WO2007057091A1 - Sulfate de flavone et son utilisation en tant qu’antioxydant - Google Patents

Sulfate de flavone et son utilisation en tant qu’antioxydant Download PDF

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Publication number
WO2007057091A1
WO2007057091A1 PCT/EP2006/010284 EP2006010284W WO2007057091A1 WO 2007057091 A1 WO2007057091 A1 WO 2007057091A1 EP 2006010284 W EP2006010284 W EP 2006010284W WO 2007057091 A1 WO2007057091 A1 WO 2007057091A1
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Prior art keywords
formula
compounds
preparation
compound
polyethylene glycol
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PCT/EP2006/010284
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German (de)
English (en)
Inventor
Christophe Carola
Herwig Buchholz
Ralf Rosskopf
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Merck Patent Gmbh
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Priority to EP06818285A priority Critical patent/EP1948632A1/fr
Publication of WO2007057091A1 publication Critical patent/WO2007057091A1/fr

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    • 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
    • C09K15/12—Anti-oxidant compositions; Compositions inhibiting chemical change containing organic compounds containing sulfur and oxygen
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • 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
    • 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
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/35—Ketones, e.g. benzophenone
    • 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
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/37—Esters of carboxylic 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
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • 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
    • A61K8/466—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing sulfur containing sulfonic acid derivatives; Salts
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
    • A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • 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
    • A61K8/67—Vitamins
    • A61K8/671—Vitamin A; Derivatives thereof, e.g. ester of vitamin A acid, ester of retinol, retinol, retinal
    • 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
    • A61K8/67—Vitamins
    • A61K8/673—Vitamin B group
    • 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
    • A61K8/67—Vitamins
    • A61K8/673—Vitamin B group
    • A61K8/675—Vitamin B3 or vitamin B3 active, e.g. nicotinamide, nicotinic acid, nicotinyl aldehyde
    • 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
    • A61K8/67—Vitamins
    • A61K8/676—Ascorbic acid, i.e. vitamin C
    • 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
    • A61K8/67—Vitamins
    • A61K8/678—Tocopherol, i.e. vitamin E
    • 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
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/08—Anti-ageing preparations
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
    • C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
    • C07D311/28—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only
    • C07D311/30—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only not hydrogenated in the hetero ring, e.g. flavones
    • 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 present invention relates to novel flavones, preparations and mixtures containing flavones, their preparation and use.
  • a field of application of the compounds according to the invention is, for example, cosmetics.
  • the task of nourishing cosmetics is to preserve the impression of a youthful skin if possible.
  • existing skin damage such as irregular pigmentation or wrinkling
  • Another approach is to protect the skin from environmental influences that lead to permanent damage and thus aging of the skin.
  • the idea is to intervene preventively and thereby delay the aging process.
  • An example of this are the UV filters already mentioned, which avoid or at least reduce damage to the skin by absorption of certain wavelength ranges. While in UV filters, the damaging event, the UV radiation is shielded from the skin, one tries in another way, the natural defense or repair mechanisms of the skin
  • the skin has the ability to scavenge radicals generated by external or internal stressors. This ability weakens with age, accelerating the aging process with age.
  • sun tan of the skin is considered attractive in modern society and an expression of dynamism and sportiness.
  • a number of undesirable side effects occur, such as sunburn or premature aging and wrinkling.
  • the wavelength range of 280 to 400 nm is the wavelength range of 280 to 400 nm.
  • This range includes UV-B rays with a wavelength between 280 and 320 nm, which play a crucial role in the formation of a sun erythema, as well as UV-A rays, with a wavelength between 320 and 400 nm, which skin
  • tanning may also age, promote the triggering of an erythematous reaction, or increase this response in certain people, or even trigger phototoxic or photoallergic and irritative reactions.
  • Skin damage is caused not only by sunlight, but also by other external influences, such as cold or heat. Furthermore, the skin is subject to natural aging, which causes wrinkles and relieves the elasticity of the skin.
  • Structural change e.g. change their color and / or lose their effectiveness.
  • Antioxidants are compounds that inhibit or prevent undesirable changes in the substances to be protected due to oxidative effects, such as oxidative effects. Fields of application are, for example, in plastics and rubber for protection against aging; in fats for protection against rancidity, in oils, animal feed, automotive gasoline and jet fuels for protection against gumming, in transformer and turbine oil against sludge formation, in flavorings against odor deterioration.
  • Effective antioxidants include phenols substituted by sterically hindering groups, Hydroquinones, catechols and aromatics. Amines and their metal complexes. According to Römpp, the effect of the antioxidants is usually that they act as radical scavengers for the free radicals which occur during the autoxidation.
  • the polyphenols which are sometimes present as natural substances, are of particular interest for applications in the pharmaceutical, cosmetic or food sector.
  • 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. It is observed there that dihydroxyflavones with an OH group adjacent to the ketone or
  • OH groups in 3'4'- or 6,7- or 7,8-position have antioxidant properties, while other mono- and Dihydroxyflavone partially have no antioxidant properties.
  • Quercetin (cyanidanol, cyanidolone 1522, meletin,
  • Sophoretine, ericin, 3,3 ', 4', 5,7-pentahydroxyflavone) 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, I.M.C.M. Rietjens; Free Radical Biology & Medicine 2001, 31 (7), 869-881 investigate the pH dependence of the antioxidant action of hydroxyflavones. Quercetin shows the highest activity of the investigated structures over the entire pH range.
  • Preferred flavone derivatives are, in particular, naturally occurring bioflavonoids, such as rutin, naringin, - A -
