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WO2000026399A2 - Procede de production de derives de quercetine et d'isoquercetine - Google Patents

Procede de production de derives de quercetine et d'isoquercetine Download PDF

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Publication number
WO2000026399A2
WO2000026399A2 PCT/EP1999/007685 EP9907685W WO0026399A2 WO 2000026399 A2 WO2000026399 A2 WO 2000026399A2 EP 9907685 W EP9907685 W EP 9907685W WO 0026399 A2 WO0026399 A2 WO 0026399A2
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WO
WIPO (PCT)
Prior art keywords
formula
compounds
reaction
derivatives
cosmetic
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/EP1999/007685
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German (de)
English (en)
Other versions
WO2000026399A3 (fr
Inventor
Herwig Buchholz
Ralf Rosskopf
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Merck Patent GmbH
Original Assignee
Merck Patent GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from DE19850282A external-priority patent/DE19850282A1/de
Priority claimed from DE19850570A external-priority patent/DE19850570A1/de
Priority to CA002348728A priority Critical patent/CA2348728A1/fr
Application filed by Merck Patent GmbH filed Critical Merck Patent GmbH
Priority to EP99953802A priority patent/EP1124980A2/fr
Priority to BR9914811-0A priority patent/BR9914811A/pt
Priority to AU10366/00A priority patent/AU1036600A/en
Priority to JP2000579771A priority patent/JP2002528132A/ja
Priority to KR1020017005369A priority patent/KR20010080347A/ko
Publication of WO2000026399A2 publication Critical patent/WO2000026399A2/fr
Publication of WO2000026399A3 publication Critical patent/WO2000026399A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P19/00—Preparation of compounds containing saccharide radicals
    • C12P19/44—Preparation of O-glycosides, e.g. glucosides
    • C12P19/60—Preparation of O-glycosides, e.g. glucosides having an oxygen of the saccharide radical directly bound to a non-saccharide heterocyclic ring or a condensed ring system containing a non-saccharide heterocyclic ring, e.g. coumermycin, novobiocin
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • 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
    • 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
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/08—Antiepileptics; Anticonvulsants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A61P39/06—Free radical scavengers or antioxidants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
    • C07H15/26—Acyclic or carbocyclic radicals, substituted by hetero rings
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
    • C12P17/02—Oxygen as only ring hetero atoms
    • C12P17/06—Oxygen as only ring hetero atoms containing a six-membered hetero ring, e.g. fluorescein
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the invention relates to a process for the preparation of compounds of the formula I.
  • tet referred to as isoquercetin derivatives.
  • the compounds of the formula II are referred to as rutin derivatives.
  • the compounds of formula I have one or more advantageous properties, e.g. antioxidative, cardiovascular, antiviral, prostaglandin metabolism influencing and / or spasmolytic properties. In mixtures with other flavonoids, they also have synergistic, for example purgative, properties.
  • the quercetin and isoquercetin derivatives of the formula I have better water solubility than quercetin and isoquercetin themselves. In addition, they are less colored and therefore more suitable for use in cosmetics. They are also advantageously suitable for use in the food sector.
  • R 1 can be prepared from a single starting compound.
  • the present invention further relates to foods which have been enriched with one or more compounds of the formula I and to the use of the compounds of the formula I as a dietary supplement.
  • the foodstuffs which can be enriched with one or more compounds of the formula I according to the present invention include all materials which are suitable for consumption by animals or for the
  • Foods that can be fortified with one or more compounds of Formula I according to the present invention are, for example, foods that come from a single natural source, such as sugar, unsweetened juice, nectar or puree from a single plant species, such as unsweetened Apple juice (eg a mixture of different types of apple juice), grapefruit juice, orange juice, apple compote, apricot nectar, tomato juice, tomato sauce, tomato puree, etc. More examples of foods that according to the present invention can be enriched with one or more compounds of the formula I are grain or cereals of a single plant species and materials which are produced from such plant species, such as, for example, cereal syrup, rye flour,
  • Foodstuffs are suitable for being enriched according to the present invention with one or more compounds of the formula I, for example multi-vitamin preparations, mineral mixtures or sugared juice.
