EP1487404A1 - Utilisation de solutes compatibles pour inhiber la liberation de ceramides - Google Patents

Utilisation de solutes compatibles pour inhiber la liberation de ceramides

Info

Publication number
EP1487404A1
EP1487404A1 EP03745259A EP03745259A EP1487404A1 EP 1487404 A1 EP1487404 A1 EP 1487404A1 EP 03745259 A EP03745259 A EP 03745259A EP 03745259 A EP03745259 A EP 03745259A EP 1487404 A1 EP1487404 A1 EP 1487404A1
Authority
EP
European Patent Office
Prior art keywords
compounds
use according
compatible solutes
preparation
acid
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
EP03745259A
Other languages
German (de)
English (en)
Inventor
Joachim BÜNGER
Jean Krutmann
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Merck Patent GmbH
Original Assignee
Merck Patent GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Merck Patent GmbH filed Critical Merck Patent GmbH
Publication of EP1487404A1 publication Critical patent/EP1487404A1/fr
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
    • 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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • 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
    • A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
    • A61K8/4953—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom containing pyrimidine ring derivatives, e.g. minoxidil
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/04—Antipruritics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/16—Emollients or protectives, e.g. against radiation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A61P39/06—Free radical scavengers or antioxidants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/08—Anti-ageing preparations

