Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
  • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
  • C07D239/06—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
• • 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
• • 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
  • A61P17/10—Anti-acne agents
• • 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
  • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P35/00—Antineoplastic agents
• • 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
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q19/00—Preparations for care of the skin
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
• • 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
  • A61K9/10—Dispersions; Emulsions
  • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
• • 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
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q5/00—Preparations for care of the hair
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q5/00—Preparations for care of the hair
  • A61Q5/06—Preparations for styling the hair, e.g. by temporary shaping or colouring

Definitions

• the invention relates to novel compounds which comprise as cationic or as anionic component a pyrimidinecarboxylic acid derivative, in particular a derivative of ectoine or hydroxyectoine, a process for their preparation and their use as ionic liquid or their use in pharmaceutical, cosmetic and dermatological formulations.
• Ionic liquids or liquid salts are ionic species consisting of an organic cation and an i.d.R. consist of inorganic anion. They contain no neutral molecules, and usually have melting points less than 373 K. The prior art discloses a large number of compounds which are used as ionic liquids.
• ionic liquids such as melting point, thermal and electrochemical stability and viscosity
• the properties of ionic liquids are strongly influenced by the nature of the anion and cation.
• the polarity and the hydrophilicity or lipophilicity can be determined by the Selection of a suitable cation / anion pair can be adjusted.
• Each new anion and each new cation opens up further possibilities for tuning the properties of ionic liquids. There is therefore a fundamental need for new ionic liquids with varied properties, which offer additional possibilities with regard to their use.
• Ectoine (S) -1, 4,5,6-tetrahydro-2-methyl-4-pyrimidinecarboxylic acid) and its derivative hydroxyectoine ((S 1 S) -1, 4,5,6-tetrahydro-5-hydroxy-2 methyl-4-pyrimidinecarboxylic acid) are naturally occurring amino acids involved in the osmoregulation of plants and microorganisms which can be isolated from these organisms. Ectoine and hydroxyectoine are used in skin-care and skin-sparing preparations as active ingredients and act as a stabilizer for proteins and cell structures and against external stress factors such as UV radiation and drought.
• the present invention therefore provides a compound comprising a cationic and an anionic component, wherein a
• Pyrimidincarbonklare derivative represents the cationic component or the anionic component, wherein Ectoinhydrochlorid is excluded.
• the compound according to the invention preferably contains as the cationic component a pyrimidinecarboxylic acid derivative which has been formed by protonation of a neutral pyrimidinecarboxylic acid derivative or, as anionic component, a pyrimidinecarboxylic acid derivative which has been formed by deprotonation of the neutral pyrimidinecarboxylic acid derivative.
• the protonation takes place at the nitrogen atom adjacent to the carboxylic acid group, whereas in the deprotonation the carboxylic acid group is converted into its carboxylate.
• the compounds according to the invention particularly preferably contain derivatives of the pyrimidinecarboxylic acids ectoine ((S) -1, 4,5,6-tetrahydro-2-methyl-4-pyrimidinecarboxylic acid) and hydroxyectoine ((S, S) -1, 4,5,6- Tetrahydro-5-hydroxy-2-methyl-4-pyrimidinecarboxylic acid).
• the compounds according to the invention are ionic liquids and / or cosmetic active ingredients.
• the compounds according to the invention show very good flexibility with regard to their solubility and their bioavailability, so that they can be used excellently as active ingredients, in particular in dermatological formulations or skin care products.
• Compounds of the invention with the anions typical of ionic liquids are preferably used as catalytic materials in the sense of ionic liquids.
• Lipophilic ionic combinations of the salts according to the invention are preferably used as cosmetically active substances. These make it possible to transport the ectoine derivatives according to the invention into the oil phase, as a result of which, in particular combinations, a synergistic effect with respect to the ectoine in the water phase occurs in selected combinations.
• the pyrimidinecarboxylic acid derivative is present in the form of its anion, the cations belonging to it are preferably organic cations, which are in particular preferably ammonium, phosphonium, uronium, thiouronium, guanidinium cations or heterocyclic cations. If the pyrimidinecarboxylic acid derivative is in the form of its cation, the associated anion is preferably an anion typical of ionic liquids.
• R ° H or alkyl having 1 -12 C atoms
• R 1 H or alkyl with 1-4 C atoms
• R 2 , R 3 , R 4 , R 5 each independently
• R F perfluorinated and straight-chain or branched alkenyl having 2-20 C atoms and one or more double bonds
• substituents R 9 are each independently of one another - H is straight-chain or branched alkyl having 1-20 C atoms,
• R 0 H or alkyl having 1 -12 C atoms
• R 1 H or alkyl having 1 -4 C atoms
• R 2 , R 3 , R 4 , R 5 each independently
• R 7 , R 8 are each independently
• Halogens in particular -F and / or -Cl, or partially with -OH, -OR ', -CN, -C (O) OH, -C (O) NR 2 , -SO 2 NR' 2 , -C (O ) X, -SO 2 OH, -SO 2 X, -NO 2 or - (CH 2 ) n -phenyl, and wherein one or two non-adjacent and non- ⁇ -carbon atoms of R 7 , by atoms and or
• heterocyclic cation [HetN] + is selected from the group
• R 1 ', R 2 ', R 3 'and / or R 4 ' together can also form a ring system, where one or more substituents R 1 ' to R 4 'partially or completely with halogens, in particular -F and / or -Cl, or -OH, -OR', -CN, -C (O) OH, -C (O) NR 2 , -SO 2 NR ' 2 , -C (O) X, -SO 2 OH, -SO 2 X, -NO 2 or - (CH 2 ) n -phenyl, but where R 1 'and R 4 ' are not at the same time completely substituted with halogens be substituted with one or two non-adjacent and not bound to the heteroatom carbon atoms of the substituents R 1
• n 1-4
• substituents R 7 and R 8 join a compound of formula (II) according to the invention
• substituents R 7 and R 8 join a compound of formula (II) according to the invention
• H are preferably: C 1 - to C 2 o, in particular C 1 - to C 14 -alkyl groups, and saturated or unsaturated, ie also aromatic , C 3 - to C 7 cycloalkyl groups, the C 1 - may be substituted to C 6 alkyl groups, especially phenyl.
• the substituents R 7 in a compound of the formula (II) may be identical or different. Preferably, the substituents R 7 are different. At the Of the four substituents R 7, ammonium is more preferably either equal to two or equal to three and one different. With sulfonium, particularly preferred of the three substituents R 7 are two.
• Compounds of the formula (II) are, independently of one another, particularly preferably methyl, ethyl, isopropyl, propyl, butyl, sec-butyl, tert-butyl, pentyl, hexyl, octyl, decyl or tetradecyl.
• substituents R 7 may each independently have a previously given or particularly preferred meaning.
• substituents R 7 and R 8 may have an above-mentioned or particularly preferred meaning independently.
• the carbocycles or heterocycles of the previously specified as particularly preferable examples guanidinium, uronium or thiouronium cations may be substituted by C r to C 6 alkyl, C r to C 6 alkenyl, NO 2, F, Cl, Br, I , OH, C 1 -C 6 -alkoxy, SCF 3 , SO 2 CF 3 , COOH, SO 2 NR ' 2 , SO 2 X or SO 3 H or substituted or unsubstituted phenyl or unsubstituted or substituted heterocycle, wherein X and R 'have a meaning given above.
• the substituents R 7 and R 8 of the guanidinium, uronium or thiouronium cation in a compound of formula (II) are each independently preferably a straight-chain or branched alkyl group having 1 to 10 C atoms.
• the substituents R 7 and R 8 may be the same or different.
