf Ag filed Critical Beiersdorf Ag
Publication of WO2013143855A2 publication Critical patent/WO2013143855A2/fr
Publication of WO2013143855A3 publication Critical patent/WO2013143855A3/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • 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
    • A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
    • 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
    • A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
    • A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/74—Biological properties of particular ingredients
    • A61K2800/78—Enzyme modulators, e.g. Enzyme agonists

Definitions

  • the invention encompasses cosmetic and dermatological preparations containing one or more substances which modulate the gene for the "crippled-like factor 9" (Klf9), in particular those preparations for use on the skin or hair of a human for the repair and regeneration of the human skin.
  • Klf9 "crippled-like factor 9”
  • the inner clocks cause a variety of chemical and biological processes, which, taken together, fundamentally affect health, performance, experience, behavior and mood.
  • Chronobiologists have found different time qualities. For example, analgesics have a stronger effect in the evening than in the morning. In the evening, pain is also felt much stronger. At night, the body temperature drops, the circulation is highly unstable, the sense of balance disturbed. The digestive power is optimal between 13 and 14 o'clock, while the brain power is minimal. Alcohol is broken down properly in the evening. Growth and regulation of the hormonal balance takes place in the nocturnal deep sleep phases, as well as the strengthening of cognitive (previously learned) skills.
  • Sleep is also subject to this circadian rhythm: It is a highly active process, divided into quite different stages of sleep.
  • Circadian rhytmic is an important regulatory function that also needs skin cells for regeneration and revitalization for a fresher appearance.
  • the epidermis can be subdivided into cell fractions with a high cell division capacity or cell division rate (stem cells and so-called transiently amplifying keratinocytes) and non-proliferative, stratified cell fractions which form the majority of the epidermis.
  • Keratinocytes were irradiated with the specified dose of UVB and harvested 3 hours and 24 hours after irradiation. Error bar: standard deviation. ( ** ) significance level p ⁇ 0.05.
  • Keratinocytes are derived from epidermal stem cells that are located in the area of the stratum basale or in the area of the outer root sheath of the hair follicles. They traverse several stages of development as they are pushed up by coming cells, until they form a layer of flattened, dead corneocytes in the stratum corneum.
  • the time between differentiation in the stratum basale and Abschidferung as corneocyte in the stratum disjunctum is about one month, but can be used in certain diseases, e.g. Psoriasis, be shortened.
  • the keratinocyte constantly changes its shape and geometric orientation.
  • the keratinocytes arise from epidermal stem cells and have a roughly cylindrical shape.
  • the remodeling of the cells begins with an increase in volume and a change in the cell axis in a more horizontal direction. Keratohyaline grains are formed and remodeling progresses rapidly. It comes to flattening of the cells, the loss of the nucleus, the shrinkage due to fluid loss and finally to keratinization. In the following stratum corneum (horny layer) one can no longer detect keratinocytes. Keratinocytes became corneocytes.
  • Keratinocytes are actively involved in the immune response, in inflammatory processes and in wound healing. They can produce a variety of cytokines, growth factors and even complement factors. In many chronic inflammatory skin diseases in particular TNF-alpha and IL-1, but also many other interleukins and chemokines are released.
  • Keratinocytes contribute to UV protection by absorbing melanosomes (melanin-containing vesicles) from melanocytes.
  • the melanin is stored around the nucleus and protects it from UV-related damage.
  • Organisms are naturally exposed to a rotation of the Earth during the day-night cycle, which has led to an evolutionary adaptation of the physiology and behavior of almost all living things to this rhythm.
  • the suprachiasmatic nucleus (SCN) of the hypothalamus serves as the central clock of the circadian clock.
  • the SCN controls i.a. the cyclical release of certain hormones (e.g., cortisol, melatonin), temperature homeostasis and neuronal signals.
  • the circadian rhythm is formed by self-regulating feedback loops that allow cyclic expression of genes and corresponding proteins of the molecular clockwork.
  • Peripheral oscillators are essential for the circadian control of tissue-specific cellular and physiological processes.
  • rhythm regulation is largely controlled by the circadian control of tissue-specific gene regulators (so-called transcription factors) or central enzymes.
  • tissue-specific gene regulators so-called transcription factors
  • central enzymes The control of circadian regulated genes has strong variations between different tissues, indicating specific functions of the circadian clock in individual organs.