Definitions

  • the invention relates to the use of compatible solutes for
  • the cell metabolism of human keratinocytes is influenced by exposure to UV light.
  • UVA radiation and the formation of singlet oxygen release a so-called “second messenger” from the cell membrane.
  • This "second messenger” activates the transcription factor AP-2.
  • the transcription factor AP-2 induces the expression of pro-inflammatory genes.
  • compatible solutes are advantageously suitable for inhibiting the release of ceramides.
  • Compatible solutes are, according to a common definition, stress protection substances from extremely halophilic and halotolerant eubacteria that cause them
  • Concentration does not impair cell metabolism, i.e. are compatible with the metabolism, (according to: E.A.
  • the invention thus relates to the use of one or more -J5 compounds selected from compatible solutes for inhibiting the release of ceramides and the use of one or more compounds selected from compatible solutes for the prophylaxis and protection of human skin against premature aging and the use of one or more compounds selected from 0 compatible solutes for the prophylaxis of and protection of human skin against wrinkles.
  • the invention further relates to the use of one or more compounds selected from the compatible solutes for the preparation of preparations suitable for inhibiting the release of ceramides or suitable for the prophylaxis and protection of human skin from premature aging or for the prophylaxis of and for protection Q human skin from wrinkles.
  • A-light inhibit induced release of ceramides from membrane-5 bound sphingomyelin.
  • the inhibition of ceramide release prevents the expression of matrix metalloproteinases. In this way, the increased breakdown of collagen fibers in the skin can be avoided.
  • compatible solutes are advantageously suitable for protecting the collagen fibers of the skin.
  • the compatible solutes are also suitable for protecting human skin from wrinkles.
  • compatible solutes are also advantageously suitable for protection against the formation of pro-inflammatory substances and the reactive oxygen species resulting therefrom.
  • UVA 320 - 400 nm Long-wave ultraviolet radiation
  • UVA radiation is crucial in the pathogenesis of photodermatoses (e.g. polymorphic light dermatosis, lupus erythematosus, light urticaria, photoallergic and phototoxic Reactions), premature and accelerated skin aging
  • mitochondrial DNA in these cells are of crucial importance for the premature aging process of human skin triggered by UVA radiation.
  • the mitochondria contain their own genomic material that codes for proteins involved in oxidative phosphorylation. It is located in the form of a circular DNA molecule in the area of the inner mitochondrial membrane and is therefore increasingly exposed to oxidative stress.
  • the resulting mutations in mitochondrial DNA are not only important for the pathogenesis of degenerative diseases, but also for cell or tissue aging. For example, normal healthy tissues show an increasing content of mitochondrial DNA mutations depending on their age. This is accompanied by a reduction in their ability to oxidative phosphorylation.
  • UVA radiation is a potent inducer of oxidative stress and is therefore able to cause mitochondrial DNA mutations in the skin.
  • compatible solutes according to the invention is preferably suitable for people with photodermatoses, in particular for people with photodermatoses selected from polymorphic light dermatosis, lupus erythematosus and light urticaria.
  • Compatible solutes preferred according to the invention are selected from
  • Sugars and polyols e.g. Trehalose, glycerin, glycosylglycerin, ß-
  • Mannosylgylcerate (Firoin), ß-Mannosylglyceramide (Firoin A), Di-myo-inositol phosphate (DIP), Cyclic 2,3-diphosphoglycerate (cDPG), 1, 1-Diglycerol-phosphate (DGP) and Di-mannosyl-di -inositol phosphate (DMIP), or amino acids and amino acid derivatives, such as the betaines, preferably glycine betaine, proline betaine or glutamate betaine, alanine,
  • Proline glutamine, N-acetyl-lysine, glutamine-1-amide, taurine, choline, choline-O-sulfate, camitin, arsenobetaine, crotonobetaine, dimethylsulfonioacetate,
  • Particularly preferred compatible solutes are selected from the compounds of the formulas Ia and Ib
  • R 3 and R 4 each independently of one another are H or OH
  • Alkyl is an alkyl radical having 1 to 4 carbon atoms
  • R 5 H alkyl, an amino acid residue, dipeptide residue or the tripeptide residue
  • Ectoin and the ectoin derivatives are low-molecular, cyclic amino acid derivatives that can be obtained from various halophilic microorganisms or can be produced synthetically. Both ectoin and hydroxyectoin have the advantage that they do not react with the cell metabolism.
  • the compounds selected from the compounds of the formulas Ia and Ib, the physiologically tolerable salts of the compounds of the formulas Ia and Ib and the stereoisomeric forms of the compounds of the formulas Ia and Ib can be in the preparations as optical isomers, diastereomers, racemates, zwitterions, cations or are present as a mixture thereof.
  • the physiologically tolerable Salts of the compounds of the formulas Ia and Ib and the stereoisomeric forms of the compounds of the formulas Ia and Ib are preferred those compounds in which R 1 is H or CH 3 , R 2 H or COOH, R 3 and R 4 are each independently H or OH and n is 2. Under the 5th
  • Compounds selected from the compounds of the formulas Ia and Ib, the physiologically tolerable salts of the compounds of the formulas Ia and Ib and the stereoisomeric forms of the compounds of the formulas Ia and Ib are the compounds (S) -1, 4,5,6-tetrahydro- 2-methyl-4-pyrimidine
  • 4-pyrimidinecarboxylic acid (hydroxyectoin) is particularly preferred.
  • amino acid residues mentioned in the radical R 5 of the compounds of the formulas Ia and Ib are derived from the corresponding amino acids.
  • amino acid means the stereoisomeric forms, for example D and L forms, of the following compounds: alanine, ⁇ -alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine and lysine , Methionine, phenylalanine, serine, 0 threonine, tryptophan, tyrosine, valine, ⁇ -aminobutyrate, N ⁇ -acetyllysine, N ⁇ -acetylornithine, N ⁇ -acetyldiaminobutyrate and N ⁇ -acetyldiaminobutyrate.
  • L-amino acids are preferred.
  • the residues of the following amino acids are preferred: alanine, ⁇ -alanine, asparagine, aspartic acid, glutamine, 5 glutamic acid, glycine, serine, threonine, valine, ⁇ -aminobutyrate, N ⁇ -acetyllysine, N ⁇ -acetylornithine, N ⁇ -acetyldiaminobutyrate and N ⁇ Acetyldiaminobutyrat.
  • the chemical nature of the di- and tripeptide residues mentioned in the radical R 5 of the compounds of the formulas Ia and Ib are acid amides and break down into 2 or 3 amino acids during hydrolysis.
  • the amino acids in the di- and tripeptide residues are linked by amide bonds.
  • Preferred di- and tripeptide residues are made up of the preferred amino acids.
  • alkyl groups mentioned in the radicals R 1 , R 2 and R 5 of the compounds of the formulas Ia and Ib include the methyl group CH 3 , the ethyl group C 2 H 5 , the propyl groups CH 2 CH 2 CH 3 and CH (CH 3 ) 2 and the butyl groups CH 2 CH2CH 2 CH 3 , H 3 CCHCH 2 CH 3) CH 2 CH (CH 3 ) 2 and
  • the preferred alkyl group is the methyl group.
  • Preferred physiologically tolerable salts of the compounds of form la and Ib are, for example, alkali, alkaline earth or ammonium salts, such as Na, K, Mg or Ca salts, and salts derived from the organic bases triethylamine or tris (2 hydroxy-ethyl) amine.
  • Further preferred physiologically compatible salts of the compounds of the formulas Ia and Ib result from reaction with inorganic acids such as hydrochloric acid, sulfuric acid and phosphoric acid or with organic carboxylic or sulfonic acids such as acetic acid, citric acid, benzoic acid, maleic acid, fumaric acid, tartaric acid and p-toluenesulfonic acid ,
  • Treatment of skin diseases can be used.
  • DE 43 42 560 describes the use of ectoin and ectoin derivatives as moisturizers in cosmetic products 10. These products are suitable e.g. for the care of aged, dry or irritated skin.
  • Derivatives such as hydroxyectoin can be used as antioxidants and free radical scavengers in cosmetic and dermatological preparations.
  • the preparations can be used for the treatment and / or prophylaxis of skin aging caused by oxidative stress and of inflammatory reactions.
