EP1296941A2 - Derives d'acides carboxyliques 3,4-dihydroxybenzyl-substitues et leur utilisation comme antioxydants - Google Patents

Derives d'acides carboxyliques 3,4-dihydroxybenzyl-substitues et leur utilisation comme antioxydants

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Publication number
EP1296941A2
EP1296941A2 EP01953166A EP01953166A EP1296941A2 EP 1296941 A2 EP1296941 A2 EP 1296941A2 EP 01953166 A EP01953166 A EP 01953166A EP 01953166 A EP01953166 A EP 01953166A EP 1296941 A2 EP1296941 A2 EP 1296941A2
Authority
EP
European Patent Office
Prior art keywords
dihydroxybenzyl
carbon atoms
group
substituted
carbonic 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.)
Withdrawn
Application number
EP01953166A
Other languages
German (de)
English (en)
Inventor
Jakob Peter Ley
William Johncock
Roland Langner
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.)
Symrise AG
Original Assignee
Haarmann and Reimer GmbH
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Filing date
Publication date
Application filed by Haarmann and Reimer GmbH filed Critical Haarmann and Reimer GmbH
Publication of EP1296941A2 publication Critical patent/EP1296941A2/fr
Withdrawn legal-status Critical Current

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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
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • 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
    • A61K8/46—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing sulfur
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C271/06—Esters of carbamic acids
    • C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
    • C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C271/16—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by singly-bound oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C271/06—Esters of carbamic acids
    • C07C271/32—Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of rings other than six-membered aromatic rings
    • C07C271/34—Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of rings other than six-membered aromatic rings with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C335/00—Thioureas, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
    • C07C335/04—Derivatives of thiourea
    • C07C335/06—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to acyclic carbon atoms
    • C07C335/10—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to acyclic carbon atoms of an unsaturated carbon skeleton
    • C07C335/12—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to acyclic carbon atoms of an unsaturated carbon skeleton the carbon skeleton containing six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K15/00—Anti-oxidant compositions; Compositions inhibiting chemical change
    • C09K15/04—Anti-oxidant compositions; Compositions inhibiting chemical change containing organic compounds
    • C09K15/20—Anti-oxidant compositions; Compositions inhibiting chemical change containing organic compounds containing nitrogen and oxygen
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K15/00—Anti-oxidant compositions; Compositions inhibiting chemical change
    • C09K15/04—Anti-oxidant compositions; Compositions inhibiting chemical change containing organic compounds
    • C09K15/26—Anti-oxidant compositions; Compositions inhibiting chemical change containing organic compounds containing nitrogen and sulfur
    • 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
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/52—Stabilizers
    • A61K2800/522—Antioxidants; Radical scavengers

Definitions

  • the invention relates to 3,4-dihydroxybenzyl-substituted carbonic acid derivatives, the
  • the invention further relates to cosmetic and / or pharmaceutical preparations and to foods and / or luxury foods comprising these 3,4-dihydroxybenzyl-substituted carbonic acid derivatives.
  • Ultraviolet light in particular ultraviolet light in the range from 290 to 400 nm, triggers photooxidative processes on or in the skin, in particular of humans and animals, various reactive oxygen compounds or radicals being formed starting from oxygen. These can e.g. Damage or destroy intracellular molecules and thus weaken the cell's vitality or even cause it to die.
  • the reactive oxygen compounds or radicals can also damage the intracellular molecules or structures.
  • the lipid layer serving as a barrier against the environment or the sebum can be destroyed by oxidative processes.
  • a major component of essential sebum is the highly unsaturated squalene.
  • Substances and preparations of these substances which support the natural defense mechanisms against free radicals and reactive oxygen compounds in physiological systems and / or which protect the lipid layer of the skin against oxidative processes as antioxidants or radical activators, protect the skin from destruction and aging. Such substances also protect materials which are sensitive to oxidation, such as components of cosmetics, pharmaceuticals or which are sensitive to oxidation
  • Antioxidants are generally organic compounds that inhibit or prevent undesirable changes in the substances to be protected, caused by the effects of oxygen, among other things, by oxidative processes (Römpp Lexikon Chemie 10th edition, 229 (1996)). Many antioxidants simultaneously act as radical scavengers and / or as complexing agents for heavy metal ions.
  • the object of the present invention is to provide antioxidants with a strong specific radical-catching and / or antioxidative effect for use in cosmetic and pharmaceutical preparations, foods and luxury foods and for protecting cells and tissues of humans and animals.
  • X 1 , X 2 and X 3 independently of one another represent oxygen atoms, sulfur atoms or groups -NR 3 ,
  • R 1 represents a hydrogen atom, a lower alkyl, lower alkenyl, 1-oxo-lower alkyl or 1-oxo lower alkenyl group having 1 to 5 carbon atoms or a group -OR 4 in which R 4 represents a hydrogen atom, a lower alkyl, Is lower alkenyl, 1-oxo-lower alkyl or 1-oxo-lower alkenyl group having 1 to 5 carbon atoms,
  • R 2 represents a hydrogen atom, a branched or unbranched, cyclic or stretched alkyl or alkenyl group having 1 to 22 carbon atoms, where one or more of the carbon atoms can be replaced by oxygen atoms, or a nucleus-substituted arylalkyl group having 7 to 15 carbon atoms with the dimension be that the core substituted
  • Arylalkyl group contains no halogen atoms
  • R 3 represents a hydrogen atom, a branched or unbranched, cyclic or stretched alkyl or alkenyl group having 1 to 22 carbon atoms, it being possible for one or more of the carbon atoms to be replaced by oxygen atoms,
  • the invention preferably relates to new 3,4-dihydroxybenzyl-substituted carbonic acid derivatives of the general formula (Ia),
  • R 1 is a hydrogen atom, a lower alkyl, lower alkenyl, 1-oxo-lower alkyl or 1-oxo-lower alkenyl group having 1 to 5 carbon atoms or one
  • Group -OR 4 represents, in which R 4 represents a hydrogen atom, a lower alkyl, lower alkenyl, 1-oxo-lower alkyl - or 1-oxo-lower alkenyl group with 1 to
  • X 1 means -NH
  • X 2 and X 3 are oxygen, and
  • R 2 represents a hydrogen atom, a methyl, an ethyl or an ethenyl group.