• R 7 and R 8 are each independently of one another methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, sec-butyl, phenyl or cyclohexyl, very particularly preferably methyl, ethyl, n-propyl, Isopropyl or n-butyl.
• R 1 to R 4 of the heterocyclic cation of a compound of the formula (II) in addition to H according to the invention, preference is given in this case to: C r to C 2 O -, in particular C r to C-
• the substituents R 1 and R 4 are each, in each case independently of one another, particularly preferably methyl, ethyl, isopropyl, propyl, butyl, sec-butyl, tert-butyl, pentyl, hexyl, octyl, decyl, cyclohexyl, phenyl or benzyl. They are very particularly preferably methyl, ethyl, n-butyl or hexyl. In pyrrolidinium, piperidinium or indolinium compounds, the two substituents R 1 and R 4 are preferably different.
• R 2 or R 3 is in each case independently of one another in particular H, methyl, ethyl, isopropyl, propyl, butyl, sec-butyl, tert-butyl, cyclohexyl, phenyl or benzyl.
• R 2 is particularly preferably H, methyl, ethyl, isopropyl, propyl, butyl or sec-butyl. Most preferably, R 2 and R 3 are H.
• the C r Ci 2 alkyl group is, for example, methyl, ethyl, isopropyl, propyl, butyl, sec-butyl or tert-butyl, and also pentyl, 1-, 2- or 3-methylbutyl, 1, 1 -, 1, 2- or 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl or dodecyl.
• a straight-chain or branched alkenyl having 2 to 20 C atoms, wherein several double bonds may also be present, is, for example, allyl, 2- or 3-butenyl, isobutenyl, sec-butenyl, furthermore 4-pentenyl, isopentenyl, hexenyl, Heptenyl, octenyl, -C 9 Hi 7 , -Ci 0 Hi 9 to -C 20 H 39 ; preferably allyl, 2- or 3-butenyl, isobutenyl, sec-butenyl, furthermore preferred is 4-pentenyl, iso-pentenyl or hexenyl.
• a straight-chain or branched alkynyl having 2 to 20 C atoms, wherein a plurality of triple bonds may also be present, is, for example, ethynyl, 1- or 2-propynyl, 2- or 3-butynyl, furthermore 4-pentynyl, 3-pentynyl, hexynyl, Heptynyl, octynyl, -C 9 Hi 5 , -C 10 H 17 to -C 20 H 37 , more preferably ethynyl, 1- or 2-propynyl, 2- or 3-butynyl, 4-pentynyl, 3-pentynyl or hexynyl.
• Unsubstituted saturated or partially or fully unsaturated cycloalkyl groups having 3-7 C atoms are therefore cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopentenyl, cyclopenta-1,3-dienyl, cyclohexenyl, cyclohexa-1,3-dienyl, cyclohexa-1 , 4-dienyl, phenyl, cycloheptenyl, cyclohepta-1,3-dienyl, cyclohepta-1, 4-dienyl or cyclohepta-1, 5-dienyl, which may be substituted with Cr to C ⁇ -alkyl groups, again the cycloalkyl group or the substituted with C 1 to C 6 alkyl groups
• examples of such modified substituents R 7 , R 8 and R 1 ' to R 4' are : -OCH 3 , -OCH (CH 3 ) 2 , -CH 2 OCH 3 , -CH 2 -CH 2 -O -CH 3 , -C 2 H 4 OCH (CH 3 ) 2 ,
• C 3 - to C 7 -cycloalkyl is, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl.
• R ' substituted phenyl, by C 1 - to C 6 -alkyl, C 1 - to C 6 -alkenyl, NO 2 , F, Cl, Br, I 1 OH, C 1 -C 6 -alkoxy, SCF 3 , SO 2 CF 3 , COOH, SO 2 X ', SO 2 NR " 2 or SO 3 H substituted phenyl, where X' is F, Cl or Br and R" is a non, partially or perfluorinated Cr to C ß -alkyl or C 3 - to C 7 -cycloalkyl as defined for R ', for example, o-, m- or p-methylphenyl, o-, m- or p-ethylphenyl, o-, m- or p-propylphenyl, o-, m- or p-isopropylphenyl, o-, m- or p-tert-buty
• heteroaryl is a saturated or unsaturated mono- or bicyclic heterocyclic radical having 5 to 13 ring members, where 1, 2 or 3 N and / or 1 or 2 S or O atoms may be present and the heterocyclic radical mono- or polysubstituted by C 1 - to C 6 -alkyl, C 1 - to C 6 -alkenyl, NO 2 , F, Cl, Br, I 1 OH, C 1 -C 6 -alkoxy, SCF 3 , SO 2 CF. 3 , COOH, SO 2 X 1 , SO 2 NR " 2 or SO 3 H, where X 'and R" are as defined above.
• the heterocyclic radical is preferably substituted or unsubstituted 2- or 3-furyl, 2- or 3-thienyl, 1-, 2- or 3-pyrrolyl, 1-, 2-, 4- or 5-imidazolyl, 3-, 4 - or 5-pyrazolyl, 2-, 4- or 5-oxazolyl, 3-, 4- or 5-isoxazolyl, 2-, 4- or 5-thiazolyl, 3-, 4- or 5-isothiazolyl, 2-, 3 or 4-pyridyl, 2-, 4-, 5- or 6-pyrimidinyl, furthermore preferably 1,2,3-triazoM-, -4- or -5-yl, 1, 2,4-triazole-1, -4- or -5-yl, 1- or 5-tetrazolyl, 1, 2,3-oxadiazol-4 or 5-yl 1, 2,4-oxadiazol-3 or -5-yl, 1, 3,4-thiadiazol-2 or -5-yl, 1, 2,4-thiadiazol-3 or -5-yl, 1, 2,3-thiadiazol
• heteroaryl-C-rC ⁇ -alkyl is according to the invention in analogy to aryl-Ci-C ⁇ -alkyl, for example, pyridinyl-methyl, pyridinyl-ethyl, pyridinyl-propyl, pyridinyl-butyl, pyridinyl-pentyl, pyridinyl-hexyl understood, wherein further heterocycles described in this way can be linked to the alkylene chain.
• the cations of the compound of the formula (II) according to the invention are preferably ammonium, phosphonium, guanidinium, sulfonium or heterocyclic cations.
• Particularly preferred cations of the compound of the formula (II) according to the invention are ammonium ions [N (R 7 ) 4 ] + and heterocyclic cations [HetNf, where R 7 is each independently
• heterocyclic cation [HetN] + is selected from the group
• anions of the compound of the formula (I) according to the invention are preferably an anion which is selected from the group consisting of
• Aryl and alkyl sulfates [R 9 O (CH 2 CH 2 O) n SO 3 ] -, [R 9 OSO 3 ] " or [HSO 4 ] " [CF 3 SO 3 ] -, [(CF 3 SO 2 ) 2 N] -, [P (R F) Y F 6 - y] ⁇ - [P (C 6 F 5) y F 6-y] ', [B (CN) 4] ", and N (CN) 2' where R 9 is a straight-chain or branched alkyl having 1-36 C atoms, preferably 1-20, particularly preferably 10-14 C atoms, or a straight-chain or branched alkenyl having 2-36 C atoms, preferably 2-20, especially preferably 10-14 C atoms, with one or more double bonds and R F is a perfluorinated, straight-chain or branched alkyl having 1-36 C atoms, preferably 1-20, particularly preferably 10-14 C atoms, or a
• the compounds of the invention with carboxylates in particular ether carboxylates [RO (CH 2 CH 2 O) n CH 2 C (O) O] " , acylglutamates [RCONHCH (COO ICH 2 CH 2 C (O) O] - or sarcosinates [RCON (CH 3 ) CH 2 C (O) O] -, particularly preferably stearates or palmitates, alkyl sulfates, in particular
• the substituent R 1 of the pyrimidinecarboxylic acid ion in a compound of the general formula (I) or (II) is a methyl or an ethyl group. Very particularly preferred are alternatively or simultaneously the substituents R 4 , R 5 and R 6 H.