  • Recent studies are increasingly providing evidence for circadian control of cell division processes by clock-controlled cell cycle regulators. Demenffleend leads a systematic disorder of the circadian system to increased occurrence of diseases associated with the loss of proliferation control (eg, cancer).
  • Klf9 can be modulated via the glucocorticoid signaling pathway by the application of polycyclic alcohols, especially oridonine / withaferin.
  • the present invention therefore relates to the use of polycyclic alcohols, in particular Oridonin / Withaferin, for stabilizing the circadian physiology of skin functions.
  • Dusk is the fluid transition between day and night before the beginning of the day or after the end of the day, which is created by light scattering in the atmosphere.
  • twilight means the period in which scattered light from the sun, which is below the horizon, is visible.
  • oridonin or withaferin administered during the period of a twilight lead to particularly relaxed skin conditions.
  • the invention therefore also the use of oridonine and / or withaferin for daytime specific modulation of Klf9 gene expression, characterized in that an effective amount of Oridonine and / or Withaferin is applied in a cosmetic preparation during the evening civil twilight on the skin.
  • the following conditions can be understood as skin functions: deficient, sensitive or hypoactive states of the skin or of skin appendages degenerative phenomena of the skin (eg skin slackening, age spots, telangiectasias and disappearance of the epidermal and dermal cell layers, the components of the connective tissue, the reed cones and capillaries of the skin) and / or the skin appendages,
  • Visible vascular dilations telangiectasia, cuperosis
  • Slackness and formation of wrinkles
  • Klf9 is described as a growth regulator in the epithelial tissue of the uterus (Pabona et al., 2009, Simmen et al., 2008; Simmen et al., 2007), but no growth-modulating effect of Klf9 has been reported to date for the skin.
  • Klf9 gene expression in non-proliferative active cells is increased by a factor of -30 ( Figure 2a).
  • the Klf9 gene dose was artificially modulated in keratinocytes.
  • Increasing the K / 9 level (overexpression) resulted in reduced cell growth ( Figure 2b).
  • an artificial reduction of Klf9 levels increased cell growth (Fig. 2c).
  • the cell growth of keratinocytes can be directly influenced by the modulation of Klf9.
  • Sun exposure of the skin is a manifestly daytime-dependent phenomenon, and UV radiation can lead to decreased keratinocyte growth.
  • 9-levels in the skin have their maximum at noon (correlating with maximum sun exposure), the question arose between UV exposure and Klf9 gene expression.
  • Klf9 is dose-dependently induced by UVB radiation (Fig. 2d). This effect is short-lived, so that the Klf9 levels 24h after irradiation are at the base level again ( Figure 2c).
  • UV-induced growth reduction can be counteracted by modulation of Klf9.
  • Klf9 modulating substances should be used for specific purposes in terms of daytime, especially in the evening hours.
  • the graph in Figure 2 indicates the altered skin lipid status at different times of the day. It can be seen that in the evening, the fatty acid content in the skin is higher.
  • Oridonine CAS No: 28957-04-2
  • stabilizing the circadian physiology of the skin is understood to mean that the substances used according to the invention put the skin into a nocturnal state of recovery, as a result of which it is also possible to restore or at least to equalize the external appearance of the recovered skin.
  • the Withaferin A and Oridonin are used in cosmetic or dermatological compositions, a content of 0.00001 - 50.0 wt .-%, in particular 0.001 to 20.0 wt .-%, based on the total weight of the composition are preferred.
  • the compositions contain 0.002 to 10.0 wt .-%, more preferably 0.002 to 5.0 wt .-% of the preservatives used in the invention, most preferably 0.005 to 3.0 wt .-%, each based on the total weight of Composition..
  • Emulsions are advantageous dosage forms in the sense of the present invention, e.g. in the form of a cream, a lotion, a cosmetic milk are advantageous and contain e.g. Fats, oils, waxes and / or other fatty substances, as well as water and one or more emulsifiers, as they are commonly used for such a type of formulation.
  • Medicinal topical compositions according to the present invention usually contain one or more drugs in effective concentration.
  • drugs for the sake of simplicity, reference is made to the clear distinction between cosmetic and medical use and corresponding products to the statutory provisions of the Federal Republic of Germany (for example, Cosmetics Regulation, Food and Medicines Act).
  • the cosmetic or dermatological preparation in the sense of the present invention is a solution or emulsion or dispersion, it is possible to use as solvent:
  • Oils such as triglycerides of capric or caprylic acid, but preferably castor oil;
  • Fats, waxes and other natural and synthetic fats preferably esters of fatty acids with lower C-number alcohols, e.g. with isopropanol, propylene glycol or glycerol, or esters of fatty alcohols with alkanoic acids of low C number or with fatty acids;