  • ectoin and ectoin derivatives in cosmetic formulations are e.g. described in WO 00/07558, WO 00/07559 and WO 00/07560, e.g. the care and prophylaxis of 5 dry and / or flaky skin, the protection of human skin against dryness and / or high salt concentrations, the protection of cells, proteins and / or biomembranes of the human skin, the protection of the microflora of the human skin, the stabilization the Q skin barrier and the protection and stabilization of the nucleic acids of human skin cells.
  • the compounds selected from compatible solutes such as, for example, the compounds of the formulas Ia and Ib, the physiologically tolerable salts of the compounds of the formulas Ia and Ib and the stereoisomeric forms of Compounds of the formulas Ia and Ib are advantageously suitable for inhibiting the release of ceramides.
  • the use according to the invention of the compounds selected from compatible solutes preferably takes place in such a way that the compounds mentioned are in the form of a cosmetic, dermatological or pharmaceutical preparation, in particular in a corresponding formulation.
  • the proportion of the compounds selected from the compounds of the compatible solutes, in particular the compounds of the formulas la and Ib, the physiologically tolerable salts of the compounds of the formulas ⁇ c la and Ib and the stereoisomeric forms of the compounds of the formulas la and Ib in cosmetic, dermatological or pharmaceutical preparation is preferably from 0.001 to 50% by weight, particularly preferably from 0.01 to 10% by weight and particularly preferably from 0.1 to 10% by weight, based on the entire preparation. Very preferably 0, the proportion of the compounds mentioned in the preparation is from 0.1 to 5% by weight, based on the preparation as a whole.
  • the preparations can also contain a further 5 cosmetic, dermatological or pharmaceutical active ingredients.
  • the preparations can contain one or more antioxidants. All common antioxidants can be contained in the preparations. It 0 are many known and ind iesem related literature proven substances that can be used, such as flavonoids, coumaranones, amino acids (eg glycine, histidine, tyrosine, tryptophan) and derivatives thereof, imidazoles (eg urocanic acid) and derivatives thereof,
  • Peptides such as D, L-carnosine, D-camosine, L-camosine and their derivatives 5
  • anserine carotenoids
  • carotenes e.g. ⁇ -carotene, ß-carotene, lycopene
  • chlorogenic acid and their derivatives e.g. dihydroliponic acid
  • lipoic acid and their derivatives e.g. dihydroliponic acid
  • aurothioglucose propylthiouracil and other thiols (e.g. thioredoxin, glutathione, cysteine, cystine, cystamine and their glycosyl, N-acetyl, methyl, ethyl) , Propyl, amyl, butyl and
  • Nucleosides and salts as well as sulfoximine compounds (e.g. buthionine sulfoximines, homocysteine sulfoximine, buthionine sulfones, penta-, hexa-, heptathionine sulfoximine) in very low tolerable dosages (e.g. pmol to ⁇ mol / kg), also (metal) chelators, (e.g. ⁇ -hydroxy fatty acids , Palmitic acid, phytic acid, lactoferrin), ⁇ -hydroxy acids (e.g.
  • sulfoximine compounds e.g. buthionine sulfoximines, homocysteine sulfoximine, buthionine sulfones, penta-, hexa-, heptathionine sulfoximine
  • very low tolerable dosages e.g. pmol to ⁇ mol /
  • citric acid citric acid, lactic acid, malic acid
  • humic acid bile acid, bile extracts, bilirubin, biliverdin, EDTA, EGTA and their derivatives, unsaturated fatty acids and their derivatives
  • vitamin C and derivatives eg ascorbyl palmitate, magnesium ascorbyl phosphate, ascorbyl acetate), tocopherols and derivatives (eg vitamin E acetate), vitamin A and derivatives (eg vitamin A palmitate) as well as coniferyl benzoate of benzoin, rutinic acid and its derivatives, ⁇ -glycosyl rutin , Ferulic acid, furfurylidene glucitol, carnosine, butylated hydroxytoluene, butylated hydroxyanisole, nordohydroguanetic acid, trihydroxybutyrophenone, quercitin, uric acid and its derivatives, Man nose and its derivatives, zinc and its derivatives (e
  • ZnO, ZnS0 4 selenium and its derivatives (e.g. selenium methionine), stilbenes and their derivatives (e.g. stilbene oxide, trans-stilbene oxide), metabisulfite salts, sulfite salts or hydrogen sulfite salts.
  • antioxidants are also suitable for use in the preparations.
  • Known and commercially available mixtures are, for example, mixtures containing lecithin, L- (+) - ascorbyl palmitate and citric acid (for example Oxynex ® AP), natural tocopherols, L - (+) - ascorbyl palmitate, L - (+) - ascorbic acid and citric acid as active ingredients.
  • acid e.g. Oxynex ® K LIQUID
  • Citric acid and lecithin e.g. Oxynex ® LM
  • Another suitable antioxidant mixture can e.g. consist of Emblicanin-A, Emblicanin-B, Punigluconin and Pendunculagin such as in WO 00/48551 under the name CAPROS TM (e.g. Emblica TM).
  • the preparation contains one or more compounds selected from flavonoids and / or coumaranones.
  • aglycones i.e. understood the sugar-free ingredients, and the derivatives of flavonoids and aglycones.
  • flavonoid is also understood to mean anthocyanidine (cyanidine).
  • coumaranones are also understood to mean their derivatives.
  • Preferred flavonoids are derived from flavanones, flavones, 3-hydroxyflavones, aurones and isoflavones, in particular from flavanones, flavones, 3-hydroxyflavones and aurones.
  • the flavonoids are preferably selected from the following compounds: 4,6,3 ', 4'-tetrahydroxyauron, quercetin, rutin, iso- quercetin, eriodictyol, taxifolin, luteolin, trishydroxyethylquercetin (troxequercetin), trishydroxyethylrutin (troxerutin), trishydroxyethylisoquercetin (troxeisoquercetin), trishydroxyethylluteolin (troxeluteolin) and their ⁇ -glycatedirosylates, as well as their ⁇ -sulfate phosphate.
  • rutin and troxerutin are particularly preferred.
  • a polar group is bound to one or more hydroxyl groups of these compounds, e.g. each independently a sulfate or phosphate group.
  • Suitable counterions are, for example, the ions of the alkali or
  • Alkaline earth metals e.g. are selected from sodium or potassium.
  • flavonoids and coumaranones occur naturally. If the preparation contains such compounds, these can also be obtained by extracting appropriate plants and introduced into the preparation either in purified form as a single substance or in the form of the extract which may have been further processed.
  • the proportion of the one or more compounds selected from flavonoids and coumaranones in the preparation is preferably from 0.001 to 5% by weight, particularly preferably from 0.01 to 2% by weight, based on the preparation as a whole.
  • the preparation contains one or more antioxidants selected from the substances citric acid, lactic acid, malic acid, EDTA, butylated hydroxytoluene, ascorbic acid, ascorbyl palmitate, magnesium ascorbyl phosphate, ascorbyl acetate, tocopherol, tocopherol acetate and from the metabisulphite or sulfate Hydrogen sulfite salts selected from alkali metal salts such as sodium and potassium salts, basic metal salts and ammonium salts.
  • the preparation contains antioxidant mixtures such as e.g. Emblica TM.
  • the proportion of the one or more antioxidants in the preparation is preferably from 0.001 to 5% by weight, particularly preferably from 0.01 to 2% by weight, based on the entire preparation.
  • the preparations can contain one or more UV filters. All UVA and UVB filters known to the person skilled in the art are suitable as suitable organic UV filters. For both UV ranges there are many well-known and proven substances known from the specialist literature, such as benzylidene camphor derivatives such as. 3- (4'-methylbenzylidene) dl camphor (e.g. Eusolex ® 6300),
  • Benzoyl or dibenzoyl methanes such as - 1- (4-tert-Butylphenyl) -3- (4-methoxyphenyl) propan-1, 3-dione (e.g. Eusolex ® 9020) or
  • Methoxy cinnamic acid esters such as
  • Isopentyl 4-methoxycinnamate for example as a mixture of the isomers (for example Neo Heliopan ® E 1000),
  • Salicylate derivatives such as
  • 2-ethyl-2-cyano-3,3-diphenylacrylate e.g. Eusolex ® OCR
  • organic UV filters are generally incorporated into the preparations in an amount of 0.5 to 10% by weight, preferably 1 to 8% by weight.
  • organic UV filters are generally used in an amount of 0.5 to 20% by weight, preferably in an amount of 1 to 15% by weight and particularly preferably in amounts of 2 to 8% by weight per individual substance incorporated into the preparations.
  • Inorganic UV filters are also conceivable from the group of titanium dioxides, such as coated titanium dioxide (e.g. Eusolex ® T-2000, Eusolex ® T-AQUA), zinc oxides (e.g. Sachtotec ® ), iron oxides or cerium oxides. These inorganic UV filters are generally incorporated into the preparations in an amount of 0.5 to 20% by weight, preferably 2 to 10% by weight.