  • the invention preferably further relates to new 3,4-dihydroxybenzyl-substituted carbonic acid derivatives of the general formula (Ib),
  • R 1 represents a hydrogen atom, a lower alkyl, lower alkenyl, 1-oxo lower alkyl or 1-oxo lower alkenyl group having 1 to 5 carbon atoms or one
  • R 4 represents a hydrogen atom, a lower alkyl, lower alkenyl, 1-oxo-lower alkyl - or 1-oxomederalkenyl group with 1 to
  • X 1 means -NH
  • X 2 and X 3 are oxygen, and
  • R 2 is a branched or unbranched, cyclic or stretched alkyl or alkenyl group having 3 to 22 carbon atoms, one or more of the
  • Carbon atoms can be replaced by oxygen atoms, or means a nucleus-substituted arylalkyl group having 7 to 15 carbon atoms, with the proviso that the nucleus-substituted arylalkyl group contains no halogen atoms.
  • the invention preferably further relates to new 3,4-dihydroxybenzyl-substituted carbonic acid derivatives of the general formula (Ic), in which
  • R 1 represents a hydrogen atom, a lower alkyl, lower alkenyl, 1-oxo lower alkyl or 1-oxo lower alkenyl group having 1 to 5 carbon atoms or a group -OR 4 , in which R 4 represents a hydrogen atom, a lower alkyl, lower alkenyl, 1-oxo lower alkyl - or 1-oxo-lower alkenyl group having 1 to 5 carbon atoms,
  • X 1 , X 2 and X 3 independently represent oxygen atoms, sulfur atoms or groups -NH, with the proviso that X 1 -NH and X 2 and X 3 are not oxygen, and
  • R 2 is a branched or unbranched, cyclic or stretched alkyl or
  • a lower alkyl group consists of 1 to 5 carbon atoms and can be, for example: methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, 2-butyl, tert-butyl, 2-methylprop-1-yl, cyclopropyl, cyclopropylmethyl , 2,2-dimethylcyclopropyl, cyclobutyl, 1-, 2- or 3-pentyl-, 2-methylbut-l-yl, 2-methylbut-2-yl, 3-methylbut-
  • a lower alkenyl group consists of 2 to 5 carbon atoms and can be, for example: ethenyl, prop-2-en-1-yl, prop-1-en-1-yl, prop-1-en-2-yl, 1- or 2- Cyclopropenyl, but-1-en-1-yl, but-1-en-2-yl, but-1-en-3-yl, but-2-en-1-yl, but-3-ene -l-yl, but-2-en-2-yl, 2-methyl ⁇ rop-l-en-l-yl, 2-methyl ⁇ rop-2-en-l-yl, 1,3-butadien-l-yl, l , 3-butadien-2-yl, pent-1-en-l-yl, pent-l-en-2-yl, pent-l-en-3-yl, pent-l-en-4-yl,
  • Pent-2-en-l-yl pent-2-en-2-yl, pent-2-en-3-yl, pent-2-en-4-yl, pent-3-en-l-yl, Pent-4-en-l-yl, 1,3-pentadien-l-yl, l, 3-pentadien-2-yl, l, 3-pentadien-3-yl, 2,4-pentadien-2-yl, 2,4-pentadien-l-yl, 1,4-pentadien-l-yl, l, 4-pentadien-2-yl, l, 4-pentadien-3-yl, l-, 2- or 3-cyclopentenyl, l-, 2- or 3-cyclopentadienyl, 3-methylbut-l-en-l-yl, 3-methylbut-l-en-2-yl, 3-methylbut-l-en-3-yl, 3-methylbut- l-en-4-yl, 3-methyl
  • a lower alkyl 1-oxo group consists of 1 to 5 carbon atoms and can be, for example: formyl, acetyl, propanoyl, butanoyl, 2-methylpropanoyl, pentanoyl, 2- or 3-methylbutanoyl, 2,2-dimethylpropanoyl, cyclopropylcarboxyl.
  • a 1-oxoalkenyl group can contain 3 to 5 carbon atoms and can be, for example: prop-2-enoyl, 2-methylprop-2-enoyl, 2-ethyl-prop-2-enoyl, E- or Z-2-butenoyl, 3- Butenoyl, E- or Z-2-methylbut-2-enoyl, E- or Z-3-methylbut-2-enoyl, Z- or E-2-pentenoyl, Z- or E-3-pentenoyl.
  • An unbranched, branched or cyclic alkyl group can contain 1 to 22, preferably 1 to 20, particularly preferably 1 to 18 carbon atoms.