  • compositions and are optimized to catch free radicals like
  • Hydroxy radicals or peroxides Particularly preferred is the
  • the object of the invention is therefore to provide compounds which are applied in cosmetic preparations a protective
  • a first subject of the present invention are therefore compounds of formula I, which are characterized in that it is a 7,8-dihydroxyflavone derivative according to formula Ia or Ib or a salt thereof
  • mixtures which are characterized in that they contain at least 2 compounds selected from the compounds according to formula Ia, Ib or Ic or their salts
  • Another object of the present invention is a preparation having antioxidant properties, containing at least one compound of formula I 1 selected from the compounds of formula Ia, Ib or Ic, as described above, or an above-described
  • the salts are preferably those with counterions which do not hinder the incorporation of the compounds of the formula Ia-c in preparations.
  • the salts are sodium, potassium or ammonium salts, in particular triethanolammonium salts.
  • the compounds or compositions according to the invention are in particular the antioxidant action and the good skin tolerance.
  • the compounds described here are only slightly colored and thus do not or only to a slight extent to discoloration of the preparations.
  • the particular profile of action of the compounds to be used according to the invention which manifests itself by stability of the compounds in the preparations and antioxidant action in or on the skin.
  • An object of the present invention is the use of the compounds of the formula Ia, Ib or Ic as well as mixtures of these compounds or their salts, as indicated above, as antioxidants or for the preparation of a
  • Preparation with antioxidant properties or for the production of Preparations which have a protective effect against oxidative stress on body cells and / or can counteract aging of the skin or can contribute to reducing the consequences of skin aging.
  • the preparations are usually either topically applicable preparations, for example cosmetic, pharmaceutical or dermatological formulations, or foods or dietary supplements.
  • the preparations in this case contain a cosmetically, pharmaceutically or dermatologically or food-suitable carrier and, depending on the desired profile of properties, optionally further suitable ingredients.
  • the compounds of the formula Ia, Ib or Ic, or a mixture thereof or salts thereof, according to the invention typically in amounts of 0.01 to 20 wt .-%, preferably in amounts of 0.1 wt .-% to 10 wt. -% and particularly preferably used in amounts of 1 to 8 wt .-%.
  • the expert does not have any difficulties in selecting the quantities according to the intended effect of the preparation.
  • the compounds of the formula Ia-c In order for the compounds of the formula Ia-c to be able to develop their positive action as radical scavengers on the skin particularly well, it may be preferable to allow the compounds of the formula Ia-c to penetrate into deeper skin layers. There are several options available. First, the compounds of the formula Ia-c have a certain
  • Lipophilicity which can be enough to penetrate through the outer skin layer in epidermal layers can.
  • suitable transport agents for example liposomes, can be provided in the preparation, which make it possible to transport the compounds of the formula Ia-c through the outer skin layers.
  • a systemic transport of the compounds of the formula la-c is conceivable.
  • the preparation is then, for example, designed to be suitable for oral administration.
  • the substances of the formula Ia-c act as radical scavengers.
  • Such radicals are not only generated by sunlight, but are formed under different conditions. Examples are anoxia which blocks the flow of electrons upstream of the cytochrome oxidases and causes the formation of superoxide radical ions; Inflammation, which is associated with the formation of superoxide anions by the membrane NADPH oxidase of leukocytes, but also with the
  • compounds of formula Ia-c also act as an enzyme inhibitor. They are believed to inhibit histidine decarboxylase, protein kinases, elastase, aldose reductase, and hyaluronidase, thus allowing the integrity of the matrix of vascular sheaths to be maintained. Furthermore, they probably do not inhibit specific enzyme inhibitor.
  • Catechol-O-methyltransferase thereby increasing the amount of catecholamines available and thereby vascular resistance. Further, they inhibit AMP phosphodiesterase, whereby the substances have a potential to inhibit platelet aggregation. Because of these properties, the invention are suitable
  • Preparations generally for immune protection and protection of DNA and RNA are suitable for the protection of DNA and RNA from oxidative attacks, from radicals and from damage by radiation, in particular UV radiation.
  • a further advantage of the preparations according to the invention is the cell protection, in particular the protection of Langerhans cells from damage by the above-mentioned influences. All these uses or the use of the compounds of the formula Ia-c, their salts or a mixture thereof for the preparation of correspondingly usable preparations are expressly the subject of the present invention.
  • compositions of the present invention are also useful in the treatment of skin diseases associated with keratinization disruption involving differentiation and cell proliferation, particularly for the treatment of acne vulgaris, acne comedonica, polymorphic acne, acne rosaceae, of nodular acne, acne conglobata, age-related acne, acne, such as acne solaris, acne-induced acne, or acne professionalis, for the treatment of other disorders of keratinization, especially ichthyosis, ichtyosi -form states, of Darrier's disease, the
  • Veruca plana Epidermodysplasia verruciformis, oral papillomatosis, Papillo-matosis florida, and growths caused by ultraviolet radiation, in particular epithelioma baso-cellulare and epithelioma spinocellulare, for the treatment of other skin diseases, such as dermatitis bullosa and collagen-related diseases, for the treatment of certain ocular diseases, in particular for diseases of the cornea, for the elimination or control of photodamaging and senile skin aging, for the reduction of pigmentation and keratosis actinica and for the treatment of all diseases associated with normal aging or to prevent or heal wounds / scars of atrophy of the epidermis and / or
  • Dermis caused by locally or systemically applied corticosteroids and all other types of dermal atrophy for the prevention or treatment of disorders of wound healing, for the prevention or repair of pregnancy strips, or for the promotion of wound healing, for combating disorders of the production of talc, such as hyperseborrhea in acne or simple seborrhea, to combating or preventing cancerous conditions or precancerous conditions, in particular promyelocytic leukemia, for the treatment of inflammatory diseases, such as arthritis, for the treatment of all viral diseases of the skin or other areas of the body, for the prevention or treatment of alopecia, for the treatment of skin diseases or diseases of other parts of the body with an immunological component, for the treatment of cardiovascular diseases, such as arteriosclerosis or hypertension, as well as insulin-independent diabetes, for the treatment of skin problems caused by UV radiation.