  • the ratios of the individual substances to one another are usually in the range from 1:10 to 10: 1, preferably in the range from 1: 5 to 5: 1 and particularly preferably in the range from 1: 2 to 2: 1.
  • UV-A- in addition to UV-B-
  • UV-B filters are used, so it is advantageous for most applications 5 if the proportion of UV-B filters predominates and the ratio of UV-A filters: UV-B filters is in the range 1: 1 to 1:10.
  • UV-filtering properties 10 3- (4 methylbenzylidene) -dl-camphor, 1- (4-tert-butylphenyl) -3- (4-methoxyphenyl) propan-1, 3-dione , 4-Isopropyldibenzoyl-methane, 2-hydroxy-4-methoxybenzophenone, octyl methoxycinnamate, 3,3,5-trimethylcyclohexyl salicylate, 2-ethyl-4- (dimethylamino) benzoate, 2-ethyl-2-cyano-3,3-diphenylacrylate -ethylhexyl ester, 2-phenylbenzimidazole-5-sulfonic acid and its potassium, sodium and trethanolamine salts and coated titanium dioxide are used.
  • UV filters mentioned can also be used in encapsulated form
  • the hydrophilicity of the capsule wall can depend on the solubility
  • UV filter 25 of the UV filter can be set.
  • hydrophobic UV filters can also be incorporated into purely aqueous preparations.
  • oily impression which is often perceived as unpleasant, is applied when the hydrophobic UV filter is applied
  • UV filters especially dibenzoylmethane derivatives, show in preparations such as cosmetic formulations only reduced photostability.
  • 35 compounds that affect the photostability of these filters such as for example, the cinnamic acid derivatives mentioned above, the photostability of the entire preparation can be increased.
  • encapsulation of individual UV filters or other ingredients can avoid formulation problems that arise from the interaction of individual formulation components with one another, such as crystallization processes, precipitation and agglomerate formation, since the interaction is prevented.
  • UV filters are in encapsulated form. It is advantageous if the capsules are so small that they cannot be observed with the naked eye. To achieve the above Effects, it is also necessary that the capsules are sufficiently stable and do not release the encapsulated active ingredient (UV filter) into the environment or only to a small extent.
  • Suitable capsules can have walls made of inorganic or organic polymers.
  • US 6,242,099 B1 describes the production of suitable capsules with walls made of C hitin, C hitin derivatives or polyhydroxylated polyamines.
  • Capsules to be used with particular preference have walls which can be obtained by a SolGel process as described in the applications WO 00/09652, WO 00/72806 and WO 00/71084.
  • capsules are preferred, the walls of which are made of silica gel (silica; undefined silicon oxide hydroxide).
  • the preparation of corresponding capsules is known to the person skilled in the art, for example, from the cited Patent applications known, the content of which expressly belongs to the subject of the present application.
  • the capsules in the preparations are preferably in such 5
  • the preparation can also contain one or more amino acids or their pharmaceutically acceptable salts.
  • Preferred amino acids are selected from the group of compounds consisting of alanine, valine, leucine, isoleucine, proline, methionine, phenylalanine, tryptophan, glycine, serine, threonine, cysteine, tyrosine, asparagine, glutamine, lysine,
  • the proportion of the amino acids or their pharmaceutically acceptable salts in the preparation is preferably from 0.1 to 10% by weight, particularly preferably 0 from 0.1 to 8% by weight and particularly preferably from 0.2 up to 5% by weight based on the entire preparation. Most preferably, the proportion of the amino acids or their pharmaceutically acceptable salts in the preparation is from 0.2 to 2% by weight, based on 5, of the entire preparation.
  • Formulations are suitable for external Q application, for example as a cream, lotion, gel, or as a solution which can be sprayed onto the skin. It is preferred if the formulation contains at least one oil and at least one water phase.
  • formulations examples include solutions, emulsions, PIT emulsions, suspensions, ointments, gels, creams, Lotions, sprays and aerosols.
  • Other forms of application include sticks. Any customary carriers, auxiliaries and, if appropriate, further active ingredients can be added to the formulation.
  • Preferred auxiliaries come from the group of preservatives, antioxidants, stabilizers, solubilizers, vitamins, colorants, odor improvers, film formers, thickeners, humectants.
  • Solutions and emulsions can contain the usual carriers such as solvents, solubilizers and emulsifiers, e.g. Water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1, 3-butyl glycol, oils, in particular cottonseed oil, peanut oil, corn oil, olive oil, castor oil and sesame oil, glycerol fatty acid esters, polyethylene glycols and fatty acid esters of these sorbitan compounds or mixtures thereof.
  • solvents e.g. Water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1, 3-butyl glycol, oils, in particular cottonseed oil, peanut oil, corn oil, olive oil, castor oil and sesame oil, glycerol fatty acid
  • the emulsions can be in various forms. So you can e.g. an emulsion or microemulsion of the water-in-oil (W / O) type, or of the oil-in-water (O / W) type, or a multiple emulsion, for example of the water-in-oil-in-water (W / O / W).
  • the formulations can also be present as emulsifier-free, disperse preparations.
  • they can be hydrodispersions or Pikkering emulsions.
  • Suspensions can contain the usual carriers such as liquid diluents, eg water, ethanol or propylene glycol, suspending agents, eg ethoxylated isostearyl alcohols, polyoxyethylene sorbitol esters and polyoxyethylene sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar and tragacanth or mixtures of these substances.
  • suspending agents eg ethoxylated isostearyl alcohols, polyoxyethylene sorbitol esters and polyoxyethylene sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar and tragacanth or mixtures of these substances.
  • Pastes, ointments, gels and creams can contain the usual carriers, e.g. animal and vegetable fats, waxes, paraffins, starch,
  • Face and body oils can contain the usual carriers such as synthetic oils such as fatty acid esters, fatty alcohols, silicone oils, natural oils such as vegetable oils and oily plant extracts, paraffin oils, lanolin oils or mixtures of these substances.
  • synthetic oils such as fatty acid esters, fatty alcohols, silicone oils, natural oils such as vegetable oils and oily plant extracts, paraffin oils, lanolin oils or mixtures of these substances.
  • Sprays can contain the usual blowing agents, eg chlorofluorocarbons, 5 propane / butane or dimethyl ether.
  • the formulation is available in various dosage forms commonly used for this application. It can be used in particular as a lotion or emulsion, such as a cream or milk (O / W, 5 W / O, O / W / O, W / O / W), in the form of an oily-alcoholic, oily-aqueous or aqueous-alcoholic Gels or solutions in the form of solid sticks or packaged as an aerosol.
  • a lotion or emulsion such as a cream or milk (O / W, 5 W / O, O / W / O, W / O / W)
  • a cream or milk O / W, 5 W / O, O / W / O, W
  • / O / W in the form of an oily-alcoholic, oily-aqueous or aqueous-alcoholic Gels or solutions in the form of solid sticks or packaged as an aerosol.
  • the formulation may contain adjuvants which are commonly used in this type of preparation, e.g. Thickeners, plasticizers, wetting agents, surfactants, emulsifiers, preservatives, anti-agents
  • adjuvants which are commonly used in this type of preparation, e.g. Thickeners, plasticizers, wetting agents, surfactants, emulsifiers, preservatives, anti-agents
  • Foaming perfumes, waxes, lanolin, blowing agents, dyes 5 and / or pigments, which color the agent itself or the skin, and other ingredients commonly used in cosmetics, dermatology or pharmacy.
  • An oil, wax or other fatty substance, a low monoalcohol or a low polyol or mixtures thereof can be used as the dispersing or solubilizing agent.
  • the particularly preferred monoalcohols or polyols include ethanol, i-propanol, propylene glycol, glycerin and sorbitol.
  • a preferred embodiment of the invention is an emulsion in the form of a cream or a milk and fatty alcohols, fatty acids, fatty acid ester, in particular triglycerides of fatty acids, lanolin,