  • Examples include: methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, 2-butyl, tert-butyl, 2-methyl, 2-methyl ⁇ rop-l-yl, cyclopropyl, cyclopropylmethyl, 2,2- Dimethylcyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and various positional isomers of methylpentyl, menthyl, 1-pentyl, 1-hexyl, 1-heptyl, 1-octyl, 2- Ethylhexyl, 1-nonyl, 1-decyl, 1-undecyl, 1-dodecyl, 1-tridecyl, 1-tetradecyl, 1-pentadecyl, 1-hexadecyl, 1-
  • An unbranched, branched or cyclic alkenyl group can contain 2 to 22, preferably 2 to 20, particularly preferably 2 to 18 carbon atoms.
  • Examples include: ethenyl, prop-2-en-1-yl, prop-1-en-1-yl, prop-1-en-2-yl, 1- or 2-cyclopropenyl, but-1-ene l-yl, but-l-en-2-yl, but-l-en-3-yl, but-2-en-l-yl, but-3-en-l-yl, but-2-en- 2-yl, 2-methylprop-l-en-l-yl, 2-methyl ⁇ ro ⁇ -2-en-l-yl, 1,3-butadien-l-yl, l, 3-butadien-2-yl, pent- 1-en-l-yl, pent-l-en-2-yl, pent-l-en-3-yl, pent-l-en-4-yl, pent-2-en-l-y
  • a nucleus-substituted arylalkyl group can consist of 7 to 15 carbon atoms, preferably 7 to 8 carbon atoms, with the proviso that at least one further substituent on the aromatic part is not hydrogen.
  • a nucleus-substituted benzyl, a 2- or 1-phenylethyl group is particularly preferred.
  • Substituents of the nucleus-substituted arylalkyl group can be, for example: hydrogen atoms, lower alkyl, hydroxy, lower alkyloxy, thio, lower alkylthio,
  • R 1 represents a hydrogen atom, a lower alkyl group with 1 to 5 carbon atoms or a group -OR 4 in which R 4 represents a hydrogen atom or a lower alkyl group with 1 to 5 carbon atoms,
  • X 1 means -NH
  • X 2 and X 3 are oxygen, and
  • R represents a hydrogen atom, a methyl, an ethyl or an ethenyl group.
  • R 1 represents a hydrogen atom, a lower alkyl group with 1 to 5 carbon atoms or a group -OR 4 in which R 4 represents a hydrogen atom or a lower alkyl group with 1 to 5 carbon atoms,
  • X 1 means -NH
  • X and X are oxygen
  • R is a branched or unbranched, cyclic or stretched alkyl or alkenyl group having 3 to 20 carbon atoms, one or more of the
  • Carbon atoms can be replaced by oxygen atoms, or means a nucleus-substituted arylalkyl group having 7 to 8 carbon atoms, with the proviso that the nucleus-substituted arylalkyl group contains no halogen atoms.
  • X and X independently represent oxygen atoms, sulfur atoms or -N-H, and
  • X 3 represents an oxygen atom or a sulfur atom, with the proviso that X 1 -NH and X 2 and X 3 do not simultaneously denote oxygen, and
  • R 1 represents a hydrogen atom, a lower alkyl group having 1 to 5 carbon atoms or a group -OR 4 in which R 4 represents a hydrogen atom or a lower alkyl group having 1 to 5 carbon atoms, and
  • R represents a branched or unbranched, cyclic or straight alkyl or alkenyl group having 1 to 20 carbon atoms, it being possible for one or more of the carbon atoms to be replaced by oxygen atoms, or a nucleus-substituted arylalkyl group having 7 to 8 carbon atoms, with the proviso that the nucleus-substituted arylalkyl group contains no halogen atoms.
  • R 1 represents a hydrogen atom, a methoxy or a hydroxy group
  • X 1 means -NH
  • R represents a methyl, an ethyl or an ethenyl group.
  • R 1 represents a hydrogen atom, a methoxy or a hydroxy group
  • X 1 means -NH
  • X 2 and X 3 are oxygen, and R 2 represents a branched or unbranched, cyclic or stretched alkyl group having 3 to 18 carbon atoms, a branched or unbranched, cyclic or stretched alkenyl group having 3 to 18 carbon atoms or a nucleus-substituted benzyl, nucleus-substituted 2-phenylethyl or nucleus-substituted 1-phenylethyl radical with which Provided that the nucleus-substituted arylalkyl group contains no halogen atoms.
  • R 1 represents a hydrogen atom, a methoxy or a hydroxy group
  • X 1 represents a group -NH
  • X 2 represents an oxygen atom, sulfur atom or -NH
  • X 3 represents an oxygen atom or a sulfur atom, with the measure that
  • X and X do not simultaneously mean oxygen
  • R 2 is a branched or unbranched, cyclic or stretched alkyl group having 1 to 18 carbon atoms, a branched or unbranched, cyclic or stretched alkenyl group having 2 to 18 carbon atoms or a nucleus-substituted benzyl, nucleus-substituted 2-phenylethyl or nucleus represents substituted 1-phenylethyl radical, with the proviso that the nucleus-substituted arylalkyl group contains no halogen atoms.
  • the compounds according to the invention can also be present in the form of their tautomers.
  • Dihydroxybenzyl-substituted carbonic acid derivatives are very good radical scavengers and particularly strong antioxidants. They are preferably suitable as antioxidants for lipids.
  • the 3,4-dihydroxybenzyl-substituted carbonic acid derivatives according to the invention are able to suppress the harmful effects of free radicals and / or oxidative processes which are induced by UV light on and / or in human skin and to suppress the natural antioxidant to support ven processes.