  • Further examples of foods which can be enriched according to the present invention with one or more compounds of the formula I include food preparations, for example prepared cereals, pastries, mixed drinks, foods specially prepared for children such as yoghurt, diet foods, low-calorie foods or animal feed.
  • the foods which can be enriched with one or more compounds of the formula I according to the present invention thus comprise all edible combinations of carbohydrates, lipids, proteins, inorganic elements, trace elements, vitamins, water and active metabolites of plants and animals.
  • the foodstuffs which can be enriched with one or more compounds of the formula I according to the present invention and the food supplements which contain one or more compounds of the formula I are preferably administered orally, e.g. in the form of food, pills, tablets, capsules, powders, syrups, solutions or suspensions.
  • the foods of the invention enriched with one or more compounds of formula I can be prepared using techniques that are well known to those skilled in the art.
  • the invention further relates to cosmetic or pharmaceutical
  • Formula I in cosmetic or pharmaceutical formulations.
  • the cosmetic formulations which contain one or more compounds of the formula I and the use of one or more
  • the skin is sensitive to the sun's rays, which can cause normal sunburn or erythema, but also more or less pronounced burns.
  • sun rays also have other negative effects: they cause the skin to lose its elasticity and wrinkles and thus lead to premature aging. Sometimes you can also see dermatoses, and in extreme cases skin cancer occurs.
  • the most dangerous part of the sun's rays is formed by the ultraviolet rays with a wavelength of less than 400 nm. It is also known that due to the presence of the ozone layer in the earth's atmosphere, which absorbs part of the sun's radiation, the lower limit of the ultraviolet rays that reach the earth's surface is approximately 280 nm.
  • Substance classes are, for example, organic or inorganic UVA and UVB filters, IR or VIS filters. The is particularly preferred
  • the invention therefore also relates to the use of one or more compounds of the formula I in cosmetic formulations, such as sunscreens, skin creams or gels, hair gels or cosmetic sticks, in particular as UV filters.
  • UVA and UVB filters known to the person skilled in the art are suitable as further suitable organic UV filters.
  • organic UV filters there are many substances that are known and proven from the specialist literature, e.g. Benzylidene camphor derivatives such as
  • 3- (4 ' -methylbenzylidene) dl-camphor e.g. Eusolex ® 6300
  • 3-benzylidene camphor e.g. Mexoryl ® SD
  • Methoxy cinnamic acid esters such as
  • Isopentyl 4-methoxycinnamate for example as a mixture of the isomers (for example Neo Heliopan ® E 1000),
  • Salicylate derivatives such as
  • organic UV filters are generally incorporated into cosmetic formulations in an amount of 0.5 to 10 percent by weight, preferably 1-8%.
  • organic UV filters are generally incorporated into cosmetic formulations in an amount of 0.5 to 20 percent by weight, preferably 1-15%.
  • inorganic UV filters those from the group of titanium dioxides such as coated titanium dioxide (eg Eusolex ® T-2000), zinc oxides (eg Sachtotec ® ), iron oxides or cerium oxides are also conceivable. These inorganic UV filters are generally incorporated into cosmetic formulations in an amount of 0.5 to 20 percent by weight, preferably 2 to 10%.
  • the compounds of the formula I act e.g. as an antioxidant and radical scavenger.
  • broad-spectrum UV protection is achieved with such formulations.
  • the invention thus also relates to the use of one or more compounds of the formula I in cosmetic or pharmaceutical formulations as a UV filter, antioxidant and / or radical scavenger.
  • the invention further relates to a method for protecting the skin and / or natural or sensitized hair from the sun's rays, a cosmetic preparation comprising one or more compounds of the formula I as a light protection filter being applied to the skin or the hair.
  • a cosmetic preparation comprising one or more compounds of the formula I as a light protection filter being applied to the skin or the hair.
  • the sunscreens according to the invention can also contain one or more chemical substances with self-tanning agents
  • formulations according to the invention can also be used for the preventive treatment of inflammation and allergies to the skin and, in certain cases, for the prevention of certain types of cancer.
  • the preparation according to the invention is used as an agent for protecting the human epidermis or the hair or else the sensitized hair or as a sunscreen.
  • hair By “sensitized hair” is meant hair that has been subjected to a permanent wave treatment, a coloring or decolorization process.