  • Alcohols, diols or polyols of low C number, and their ethers preferably ethanol, isopropanol, propylene glycol, glycerol, ethylene glycol, ethylene glycol monoethyl or monobutyl ether, propylene glycol monomethyl, monoethyl or monobutyl ether, diethylene glycol monomethyl or monoethyl ether and analogous products ,
  • ethers preferably ethanol, isopropanol, propylene glycol, glycerol, ethylene glycol, ethylene glycol monoethyl or monobutyl ether, propylene glycol monomethyl, monoethyl or monobutyl ether, diethylene glycol monomethyl or monoethyl ether and analogous products .
  • mixtures of the abovementioned solvents are used.
  • water can be another ingredient.
  • the oil phase of the emulsions, oleogels or hydrodispersions or lipodispersions in the context of the present invention is advantageously selected from the group of esters of saturated and / or unsaturated, branched and / or unbranched alkanecarboxylic acids having a chain length of 3 to 30 carbon atoms and saturated and / or or unsaturated, branched and / or unbranched alcohols having a chain length of 3 to 30 carbon atoms, from the group of esters of aromatic carboxylic acids and saturated and / or unsaturated, branched and / or unbranched alcohols having a chain length of 3 to 30 carbon atoms.
  • ester oils can then advantageously be selected from the group isopropyl myristate, isopropyl palmitate, isopropyl stearate, isopropyl oleate, n-butyl stearate, n-hexyl laurate, n-decyl oleate, isooctyl stearate, isononyl stearate, isononyl isononanoate, 2-ethylhexyl palmitate, 2-ethylhexyl laurate, 2-hexyldecyl stearate, 2 Octyldodecyl palmitate, oleyl oleate, oleyl erucate, erucyl oleate, erucyl erucate and synthetic, semi-synthetic and natural mixtures of such esters, eg Jojoba oil.
  • the oil phase can be advantageously selected from the group of branched and unbranched hydrocarbons and waxes, the silicone oils, the dialkyl ethers, the group of saturated or unsaturated, branched or unbranched alcohols, and the fatty acid triglycerides, namely the triglycerol esters of saturated and / or unsaturated, branched and / or unbranched alkanecarboxylic acids of a chain length of 8 to 24, in particular 12 to 18 carbon atoms.
  • the fatty acid triglycerides can be advantageously selected from the group of synthetic, semi-synthetic and natural oils, e.g. Olive oil, sunflower oil, soybean oil, peanut oil, rapeseed oil, almond oil, palm oil, coconut oil, palm kernel oil, and the like.
  • the aqueous phase of the preparations according to the invention advantageously contains alcohols, diols or polyols of low C number, and their ethers, preferably ethanol, isopropanol, propylene glycol, glycerol, ethylene glycol, ethylene glycol monoethyl or monobutyl ether, propylene glycol monomethyl, monoethyl or monobutyl ether , Diethylene glycol monomethyl or monoethyl ether and analogous products, furthermore low-C alcohols, for example ethanol, isopropanol, 1,2-propanediol, glycerol and, in particular, one or more thickeners, which may advantageously be selected from the group silicon dioxide, Aluminum silicates, polysaccharides or their derivatives, for example hyaluronic acid, xanthan gum, hydroxypropylmethylcellulose, particularly advantageously from the group of polyacrylates, preferably a polyacrylate from the group of so-called Carb
  • Gels used in the present invention usually contain low C number alcohols, e.g. Ethanol, isopropanol, 1, 2-propanediol, glycerol and water or an above-mentioned oil in the presence of a thickener which is preferably silica or an aluminum silicate in oily-alcoholic gels, preferably a polyacrylate in aqueous-alcoholic or alcoholic gels.
  • a thickener which is preferably silica or an aluminum silicate in oily-alcoholic gels, preferably a polyacrylate in aqueous-alcoholic or alcoholic gels.
  • Fixed pins contain e.g. natural or synthetic waxes, fatty alcohols or fatty acid esters.
  • liquid oils for example paraffin oils, castor oil, isopropyl myristate
  • semi-solid constituents eg petrolatum, lanolin
  • solid constituents eg beeswax, ceresin and microcrystalline Waxes or ozokerite
  • high-melting waxes eg carnauba wax, candelilla wax
  • Suitable propellants for sprayable from aerosol containers cosmetic and / or dermatological preparations in the context of the present invention the usual known volatile, liquefied propellants, such as hydrocarbons (propane, butane, isobutane) are suitable, which can be used alone or in mixture with each other. Also, compressed air is advantageous to use.
  • hydrocarbons propane, butane, isobutane
  • Titanium dioxide - 1.0 - -
  • PEG-40 Stearate 0.80 1, 00 1, 00 1, 00
  • Oridonin 0.5 0, 1 0.2 1, 0
  • Methyl Methacrylate Crosspolymer 1 0 1, 0
  • Mexoryl SX hemihydrate 0, 1 0.5 1 2
  • Nylon 12 1.0 1.0 1.0 1.0 1.0
  • Glyceryl stearates self-emulsifying 2 2 1, 5 1, 5
  • Phenoxyethanol 0.35 0.25 0.3 0.3
  • Oridonine 0, 1 0, 1 0.5 1, 0
  • Glyceryl stearate self-emulsifying 1.0 1.0 1.0 1.0
  • Phenylbenzimidazole sulfonic acid 1.0 1.0 1.0
  • Cetylstearyl alcohol 5.0 3.5 4.0 3.0
  • Caprylic acid / capric acid triglycerides 2.0 2.5 1, 0 2.0
  • Phenylbenzimidazole sulfonic acid 1, 0 1, 0