• R 2 has the meaning H or a hydroxyl group, ie very particularly preferred are compounds which contain an ectoine cation, a hydroxyectoine cation, an ectoine anion or a hydroxyectoine anion.
• Another object of the present invention is a method for
• a pyrimidinecarboxylic acid derivative is the cationic or anionic component in which the neutral pyrimidinecarboxylic acid derivative is quaternized by protonation with a Bronsted free acid or by deprotonation by means of a base to give the invention Connection is implemented.
• trifluoromethanoic acid, trifluoroacetic acid, HNO 3 , HkSO 4 or HCl can be used according to the invention as Bronsted acids.
• the base according to the invention is for example selected from the group consisting of a heterocyclic compound, an amine, a tetraalkylammonium hydroxide and a phosphine.
• the heterocyclic compound may be, for example, imidazole or a pyridine having an alkyl-SO 3 H side chain, wherein the alkyl side chain has 1-4 C atoms, such as pyridinopropane-1-sulfonate.
• the amine for example, NH 3 or NR 3 , wherein R is an alkyl having 1-4 C atoms
• Suitable phosphines are, for example, PR 3 , where R is an alkyl having 1-4 C atoms.
• the reaction can be carried out at temperatures in the range from 0 to 150 ° C., preferably at 0 to 50 ° C., and more preferably at room temperature.
• the Bronsted free acid or base is added in this reaction relative to the neutral pyrimidinecarboxylic acid derivative in an amount that is between a catalytic and an equimolar addition of the Bronsted acid or the base.
• the Bronsted free acid or base is added in an equimolar amount relative to the pyrimidinecarboxylic neutral derivative.
• Suitable solvents or solvent mixtures are water, alcohols, dialkyl ethers, esters, nitriles, dialkyl carbonates, dichloromethane or mixtures thereof.
• the solvent is water, methanol, ethanol, i-propanol, acetonitrile, propionitrile, diethyl ether, 1, 2-dimethoxyethane, dimethyl carbonate or diethyl carbonate.
• water is used as the solvent.
• Another object of the present invention is the use of the compounds according to the invention as ionic liquids.
• the compounds of the present invention can be used as a solvent or solvent additive for many synthetic or catalytic reactions, e.g. Friedel-Crafts acylation and alkylation, Diels-Alder cycloadditions, transition-metal or enzyme-catalyzed reactions, hydrogenation and oxidation reactions, Heck reactions, Suzuki couplings, esterifications, isomerization reactions,
• synthetic or catalytic reactions e.g. Friedel-Crafts acylation and alkylation, Diels-Alder cycloadditions, transition-metal or enzyme-catalyzed reactions, hydrogenation and oxidation reactions, Heck reactions, Suzuki couplings, esterifications, isomerization reactions,
• the present invention furthermore relates to the use of the compounds according to the invention as extractants, as heat carriers, as surface-active substances, as plasticizers, as lubricants, as antistatic agents, as flame retardants, as non-aqueous electrolyte, optionally in combination with other electrolytes known to the person skilled in the art or as conductive salt or Additive in electrochemical cells.
• the compound of the invention for the separation of reaction products but also for the separation of impurities can be used, depending on how the solubility of the respective component in the compound of the invention.
• the compounds according to the invention can also serve as release agents in the separation of a plurality of components, for example in the distillative separation of a plurality of components of a mixture.
• salts according to the invention can be used as nonaqueous polar substances in suitable reactions as phase transfer catalyst, as surfactant (surface active agent), as surfactant or as medium for heterogenizing homogeneous catalysts.
• plasticizers in polymer materials, as flame retardants for a range of materials or applications as well as conductive salt or additive in different electrochemical cells and applications, eg in galvanic cells, in capacitors or in fuel cells.
• Another object of the present invention is the use of the compounds of the invention as a cosmetic active ingredient.
• the salts according to the invention show advantageous cosmetic effects, for example anti-aging, anti-photoaging, antioxidant effects,
• UV filters such as butylmethoxydibenzoylmethane and ethylhexylmethoxycinnamate
• boosting effects e.g. with regard to the UV protection performance of cosmetic formulations
• effects as a solubilizer on non-sufficiently soluble components in cosmetic formulations generally stabilizing effects on formulation properties such
• the compounds of the invention show skin-friendly and skin care properties. Therefore, they can also be used as compatible solutes.
• the compounds according to the invention stabilize as compatible solutes enzymes, cell structures and other biomolecules in aqueous solutions and organic solvents.
• they stabilize enzymes against denaturing conditions such as salts, extreme pH, surfactants, urea, guanidinium chloride and other compounds.
• the invented proper compounds primarily as a moisturizer for the skin and scalp.
• the compounds according to the invention can furthermore be used for the preparation of a preparation for the treatment of hair. Incorporated into common hair treatment and hair cleansing compositions, these compounds are able to restructure damaged hair and reduce oxidative damage in oxidative hair dyeing.
• the salts according to the invention can advantageously be used for the cosmetic treatment of the keratin fraction, in particular the keratin fibers, for example the hair.
• the compounds according to the invention can be incorporated in hair shampoos, hair rinses, hair treatments, perming and hair dyes, hair coloring shampoos, hair tonics, hair setting agents, hair dressings and / or hair styling preparations. An application thereof is preferably carried out during washing and / or during conditioning.
• a further field of application of the compounds according to the invention is the preparation of a cosmetic or dermatological preparation for regeneration and for the protection and / or revitalization of the skin by combining the compounds according to the invention with a further active ingredient, in particular a dried "vine shoof" extract.
• the compounds according to the invention find use for stabilizing the p53 gene. These compounds are usually used in the form of a topical composition.
• the salts according to the invention can advantageously also be used in preparations for oral care.
• the compounds according to the invention protect the microflora of the skin and mucosa, which are important for an intact skin barrier, against stress due to dehydration, free radicals, surfactants and high ion concentrations and do not react with the cell metabolism.
• the compounds according to the invention can furthermore advantageously be used in medicaments and pharmaceutical formulations.
• they can be used for the manufacture of a medicament or a dermatological preparation for the topical prophylaxis, treatment and / or care of skin diseases, in particular eczema.
• the medicine or the Dermatological preparation is preferably mixed together with conventional excipients to form a tincture, a lotion, an O / W emulsion, a W / O emulsion, a cream, an ointment, a hydrogel or a spray.
• ectoine derivatives are typically in areas where e.g. Trehalose is used as an additive.
• ectoine derivatives can be used as a protective substance in dried yeast and bacterial cells.
• pharmaceutical products such as non-glycosylated, pharmaceutically active peptides and proteins e.g. t-PA can be protected with ectoine derivatives.
• Another object of the present invention are pharmaceutical, cosmetic and dermatological preparations containing at least one inventive Pyrimidincarbonklaren derivative.
• These formulations preferably contain the compounds according to the invention in amounts of from 0.01 to 15% by weight, more preferably from 0.1 to 10% by weight and very preferably from 0.5 to 5% by weight.
• the preparations are usually topically applicable preparations, for example cosmetic or dermatological formulations.
• the preparations in this case contain a cosmetically or dermatologically suitable carrier and, depending on the desired property profile, optionally further suitable ingredients.
• the preparations in this case contain a pharmaceutically acceptable carrier and optionally further pharmaceutical active ingredients.