  • the cosmetic preparation according to the invention is used to protect the human epidermis against solar radiation. It is available in various forms commonly used for this type. In particular, it can be in the form of a lotion or emulsion, such as a cream or milk (OW, W / O), in the form of oily-alcoholic, oily-aqueous or aqueous-alcoholic gels, or as solid sticks, or as an aerosol.
  • a lotion or emulsion such as a cream or milk (OW, W / O)
  • OW, W / O oily-alcoholic, oily-aqueous or aqueous-alcoholic gels, or as solid sticks, or as an aerosol.
  • the formulation may contain cosmetic adjuvants that are commonly used in this type of preparation, such as thickeners, plasticizers, wetting agents, surfactants, emulsifiers, preservatives, anti-foaming agents, perfumes, waxes, lanolin, blowing agents, dyes and / or pigments which color the agent itself or the skin, and other ingredients commonly used in cosmetics.
  • cosmetic adjuvants that are commonly used in this type of preparation, such as thickeners, plasticizers, wetting agents, surfactants, emulsifiers, preservatives, anti-foaming agents, perfumes, waxes, lanolin, blowing agents, dyes and / or pigments which color the agent itself or the skin, and other ingredients commonly used in cosmetics.
  • An oil, wax or other fatty substance, a low monoalcohol or a low polyol or mixtures thereof can be used as the dispersing or solubilizing agent.
  • the particularly preferred monoalcohols or polyols include ethanol, i-propanol,
  • a preferred embodiment of the invention is an emulsion which is present as a protective cream or milk and, in addition to the compound or compounds of the formula I as a UV filter - and, if appropriate, further light protection filters - fatty alcohols, fatty acids, fatty acid esters, in particular triglycerides of fatty acids, lanolin, natural or synthetic oils or waxes and emulsifiers in the presence of water.
  • the cosmetic preparation according to the invention can also be in the form of an alcoholic gel which contains one or more lower alcohols or polyols, such as ethanol, propylene glycol or glycerol
  • Thickeners 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 fat bodies.
  • a preparation is packaged as an aerosol, the usual propellants, such as alkanes, fluoroalkanes and chlorofluoroalkanes, are generally used.
  • the agent according to the invention is intended to protect natural or sensitized hair from the sun, it can be in the form of a shampoo, lotion, gel or emulsion for rinsing, the respective formulation before or after shampooing, before or after dyeing or decoloring, before or after the perm is applied; or the agent is in the form of a lotion or gel for styling and treatment, as a lotion or gel for brushing or laying a water wave, as a hair varnish, permanent waving agent, dye or decolorizer for the hair.
  • this agent can contain various adjuvants used in this type of agent, such as surfactants, thickeners, polymers, plasticizers,
  • fragrances silicone derivatives, oils, waxes, anti-greasing agents, dyes and / or pigments that color the agent itself or the hair or other ingredients commonly used for hair care.
  • the cosmetic preparations according to the invention can be produced using techniques which are well known to the person skilled in the art.
  • the compounds of the formula I include those compounds
  • n *, n * and p * each independently represent 2 to 8.
  • the present invention also relates to these compounds of the formula I * .
  • the compounds of the formula I * are colorless.
  • m, n and p or m *, n * and p * are each independently 2, 3, 4, 5, 6, 7 or 8.
  • m, n and p or m are *, n * and p * each independently of the other 2, 3 or 4.
  • m, n and p or m *, n * and p * are particularly preferably the same, very particularly preferably m, n and p or m * , n * and p * 2.
  • Foodstuffs according to the invention which are enriched with one or more compounds of the formula I * and cosmetic formulations according to the invention which contain one or more compounds of the formula I * are particularly preferred. Accordingly, the use of one or more compounds of the formula I * as a dietary supplement or their use in cosmetic formulations, for example as a UV filter, is particularly preferred.
  • the present invention provides an advantageous process for the preparation of compounds of the formula I by enzymatic cleavage of compounds of the formula II which takes place in an aqueous medium.
  • the compounds of formula II are dissolved in water and contacted with a suitable amount of an enzyme.
  • the reaction is carried out with thorough mixing, e.g. by stirring.
  • Both the quercetin derivatives of the formula I and the isoquercetin derivatives of the formula I can be prepared by the process according to the invention.
  • essentially only the quercetin derivatives of the formula I or essentially only the isoquercetin derivatives of the formula I are prepared by the process according to the invention.