  • talc such as hyperseborrhea in acne or simple seborrhea
  • cancerous conditions or precancerous conditions in particular promyelocytic leukemia
  • the solution is dark violet colored.
  • a radical scavenger the electron is paired, the absorption disappears, and the staining proceeds stoichiometrically, taking into account the absorbed electrons. The extinction is measured in the photometer.
  • the antiradical property of the substance to be tested is determined by determining the concentration at which 50% of the 2,2-diphenyl-1-picrylhydrazyl used reacted with the radical scavenger. This concentration is expressed as EC 50 , a value which under the given measurement conditions is to be regarded as a substance property. The examined is compared
  • the EC 50 WhiI is a measure of the capacity of each compound to catch radicals. The lower the EC 50 , the higher the capacity to trap radicals. Another important aspect of the effect of the antioxidants is the time this EC 50 value is reached. This time measured in
  • AE Antiradical Efficiency
  • a low AE (x10 "3 ) is in the range up to about 10, an average AE is spoken in the range of 10 to 20, and a high AE is present according to the invention at values above 20.
  • fast-acting antioxidants it may be particularly preferred according to the invention to combine fast-acting antioxidants with those with a slow or delayed action.
  • Typical weight ratios of the fast-acting antioxidants to delayed-acting antioxidants are in the range from 10: 1 to 1:10, preferably in the range from 10: 1 to 1: 1, and for skin-protecting preparations in particular from 5: 1 to 2: 1.
  • Antioxidants are present. Typical compositions then show weight ratios of the fast-acting antioxidants to time-delayed antioxidants in the range 1: 1 to 1:10, preferably in the range 1: 2 to 1: 8.
  • the protective effect against oxidative stress or against the action of radicals can thus be further improved if the preparations contain one or more further antioxidants, wherein the skilled person has no difficulty in selecting suitable fast or delayed-acting antioxidants.
  • the preparation is therefore a preparation for protecting body cells against oxidative stress, in particular for reducing skin aging, which comprises, in addition to the one or more compounds of the formulas Ia to Ic or their salts or a mixture of these compounds containing one or more additional antioxidants.
  • antioxidants e.g. Amino acids (eg glycine, histidine, tyrosine, tryptophan) and their derivatives, imidazoles, (eg urocanic acid) and their derivatives, peptides such as D, L-carnosine, D-carnosine, L-camosine and their derivatives (eg anserine), carotenoids, Carotenes (eg ⁇ -carotene, ⁇ -carotene, lycopene) and their derivatives,
  • Amino acids eg glycine, histidine, tyrosine, tryptophan
  • imidazoles eg urocanic acid
  • peptides such as D, L-carnosine, D-carnosine, L-camosine and their derivatives (eg anserine)
  • carotenoids eg ⁇ -carotene, ⁇ -carotene, lycopene
  • Chlorogenic acid and its derivatives, lipoic acid and its derivatives eg dihydrolipoic acid), aurothioglucose, propylthiouracil and other thiols (eg thioredoxin, glutathione, cysteine, cystine, cystamine and their glycosyl, N-acetyl, methyl, ethyl, propyl, Amyl, butyl and lauryl, palmitoyl, oleyl, ⁇ -linoleyl, cholesteryl and glyceryl esters) and their
  • Salts dilauryl thiodipropionate, distearyl thiodipropionate, thiodipropionic acid and derivatives thereof (esters, ethers, peptides, lipids, nucleotides, nucleosides and salts) and sulfoximine compounds (eg buthionine sulfoximines, homocysteinesulfoximine, buthionine sulfones, penta, hexa, heptathionine sulfoximine) in very low tolerated dosages (eg pmol to ⁇ mol / kg), furthermore (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,
  • benzoic acid coniferyl benzoate rutinic acid and derivatives thereof, ⁇ -glycosyl
  • Suitable antioxidants are also compounds of the general formula
  • R 1 can be selected from the group consisting of -C (O) CH 3 , -CO 2 R 3 , -C (O) NH 2 and -C (O) N (R 4 ) 2 , XO 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 H or linear or branched
  • R 6 denotes linear or branched alkyl having 1 to 8 C atoms, preferably derivatives of 2- (4-hydroxy-3,5-dimethoxybenzylidene) malonic acid, more preferably 2- (4-hydroxy-3,5-dimethoxybenzylidene) - malonic acid-bis (2-ethylhexyl) ester (for example Oxynex ® ST Liquid).
  • 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 (e.g.
  • antioxidants are usually in proportions with compounds of formula I in such compositions in the range of 1000: 1 to 1: 1000, preferably used in amounts of 100: 1 to 1: 100.
  • the preparations according to the invention may contain vitamins as further ingredients. Preference is given to vitamins and vitamin derivatives selected from vitamin A, vitamin A propionate, vitamin A palmitate, vitamin A acetate, retinol, vitamin B, thiamine hydrochloride (vitamin Bi), riboflavine (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 thiamine (vitamin B 1 ), nicotinic acid (niacin), pyridoxine, pyridoxal, pyridoxamine, (vitamin B 6 ), pantothenic acid, biotin, folic acid and cobalamin (vitamin B 12 ) in the cosmetic preparations according to the invention particularly preferably vitamin A palmitate, vitamin C and its derivatives, DL- ⁇ -tocopherol,
  • Vitamins are used with compounds of the formula I usually in ratios in the range of 1000: 1 to 1: 1000, preferably used in amounts of 100: 1 to 1: 100.
  • compositions according to the invention comprise, in addition to the compounds of the formula Ia-c or their mixture, as described above, also pure UV filters.
  • Dibenzoylmethander / vate in combination with the compounds of formula la-c or the mixture gives an additional advantage:
  • the UV-sensitive Dibenzoylmethanderivate be additionally stabilized by the presence of the compounds of formula la-c.
  • Another object of the present invention is therefore the use of
  • UV filters for a combination according to the invention with the compounds of the formula Ia-c, their salts or a mixture in question. Particularly preferred are those UV filters whose physiological harmlessness has already been demonstrated. Both for UVA and UVB filters, there are many well-known and proven substances from the literature, eg
  • 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-oxobom-3- ylidene) methyl] benzyl ⁇ -acrylamide (eg Mexoryl® SW), N, N, N-trimethyl-4- (2-oxobrom-3-ylidenemethyl) anilinium methylsulfate (eg Mexoryl® SK) or (2-oxoborn-3-yl) yliden) toluene-4-sulfonic acid (eg
  • Benzoyl or dibenzoylmethanes such as 1- (4-tert-butylphenyl) -3- (4-methoxyphenyl) propane-1,3-dione (e.g., Eusolex® 9020) or 4-isopropyldibenzoylmethane (e.g., Eusolex® 8020),
  • Benzophenones such as 2-hydroxy-4-methoxybenzophenone (e.g., Eusolex® 4360) or 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid and its sodium salt (e.g., Uvinul® MS-40),
  • Methoxycinnamic acid esters such as octyl methoxycinnamate (e.g., Eusolex® 2292), isopentyl 4-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®
  • 3,3,5-Aminopropylbenzyl salicylate e.g., Megasol®