• agent or formulation is used synonymously in addition to the term preparation. Any compounds or components which may be used in the compositions are either known and commercially available or may be synthesized by known methods.
• pigments can furthermore also be present, the layer structure of the pigments not being limited.
• the color pigment should be skin colored or brownish at a level of from 0.5 to 5% by weight.
• the selection of a corresponding pigment is familiar to the person skilled in the art.
• advantageous color pigments are titanium dioxide, mica, iron oxides (eg Fe 2 O 3 , Fe 3 O 4 , FeO (OH)) and / or tin oxide.
• Advantageous dyes are, for example, carmine, Berlin blue, chrome oxide green, ultramarine blue and / or manganese violet.
• the Color Index Numbers are taken from the Rowe Color Index, 3rd Edition, Society of Dyers and Colourists, Bradford, England, 1971.
• 3rd layer substrate pigments z. Mica / metal oxide
• pearlescent pigments are, for example, pulverulent pigments or castor oil dispersions of bismuth oxychloride and / or titanium dioxide, and Bismuth oxychloride and / or titanium dioxide on mica. Particularly advantageous is z. For example, listed under the CIN 77163 luster pigment.
• pearlescent pigment types based on mica / metal oxide are also advantageous, for example, are the following pearlescent pigment types based on mica / metal oxide:
• pearlescent pigments available from Merck under the trade names Timiron®, Colorona®, Dichrona®, Xirona® or Ronastar®.
• pearlescent pigments which are advantageous in the context of the present invention are obtainable in numerous ways known per se.
• other substrates except mica can be coated with other metal oxides such.
• silica and the like As silica and the like.
• pearlescent pigments which under the Use of SiO 2 are produced.
• Such pigments which may also have additional gonichromatic effects are, for. B. under the trade name Sicopearl Fantastico available from BASF.
• Particularly suitable pigments in premixes are, for example, Ronastar® Silver or Colorona® Bronze.
• the cosmetic preparation according to the invention may preferably also contain other active substances, such as, for example, repellents, in particular insect repellents, UV filters, flavone derivatives, chromone derivatives, aryloximes and parabens.
• repellents in particular insect repellents
• UV filters flavone derivatives
• chromone derivatives chromone derivatives
• parabens parabens
• repellent agents belong to the classes of amides, alcohols, esters and ethers.
• Repellents should usually meet the following conditions: they must not evaporate too quickly and should not penetrate the skin. They should not be primarily irritating or sensitizing to the skin, nor should they be toxic. Their effectiveness must also be preserved under the action of skin fluid and / or UV radiation.
• Preferred repellents are selected from N, N-diethyl-3-methylbenzamide, ethyl 3- (acetyl-butyl-amino) -propionate, dimethyl phthalate, butopyronoxyl, 2,3,4,5-bis (2-butylene) -tetrahydro- 2-furaldehyde, N, N-Capryl Aciddiethylamid, N 1 N- diethylbenzamide, o-chloro-N, N-diethyl-benzamide, N- (2-ethylhexyl) -8,9,10- trinorbom-5-en-2,3- dicarboximide, dimethyl carbate, di-n-propyl isocin chomeronate, (R) -p-mentha-i, 8-diol, 2-ethylhexane-1,3-diol, N-octyl-bi-cyclohepetiene carboximide, piperony
• Parabens are 4-hydroxybenzoic acid esters which are used in free form or as sodium salts for the preservation of preparations in the field of food, cosmetics and pharmaceuticals.
• the effect of the ester is directly proportional to the chain length of the alkyl radical, but vice versa
• the esters are largely pH independent and operate in a pH range of 3.0-8.0.
• the antimicrobial mechanism of action is based on damage to the microbial membranes by the surface activity of the PHB esters and on protein denaturation. In addition, interactions with coenzymes occur. The effect is directed against fungi, yeasts and bacteria.
• the most important as preservatives parabens are 4-hydroxybenzoate, ethyl 4-hydroxybenzoate, propyl 4-hydroxybenzoate, butyl 4-hydroxybenzoate.
• 2-hydroxy-5-methyllaurophenone oxime which is also referred to as HMLO, LPO or F5
• HMLO 2-hydroxy-5-methyllaurophenone oxime
• LPO 2-hydroxy-5-methyllaurophenone oxime
• Preparations containing 2-hydroxy-5-methyllaurophenone oxime are accordingly suitable for the treatment of skin diseases which are associated with inflammation. It is known that such preparations, e.g. can be used for the treatment of psoriasis, various eczema forms, irritative and toxic dermatitis, UV dermatitis and other allergic and / or inflammatory diseases of the skin and the skin appendages.
• the preparations preferably contain from 0.01 to 10% by weight of the aryloxime, and it is particularly preferred if the preparation contains from 0.05 to 5% by weight of aryloxime.
• this also includes the aglycones, ie the sugar-free constituents, and the derivatives of the flavonoids and the aglycones.
• flavonoid is also understood to mean anthocyanidin (cyanidin).
• coumaranones are also understood as meaning their derivatives. Among the coumaranones is 4,6,3 ', 4' tetrahydroxybenzylcoumaranone coumaranone-3 preferred.
• Chromone derivatives are preferably understood as meaning certain chromene-2-one derivatives which are suitable as active ingredients for the preventive treatment of human skin and hair against aging processes and damaging environmental influences. At the same time they show a low irritation potential for the skin, positively influence the water binding in the skin, maintain or increase the elasticity of the skin and thus promote a smoothing of the skin. These compounds preferably correspond to the following formula
• R 1 and R 2 may be the same or different and are selected from
• R 3 is H or straight-chain or branched C 1 to C 2 o-alkyl groups
• R 4 is H or OR 8 ,
• R 5 and R 6 may be the same or different and are selected from --H 1 -OH,
• R 7 is H, straight or branched Cr to C 2 o-alkyl groups, a polyhydroxy compound, such as preferably an ascorbic acid residue or glycosidic residues and
• the proportion of one or more compounds selected from chromone derivatives and coumaranones in a preparation is preferably from 0.001 to 5% by weight, particularly preferably from 0.01 to 2% by weight, based on the total preparation.
• the protective effect of preparations against oxidative stress or against the action of radicals can be improved if the preparations contain one or more antioxidants, wherein the skilled person has no difficulty in selecting suitable fast or delayed-acting antioxidants.
• the preparation is a preparation for protecting body cells against oxidative stress, in particular for reducing skin aging, characterized in that it contains one or more antioxidants in addition to the other ingredients.
• antioxidants there are many known and proven substances in the literature that can be used as antioxidants, e.g. Amino acids (eg glycine, histidine, tyrosine, tryptophan) and their derivatives, imidazoles, (eg urocanic acid) and derivatives thereof, peptides such as D, L-carnosine, D-carnosine, L-carnosine and their derivatives (eg anserine), carotenoids, Carotenes (eg ⁇ -carotene, ⁇ -carotene, lycopene) and their derivatives, chlorogenic acid and its derivatives, lipoic acid and derivatives thereof (eg dihydrolipoic acid), aurothioglucose, propylthiouracil and other thiols (eg thioredoxin, glutathione, cysteine, cystine, cystamine and their derivatives) Glycosyl, N-acetyl, methyl, ethyl, prop
• Dilaurylthiodipropionat, distearylthiodipropionate, thiodipropionic acid and its derivatives esters, ethers, peptides, lipids, nucleotides, nucleosides and salts
• sulfoximine compounds eg Buthioninsulfoximine, Homocysteinsulfoximin, Buthioninsulfone, penta-, hexa-, Heptathioninsulfoximin
• very low tolerated dosages eg pmol bis ⁇ mol / kg
• metal chelators eg ⁇ -hydroxy fatty acids, palmitic acid, phytic acid, lactoferrin
• ⁇ -hydroxy acids eg 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
• Suitable antioxidants are also compounds of the general formulas A or B.