  • the 3,4-dihydroxybenzyl-substituted carbonic acid derivatives according to the invention support the natural defense mechanisms against free radicals and reactive oxygenation in physiological systems of the skin, hair or nails. bindings and protect their oxidation-sensitive components in cosmetics, pharmaceuticals or foodstuffs against auto-oxidation or photo-oxidation.
  • the 3,4-dihydroxybenzyl-substituted carbonic acid derivatives according to the invention can therefore be used in cosmetic or pharmaceutical, in particular cosmetic or dermatological, preparations for protecting cells and tissues of mammals, in particular humans, against the harmful influence of free radicals and reactive oxygen species.
  • the 3,4-dihydroxybenzyl-substituted carbonic acid derivatives according to the invention can also be used in other preparations, for example pharmaceutical preparations or preparations, preparations for protecting or influencing plants, in foods or luxury foods or preparations for nutritional supplements, or in other products, for example oxidation-sensitive natural or synthetic polymers (eg rubber, polyolefins), as antioxidants or free radical scavengers.
  • the amount of the 3,4-dihydroxybenzyl-substituted carbonic acid derivatives according to the invention in a cosmetic or pharmaceutical preparation is 0.001% by weight to 10% by weight, preferably 0.001 to 5% by weight, particularly preferably 0.001% by weight to 1% .-%, based on the total weight of the preparation.
  • the 3,4-dihydroxybenzyl-substituted carbonic acid derivatives according to the invention can be prepared by methods known per se, in that a 3,4-dihydroxybenzyl derivative of the general formula (IT)
  • X 1 represents a group -OH, -SH, -NH 2 or - (NH 3 ) + , and
  • R 1 has the meaning given above
  • R 5 can be a lower alkyl, 1-oxo-lower alkyl, lower alkenyl, 1-oxo-lower alkenyl, aryl, arylalkyl, aryl-1-oxoalkyl or lower alkyloxycarbonyl group,
  • X 4 represents an oxygen atom or a sulfur atom
  • R 2 has the meaning given above, or with phosgene or triphosgene with or without solvent and optionally with the addition of an auxiliary base and either directly after purification with a compound of the general formula (V)
  • Z represents a group -OH, -SH, -NH 2 or - (NH 3 ) + , and
  • R 2 has the meaning given above
  • the particularly preferred 3,4-dihydroxybenzyl-substituted carbonic acid derivatives where X 1 is -NH, X 2 and X 3 each represent an oxygen atom and R 1 and R 2 have the meaning given above, can for example by reacting a 3,4-dihydroxybenzylamine of the general formula (II), wherein X 1 represents a group -NH 2 or - (NH 3 ) + and R 1 has the meaning given above, with a
  • Solvents e.g. chloroform
  • aromatic solvents e.g. benzene, toluene
  • one or more auxiliary bases preferably selected from the group of alkali metal hydroxides (e.g. NaOH), alkali metal carbonates (e.g. Na 2 CO 3 or NaHCO 3 ), the Alkaline earth metal hydroxides (e.g. Mg (OH) 2 ), the alkaline earth metal oxides (e.g. CaO) or the alkaline earth metal carbonates
  • alkaline earth metal hydroxides e.g. Mg (OH) 2
  • the alkaline earth metal oxides e.g. CaO
  • the alkaline earth metal carbonates e.g. CaCO 3
  • ammonia the aliphatic amines (e.g. triethylamine or diisopropylamine) or the heterocyclic amines
  • pyridine e.g. pyridine or 4- (N, N-dimethylamino) pyridine
  • the basic inorganic or organic ion exchanger e.g. pyridine or 4- (N, N-dimethylamino) pyridine
  • the basic inorganic or organic ion exchanger e.g. pyridine or 4- (N, N-dimethylamino) pyridine
  • a saponification step is advantageously followed, in particular basic saponification with one of the bases mentioned in the abovementioned solvents or solvent mixtures, preferably water or water-containing solvent mixtures, at temperatures of 30 to 130 ° C, preferably 50 to 100 ° C, at which the phenyl esters are selectively cleaved and the 3,4-dihydroxybenzyl-substituted carbonic acid derivatives of the general formula (Ia) to (Ic) after adjustment the pH to values ⁇ 7, preferably with mineral acids (eg hydrochloric acid), can be obtained in free form.
  • one of the bases mentioned in the abovementioned solvents or solvent mixtures preferably water or water-containing solvent mixtures
  • the 3,4-dihydroxybenzyl-substituted carbonic acid derivatives according to the invention can be further purified using the processes known to the person skilled in the art, preferably crystallization, chromatographic processes or distillation.
  • 3,4-Dihydroxybenzyl derivatives of the general formula (II) are, in particular, 3,4-dihydroxybenzylamine or its ammonium salts, 3,4-dihydroxy-5-methylbenzylamine or its ammonium salts, 3,4-dihydroxy-5-methoxybenzylamine or its ammonium salts , 3,4,5-trihydroxybenzylamine or its ammonium salts, 3,4-dihydroxybenzyl alcohol or 3,4,5-trihydroxybenzyl alcohol used.