  • 3,3,5-Aminopropylbenzyl salicylate e.g., Megasol®
  • 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),
  • Phenylbenzimidazolesulfonic 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 their Salts (eg Neoheliopan® AP) or 2,2- (1,4-phenylene) bisbenzimidazole-6-sulfonic acid;
  • 2-cyano-3,3-diphenylacrylic acid 2-ethylhexyl ester e.g., Eusolex® OCR
  • organic UV filters are usually incorporated in an amount of 0.5 to 10 weight percent, preferably 1-8%, in cosmetic formulations.
  • UV filters are also Methoxyflavone en Schemeend the older German patent application DE 10232595.2.
  • Organic UV filters are usually incorporated in an amount of 0.5 to 20 percent by weight, preferably 1-15%, in cosmetic formulations.
  • 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, Eusolex ® T-OLEO), zinc oxides (eg Sachtotec.RTM) Iron oxides or cerium oxides conceivable.
  • coated titanium dioxide for example Eusolex® T-2000, Eusolex ® T-AQUA, Eusolex ® T-AVO, Eusolex ® T-OLEO
  • zinc oxides eg Sachtotec.RTM Iron oxides or cerium oxides conceivable.
  • These inorganic UV filters are usually incorporated in an amount of 0.5 to 20 weight percent, preferably 2-10%, 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-benzo-phenone, octyl methoxycinnamate, 3,3,5-trimethyl-cyclo-hexyl-salicylate, 4- (dimethylamino) -benzoic acid 2-ethyl- hexyl ester, 2-cyano-3,3-di-phenyl-2-ethylhexyl acrylate, 2-phenyl-benzimidazole-5-sulfonic acid and their potassium, sodium and triethanolamine salts.
  • Optimized compositions may be, for example, the combination of the organic UV filters 4'-methoxy-6-hydroxyflavone with 1- (4-tert-butylphenyl) -3- (4-methoxyphenyl) propane-1,3-dione and 3- (4 ' -
  • Methylbenzylidene -dl camphor. This combination results in a broadband protection that can be achieved by adding inorganic UV filters, such as
  • Titanium dioxide microparticles can still be added. - -
  • 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 dibenzoylmethane derivatives, show only reduced photostability in cosmetic preparations.
  • 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.
  • UV filters it is preferred according to the invention if one or more of the abovementioned UV filters are present in encapsulated form. It is advantageous if the capsules are so small that they can not be observed with the naked eye. To achieve the o.g. Effects it is still necessary that the capsules are sufficiently stable and donate the encapsulated active ingredient (UV filter) not or only to a small extent to the environment.
  • Suitable capsules may be walls of inorganic or organic
  • capsules whose walls are made up of silica gel (silica, undefined silicon oxide hydroxide) are preferred.
  • silica gel silicon, undefined silicon oxide hydroxide
  • the capsules in preparations according to the invention are preferably present in amounts which ensure that the encapsulated UV filters are present in the preparation in the amounts indicated above.
  • the preparations according to the invention may additionally contain further customary skin-sparing or skin-care active substances.
  • these can be all active ingredients known to the person skilled in the art.
  • Particularly preferred active ingredients are pyrimidinecarboxylic acids and / or aryloximes.
  • Pyrimidinecarboxylic acids occur in halophilic microorganisms and play a role in the osmoregulation of these organisms
  • Biomolecules in aqueous solutions and organic solvents Biomolecules in aqueous solutions and organic solvents.
  • Conditions such as salts, extreme pH, surfactants, urea,
  • 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 applications of hydroxyectoins and other ectoine derivatives are typically in areas where, for example
  • 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.
  • European Patent Application EP-A-0 671 161 describes in particular that ectoine and hydroxyectoine are used in cosmetic preparations such as powders, soaps, surfactant-containing cleansing products, lipsticks, blushes, make-ups, skin care creams and sunscreen preparations.
  • a pyrimidinecarboxylic acid according to formula II below is preferably used.
  • R 1 is a radical H or Ci -8 alkyl
  • R 2 is a radical H or C 4 alkyl and R 3,
  • R 4, R 5 and R 6 is a radical from the group H, OH, NH 2 and C are each independently -4 alkyl.
  • the preparations according to the invention preferably contain such pyrimidinecarboxylic acids
  • the pyrimidinecarboxylic acids are preferably used in ratios of 100: 1 to 1: 100 to give the compounds of the formula Ia-c, with ratios in the range from 1:10 to 10: 1 being particularly preferred.
  • 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 accompany 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.
  • compositions according to the invention which, in addition to a compound of the formula Ia-c, additionally contain an aryloxime, preferably 2-hydroxy-5-methyllaurophenone oxime, show surprising antiinflammatory suitability.
  • 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.
  • compositions are either known and commercially available or may be synthesized by known methods.
  • the one or more compounds of formula Ia-c, their salts or a mixture of these compounds can be prepared in the usual way in cosmetic or dermatological preparations are incorporated. Suitable preparations for external use, for example as a cream, lotion, gel, or as a solution that can be sprayed on the skin. For internal use, administration formulas such as capsules, dragees, powders, tablet solutions or solutions are suitable.
  • preparations according to the invention e.g. called: solutions, suspensions, emulsions, PIT emulsions, pastes, ointments, gels, creams, lotions, powders, soaps, surfactant-containing cleaning preparations, oils, aerosols and sprays.
  • Other applications are e.g. Sticks, shampoos and shower baths. Any customary carrier substances, adjuvants and optionally further active ingredients can be added to the preparation.
  • Preferable excipients come from the group of preservatives, antioxidants, stabilizers, solubilizers, vitamins, 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 carriers, e.g. Lactose, talc, silicic acid, aluminum hydroxide, calcium silicate and polyamide powder or mixtures of these substances.
  • Sprays may additionally contain the usual propellants, e.g. Chlorofluorocarbons, propane / butane or dimethyl ether.
  • Solutions and emulsions may include the customary carriers such as solvents, solubilizers and emulsifiers, for example water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylglycol, dimethyl capramide, oils, in particular cottonseed oil, peanut oil, corn oil , Olive oil, castor oil and sesame oil, Glycerin fatty acid esters, polyethylene glycols and fatty acid esters of sorbitan or mixtures of these substances.
  • solvents such as solvents, solubilizers and emulsifiers, for example water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylglycol, dimethyl capramide, oils, in particular cottons
  • Suspensions may be 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 carriers such as alkali salts of fatty acids,
  • Surfactant-containing cleaning products may include the usual carriers such as