  • 5 includes natural or synthetic oils or waxes and emulsifiers in the presence of water.
  • oily lotions based on natural or synthetic oils and waxes, lanolin, 0 fatty acid esters, in particular triglycerides of fatty acids, or oleo-alcoholic lotions based on a lower alcohol, such as ethanol, or a glycol, such as propylene glycol, and / or a polyol, such as glycerin, and oils, waxes and fatty acid esters such as triglycerides of 5 fatty acids.
  • the formulation may also be in the form of an alcoholic gel comprising one or more lower alcohols or polyols, such as ethanol, Q propylene glycol or glycerin, and a thickener, such as silica.
  • the oily-alcoholic gels also contain natural or synthetic oil or wax.
  • the solid sticks consist of natural or synthetic waxes 5 and oils, fatty alcohols, fatty acids, fatty acid esters, lanolin and other fatty substances. If a preparation is made up as an aerosol, use in the
  • blowing agents such as alkanes, fluoroalkanes and
  • the preparations as described above are applied to the skin.
  • formulations can be made using techniques well known to those skilled in the art.
  • Example B1 Inhibition of UV-A-induced ceramide formation
  • a quantitative HPTLC method is used to measure the concentration of a second messenger (ceramide) in UVA-irradiated normal human keratinocytes, which have either been pretreated with 1 mM RonaCare TM Ectoin or untreated, compared to unirradiated keratinocytes.
  • the cells pretreated in this way are irradiated with a single dose of UVA 30 J / cm 2 (radiation source: Sellamed 24000).
  • Example B2 Inhibition of UV-A-induced AP-2 activation
  • the activation of the transcription factor AP-2 is determined with
  • a nucleus extract (according to J.D. Dignam, P.L. Martin, B.S.
  • ICAM-1 The expression of ICAM-1 is measured with the differential reverse transcriptase-PCR (RT-PCR) and the kit from Applied Biosystem. In order to take into account the normal fluctuations in the gene expression of the skin cells, the ICAM-1 expression is compared in relation to the constitutively formed house-keeping gene ⁇ -actin. The semi-quantitative analysis of the RT-PCR is carried out with an ion exchange chromatography with a UV spectrophotometer (A260).
  • RT-PCR differential reverse transcriptase-PCR
  • A260 UV spectrophotometer
  • Keratinocytes with 1 mM ectoine can be induced by UVA radiation
  • Example B4 Effect of ectoin on the formation of mutations in mitochondrial DNA induced by UVA radiation
  • Dermal human fibroblasts are cultivated in Eagle minimal medium.
  • the cells are irradiated three times a day with 8 J / cm 2 UVA for four consecutive days for a total of three weeks. Then the mt-
  • FIG. 4 shows the agarose gel of the reference fragment reproduced by means of PCR to represent the "common deletion", as a sign of extensive UV-A-induced DNA mutations in primary human skin fibroblasts. Pretreatment of the fibroblasts with 1 mM Ronacare TM Ectoin prevented the formation of the mt-DNA mutations, as can be seen in the direct comparison.
  • a Sepigel 305 (1) LAURETH-7, POLYACRYLAMIDE, 2.0
  • phase A Sepigel 305 is mixed intimately with water and a preservative.
  • Phase B is dissolved and incorporated into phase A.
  • the Eusolex ® UV-Pearls TM OMC are added with stirring and the pH is adjusted to 5 with citric acid.
  • a EUSOLEX ® TS (1) TITANIUM DIOXIDE, ALUMINA, 10.0
  • UV-Pearls TM (1) AQUA (WATER), ETHYLHEXYL 20.0 OMC METHOXYCINNAMATE, SILICA, PVP, CHLORPHENESIN, BHT
  • Phase A is combined except for Eusolex ® TS and heated to 80 ° C. Then Eusolex ® TS is slowly stirred in. Phase B is heated to 75 ° C. and slowly added to phase A with stirring. The Eusolex ® UV-Pearls TM OMC are then added at 40 ° C and then phase D is incorporated. Finally, it is homogenized and cooled with stirring.
  • Viscosity 6,000 mPas (Brookfield LV, spindle 4, 60 rpm) at 25 ° C.
  • EUSOLEX ® OCR (1) OCTOCRYLENE 7.0 Arlacel P135 (2) PEG-30 DIPOLYHYDROXYSTEARATE 2.5 Abil WE 09 (3) POLYGLYCERYL-4 ISOSTEARATE, CETYL 2.5
  • Cetiol 868 (6) ETHYLHEXYL STEARATE 4.0 Raw material INCI% by weight
  • CERESIN MICROCRYSTALLINE WAX
  • RonaCare TM Allantoin (D ALLANTOIN 0.2
  • Phase A is combined except for EUSOLEX, ® ⁇ T-ECO and heated to 80 ° C.
  • EUSOLEX ® T-ECO is slowly stirred into the hot oil phase.
  • phase B is heated to 80 ° C. and slowly added to phase A with stirring.
  • Homogenization is carefully carried out at 50-40 ° C to enable optimal dispersion of the Eusolex ® T-ECO particles.
  • Phase C is then added at 40 ° C. and the mixture is cooled with stirring.
  • Viscosity 11,800 mPas (Brookfield RVT, Sp. C, 10 rpm) at 26 ° C. Sources:
  • EUSOLEX ® 2292 (1) ETHYLHEXYL METHOXYCINNAMATE, BHT 5.0 Emulium delta (2) GLYCERYL STEARATE, CETYL ALCOHOL, 3.3
  • Crodamol AB C12-15 ALKYL BENZOATE 3.0
  • Phase A is combined except for EUSOLEX, ® 1 * T-2000 and heated to 60 ° C.
  • EUSOLEX ® T-2000 is slowly incorporated into the molten oil phase.
  • Phase B is heated to 60 ° C., then phase C is dispersed in with stirring and then P hase A is stirred into phase B / C with vigorous stirring. It is cooled with stirring and phase D is added at 40.degree. The mixture is then homogenized (1 min with the magic wand at level II) and cooled to 25 ° C. with stirring.
  • Isolan PDI DIISOSTEAROYL POLYGLYCERYL-3 4.0 DIISOSTEARATE
  • Phase A and phase B are heated separately to 80 ° C. Phase B is added to phase A with stirring. The mixture is then cooled and homogenized with stirring.
  • Viscosity (23 ° C): 32,000 mPa.s (Brookfield RVT, spindle C, 5 rpm,
  • Isolan PDI DIISOSTEAROYL POLYGLYCERYL-3 4.0 DIISOSTEARATE
  • Phase A is heated to 80 ° C. Then phase B is dissolved with stirring and slowly added to phase A with stirring. The mixture is then homogenized and stirred until cold.
  • Viscosity (27 ° C): 16,000 mPa.s (Brookfield RVT, spindle C, 20 rpm,
  • Phase A is weighed in and stirred until homogeneous.
  • Viscosity 28 ° C: 1700 mPa.s (Brookfield RVT, spindle B, 10 rpm,
  • Phases A and B are heated separately to 80 ° C. Phase B is then added to phase A with stirring and homogenized. It is then neutralized and cooled with stirring. Remarks: pH value (25 ° C): 5.80
  • Viscosity 25 ° C: 28000 mPa.s (Brookfield RVT, spindle C, 5 rpm,
  • Jojoba oil (4) BUXUS CHINENSIS (JOJOBA OIL) 2.0
  • Citric acid monohydrate ((11)) CITRIC ACID 0.03 glycerin (87% pure) (1) GLYCERIN 3.0 preservative qs RonaCare TM Ectoin (D ECTOIN 1.0 Raw material INCI% by weight
  • Phases A and B are mixed well. Phase B is then added to phase A with stirring and homogenized. It is then neutralized with phase C and stirred.
  • Eusolex ® 2292 (1) ETHYLHEXYL METHOXYCINNAMATE, BHT 4.0
  • Phases A and B are heated separately to 80 ° C. Phase B is then added to phase A with stirring and homogenized. It is then neutralized with sodium hydroxide solution and cooled with stirring.
  • Viscosity (26 ° C): 24000 mPa.s (Brookfiel RVT, spindle C, 5 rpm,
  • Aerosil R 972 (4) SILICA 1, 0
  • Viscosity 24 ° C: 350,000 mPa.s (Brookfield RVT, spindle D, 5 rpm,
  • Example 12 Bodymilk (W / O)
  • OXYNEX ® K liquid D PEG-8, TOCOPHEROL, ASCORBYL 0.05 PALMITATE, ASCORBIC ACID, CITRIC ACID
  • Phase A and phase B are heated separately to 80 ° C. Phase B is then introduced into phase A with homogenization. It is cooled to 65 ° C. with stirring and homogenized again. Perfume with phase C at 35 ° C.
  • Viscosity 14,900 mPa.s (Brookfield RVT, spindle C, 10 rpm, Helipath),
  • Figure 1 UVA-induced "second messenger” release in keratinocytes after 24 h of ectoin pretreatment.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Dermatology (AREA)
  • Medicinal Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Gerontology & Geriatric Medicine (AREA)
  • Birds (AREA)
  • Toxicology (AREA)
  • Biochemistry (AREA)
  • Cosmetics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Utilisation de solutés compatibles pour inhiber la libération de céramides, en particulier pour la prophylaxie et la protection de la peau humaine contre le vieillissement prématuré, ainsi que pour la prophylaxie et la protection de la peau humaine contre la formation de rides.
EP03745259A 2002-03-28 2003-03-03 Utilisation de solutes compatibles pour inhiber la liberation de ceramides Ceased EP1487404A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE10214257 2002-03-28
DE10214257A DE10214257A1 (de) 2002-03-28 2002-03-28 Verwendung von kompatiblen Soluten zur Inhibierung der Freisetzung von Ceramiden
PCT/EP2003/002146 WO2003082239A1 (fr) 2002-03-28 2003-03-03 Utilisation de solutes compatibles pour inhiber la liberation de ceramides