  • the activated carbonic acid derivatives of the general formula (III) are preferably methyl chloroformate, ethyl chloroformate, propyl chloroformate, isopropyl chloroformate, n-butyl chloroformate, chloroformate, 2- (tert-butoxycarbonyloxyimino) -2-phenylacetonitrile acid, pyro- butyl ester, chloroformic acid - (-) - menthyl ester, chloroformic acid n-hexyl ester, chloroformic acid 2-ethylhexyl ester or other chloroformic acid esters branched or unbranched, stretched or cyclic alkanes or
  • heterokumulenes of the general formula (IN) are preferably selected from the group consisting of methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, the various straight or cyclic isomers of the pentyl, the
  • the compounds of the general formula (V) are preferably selected from the
  • the present invention also relates to cosmetic and pharmaceutical preparations, in particular cosmetic and dermatological preparations, which comprise the 3,4-dihydroxybenzyl-substituted carbonic acid derivatives according to the invention in an effective amount, in addition to other, otherwise customary composition components.
  • 4-Dihydroxybenzyl-substituted carbonic acid derivatives and can be used as "water in oil”, “oil in water”, “water in oil in water” or “oil in water in oil” emulsions, as microemulsions , as gels, as solutions eg in oils, alcohols or silicone oils, as soaps, as sticks, as aerosols, sprays or foams.
  • compositions can contain water in an amount of up to 99.999% by weight, preferably 5-80% by weight, based on the total weight of the formulation.
  • cosmetic or dermatological preparations according to the invention are produced using customary processes which are well known to those skilled in the art, in such a way that one or more of the 3,4-dihydroxybenzyl-substituted carbonic acid derivatives according to the invention are incorporated into cosmetic or dermatological formulations which are composed as usual and for the treatment of the Protection
  • Dihydroxybenzyl-substituted carbonic acid derivatives also previously in liposomes, e.g. starting from phosphatidylcholine, in microspheres, in nanospheres or also in capsules from a suitable matrix, for example from natural or synthetic waxes, for example beeswax, carnauba wax, silicone wax or paraffin waxes, and stearyl alcohol, eicosanol, cetyl alcohol, stearin or from gelatin.
  • a suitable matrix for example from natural or synthetic waxes, for example beeswax, carnauba wax, silicone wax or paraffin waxes, and stearyl alcohol, eicosanol, cetyl alcohol, stearin or from gelatin.
  • the cosmetic and dermatological preparations according to the invention are applied to the skin, nails and / or hair in a sufficient amount in the manner customary for cosmetics.
  • the cosmetic and dermatological preparations according to the invention can contain cosmetic auxiliaries and additives, as are usually used in such preparations, e.g. Sunscreens (e.g. organic or inorganic light filter substances, preferably micropigments), preservatives, bactericides, fungicides, virucides, cooling agents, plant extracts, anti-inflammatory agents, substances that accelerate wound healing (e.g. chitin or chitosan and its derivatives), film-forming substances (e.g. polyvinylpyranolidones or choline or choline) Derivatives), common antioxidants, vitamins (e.g. vitamin C and derivatives, tocopherols and derivatives, vitamin A and derivatives), 2-hydroxycarboxylic acids (e.g. citric acid, malic acid, L-, D- or dl-lactic acid),
  • Sunscreens e.g. organic or inorganic light filter substances, preferably micropigments
  • preservatives bactericides, fungicides, vir
  • Skin lightening agents e.g. kojic acid, hydroquinone or arbutin
  • skin coloring agents e.g. walnut extracts or dihydroxyacetone
  • perfumes substances to prevent foaming, dyes, pigments that have a coloring effect, thickeners, surface-active substances, emulsifiers, softening, moisturizing and / / or moisturizing substances (e.g. glycerin or urea), fats,
  • Oils, unsaturated fatty acids or their derivatives e.g. linoleic acid, ⁇ -linolenic acid, ⁇ -linolenic acid or arachidonic acid and their respective natural or synthetic esters
  • waxes or other common components of a cosmetic or dermatological formulation such as alcohols, polyols, polymers, foam stabilizers, Electrolytes, organic solvents, silicone derivatives or chelating agents
  • auxiliary substances and additives to be used in each case can easily be determined by a person skilled in the art depending on the nature of the respective product by simply trying them out.
  • the preparations according to the invention can preferably also contain other antioxidants.
  • all antioxidants which are suitable or customary for cosmetic and / or dermatological applications can be used as other antioxidants.
  • the antioxidants are advantageously selected from the group consisting of amino acids (eg glycine, histidine, 3,4-dihydroxyphenylalanine, tyrosine, tryptophan) and their derivatives, imidazoles (eg urocanic acid) and their derivatives, peptides (D, L-carnosine, D- Carnosine, L-carnosine, anserine) and their derivatives, carotenoids, carotenes (e.g.
  • amino acids eg glycine, histidine, 3,4-dihydroxyphenylalanine, tyrosine, tryptophan
  • imidazoles eg urocanic acid
  • peptides D, L-carnosine, D- Carnosine, L-carnosine, anserine
  • carotenoids e.g.
  • ⁇ -carotene, ß-carotene, lycopene) and their derivatives chlorogenic acid and their derivatives, lipoic acid and their derivatives, aurothioglucose, propylthiouracil and other thiols (e.g. thioredoxin, glutathione, cysteine, cystine, cystamine and their glycosyl and N-acyl derivatives or their alkyl esters) and their salts, dilaurylthiodipropionate, distearylthiodipropionate, thiodipropionic acid and their derivatives as well as phenolic acid amides of phenolic benzylamine acid (e.g.