  • Suitable enzymes for the process according to the invention are hydrolases. Hydrolases obtained from the Penicillium decumbens strain are preferably used, in particular the enzymes naringinase and hesperidinase. The enzyme naringinase is very particularly preferred.
  • the starting materials and the enzymes for the process according to the invention are commercially available or can be prepared using methods which are well known to the person skilled in the art and are described in the literature (for example in standard works such as Houben-Weyl, Methods of Organic Chemistry, Georg-Thieme-Verlag, Stuttgart), won or manufactured.
  • Suitable reaction temperatures for the process according to the invention are temperatures between 15 and 80 ° C.
  • the process according to the invention is preferably carried out at reaction temperatures of 30 to 50 ° C., in particular at reaction temperatures of 35 to 45 ° C.
  • reaction temperature is too low, the reaction proceeds at an inappropriately slow reaction rate. On the other hand, if the reaction temperature is too high, the enzyme, which is a protein, is denatured and thus deactivated.
  • Suitable pH values for the method according to the invention are pH values between 3 and 8.
  • the method according to the invention is preferably carried out at pH values from 4.5 to 7, in particular at pH values from 4.8 to 6.8.
  • further preferred pH values can vary within the given limits, depending on the enzyme used.
  • pH values of 6.4 to 6.8 are extremely preferred when using the enzyme naringinase.
  • the method is preferably carried out in such a way that the pH is adjusted using a buffer system. In principle, all common buffer systems that are suitable for setting the above-mentioned pH values can be used. However, preference is given to aqueous
  • Suitable weight ratios of starting material: water for the process according to the invention are ratios from 0.001: 99.999 to 40:60.
  • the process according to the invention is preferably carried out with weight ratios of starting material: water from 0.005: 99.995 to 20:80, in particular with weight ratios of 0.5: 99, 5 to 10: 90.
  • Processes are ratios from 0.005: 99.995 to 50:50.
  • the process according to the invention is preferably carried out with weight ratios of enzyme:
  • the process according to the invention is carried out, for example, in such a way that the reaction when the enzyme naringinase is used preferably takes place at a temperature of 35 to 45 ° C. and a pH of 4.8 to 6.8 and after about 12 to 18 hours.
  • the reaction is preferably continuously checked analytically.
  • the formation or production of the quercetin derivatives of the formula I can be achieved, for example, by suitably extending the reaction time.
  • the progress or the end of the reaction and the analysis of the reaction products can be carried out, for example, by means of HPLC, for example using standard HPLC devices and columns containing reversed-phase materials with C 18 alkyl coating.
  • the progress or the end of the reaction can also be checked by means of thin layer chromatography (TLC).
  • reaction mixture consists mainly of water, buffer, enzyme, small amounts of unreacted
  • the quercetin and / or isoquercetin derivatives of the formula I are isolated by customary methods. Under
  • customary workup is understood to mean the following:
  • the reaction mixture is cooled, for example to a temperature of 0 ° C.
  • the quercetin and / or isoquercetin derivative of the formula I which crystallizes out is separated from the remaining reaction mixture, for example by suction or filtration under reduced pressure or by centrifuging off the precipitated crystals.
  • the solid is then washed, preferably with water, and then dried, e.g. at a temperature of 50 ° C and a pressure of 200 mbar.
  • the substances remaining in the filtrate can be separated off by known methods, for example by ultrafiltration, by passing the filtrate over cations and / or
  • Anion exchangers by crystallization and by mechanical Separation such as filtration. Any glucose present in the filtrate can also be separated, for example, by yeast fermentation.
  • Enzyme can be recirculated and thus used for further reactions.
  • the sources of supply for the substances used are as follows:
  • HPLC HPLC conditions when using a standard HPLC system:
  • Sample preparation dissolve 5 mg of the sample in 3 ml of methanol and make up to 10 ml with the eluent
  • Trihydroxyethyl isoquercetin 11.4 min, trihydroxyethylquercetin: 42.7 min.
  • Th (hydroxyethyl) rutin 5 g are dissolved in 150 ml of deionized water and adjusted to a pH of 6.6 by adding 0.64 g of citric acid and 1.4 g of 32% strength aqueous sodium hydroxide solution. Then 0.5 g of naringinase is introduced and the reaction mixture is stirred at a reaction temperature of 40 ° C. for 16 h. After the usual work-up, 2.41 g of tri (hydroxyethyl) isoquercetin are obtained in a purity of 96%.