• R 1 can be selected from the group -C (O) CH 3 , -CO 2 R 3 , -C (O) NH 2 and -C (O) N (R 4 ) 2 ,
• X is O or NH
• R 2 is linear or branched alkyl having 1 to 30 C atoms
• R 3 is linear or branched alkyl having 1 to 20 C atoms
• R 4 are each independently of one another H or linear or branched alkyl having 1 to 8 C atoms,
• R 5 is linear or branched alkyl having 1 to 8 C atoms or linear or branched alkoxy having 1 to 8 C atoms and
• R 6 denotes linear or branched alkyl having 1 to 8 C atoms, preferably derivatives of 2- (4-hydroxy-3,5-dimethoxybenzylidene) malonic acid and / or 2- (4-hydroxy-3,5-dimethoxybenzyl) - malonic acid, particularly preferably 2- (4-hydroxy-3,5-dimethoxybenzylidene) malonic acid-bis (2-ethylhexyl) ester (for example Oxynex ® ST Liquid) and / or 2- (4-hydroxy-3,5-dimethoxybenzy ) - malonic acid bis- (2-ethylhexyl) ester (example RonaCare ® AP).
• antioxidants are also suitable for use in the cosmetic preparations according to the invention.
• Known and commercially available mixtures are, for example, mixtures containing as active ingredients lecithin, L - (+) - ascorbyl palmitate and citric acid (for example (e.g.
• Oxynex ® AP natural tocopherols, L - (+) - ascorbyl palmitate, L - (+) - ascorbic acid and citric acid (for example Oxynex ® K LIQUID) tocopherol extracts from natural sources, L - (+) - ascorbyl palmitate, L - (+ ) -Ascorbic acid and citric acid (eg Oxynex ® L LIQUID), DL- ⁇ -tocopherol, L - (+) - ascorbyl palmitate, citric acid and lecithin (for example Oxynex ® LM) or butylhydroxytoluene (BHT), L - (+) - ascorbyl palmitate and citric acid (for example Oxynex ® 2004) ,
• Such antioxidants are used with the compounds of the invention in such compositions usually in weight percent ratios in the range of 1000: 1 to 1: 1000, preferably in weight percent ratios of 100: 1 to 1: 100.
• the polyphenols which occur in part as natural substances, are of particular interest for applications in the pharmaceutical, cosmetic or nutritional field.
• the flavonoids or bioflavonoids which are mainly known as plant dyes, frequently have an antioxidant potential. Effects of the substitution pattern of mono- and dihydoxy flavones are dealt with by K. Lemanska, H. Szymusiak, B. Tyrakowska, R. Zielinski, I. M. C. M. Rietjens; Current Topics in Biophysics 2000, 24 (2), 101-108.
• dihydroxyflavones having an OH group adjacent to the keto function or OH groups in the 3'4 'or 6,7 or 7,8 position have antioxidant properties, while other mono- and dihydroxyflavones have in part no antioxidant properties exhibit.
• Quercetin (cyanidanol, cyanidolone 1522, meletin, sophoretine, ericin, 3,3 ', 4', 5,7-pentahydroxyflavone) is often cited as a particularly effective antioxidant (eg, CA Rice-Evans, NJ Miller, G. Paganga, Trends in Plant Science 1997, 2 (4), 152-159).
• K. Lemanska, H. Szymusiak, B. Tyrakowska, R. Zielinski, A.E. M.F. Soffers and I.M.C.M. Rietjens (Free Radical Biology & Medicine 2001, 31 (7), 869-881 investigate the pH dependence of the antioxidant activity of hydroxyflavones, and quercetin shows the highest activity of the investigated structures over the entire pH range.
• Suitable antioxidants are furthermore compounds of the formula (C)
• R 1 to R 10 may be the same or different and are selected from - H
• the preparations according to the invention may contain vitamins as further ingredients.
• vitamins and vitamin derivatives selected from vitamin A, vitamin A propionate, vitamin A palmitate, vitamin A acetate, retinol, vitamin B, thiamin chloride hydrochloride (vitamin B 1 ), riboflavin (vitamin B 2 ), nicotinamide , Vitamin C (ascorbic acid), vitamin D, ergocalciferol (vitamin D 2 ), vitamin E, DL- ⁇ -tocopherol, tocopherol-E-acetate, tocopherol hydrogen succinate, vitamin Ki, esculin (vitamin P active ingredient), thiamin (vitamin bi) , Nicotinic acid (niacin), pyridoxine, pyridoxal, pyridoxamine, (vitamin B 6 ), pantothenic acid, biotin, folic acid and cobalamin (vitamin Bi 2 ), particularly preferably vitamin A palmitate, vitamin C and its derivatives, DL- ⁇ Tocopherol, tocopherol E acetate,
• Preferred preparations may also serve for the sunscreen and then also contain UV filters in addition to the compounds according to the invention and optionally other ingredients.
• UV filters are suitable for combination with the DHA derivatives to be used according to the invention. Particularly preferred are those UV filters whose physiological harmlessness has already been demonstrated.
• UVA and UVB filters there are many known and proven substances in the literature, e.g.
• Benzylidenecamphor derivatives such as 3- (4'-methylbenzylidene) -dl-camphor (for example Eusolex 6300), 3-benzylidenecamphor (for example Mexoryl® SD), polymers of N - ⁇ (2 and 4) - [2- (oxoborn-3- ylidene) methyl] benzyl ⁇ -acrylamide (eg Mexoryl® SW), N, N, N-trimethyl-4- (2-oxoborn-3-ylidenemethyl) anilinium methylsulfate (eg Mexoryl® SK) or (2-oxobrom-3-yl) yliden) toluene-4-sulfonic acid (eg Mexoryl® SL),
• 3- (4'-methylbenzylidene) -dl-camphor for example Eusolex 6300
• 3-benzylidenecamphor for example Mexoryl® SD
• Benzoyl or dibenzoylmethanes such as 1- (4-tert-butylphenyl) -3- (4-methoxyphenyl) propane-1,3-dione (eg Eusolex® 9020) or 4-isopropyldibenzoylmethane (eg Eusolex® 8020),
• Benzophenones such as 2-hydroxy-4-methoxybenzophenone (eg Eusolex® 4360) or 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid and its sodium salt (eg Uvinul® MS-40),
• Methoxycinnamate such as octyl methoxycinnamate (e.g., Eusolex® 2292), isopentyl A-methoxycinnamate, e.g. as a mixture of isomers (e.g., Neo Heliopan® E 1000),
• Salicylate derivatives such as 2-ethylhexyl salicylate (e.g., Eusolex® OS), 4-isopropylbenzyl salicylate (e.g., Megasol®), or 3,3,5-trimethylcyclohexyl salicylate (e.g., Eusolex® HMS),
• 4-aminobenzoic acid and derivatives such as 4-aminobenzoic acid, 2-ethylhexyl 4- (dimethylamino) benzoate (e.g., Eusolex® 6007), ethoxylated 4-aminobenzoic acid ethyl ester (e.g., Uvinul® P25),
• Phenylbenzimidazole sulfonic acids such as 2-phenylbenzimidazole-5-sulfonic acid, and their potassium, sodium and triethanolamine salts (eg Eusolex® 232), 2,2- (1,4-phenylene) bisbenzimidazole-4,6-disulfonic acid or salts thereof ( eg Neoheliopan® AP) or 2,2- (1,4-phenylene) bisbenzimidazole-6-sulfonic acid;
• 2-ethylhexyl 2-cyano-3,3-diphenylacrylate eg Eusolex® OCR
• 3,3 ' - (1,4-phenylenedimethylene) bis- (7,7-dimethyl-2-oxobicyclo- [2.2 .1] hept-1-ylmethanesulfonic acid and its salts eg Mexoryl® SX
• Mexoryl® SX 2-ethylhexyl 2-cyano-3,3-diphenylacrylate
• Hexyl 2- (4-diethylamino-2-hydroxybenzoyl) benzoate e.g., Uvinul® UVA Plus, BASF.