  • (Metal) chelators for example 2-hydroxyfatty acids, phytic acid, lactoferrin), humic acid, bile acids, bile extracts, bilirabine, biliverdin, folic acid and its derivatives, ubiquinone and ubiquinol and their derivatives, vitamin C and its derivatives (for example ascorbyl palmitate, magnesium ascorbyl phosphate , Ascorbyl acetate), tocopherols and derivatives (e.g. vitamin E acetate), vitamin A and derivatives (e.g.
  • Vitamin A palmitate rutinic acid and its derivatives
  • flavonoids e.g. quercetin, ⁇ - Glucosylrutin
  • phenolic acids e.g. gallic acid, feralic acid
  • derivatives e.g.
  • propyl gallate ethyl ester, octyl ester
  • furfurylidene glucitol dibutylhydroxytoluene, butylated hydroxyanisole
  • uric acid and its derivatives mannose and its derivatives (zinc and its derivatives) eg ZnO, ZnSO 4 ), selenium and its derivatives (eg selenomethionine), stilbenes and their derivatives (eg stilbene oxide, resverafrol) and the derivatives of these active substances which are suitable according to the invention.
  • the amount of the further antioxidants in the preparations according to the invention can generally be 0.001 to 30% by weight, preferably 0.001 to 20% by weight, particularly preferably 0.001 to 5% by weight, based on the total weight of the preparation.
  • UV-A and / or UN-B filter substances can also be used in the cosmetic or dermatological preparations according to the invention, the total amount of filter substances being 0.1 to 30% by weight, preferably 0.5 to 10% by weight , based on the total weight of the preparations, can be obtained, for example, sunscreens for skin and hair.
  • UV-A and / or UV-B filter substances for example, 3-benzylidene camphor derivatives (for example 3- (4-methylbenzylidene) -dl-camphor), aminobenzoic acid derivatives (for example 4- ( ⁇ , ⁇ -dimethylamino)) benzoic acid-2 -ethylhexyl ester or menthyl anthranate), 4-methoxycinnamate (e.g. 2-ethylhexyl p-methoxycinnamate or isoamyl p-methoxycinnamate), benzophenones (e.g. 2-hydroxy-4-methoxybenzophenone), single or multiple sulfonated UV filters [e.g.
  • triazines ⁇ e.g. 2,4-bis- [4- (2-ethylhexyloxy) -2-hydroxy- phenyl] -6- (4-methoxyphenyl) -l, 3,5-triazine, 4,4 '- ([6 - ([(l J-dimethylethyl) aminocarbonyl] phenylamino) -l, 3,5- triazine-2,4-diyl] diimino) bisbenzoic acid bis (2-ethylhexyl) ester) ⁇ , 2-cyanopropenoic acid derivatives (e.g.
  • 2-ethylhexyl-2-cyano-3,3-diphenyl-2-propenoate Dibenzoyl derivatives (e.g. 4-tert-butyl-4'-methoxydibenzoylmethane), polymer-bound UN filters (e.g. polymer of ⁇ - [2- (or 4) - (2-oxo-3-bomylidene) methyl] benzylacrylamide) or Pigments (eg titanium dioxide, zirconium oxide, iron oxide, silicon dioxide, manganese oxide, aluminum oxide, cerium oxide or zinc oxide) can be used.
  • Dibenzoyl derivatives e.g. 4-tert-butyl-4'-methoxydibenzoylmethane
  • polymer-bound UN filters e.g. polymer of ⁇ - [2- (or 4) - (2-oxo-3-bomylidene) methyl] benzylacrylamide
  • Pigments eg titanium dioxide, zirconium oxide, iron
  • the lipid phase in the cosmetic and / or dermatological preparations according to the invention can advantageously be selected from the following substance groups: mineral oils (advantageously paraffin oil), mineral waxes, hydrocarbons (advantageously squalane or squalene), synthetic or semisynthetic triglyceride oils (for example triglycerides of capric or Caprylic acid), natural oils (e.g. castor oil, olive oil, sunflower oil, soybean oil, peanut oil, rapeseed oil, almond oil, palm oil, coconut oil,
  • Palm kernel oil, borage seed oil and the like more natural ester oils (eg jojoba oil), synthetic ester oils (preferably esters of saturated and / or unsaturated, linear and / or branched alkane carboxylic acids of 3 to 30 carbon atoms with saturated and / or unsaturated, linear and / or branched alcohols with 3 to 30 carbon atoms and esters of aromatic carboxylic acids with saturated and / or unsaturated, linear and / or branched alcohols with 3 to 30 carbon atoms, particularly selected from the group of isopropyl myristate, isopropyl stearate, isopropyl palmitate, isopropyl oleate , n-butyl stearate, n-hexyl laurate, n-decyl laurate palmitate, isooctyl stearate, Isononylstearat, isononyl isononanoate, 2-ethylhexyl
  • alkyl benzoates e.g. mixtures of n-dodecyl, n-tridecyl, n-tetradecyl) and n-pentadecyl benzoate
  • cycli- cal or linear silicone oils such as dimethylpolysiloxanes, diethylpolysiloxanes, diphenylpolysiloxanes and mixed forms thereof
  • the aqueous phase of the cosmetic and / or dermatological preparations according to the invention optionally 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 ether, monoethyl or monobutyl ether, diethylene glycol monomethyl or monoethyl ether and analog products, furthermore alcohols with a low C number, for example Ethanol, isopropanol, 1,2-propanediol, glycerol, further - or ⁇ -hydroxy acids, preferably lactic acid, citric acid or salicylic acid, in addition emulsifiers, which can advantageously be selected from the group of ionic, nonionic, polymeric, phosphate-containing and zwitterionic emulsifiers , and in particular
  • Hyaluronic acid, guar gum, xanthan gum, hydroxypropylmethyl cellulose or allulose derivatives particularly advantageously from the grape group of the polyacrylates, preferably a polyacrylate from the group of the so-called carbopoles, in each case individually or in combination or from the group of the polyurethanes.