  • 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
  • the preferred preparation forms according to the invention include in particular emulsions.
  • Emulsions of the invention are advantageous and contain z.
  • mineral oils mineral waxes - oils such as triglycerides of capric or caprylic acid, furthermore natural
  • Oils such as 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 low C-alkanoic acids 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 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 3 to 30 carbon 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
  • the oil phase can advantageously be chosen 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 saturated and / or unsaturated glycerol esters, 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. Olive oil, sunflower oil, soybean oil, peanut oil, rapeseed oil, almond oil, palm oil, coconut oil,
  • 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 oil phase selected from the group 2-ethylhexyl isostearate, octyldodecanol, isotridecyl isononanoate, isoeicosane, 2-ethyl hexylcocoat, C 12 -i 5 alkyl benzoate, caprylic-capric acid triglyceride, Dicap- rylether.
  • Particularly advantageous are mixtures of C 2 -is-alkyl benzoate and 2-ethylhexyl isostearate, mixtures of C 2-15 alkyl benzoate and isotridecyl isononanoate and mixtures of C 2 -i 5 alkyl benzoate, 2-ethylhexyl isostearate and isotridecyl isononanoate.
  • hydrocarbons paraffin oil, squalane and squalene are to be used advantageously in the context of the present invention.
  • the oil phase can also have a content of cyclic or linear silicone oils or consist entirely of such oils, although it is preferred to use an additional content of other oil phase components in addition to the silicone oil or silicone oils.
  • cyclomethicone octamethylcyclotetrasiloxane
  • other silicone oils are also advantageous for the purposes of the present invention, for example hexamethylcyclotrisiloxane, polydimethylsiloxane, poly (methylphenylsiloxane).
  • mixtures of cyclomethicone and Iso tridecylisononanoat from cyclomethicone and 2-Ethylhexylisostearat.
  • the aqueous phase of the preparations according to the invention may advantageously contain 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 - Glykolmonomethyl- or monoethyl ether and analogous products, further
  • 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 - Glykolmonomethyl- or monoethyl ether and analogous products, further
  • Low C-number alcohols e.g. As ethanol, 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 of the invention are advantageous and contain z.
  • the preparations according to the invention contain hydrophilic surfactants.
  • the hydrophilic surfactants are preferably selected from the group of alkylglucosides, acyl lactylates, betaines and cocoamphoacetates.
  • alkylglucosides in turn are advantageously selected from the group of alkylglucosides, which are represented by the structural formula
  • R represents a branched or unbranched alkyl radical having 4 to 24 carbon atoms and wherein DP means a mean Glucosyl michsgrad of up to 2.
  • the value DP represents the degree of glucosidation of the alkylglucosides used in the invention and is defined as
  • pi, p 2 , p ⁇ ... Or p 1 represent the proportion of products which are mono-, di-trisubstituted ... times glucosylated in percent by weight.
  • Products having degrees of glucosylation of 1-2, in particular advantageously 1, 1, are advantageous according to the invention to 1, 5, very particularly advantageous from 1, 2-1, 4, in particular selected from 1, 3.
  • the value of DP takes into account the fact that alkylglucosides usually mixtures of mono- and Oligoglucosiden represent.
  • Advantageously in accordance with the invention is a relatively high content of monoglucosides, typically of the order of 40-70% by weight.
  • Alkylglylcosides used particularly advantageously according to the invention are selected from the group octylglucopyranoside, nonylglucopyranoside, decylglucopyranoside, undecylglucopyranoside, dodecylglucopyranoside, tetradecylglucopyranoside and hexadecylglucopyranoside.
  • R 1 is a branched or unbranched alkyl radical having 1 to 30 carbon atoms and M + is selected from the group of the alkali metal ions and the group of ammonium ions substituted by one or more alkyl and / or by one or more hydroxyalkyl radicals or half Equivalent of an alkaline earth metal ion corresponds.
  • sodium is advantageous, for example the product Pathionic ® ISL from the American Ingredients Company.
  • R is a branched or unbranched alkyl radical having 1 to 30 carbon atoms.
  • R 2 is a branched or unbranched alkyl radical having 6 to 12 carbon atoms.
  • Capramidopropylbetaine for example, is advantageous
  • sodium elected cocoamphoacetate invention beneficial as under the name Miranol ® Ultra C32 from Miranol Chemical Corp. is available.
  • the preparations according to the invention are advantageously characterized in that the hydrophilic surfactant or surfactants in concentrations of 0.01-20 wt .-%, preferably 0.05-10 wt .-%, particularly preferably 0.1-5 wt .-%, respectively based on the total weight of the composition, is present or present.
  • the cosmetic and dermatological preparations according to the invention are applied to the skin and / or the hair in a sufficient amount in the manner customary for cosmetics.
  • Cosmetic and / or dermatological preparations according to the invention can be present in various forms. So they can z.
  • Oil-in-water (W / O / W) Oil-in-water (W / O / W), a gel, a solid stick, an ointment or even an aerosol.
  • ectoine in encapsulated form, z.
  • 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-OS 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 further customary co-emulsifiers in the preferred O / W emulsions according to the invention.
  • suitable co-emulsifiers are, for example, O / W emulsifiers, primarily 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 W emulsifiers have saturated radicals R and R '. If the O / W emulsifiers have unsaturated radicals R and / or R 1 , or if isoalkyl derivatives are present, the preferred HLB value of such emulsifiers may also be lower or higher.
  • fatty alcohol ethoxylates from the group of ethoxylated stearyl alcohols, cetyl alcohols, cetylstearyl alcohols (cetearyl alcohols). Particularly preferred are: polyethylene glycol (13) stearyl ether (steareth-13), polyethylene glycol (14) stearyl ether
  • Step-14 polyethylene glycol (15) stearyl ether (steareth-15),
  • isosteareth-12 polyethylene glycol (13) isostearyl ether (isosteareth-13), polyethylene glycol (14) isostearyl ether (isosteareth-14), polyethylene glycol (15) isostearyl ether (isosteareth-15), polyethylene glycol (16) - isostearyl ether (isosteareth- 16), polyethylene glycol (17) isostearyl ether (isosteareth-17), polyethylene glycol (18) isostearyl ether (isosteareth-18),
  • cetyl stearyl ether (Ceteareth-18), polyethylene glycol (19) cetyl stearyl ether (Ceteareth-19), polyethylene glycol (20) cetyl stearyl ether (Ceteareth-20).
  • Polyethylene glycol (14) isostearate, polyethylene glycol (15) isostearate, polyethylene glycol (16) isostearate, polyethylene glycol (17) isostearate, polyethylene glycol (18) isostearate, polyethylene glycol (19) isostearate, polyethylene glycol (20) isostearate, polyethylene glycol (21) isostearate, polyethylene glycol ( 22) isostearate, polyethylene glycol (23) isostearate,