• UV filters are also Methoxyflavone enschend the German patent application DE-A-10232595 or ascorbic acid derivatives according to the PCT application WO 2008/17346 A2.
• Organic UV filters are usually in an amount of 0.5 to 20
• Weight percent preferably 1 to 15 wt .-%, incorporated in formulations.
• preparations with light protection properties also contain inorganic UV filters.
• Conceivable inorganic UV filters are those from the group of titanium dioxides, such as coated titanium dioxide (for example Eusolex® T-2000, Eusolex ® T-AQUA, Eusolex® T-AVO), zinc oxides (eg Sachtotec.RTM), iron oxides and also cerium oxides are conceivable.
• These inorganic UV filters are usually incorporated in an amount of 0.5 to 20 percent by weight, preferably 2 to 10 wt .-%, in cosmetic preparations.
• Preferred compounds having UV-filtering properties are 3- (4 '- methylbenzylidene) -dl-camphor, 1- (4-tert-butylphenyl) -3- (4-methoxy-phenyl) -Pro-pan-1, 3-dione , 4-isopropyldibenzoylmethane, 2-hydroxy-4-methoxy-benzophenone, octyl methoxycinnamate, SS ⁇ -trimethyl-cyclo-hexyl-salicylate, 4- (dimethylamino) -benzoic acid 2-ethylhexyl ester, 2-cyano-3,3- di-phenyl 2-ethylhexyl acrylate, 2-phenyl-benzimidazole-5-sulfonic acid and their potassium, sodium and triethanol amine salts.
• UV filters can also be used in encapsulated form.
• organic UV filters in encapsulated form.
• hydrophilicity of the capsule wall can be adjusted independently of the solubility of the UV filter.
• hydrophobic UV filters can also be incorporated into purely aqueous preparations.
• the often perceived as unpleasant oily impression when applying the hydrophobic UV filter containing preparation is suppressed.
• Certain UV filters in particular Dibenzoylmethanderivate, show in cosmetic preparations only a reduced Photostabjltician.
• these filters or compounds that affect the photostability of these filters such as cinnamic acid derivatives, the photostability of the entire formulation can be increased.
• Suitable capsules may have walls of inorganic or organic polymers.
• US Pat. No. 6,242,099 B1 describes the preparation of suitable capsules having walls made of chitin, chitin derivatives or polyhydroxylated polyamines.
• capsules have walls which can be obtained by a SolGel process as described in applications WO 00/09652, WO 00/72806 and WO 00/71084. Again, capsules whose walls are made up of silica gel (silica, undefined silicon oxide hydroxide) are preferred. The production of such capsules is known to the skilled worker, for example, from the cited patent applications, whose contents are expressly also part of the subject of the present application.
• the capsules in preparations to be used according to the invention are preferably present in amounts which ensure that the encapsulated UV filters are present in the preparation in the above-indicated weight percentages.
• the preparations to be used according to the invention may additionally contain further customary skin-friendly or skin-care active substances.
• these can be all active ingredients known to the person skilled in the art.
• Particularly preferred active ingredients are, for example, also so-called compatible solutes. These are substances that are involved in the osmoregulation of plants or microorganisms and can be isolated from these organisms. Under the generic term compatible solutes also the described in the German patent application DE-A-10133202 osmolytes are taken. Suitable osmolytes are, for example, the polyols, methylamine compounds and amino acids and in each case their precursors.
• osmolytes are understood as meaning, in particular, substances from the group of polyols, such as, for example, myo-inositol, mannitol or sorbitol and / or one or more of the osmolytically active substances mentioned below: taurine, choline, betaine, Phosphorylcholine, glycerophosphoryl choline, glutamine, glycine, ⁇ -alanine, glutamate, aspartate, proline, and taurine.
• Precursors of these substances are, for example, glucose, glucose polymers,
• Precursors are z.
• solute substances selected from the group consisting of pyrimidinecarboxylic acids (such as ectoine and hydroxyectoine), proline, betaine, glutamine, cyclic diphosphoglycerate, N-acetylornithine, trimethylamine-N-oxide di-myo-inositol-phosphate (DIP) , cyclic 2,3-diphosphoglycerate (cDPG), 1,1-diglycerol phosphate (DGP), ⁇ -mannosylglycerate (firoin), ⁇ -mannosylglyceramide (firoin-A) or / and di-mannosyl-di-inositol phosphate (DMIP) or an optical isomer, derivative, eg an acid, a salt or ester of these compounds or combinations thereof.
• pyrimidinecarboxylic acids such as ectoine and hydroxyectoine
• proline betaine
• glutamine cyclic diphosphogly
• ectoine (S) -1, 4,5,6-tetrahydro-2-methyl-4-pyrimidinecarboxylic acid) and hydroxyectoine ((S 1 S) -1, 4, 5, 6-tetrahydro-5 are among the pyrimidinecarboxylic acids hydroxy-2-methyl-4-pyrimidinecarboxylic acid) and their derivatives.
• These compounds stabilize enzymes and other biomolecules in aqueous solutions and organic solvents. In particular, they stabilize enzymes against denaturing conditions such as salts, extreme pH, surfactants, urea, guanidinium chloride and other compounds.
• Ectoine and ectoine derivatives such as hydroxyectoine can be used to advantage in medicines.
• hydroxyectoine can be used for the manufacture of a medicament for the treatment of skin diseases.
• Other uses of hydroxyectoine and other ectoine derivatives are typically in areas where e.g. Trehalose is used as an additive.
• ectoine derivatives, such as hydroxyectoine can be used as a protective substance in dried yeast and bacterial cells.
• pharmaceutical products such as non-glycosylated, pharmaceutically active peptides and proteins e.g. t-PA can be protected with Ectoin or its derivatives.
• EP-A-0 671 161 describes that ectoine and hydroxyectoine are used in cosmetic preparations such as powders, soaps, surfactant-containing cleaning products,
• a pyrimidinecarboxylic acid according to the following formula is preferably used,
• R 1 is a radical H or C 1-8 -alkyl
• R 2 is a radical H or C 1-4 -alkyl
• R 3 , R 4 , R 5 and R 6 are each independently a radical from the group H, OH, NH 2 and C1-4 alkyl.
• Preference is given to using pyrimidinecarboxylic acids in which R 2 is a methyl or an ethyl group and R 1 or R 5 and R 6 are H.
• the pyrimidinecarboxylic acids ectoine ((S) -1, 4,5,6-tetrahydro-2-methyl-4-pyrimidine-carboxylic acid) and hydroxyectoine ((S, S) -1, 4,5,6-tetrahydro-) 5-hydroxy-2-methyl-4-pyrimidine-carboxylic acid).
• the preparations to be used according to the invention preferably contain such pyrimidinecarboxylic acids in amounts of up to 15% by weight.
• the compatible solutes are selected from di-myo-inositol phosphate (DIP), cyclic 2,3-diphosphoglycerate (cDPG), 1, 1-diglycerol phosphate (DGP), ß-mannosylglycerate (Firoin ), ⁇ -mannosylglyceramide (Firoin-A) or / and di-mannosyl-di-inositol phosphate (DMIP), ectoine, hydroxyectoine or mixtures thereof.