Publications (1)

Publication Number Publication Date
EP1487404A1 true EP1487404A1 (fr) 2004-12-22

Family

ID=28050987

Family Applications (1)

Application Number Title Priority Date Filing Date
EP03745259A Ceased EP1487404A1 (fr) 2002-03-28 2003-03-03 Utilisation de solutes compatibles pour inhiber la liberation de ceramides

Country Status (6)

Country Link
US (1) US7981899B2 (fr)
EP (1) EP1487404A1 (fr)
JP (1) JP2005521709A (fr)
AU (1) AU2003215621A1 (fr)
DE (1) DE10214257A1 (fr)
WO (1) WO2003082239A1 (fr)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100789344B1 (ko) 2004-12-10 2007-12-28 주식회사 엘지생활건강 올리고뉴클레오타이드를 포함하는 피부 노화 방지제
WO2006065920A1 (fr) * 2004-12-13 2006-06-22 Aquaphotonics, Inc. Procedes anti-vieillissement et composition associee
FR2896990B1 (fr) * 2006-02-03 2008-05-02 Lvmh Rech Composition protectrice et regenerante
DE102006053360A1 (de) 2006-11-10 2008-05-15 Evonik Stockhausen Gmbh Hautreinigungsmittel, insbesondere Kälteschutzcreme
FR2932680B1 (fr) * 2008-06-19 2010-08-27 Clarins Lab Association de tiliroside et d'un peptide
CA2980792C (fr) * 2008-07-31 2020-04-28 Sol-Gel Technologies Ltd. Microcapsules comportant des principes actifs et un enrobage d'oxyde metallique, leur procede de preparation et leurs utilisations
DE102014113781A1 (de) * 2014-09-23 2016-03-24 Bitop Ag Solut und Solutgemisch sowie eine Zusammensetzung enthaltend mindestens ein Solut zur Verwendung bei der Prävention oder Behandlung von durch Schwebstaub verursachter kosmetischer oder pathologischer Effloreszenzen
JP7132935B2 (ja) * 2017-03-06 2022-09-07 メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング 適合溶質の使用
JP7194517B2 (ja) * 2017-05-30 2022-12-22 花王株式会社 皮膚化粧料
WO2021018990A1 (fr) 2019-08-01 2021-02-04 Merck Patent Gmbh Prévention et réduction des troubles de la kératinisation, et agents cosmétiques associés