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Birds (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Cosmetics (AREA)

Abstract

L'invention concerne l'utilisation d'alcools polycycliques pour stabiliser la physiologie circadienne, ainsi que leur utilisation pour moduler l'expression génique de Klf9.
PCT/EP2013/055146 2012-03-29 2013-03-13 Préparations cosmétiques et dermatologiques contenant une ou plusieurs substances qui modulent le gène du facteur de type krüppel 9 ("krüppel-like factor 9" (klf9)) WO2013143855A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102012205059.0 2012-03-29
DE201210205059 DE102012205059A1 (de) 2012-03-29 2012-03-29 Kosmetische und dermatologische Zubereitungen enthaltend eine oder mehrere Substanzen die das Gen für den "Krüppel-like factor 9" (Klf9) modulieren

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WO2013143855A2 true WO2013143855A2 (fr) 2013-10-03
WO2013143855A3 WO2013143855A3 (fr) 2014-02-27

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DE (1) DE102012205059A1 (fr)
WO (1) WO2013143855A2 (fr)

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002167330A (ja) * 2000-11-29 2002-06-11 Shiseido Co Ltd 美白用皮膚外用剤およびメラニン生成抑制剤
US8703161B2 (en) * 2007-08-13 2014-04-22 Elc Management, Llc Skin repair compositions comprising circadian gene activators and a synergistic combination of Sirt1 gene activators
WO2009067245A2 (fr) * 2007-11-20 2009-05-28 University Of Florida Research Foundation, Inc. Compositions et procédés de réparation de tissu
JP2010098965A (ja) * 2008-10-21 2010-05-06 Hitoshi Okamura 化粧品素材のスクリーニング方法
FR2940969B1 (fr) * 2009-01-09 2012-05-04 Isp Investments Inc Nouveaux peptides anti-age et composition cosmetique et/ou pharmaceutique les contenant
FR2944435B1 (fr) * 2009-04-17 2011-05-27 Sederma Sa Composition cosmetique comprenant de l'oridonine
KR101770706B1 (ko) * 2010-03-31 2017-08-23 가부시키가이샤 시세이도 시계 유전자 Ｐｅｒｉｏｄ의 발현 조절제

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
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WO2013143855A3 (fr) 2014-02-27
DE102012205059A1 (de) 2013-10-02

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