• DIP di-myo-inositol phosphate
• cDPG cyclic 2,3-diphosphoglycerate
• DGP 1, 1-diglycerol phosphate
• ß-mannosylglycerate Firoin
• ⁇ -mannosylglyceramide Firoin-A
• DMIP di-mannosyl-di-inositol phosphate
• preparations according to the invention may contain at least one self-tanner as further ingredient.
• HC OH "(> OH
• the compounds according to the invention and optionally further active compounds can be incorporated in the customary manner, for example by mixing, into cosmetic, dermatological or pharmaceutical preparations.
• Suitable preparations for external use for example as a cream, lotion, gel, or as a solution that can be sprayed on the skin.
• administration formulas such as capsules, dragees, powders, tablet solutions or solutions are suitable.
• preparations to be used e.g. called: solutions, suspensions, emulsions, PIT emulsions, pastes, ointments, gels, creams, lotions, powders, soaps, surfactant-containing cleaning preparations, oils, aerosols and sprays.
• Preferred forms of application are also shampoos, sun baths and shower baths, which are also known as so-called "spray tanning, airbrush tanning or sun showers" from commercial self-tanning studios.
• Preferred excipients come from the group of preservatives, stabilizers, solubilizers, colorants, odor improvers.
• Ointments, pastes, creams and gels may contain the usual excipients, e.g. animal and vegetable fats, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicic acid, talc and zinc oxide or mixtures of these substances.
• excipients e.g. animal and vegetable fats, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicic acid, talc and zinc oxide or mixtures of these substances.
• Powders and sprays may contain the usual excipients, for example lactose, talc, silicic acid, aluminum hydroxide, calcium silicate and polyamide powder or Mixtures of these substances.
• Sprays may additionally contain the usual volatile, liquefied propellants, eg chlorofluorohydrocarbons, propane / butane or dimethyl ether. Also, compressed air is advantageous to use.
• Solutions and emulsions may contain the usual excipients such as solvents, solubilizers and emulsifiers, e.g. Water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylglycol, 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 sorbitan or mixtures of these substances contain.
• solvents e.g. Water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylglycol, oils, in particular cottonseed oil, peanut oil, corn oil, olive oil, castor oil and sesame oil,
• Suspensions may include the usual carriers such as liquid diluents, e.g. Water, ethanol or propylene glycol, suspending agents, e.g. ethoxylated isostearyl alcohols, polyoxyethylene sorbitol esters and polyoxyethylene sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth or mixtures of these substances.
• liquid diluents e.g. Water, ethanol or propylene glycol
• suspending agents e.g. ethoxylated isostearyl alcohols, polyoxyethylene sorbitol esters and polyoxyethylene sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth or mixtures of these substances.
• Soaps may contain the usual excipients such as alkali salts of fatty acids, salts of fatty acid monoesters, fatty acid protein hydrolysates, isothionates, lanolin, fatty alcohol, vegetable oils, plant extracts, glycehn, sugar or mixtures of these substances.
• excipients such as alkali salts of fatty acids, salts of fatty acid monoesters, fatty acid protein hydrolysates, isothionates, lanolin, fatty alcohol, vegetable oils, plant extracts, glycehn, sugar or mixtures of these substances.
• Surfactant-containing cleaning products the usual carriers such as salts of fatty alcohol sulfates, fatty alcohol ether sulfates, Sulfobemsteinklad, fatty acid hydrolysates, isothionates, Imidazoliniumderivate, methyltaurates, sarcosinates, Fettchureamidethersulfate, Alkylamidobetaine, fatty alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable and synthetic oils, lanolin derivatives, ethoxylated glycerol fatty acid esters or mixtures of these substances contain.
• Facial and body oils may contain the usual excipients such as synthetic oils such as fatty acid esters, fatty alcohols, silicone oils, natural oils such as vegetable oils and oily vegetable 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 vegetable extracts, paraffin oils, lanolin oils or mixtures of these substances.
• natural oils such as vegetable oils and oily vegetable extracts, paraffin oils, lanolin oils or mixtures of these substances.
• Further typical cosmetic application forms are also lipsticks, lip balm sticks, powder, emulsion and wax make-up as well as sunscreen, pre-sun and after-sun preparations.
• the preferred preparation forms include, in particular, emulsions.
• Emulsions are advantageous and contain z.
• Oils such as triglycerides of capric or caprylic, further natural oils such. Castor oil; Fats, waxes and other natural and synthetic fats, preferably esters of fatty acids with lower C-number alcohols, e.g. with isopropanol, propylene glycol or glycerol, or esters of fatty alcohols with alkanoic acids of low C number or with fatty acids;
• Silicone oils such as dimethylpolysiloxanes, diethylpolysiloxanes, diphenylpolysiloxanes and mixed forms thereof.
• the oil phase of the emulsions, oleogels or hydrodispersions or lipodispersions in the context of the present invention is advantageously selected from the group of esters of saturated and / or unsaturated, branched and / or unbranched alkanecarboxylic acids having a chain length of 3 to 30 carbon atoms and saturated and / or unsaturated, branched and / or unbranched alcohols having a chain length of from 3 to 30 carbon atoms, from the group of esters of aromatic carboxylic acid and saturated and / or unsaturated, branched and / or unbranched alcohols having a chain length of from 3 to 30 carbon atoms. atoms.
• ester oils can then advantageously be selected from the group consisting of isopropyl myristate, isopropyl palmitate, isopropyl stearate, isopropyl oleate, n-butyl stearate, n-hexyl laurate, n-decyl oleate, isooctyl stearate, isononyl stearate, isononyl isononanoate, 2-ethylhexyl palmitate, 2-ethylhexyl laurate, 2-hexadecyl stearate, 2-octyl dodecyl palmitate, oleyl oleate, oleyl erucate, erucyl oleate, erucyl erucate and synthetic, semi-synthetic and natural mixtures of such esters, e.g.
• the oil phase can advantageously be selected from the group of branched and unbranched hydrocarbons and waxes, silicone oils, dialkyl ethers, the group of saturated or unsaturated, branched or unbranched alcohols, and fatty acid triglycerides, in particular the triglycerol esters of saturated and / or unsaturated, branched and / or unbranched alkanecarboxylic acids of a chain length of 8 to 24, in particular 12-18 C-atoms.
• the fatty acid triglycerides can be selected, for example, advantageously from the group of synthetic, semi-synthetic and natural oils, for. For example, olive oil, sunflower oil, soybean oil, peanut oil, rapeseed oil, almond oil, palm oil, coconut oil, palm kernel oil and the like.
• any mixtures of such oil and wax components are also advantageous to use in the context of the present invention. It may also be advantageous, if appropriate, to use waxes, for example cetyl palmitate, as the sole lipid component of the oil phase.
• the aqueous phase of the preparations to be used advantageously contains alcohols, diols or polyols of low C number, and their ethers, preferably ethanol, isopropanol, propylene glycol, glycerol, ethylene glycol, ethylene glycol monoethyl or monobutyl ether, propylene glycol monomethyl, monoethyl or monobutyl ether, diethylene glycol monomethyl or mono-ethyl ether and analogous products, furthermore lower C-number alcohols, eg.
• isopropanol, 1, 2-propanediol, glycerol and in particular one or more thickening agents which or which can be advantageously selected from the group of silica, aluminum silicates, polysaccharides or their derivatives, e.g. Hyaluronic acid, xanthan gum, hydroxypropylmethylcellulose, particularly advantageous from the group of polyacrylates, preferably a polyacrylate from the group of so-called Carbopols, for example Carbopols types 980, 981, 1382, 2984, 5984, each individually or in combination.
• Carbopols for example Carbopols types 980, 981, 1382, 2984, 5984, each individually or in combination.