  • Polyethylene glycol (24) isostearate, polyethylene glycol (25) isostearate, Polyethylene glycol (12) oleate, polyethylene glycol (13) oleate, polyethylene glycol (14) oleate, polyethylene glycol (15) oleate, polyethylene glycol (16) oleate, polyethylene glycol (17) oleate, polyethylene glycol (18) oleate, polyethylene glycol (19) oleate, polyethylene glycol (20) oleate,
  • the sodium laureth-11-carboxylate can be advantageously used.
  • the alkyl ether sulfate sodium laureth sulfate can be advantageously used.
  • polyethylene glycol (30) cholesteryl ether can be advantageously used.
  • polyethylene glycol (25) soybean oil has been proven.
  • polyethylene glycol glycerol fatty acid esters from the group consisting of polyethylene glycol (20) glyceryl laurate, polyethylene glycol (21) glyceryl laurate, polyethylene glycol (22) glyceryl laurate, polyethylene glycol (23) glyceryl laurate, polyethylene glycol (6) glyceryl caprate / citrate, polyethylene glycol (20 ) glyceryl oleate, polyethylene glycol (20) glyceryl isostearate, polyethylene glycol (18) glyceryl oleate (cocoate).
  • polyethylene glycol (20) glyceryl laurate polyethylene glycol (21) glyceryl laurate
  • polyethylene glycol (22) glyceryl laurate polyethylene glycol (23) glyceryl laurate
  • polyethylene glycol (6) glyceryl caprate / citrate polyethylene glycol (20 ) glyceryl oleate
  • 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, propylene glycol monolaurate, sorbitan monoisostearate, sorbitan monolaurate,
  • Preparations preferred according to the invention are particularly 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, as solid pins or present as
  • 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 as solid pins or present as
  • Aerosol be made up.
  • the preparation may contain cosmetic adjuvants which are commonly used in this type of preparations, such as thickeners, emollients, humectants, surfactants, emulsifiers, preservatives, antifoaming agents Foaming, perfumes, waxes, lanolin, propellants, dyes and / or pigments which color the agent itself or the skin, and other ingredients commonly used in cosmetics.
  • cosmetic adjuvants which are commonly used in this type of preparations, such as thickeners, emollients, humectants, surfactants, emulsifiers, preservatives, antifoaming agents Foaming, perfumes, waxes, lanolin, propellants, dyes and / or pigments which color the agent itself or 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 except the or the compounds of formula Ia-c, their salts or mixtures of these compounds, for example fatty alcohols, fatty acids, fatty acid esters, especially 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 glycerol, and oils, waxes and fatty acid esters, such as triglycerides of fatty acids.
  • the preparation according to the invention may also be in the form of an alcoholic gel which comprises one or more lower alcohols or polyols, such as ethanol, propylene glycol or glycerol, and a thickening agent, 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. If a preparation is formulated as an aerosol, the customary propellants, such as alkanes, fluoroalkanes and chlorofluoroalkanes, are generally used.
  • the cosmetic preparation may also be used to protect the hair against photochemical damage to prevent changes in hues, discoloration or damage of a mechanical nature.
  • it is suitably carried out as a shampoo, lotion, gel or emulsion for rinsing, wherein the respective preparation before or after shampooing, before or after the
  • the composition with photoprotective properties may contain various adjuvants used in this middle type, such as active agents, thickeners, polymers, emollients, preservatives, foam stabilizers, electrolytes, organic solvents,
  • Silicone derivatives, oils, waxes, anti-fatting agents, dyes and / or pigments which dye the agent itself or the hair or other ingredients commonly used for hair care.
  • Preparation of a preparation which is characterized in that at least one compound of the formula Ia-c, a salt or a mixture of these compounds, is mixed with a cosmetically, pharmaceutically or dermatologically or food-suitable carrier, and the use of a compound of the formula Ia -c, a salt or a mixture of these compounds, for the preparation of a preparation with antioxidant properties.
  • the preparations according to the invention can be prepared using techniques which are well known to the person skilled in the art.
  • the mixing may result in dissolution, emulsification or dispersion of the compounds described in the carrier.
  • compositions or preparations may comprise or contain, consist essentially of or consist of the stated necessary or optional ingredients or restrictions.
  • the compounds of the formula Ia-c or the mixture described above are prepared in a process in which 7,8-dihydroxyflavone is used as
  • the preparation is carried out by esterification of said 7,8-dihydroxyflavone with sulfur trioxide, in particular with sulfur trioxide-pyridine complex under slightly alkaline conditions.
  • the lithium compound is selected from inorganic lithium compounds because they are inexpensive and readily available in large quantities. Furthermore, they offer the advantage that they are little or not at all soluble in organic solvents, so that they can easily be filtered out of the reaction mixture after a metallization reaction conducted under heterogeneous conditions if they are used in excess.
  • the ratio of lithium compound to the functional groups of the 2-hydroxyacetophenone compound to be metallized is exactly one. This ensures that no possibly dissolved lithium compounds occur as impurities in the final product, since these can usually not be removed by purification steps, such as recrystallization from the intermediates and end products.
  • the metallation is carried out in an ethereal solvent, since this the metallation reaction by its polarity Training of Li solvaten supported, whereby the basicity of the lithium base is increased.
  • the 2-hydroxyacetophenone used in the process according to the invention preferably has the following structure:
  • R 1 and R 2 independently of one another, represent hydroxyl or sulfate groups or represent groups which undergo chemical modifications, such as cleavage of
  • the keto compound for carrying out the process according to the invention preferably has the following structure:
  • R y is a halide, alkoxyl or ester group.
  • the hydroxyl groups of the 2-hydroxyacetophenone compound are unprotected. This will be elaborate reactions to
  • the compound is an acid chloride, an alkoxyl group, ie the compound is an ester, or an ester group, ie the compound is an acid anhydride.
  • the reaction time when using an acid chloride or an acid anhydride is between 2-6 hours, most often between 4-5 hours.
  • the reaction time is more than 8 hours, usually more than 10, but often also about 16-20 hours.
  • the 2-hydroxyacetophenone compound is preferably with the ketone and a lithium compound in dry THF at low temperatures condensed (-78 0 C to -50 0 C), and produces a stable diketone intermediate.