Family Cites Families (56)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2649397A (en) 1950-05-31 1953-08-18 Shell Dev Fungicidal compositions and method of fungus control comprising hydrocarbyl-substituted pyrimidines
DE2132079C3 (de) 1971-06-28 1980-04-10 Basf Ag, 6700 Ludwigshafen Verfahren zur Herstellung von 1 ,3-Diazacycloalkenen
DE2154948A1 (de) 1971-11-05 1973-05-10 Huels Chemische Werke Ag Verfahren zur herstellung von cyclischen amidinen
DE2614723C2 (de) 1976-04-06 1986-01-02 Wella Ag, 6100 Darmstadt Kosmetisches Mittel
LU77316A1 (fr) 1977-05-11 1979-01-19
DE2746650A1 (de) 1977-10-17 1979-04-26 Henkel Kgaa Kosmetische mittel mit einem gehalt an haut-feuchthaltemitteln
US4877805A (en) 1985-07-26 1989-10-31 Kligman Albert M Methods for treatment of sundamaged human skin with retinoids
US4529587A (en) 1982-02-19 1985-07-16 Lever Brothers Company Method of reducing sebum on the hair and skin
IT1214611B (it) 1985-05-22 1990-01-18 Schiena Ricerche Composti per uso cosmetico dermatologico e relative composizioni.
JPS63233912A (ja) 1986-12-30 1988-09-29 チャールス　オブ　ザ　リッツ　グループ　リミテッド 紫外線吸収性化合物および遮光剤
JP2699181B2 (ja) 1988-10-14 1998-01-19 広栄化学工業株式会社 テトラヒドロピリミジン化合物の製造法
US5476852A (en) * 1989-05-03 1995-12-19 Janssen Pharmaceutica N.V. Method of topically treating acne vulgaris, hyperkeratotic dermatoses, and photo-aging of the skin
JPH0386867A (ja) 1989-06-26 1991-04-11 Takeda Chem Ind Ltd 含窒素複素環化合物
JPH0331265A (ja) 1989-06-26 1991-02-12 Takeda Chem Ind Ltd テトラヒドロピリミジン誘導体の製造方法
FR2658076B1 (fr) 1990-02-12 1992-06-12 Sanofi Sa Composition cosmetique contenant des copolymeres d'aminoacides, utile comme agent hydratant.
US5175166A (en) 1991-08-27 1992-12-29 The University Of Toledo Muscarinic agonists
IL100810A (en) 1992-01-30 1996-12-05 Yeda Res & Dev Pharmaceutical preparations including 2 - methyl - carboxy - 5 - hydroxy - tetrahydropyrimidine and / or 2 - methyl - 4 - carboxy - tetrahydropyrimidine, plywood methods
ES2102670T3 (es) 1992-08-26 1997-08-01 Beiersdorf Ag Uso de captadores de radicales como agentes inmunomoduladores en composiciones cosmeticas y dermatologicas.
DE4305788C2 (de) 1993-02-25 1997-06-12 Beiersdorf Ag Kosmetische und dermatologische Formulierungen zum Schutze der Haut gegen Oxidationsprozesse
DE4244580A1 (de) 1992-12-31 1994-07-07 Galinski Erwin A Verfahren zur in vivo Gewinnung von Inhaltsstoffen aus Zellen
EP0719133A1 (fr) 1993-09-15 1996-07-03 Unilever Plc Soin pour la peau et composition
CA2132289A1 (fr) 1993-10-12 1995-04-13 Bharat Desai Surfactifs de type amphoacetate tres purs a base d'imidazoline et procedes pour leur preparation
DE4342560A1 (de) 1993-12-14 1995-06-22 Marbert Gmbh Ectoin und Ectoinderivate als Feuchtigkeitsspender in Kosmetikprodukten
GB9424521D0 (en) 1994-12-05 1995-01-25 Procter & Gamble Cleansing compositions
US6153176A (en) 1995-01-20 2000-11-28 The Procter & Gamble Company Low pH sunscreen compositions
JPH09143167A (ja) 1995-11-17 1997-06-03 Dainippon Pharmaceut Co Ltd 酵素の安定化法
US5972718A (en) 1996-02-28 1999-10-26 The Blood Center Research Foundation Method of detecting heparin-induced thrombocytopenia
US5827508A (en) 1996-09-27 1998-10-27 The Procter & Gamble Company Stable photoprotective compositions
US5738858A (en) 1996-09-27 1998-04-14 Cheseborough-Pond's Usa Co., Division Of Conopco, Inc. Skin care compositions containing fatty hydroxyethyl imidazoline surfactants and retinol or retinyl ester
WO1998013020A1 (fr) 1996-09-27 1998-04-02 Unilever Plc Compositions pour le soin de la peau contenant des combinaisons de composes permettant de reproduire l'effet sur la peau de l'acide retinoique
JP3031265B2 (ja) 1996-10-24 2000-04-10 日本電気株式会社 圧電トランスの駆動回路および駆動方法
JP3086867B2 (ja) 1997-01-09 2000-09-11 工業技術院長 合成ガスの製造用触媒及び合成ガスの製造方法
DE19711082A1 (de) 1997-03-18 1998-09-24 Degussa Verfahren zur Abtrennung von Tetrahydropyrimidinen aus wäßrigen Lösungen
US6599513B2 (en) * 1997-05-27 2003-07-29 Sembiosys Genetics Inc. Products for topical applications comprising oil bodies
TWI234467B (en) * 1997-06-04 2005-06-21 Univ Michigan Composition for inhibiting photoaging of skin
JPH11181477A (ja) * 1997-12-18 1999-07-06 Kao Corp 洗浄剤組成物
US6406366B1 (en) 1998-02-20 2002-06-18 University Of Alaska Fairbanks Method and apparatus for removing pin bones
DE19933463A1 (de) 1998-07-10 2000-01-13 Beiersdorf Ag W/O-Emulsionen mit einem Gehalt an Ectoinen
US20040047828A1 (en) 1998-08-01 2004-03-11 Merck Patent Gmbh Ectoin or ection derivatives and surfactants
DE19834818A1 (de) 1998-08-01 2000-02-03 Merck Patent Gmbh Kosmetische Formulierung
DE19834816A1 (de) 1998-08-01 2000-02-03 Merck Patent Gmbh Verwendung von Ectoin oder Ectoin-Derivaten in kosmetischen Formulierungen
US20030157040A1 (en) 1998-08-01 2003-08-21 Merck Patent Gmbh Use of ectoine or ectoine derivatives in cosmetic formulations
ES2228089T3 (es) 1998-08-01 2005-04-01 Merck Patent Gmbh Empleo de ectoina o derivados de ectoina en formulaciones cosmeticas.
DE19911775A1 (de) 1998-08-01 2000-02-03 Merck Patent Gmbh Verwendung von Ectoin oder Ectoin-Derivaten in kosmetischen Formulierungen
US6268275B1 (en) 1998-10-08 2001-07-31 Micron Technology, Inc. Method of locating conductive spheres utilizing screen and hopper of solder balls
JP2003501479A (ja) 1999-06-12 2003-01-14 ビトプ ゲゼルシャフト ミット ベシュレンクテル ハフツング 薬 剤
EP1125583A1 (fr) * 2000-02-14 2001-08-22 Bitop Gesellschaft für biotechnische Optimierung MbH Utilisation de solutés compatibles en tant qu inhibiteur de la dégradation enzymatique de biopolymères macromoléculaires
DE10006578C2 (de) 2000-02-14 2002-10-31 Bitop Ag Verwendung von kompatiblen Soluten als Inhibitoren des enzymatischen Abbaus von makromolekularen Biopolymeren
DE10014632A1 (de) * 2000-03-24 2001-09-27 Merck Patent Gmbh Verwendung von Ectoin oder Ectoin-Derivaten zum Schutz der Streßproteine in der Haut
DE10014631A1 (de) 2000-03-24 2001-09-27 Merck Patent Gmbh Verwendung von Ectoin oder Ectoin-Derivaten zur Prophylaxe und/oder Behandlung von UV-induzierter Immunsuppression
ATE283054T1 (de) 2000-04-12 2004-12-15 Bitop Ag Verwendung von kompatiblen soluten als substanzen mit radikalfangenden eigenschaften
DE10043456A1 (de) 2000-09-04 2002-03-14 Merck Patent Gmbh Verwendung von Ectoin oder Ectoin-Derivaten zur Stabilisierung von p53
US7048910B2 (en) 2000-09-07 2006-05-23 Merck Patent Gmbh Use of ectoine or ectoine derivatives for oral care
AU2002255627B2 (en) 2001-02-27 2008-01-17 The Regents Of The University Of Michigan Use of natural EGFR inhibitors to prevent side effects due to retinoid therapy, soaps, and other stimuli that activate the epidermal growth receptor
ATE315038T1 (de) * 2001-05-30 2006-02-15 Warner Lambert Co Antibakterielle mittel
DE10133201A1 (de) * 2001-07-07 2003-01-23 Beiersdorf Ag Elektrolythaltige kosmetische und dermatologische Zubereitungen zur Behandlung und aktiven Prävention trockener Haut und anderer negativer Veränderungen der physiologischen Homöostase der Haut