• mixtures of the abovementioned solvents are used.
• alcoholic solvents water can be another ingredient.
• Emulsions are advantageous and contain z.
• fats, oils, waxes and other fatty substances, and water and an emulsifier as it is commonly used for such a type of formulation.
• the preparations to be used contain hydrophilic surfactants.
• the hydrophilic surfactants are preferably selected from the group of alkylglucosides, acyl lactylates, betaines and coco amphoacetates.
• the cosmetic and dermatological preparations can be in various forms. So they can z.
• Oil-in-water (W / O / W) a gel, a solid stick, an ointment or even an aerosol.
• Ectoine in encapsulated form, e.g. In collagen matrices and other common encapsulating materials, e.g.
• wax matrices As encapsulated cellulose, in gelatin, wax matrices or liposomally encapsulated. In particular wax matrices as described in DE-A-43 08 282, have been found to be favorable. Preference is given to emulsions. O / W
• Emulsins are especially preferred. Emulsions, W / O emulsions and O / W emulsions are available in the usual way.
• emulsifiers for example, the known W / O and O / W emulsifiers can be used. It is advantageous to use other conventional co-emulsifiers in the preferred O / W emulsions.
• O / W emulsifiers are selected as co-emulsifiers, principally from the group of substances with HLB values of 11-16, very particularly advantageously with HLB values of 14.5-15.5, provided that the O / W Emulsifiers have saturated radicals R and R 1 . If the O / W emulsifiers have unsaturated radicals R and / or R ', or if isoalkyl derivatives are present, the preferred HLB value of such emulsifiers may also be lower or higher.
• Particularly preferred are: polyethylene glycol (13) stearyl ether (steareth-13), Polyethylene glycol (14) stearyl ether (steareth-14), polyethylene glycol (15) stearyl ether (steareth-15), polyethylene glycol (16) stearyl ether (steareth-16), polyethylene glycol (17) stearyl ether (steareth-17), polyethylene glycol (18) stearyl ether (steareth-18), polyethylene glycol (19) stearyl ether (steareth-19), polyethylene glycol (20) stearyl ether (steareth-20), polyethylene glycol (12) isostearyl ether (isosteareth-12), polyethylene glycol (13) isostearyl ether (isosteareth-13 ), Polyethylene glycol (14) - isostearyl ether (isosteareth-14),
• fatty acid ethoxylates of the following group: polyethylene glycol (20) stearate, polyethylene glycol (21) stearate, polyethylene glycol (22) stearate, polyethylene glycol (23) stearate, polyethylene glycol (24) stearate, polyethylene glycol (25) stearate,
• the sodium laureth-11-carboxylate can be advantageously used.
• the alkyl ether sulfate sodium laureth-4 sulfate can be advantageously used.
• polyethylene glycol (30) cholesteryl ether can be advantageously used.
• polyethylene glycol (25) soybean oil has been proven.
• sorbitan esters from the group of polyethylene glycol (20) sorbitan monolaurate, polyethylene glycol (20) sorbitan monostearate, polyethylene glycol (20) sorbitan monoisostearate, polyethylene glycol (20) sorbitan monopalmitate, polyethylene glycol (20) sorbitan monooleate.
• W / O emulsifiers can be used:
• W / O emulsifiers are glyceryl monostearate, glyceryl monoisostearate, glyceryl monomyristate, glyceryl monooleate, diglyceryl monostearate, diglyceryl monoisostearate, propylene glycol monostearate, propylene glycol monoisostearate, propylene glycol monocaprylate,
• compositions which are preferred according to the invention are also suitable for protecting human skin against aging processes as well as against oxidative stress, i. against damage by radicals, as e.g. be generated by sunlight, heat or other influences. It is present in various dosage forms commonly used for this application. Thus, it can be used in particular as a lotion or emulsion, such as cream or milk (O / W, W / O, O / W / O, W / O / W), in the form of oily-alcoholic, oily-aqueous or aqueous-alcoholic gels or solutions, be present as solid pins or formulated as an aerosol.
• a lotion or emulsion such as cream or milk (O / W, W / O, O / W / O, W / O / W)
• oily-alcoholic, oily-aqueous or aqueous-alcoholic gels or solutions be present as solid pins or formulated as an aerosol.
• the preparation may contain cosmetic adjuvants commonly used in this type of preparation, such as thickeners, emollients, humectants, surfactants, emulsifiers, preservatives, antifoaming agents, perfumes, waxes, lanolin, propellants, dyes and / or or pigments containing the agent itself or staining the skin, and other ingredients commonly used in cosmetics.
• cosmetic adjuvants commonly used in this type of preparation, such as thickeners, emollients, humectants, surfactants, emulsifiers, preservatives, antifoaming agents, perfumes, waxes, lanolin, propellants, dyes and / or or pigments containing the agent itself or staining the skin, and other ingredients commonly used in cosmetics.
• dispersion or solubilizing agent an oil, wax or other fatty substance, a low monoalcohol or a low polyol or mixtures thereof.
• Particularly preferred monoalcohols or polyols include ethanol, i-propanol, propylene glycol, glycerine and sorbitol.
• a preferred embodiment of the invention is an emulsion which is present as a protective cream or milk and, for example, fatty alcohols, fatty acids,
• Fatty acid esters in particular triglycerides of fatty acids, lanolin, natural and synthetic oils or waxes and emulsifiers in the presence of water.
• oily lotions based on natural or synthetic oils and waxes, lanolin, fatty acid esters, in particular triglycerides of fatty acids, or oily-alcoholic lotions based on a lower alcohol, such as ethanol, or a glycerol, such as propylene glycol, and / or a polyol such as glycerine, and oils, waxes and fatty acid esters, such as triglycerides of fatty acids.
• a lower alcohol such as ethanol, or a glycerol, such as propylene glycol, and / or a polyol such as glycerine
• oils, waxes and fatty acid esters such as triglycerides of fatty acids.
• the preparation may also be in the form of an alcoholic gel comprising one or more lower alcohols or polyols, such as ethanol, 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 and oils, fatty alcohols, fatty acids, fatty acid esters, lanolin and other fatty substances.
• blowing agents are generally used, such as alkanes, fluoroalkanes and chlorofluoroalkanes, preferably alkanes.
• preparations to be used can be prepared using techniques that are well known to the person skilled in the art.
• the preparations as described above may contain, comprise, consist essentially of or consist of the necessary or optional ingredients mentioned.
• the NMR spectra were measured HZBB on solutions in deuterated solvents at 20 0 C on a Bruker Avance 300 spectrometer with a 5 mm broadband head 1 with deuterium lock, unless indicated in the examples.
• the measurement frequency for the 1 H-NMR is 300.13 MHz.
• phase A The components of phase A are combined at room temperature and stirred. Subsequently, phase B is mixed and added with stirring to phase B.
• phase A The components of phase A are combined at room temperature and stirred. Subsequently, phase B is mixed and added with stirring to phase B.
• Pre-dissolve phase A Add phase B to phase A with stirring.
• Premix phase C and add to the rest, stirring until a homogeneous mixture has formed.
• Pre-dissolve phase A Add phase B to phase A with stirring.
• Premix phase C and add to the rest, stirring until a homogeneous mixture has formed.
• Example 16 W / O Emulsions
• Example 17 W / O Emulsions
• Example 25 O / W emulsions
• Example 28 Hydrodisperions (lotions and sprays)
• Example 29 Hydrodisperions (lotions and sprays)
• Example 30 aqueous and aqueous / alcoholic formulations
• Example 31 aqueous and aqueous / alcoholic formulations
• Example 33 Cosmetic foams
• Example 34 cosmetic foams

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