  • a particularly advantageous embodiment of the present invention is the use of the cosmetic or dermatological preparations according to the invention, containing an active component of the 3,4-dihydroxybenzyl-substituted carbonic acid derivatives according to the invention, for protecting tissues and cells of mammals, in particular the skin and / or the Hair, before oxidative stress and the harmful influence of radicals.
  • the present invention also includes a method for protecting cosmetic or dermatological preparations and foodstuffs and luxury foods against oxidation or photooxidation, the components of which pose stability problems. due to oxidation or photooxidation during storage, characterized in that the preparations have an effective content of 3,4-dihydroxybenzyl-substituted carbonic acid derivatives according to the invention.
  • 3,4-Dihydroxybenzylamine hydrochloride (1.5 g, 8.55 nmol) was dissolved in water (15 ml) and 1,4-dioxane (15 ml) and sodium hydrogen carbonate (0.72 g, 8.55 mmol) was added.
  • the reaction mixture was brought to pH 4 with 5% H 2 SO 4 , extracted with tert-butyl methyl ether (3 times 20 ml), the combined organic phase with sat. NaCl solution. washed, dried over Na SO 4 , filtered and the filtrate evaporated at 50 ° C / 20 mbar (1.89 g).
  • the product was on silica gel 60 with the
  • Part A was mixed and heated to 80 ° C.
  • Part B was mixed and heated to 90 ° C and added to Part A with stirring.
  • Carbopol was carefully dispersed in water and neutralized with sodium hydroxide solution (pH 5.4). Part C was then added to the mixture of parts A and B at 60 ° C.
  • Example 8 Water in Oil sunscreen emulsion with UVA / B broadband protection
  • part A all substances except the zinc oxide were heated to 85 ° C. and the zinc oxide was carefully dispersed in the mixture.
  • the components of Part B were mixed, heated to 85 ° C and added to Part A with stirring. To the Mixture of parts A and B was added to part C and then the mixture was homogenized using a dispersing tool.
  • Example 9 Oil in water” sunscreen emulsion with UVA / B broadband protection
  • Part A all substances were mixed except for the titanium dioxide and heated to 85 ° C; the titanium dioxide was carefully dispersed into the mixture.
  • part B all substances except Veegum and Nafrosol were mixed, heated to 90 ° C, Nafrosol and Veegum dispersed and the mixture was added to Part A with stirring.
  • Part C was added to the mixture of parts A and B and then the mixture was homogenized (pH 5.6) using a dispersing tool.
  • Example 10 Oil in water” sunscreen emulsion with UVA / B broadband protection
  • Part A was heated to 85 ° C.
  • Part B Carbopol and Keltrol were cold-dispersed in the remaining constituents, the mixture was heated to 85 ° C. and added to Part A.
  • Part C was immediately added to the mixture of parts A and B at 80 ° C. and homogenized for 5 minutes using a dispersing tool.
  • Part D was finally added at room temperature and the mixture was homogenized (pH 6.6) using a dispersing tool.
  • the activity of the exemplary compounds as radical scavengers was compared to that of conventional radical scavengers.
  • the DPPH (1,1-diphenyl-2-picryl-hydrazyl) test was used to remove radicals.
  • DPPH was dissolved in methanol to a concentration of 100 ⁇ mol / 1.
  • a number of dilutions of the exemplary compounds, vitamin C, ⁇ -tocopherol and 3,5-di-tert-butyl-4-hydroxytoluene were made in methanol.
  • Methanol served as a control. 2500 ⁇ l of the DPPH solution were mixed with 500 ⁇ l of each test solution and the decrease in absorption at 515 nm was read until the
  • Active, as radical scavenger (%) 100 - (absorption of test compounds) / (absorption of control) x 100.
  • Test compound (example number) EC 5 o / (mol / mol)
  • Vitamin C 0.27 ⁇ -tocopherol 0.25
  • the exemplary compounds, vitamin C, ⁇ -tocopherol and 3,5-di-tert-butyl-4-hydroxytoluene were dissolved in methanol or acetone and 100 ⁇ l of the respective test solution was added to a prepared oil sample of 3 g. Only solvent was added to a control sample. A constant, dry air flow (20 l / h) was blown through the heated oil sample containing the test solution and the volatile oxidation products (mainly short-chain fatty acids such as ant or
  • IP induction period
  • the antioxidative index (AOI) was obtained according to the following equation:
  • AOI IP (with test solution) IP (control sample).
  • Test compound (example number) AOI in soybean oil
  • Test compound (sample number) AOI in squalene at
  • Vitamin C 0.7 ⁇ -tocopherol 39
  • Example 13 Determination of the protective action against ultraviolet light-induced sebum oxidation
  • solution A As an internal standard, a 0.2% ethanolic solution of tocopherol was prepared (solution A). A dose of 2 mg / cm 2 of the formulation from Example 7 was applied to the back skin twice a day for 12 test subjects. Before the following irradiation, solution A was applied to a control area
  • the 2 treated and one untreated area were irradiated with ultraviolet light (320 to 400 nm, 10 joules / cm 2 ).