  • the reaction is either no longer or too fast, ie with unwanted by-products or decomposition of the starting material, so that the range of -78 ° C to -50 0 C is preferred.
  • the diketone is subsequently cyclized under acidic conditions at 95-100 0 C, to give a flavone derivative.
  • lithium bases which are used in a process according to the invention, the lithium bases listed below are particularly suitable:
  • LiOCR CR ' 2 , where R and R ' is an aliphatic or aromatic radical, LiOSi (CH 3 ) 3 , Li (Si (CH 3 ) 3 ) 2 , Li 2 CO 3 , lithium 2,2,6,6 tetramethylpiperidine (LiTMP).
  • an ethereal solvent such as diethyl ether, tetrahydrofuran (THF) or dibutyl ether is preferably used as described above.
  • other polar solvents such as methyl ethyl ketone and the like can also be used, but also depending on the hydroxyacetophenone used apolar solvent such as n-hexane, heptane, benzene, toluene, etc.
  • the invention therefore provides a process for the preparation of the compounds of formula Ia-c or of a mixture, characterized in that a 2-hydroxyacetophenone
  • R 1 and R 2 independently of one another represent hydroxyl or sulfate groups or represent groups which can be converted into groups with the abovementioned meanings by chemical modifications, such as, for example, removal of protective groups, oxidation or reduction, with a keto compound
  • R y is a halide, alkoxyl or ester group, in the presence of a lithium compound, as described above, is reacted, the resulting diketone intermediate is cyclized under acidic conditions, if necessary, the radicals R 1 and R 2 in sulfate Groups are converted, the mixture of the compounds of the formula Ia, Ib or Ic is optionally separated and, if appropriate, the compounds of the formula Ia, Ib or Ic or a mixture thereof are converted into the corresponding salts.
  • the compounds of formula Ia-c can be reacted with bases (e.g., sodium or
  • Potassium hydroxide or carbonate into the corresponding metal, in particular alkali metal or alkaline earth metal or in the corresponding ammonium salts.
  • Salts or mixtures of these compounds stabilizing effect on preparations. When used in corresponding products, they therefore remain stable for longer and do not change their appearance. In particular, even with prolonged use or prolonged storage, the effectiveness of the ingredients, e.g.
  • Vitamins, dyes, fragrances or flavorings are particularly advantageous in compositions for protecting the skin against the action of UV rays, since these cosmetics are exposed to particularly high levels of exposure to UV radiation.
  • the foods which can be enriched according to the present invention with one or more compounds of the formula Ia-c, their salts or mixtures of these compounds all include
  • the foods may be solid or liquid, that is, in the form of beverages Accordingly, the use of a compound of formula Ia-c, their salts or mixtures of these compounds as a food additive for human or animal nutrition and preparations containing food or dietary supplements and containing appropriate carriers.
  • Foodstuffs which can be enriched according to the present invention with one or more compounds of the formula I-C, their salts or mixtures of these compounds are, for example, also foodstuffs originating from a single natural source, e.g. Sugar, unsweetened juice, nectar or puree from a single natural source, e.g. Sugar, unsweetened juice, nectar or puree from a single natural source, e.g. Sugar, unsweetened juice, nectar or puree from a single
  • Plant species such as unsweetened apple juice (eg also a mixture of different types of apple juice), grapefruit juice, orange juice, apple compote, apricot nectar, tomato juice, tomato sauce, tomato puree, etc.
  • Further examples of foods which according to the present invention are mixed with one or more compounds of the formula c, whose salts or mixtures of these compounds can be enriched are grains or cereals of a single plant species and materials made from such plant species, such as corn syrup, rye flour, wheat flour or oat bran.
  • mixtures of such foods are suitable for use in the present invention with one or more compounds of the formula la-c, their salts or mixtures of these compounds to be enriched, for example, multi-vitamin preparations, mineral mixtures or sweetened juice.
  • foods which can be enriched according to the present invention with one or more compounds of formula Ia-c, their salts or mixtures of these compounds, are food preparations, such as prepared cereals, biscuits, mixed drinks, foods specially prepared for children, yoghurt , Diet foods, low calorie foods or animal foods, called.
  • the foods that can be enriched according to the present invention with one or more compounds of formula Ia-c, their salts or mixtures of these compounds thus include all edible combinations of carbohydrates, lipids, proteins, inorganic elements, trace elements, vitamins, water or active metabolites of plants and animals.
  • the foods which can be fortified according to the present invention with one or more compounds of formula Ia-c, their salts or mixtures of these compounds, are preferably administered orally, e.g. in the form of food, pills, tablets, capsules, powders, syrups, solutions or suspensions.
  • Foodstuffs can be prepared by techniques well known to those skilled in the art.
  • Salts or mixtures of these compounds can be partially compared in their effect with radical scavengers such as vitamin C.
  • Compounds of the formula Ia-c, their salts or mixtures of these Compounds may be used, for example, for the preventive treatment of inflammation and allergies of the skin and, in certain cases, for the prevention of certain cancers.
  • compounds of the formula Ia-c, their salts or mixtures of these compounds are suitable for the preparation of a medicament for the treatment of inflammations, allergies and irritations, in particular of the skin.
  • drugs can be produced in an action as a vein tonic, as an agent for increasing the strength of blood capillaries, as an inhibitor of cuperose, as an inhibitor of chemical, physical or actinic erythema, as a treatment agent for sensitive skin, as a decongestant, as a dehydrating agent, as a means for Slimming, as anti-wrinkle agents, as stimulators of the synthesis of extracellular matrix components, as a tonicityener to improve skin elasticity and as an acidulant.
  • compounds of the formula Ia-c, their salts or mixtures of these compounds show antiallergic and antiinflammatory and anti-irritant effects. They are therefore suitable for the preparation of medicaments for the treatment of inflammation or allergic reactions.
  • the separation of the individual sulfates can be carried out with a Büchi Sepacore (UV-Photometer C-635, Fraction collector C-660, Pump C-605, Pump manager
  • UV-Pearl, OMC stands for the preparation with the INCI name: Water (for EU: Aqua), Ethylhexyl Methoxycinnamate, Silica, PVP, Chlorphenesin, BHT; this preparation is commercially available under the INCI name: Water (for EU: Aqua), Ethylhexyl Methoxycinnamate, Silica, PVP, Chlorphenesin, BHT; this preparation is commercially available under the
  • UV-Pearls listed in the tables are each assembled analogously, with OMC being replaced by the specified UV filters.