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO03082239A1 *

Also Published As

Publication number Publication date
DE10214257A1 (de) 2003-10-16
WO2003082239A1 (fr) 2003-10-09
US20050201955A1 (en) 2005-09-15
US7981899B2 (en) 2011-07-19
AU2003215621A1 (en) 2003-10-13
JP2005521709A (ja) 2005-07-21

Similar Documents

Publication Publication Date Title
EP1363594B1 (fr) Formulations cosmetiques renfermant des derives de flavonoides
EP1251818B1 (fr) Formulation galenique
EP1961453A2 (fr) Composés de benzyliden-ß-dicarbonyl comme des absorbeurs d'UV
EP1205475B1 (fr) Composés flavonoides utilisés contre le stress oxydatif et les rayons UV
EP1411891B1 (fr) Formulation cosmetique contenant de l'acetone dihydroxy
EP1893207B1 (fr) Utilisation de derives de piperazine et de morpholine substitues
EP1487404A1 (fr) Utilisation de solutes compatibles pour inhiber la liberation de ceramides
EP1066821A1 (fr) Agent cosmétique topique contenant des benzaldoximes
WO2009021589A1 (fr) Inhibiteurs de la tyrosinase
EP1311234A2 (fr) Substances permettant d'induire et d'intensifier les mecanismes de bronzage de la peau
EP1689734B1 (fr) Derive de flavonoide
EP1286654A1 (fr) Utilisation d'aryloximes pour assurer la prophylaxie et/ou le traitement de la formation d'erytheme et/ou de reactions inflammatoires de la peau
EP1286655B1 (fr) Composition topique comprenant au moins une aryloxime, et son procede de preparation
EP1909919B1 (fr) Flavonoides utilises comme synergistes pour renforcer l'effet de substances autobronzantes
EP2229169A1 (fr) Préparation contenant des dérivés de chroman-2-one
EP1890672B1 (fr) Utilisation de derives de chromone
DE10044985A1 (de) Verwendung von Ectoin oder Ectoin-Derivaten zum Schutz vor Allergenen und/oder Irritantien
EP1811989A1 (fr) Preparation contenant des derives de flavonoide oxydes
EP1311233A1 (fr) Substances permettant d'induire et d'intensifier les mecanismes de bronzage de la peau et formulations cosmetiques ou dermatologiques contenant ces substances
WO2013020624A1 (fr) Extraits de tradescantia virginiana
DE10025557A1 (de) Verwendung von Aryloximen zur Prophylaxe und/oder Behandlung von Entzündungsreaktionen der Haut
WO2009021590A1 (fr) Inhibiteurs de la tyrosinase

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20040722

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LI LU MC NL PT RO SE SI SK TR

AX Request for extension of the european patent

Extension state: AL LT LV MK

RIN1 Information on inventor provided before grant (corrected)

Inventor name: KRUTMANN, JEAN

Inventor name: BUENGER, JOACHIM

17Q First examination report despatched

Effective date: 20051024

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION HAS BEEN REFUSED

18R Application refused

Effective date: 20070504