  • the respective test areas were treated with 4 ml of ethanol for 2 min, the solutions were dried under nitrogen at room temperature and the residue was taken up in 1 ml of ethanol.
  • the latter solutions were examined by HPLC for their squalene content (detection at 210 nm against standard) or squalene hydroperoxide (SQOOH, determination of the peroxide content using cytochrome C / luminol-enhanced chemiluminescence).
  • the squalene peroxide content was given relative to squalene in the form of picomol peroxide per ⁇ g of squalene.
  • the inhibition based on the untreated area was calculated using the following equation:

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Abstract

L'invention concerne des dérivés d'acides carboxyliques 3,4-dihydroxybenzyl-substitués, leur fabrication, leur utilisation comme antioxydants ou fixateurs de radicaux, en particulier dans des préparations cosmétiques et pharmaceutiques, ainsi que dans des produits alimentaires ou des condiments, en vue de protéger les cellules et les tissus contre les influences nuisibles, accélérant le vieillissement, des radicaux et des composés oxygénés réactifs. L'invention concerne en outre des préparations cosmétiques et pharmaceutiques, ainsi que des produits alimentaires et des condiments renfermant les dérivés d'acides carboxyliques 3,4-dihydroxybenzyl-substitués selon l'invention.
EP01953166A 2000-06-23 2001-06-11 Derives d'acides carboxyliques 3,4-dihydroxybenzyl-substitues et leur utilisation comme antioxydants Withdrawn EP1296941A2 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE10030891 2000-06-23
DE10030891A DE10030891A1 (de) 2000-06-23 2000-06-23 3,4-Dihydroxybenzyl-substituierte Kohlensäurederivate und ihre Verwendung als Antioxidantien in kosmetischen und pharmazeutischen Präparaten
PCT/EP2001/006568 WO2001098235A2 (fr) 2000-06-23 2001-06-11 Derives d'acides carboxyliques 3,4-dihydroxybenzyl-substitues et leur utilisation comme antioxydants

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EP1296941A2 true EP1296941A2 (fr) 2003-04-02

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WO2003101927A1 (fr) * 2002-05-31 2003-12-11 Proteotech, Inc. Composes, compositions et procedes de traitement de maladies amyloides et de synucleinopathies, notamment de la maladie d'alzheimer, du diabete de type 2 et de la maladie de parkinson
AR046078A1 (es) 2003-08-06 2005-11-23 Senomyx Inc Nuevos sabores, modificadores de sabores, sustancias gustativas, mejoradores de gusto, sustancias gustativas y/o mejoradoras del gusto umani o dulce y uso de los mismos.
EP1855548A2 (fr) * 2005-02-04 2007-11-21 Senomyx, Inc. Molecules comprenantdes fractions organiques liées telles que des agents de sapidite destinés à des compositions comestibles
JP4734346B2 (ja) * 2005-02-04 2011-07-27 セノミックス インコーポレイテッド 連結ヘテロアリール部分を含む化合物、ならびに食用組成物のための新規なうまみフレーバー改変剤、味物質および味覚増強剤としての使用
TW200715993A (en) * 2005-06-15 2007-05-01 Senomyx Inc Bis-aromatic amides and their uses as sweet flavor modifiers, tastants, and taste enhancers
WO2007013811A2 (fr) * 2005-07-29 2007-02-01 Quest International Services B.V. Substances modulant la saveur
EP1960395A4 (fr) * 2005-12-07 2009-12-02 American Diagnostica Inc Inhibiteurs de l'inhibiteur 1 d'activateur de plasminogene
US8007849B2 (en) * 2005-12-14 2011-08-30 International Flavors & Fragrances Inc. Unsaturated cyclic and acyclic carbamates exhibiting taste and flavor enhancement effect in flavor compositions
ES2640453T3 (es) 2006-04-21 2017-11-03 Senomyx, Inc. Procesos para preparar composiciones saborizantes sólidas
DE102007026975A1 (de) * 2007-06-01 2008-12-04 Südzucker Aktiengesellschaft Mannheim/Ochsenfurt Antioxidationsmittel für Lebensmittel
GB0909768D0 (en) * 2009-06-08 2009-07-22 Nanyang Polytechnic Novel compounds and uses thereof
BR112012029959B1 (pt) * 2010-05-25 2018-01-23 Symrise Ag Compostos de carbamato de mentila, seus usos, composições e métodos cosméticos para clareamento da pele e/ou cabelo
EP2389922A1 (fr) 2010-05-25 2011-11-30 Symrise AG Composés de carbamate de cyclohexyle en tant qu'actifs anti-vieillissements
EP2593078B1 (fr) 2010-05-25 2016-11-30 Symrise AG Composés carbamate de cyclohéxyle servant de principes actifs anti-cellulite
BR112012029961B1 (pt) * 2010-05-25 2017-06-06 Symrise Ag compostos de carbamato de ciclo-hexila, seus usos, composições cosméticas e métodos cosméticos para clareamento da pele e/ou cabelo
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CN111620794B (zh) * 2020-05-29 2021-08-10 北京化工大学 一种多巴胺衍生物抗菌剂及其制备方法与应用

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JP2003535915A (ja) 2003-12-02
WO2001098235A3 (fr) 2002-05-23
AU2001275677A1 (en) 2002-01-02
WO2001098235A2 (fr) 2001-12-27
DE10030891A1 (de) 2002-01-03
US20030139470A1 (en) 2003-07-24

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