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Abstract

La présente invention concerne une nouvelle flavone, caractérisée en ce qu'il s'agit d'un dérivé de 7,8-dihydroxyflavone selon la formule Ia ou Ib ou un de ses sels, des préparations et des mélanges contenant ladite flavone, leur fabrication et leur utilisation.
PCT/EP2006/010284 2005-11-18 2006-10-25 Sulfate de flavone et son utilisation en tant qu’antioxydant WO2007057091A1 (fr)

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EP06818285A EP1948632A1 (fr) 2005-11-18 2006-10-25 Sulfate de flavone et son utilisation en tant qu antioxydant

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DE102005055577A DE102005055577A1 (de) 2005-11-18 2005-11-18 Flavone
DE102005055577.2 2005-11-18

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Cited By (1)

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Publication number Priority date Publication date Assignee Title
CN117656630A (zh) * 2024-02-01 2024-03-08 广东骊虹新材料有限公司 一种高强度多层复合包装膜材料及其制备方法

Citations (1)

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Publication number Priority date Publication date Assignee Title
WO2005054222A2 (fr) * 2003-12-05 2005-06-16 Merck Patent Gmbh Derive de flavonoide

Patent Citations (1)

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Publication number Priority date Publication date Assignee Title
WO2005054222A2 (fr) * 2003-12-05 2005-06-16 Merck Patent Gmbh Derive de flavonoide

Non-Patent Citations (4)

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Title
FOTI M ET AL: "Flavanoids, coumarins, and cinnamic acids as antioxidants in a micellar system. Structure-activity relationship", JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, vol. 44, no. 2, 1 February 1996 (1996-02-01), pages 497 - 501, XP000551096 *
LEMANSKA K ET AL: "Effect of substitution pattern on TEAC antioxidant activity of mono- and dihydroxyflavones", CURRENT TOPICS IN BIOPHYSICS, vol. 24, no. 2, 2000, pages 101 - 108, XP009021750 *
NARASIMHACHARI N ET AL: "Nuclear oxidation in the flavone series. Part VIII. 7:8-Dihydroxy-flavone and -flavonol", PROCEEDINGS OF THE INDIAN ACADEMY OF SCIENCES, SECTION A, vol. 27, 1948, pages 37 - 43, XP008073395 *
YAGI A ET AL: "Antioxidative sulphated flavanoids in leaves of Polygonum hydropiper", PHYTOCHEMISTRY, vol. 35, no. 4, 1994, pages 885 - 887, XP002412990 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN117656630A (zh) * 2024-02-01 2024-03-08 广东骊虹新材料有限公司 一种高强度多层复合包装膜材料及其制备方法
CN117656630B (zh) * 2024-02-01 2024-04-16 广东骊虹新材料有限公司 一种高强度多层复合包装膜材料及其制备方法

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