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Abstract

L'invention concerne un procédé de production de composés de la formule (I), dans laquelle m, n, p et R1 correspondent à la définition donnée dans la revendication 1. Ces composés peuvent être, de façon avantageuse, utilisés en tant que complément alimentaire. Ils peuvent en outre, de façon remarquable, être utilisés dans des compositions cosmétiques, par exemple en tant que filtre anti-UV.
PCT/EP1999/007685 1998-10-30 1999-10-13 Procede de production de derives de quercetine et d'isoquercetine Ceased WO2000026399A2 (fr)

Priority Applications (6)

Application Number Priority Date Filing Date Title
KR1020017005369A KR20010080347A (ko) 1998-10-30 1999-10-13 퀘르세틴 및 이소퀘르세틴 유도체의 제조방법
JP2000579771A JP2002528132A (ja) 1998-10-30 1999-10-13 クエルセチン及びイソクエルセチン誘導体の製造方法
CA002348728A CA2348728A1 (fr) 1998-10-30 1999-10-13 Procede de production de derives de quercetine et d'isoquercetine
EP99953802A EP1124980A2 (fr) 1998-10-30 1999-10-13 Procede de production de derives de quercetine et d'isoquercetine
BR9914811-0A BR9914811A (pt) 1998-10-30 1999-10-13 Processo para a preparação de derivados de quercetina e isoquercetina
AU10366/00A AU1036600A (en) 1998-10-30 1999-10-13 Method for the production of quercetin and isoquercetin derivatives

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
DE19850282.6 1998-10-30
DE19850282A DE19850282A1 (de) 1998-10-30 1998-10-30 Verfahren zur Herstellung von Quercetin und Isoquercetin-Derivaten
DE19850570.1 1998-11-02
DE19850570A DE19850570A1 (de) 1998-11-02 1998-11-02 Verfahren zur Herstellung von Quercetin- und Isoquercetin-Derivaten

Publications (2)

Publication Number Publication Date
WO2000026399A2 true WO2000026399A2 (fr) 2000-05-11
WO2000026399A3 WO2000026399A3 (fr) 2000-08-10

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PCT/EP1999/007685 Ceased WO2000026399A2 (fr) 1998-10-30 1999-10-13 Procede de production de derives de quercetine et d'isoquercetine

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EP (1) EP1124980A2 (fr)
JP (1) JP2002528132A (fr)
KR (1) KR20010080347A (fr)
CN (1) CN1325452A (fr)
AU (1) AU1036600A (fr)
BR (1) BR9914811A (fr)
CA (1) CA2348728A1 (fr)
WO (1) WO2000026399A2 (fr)

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000076992A1 (fr) * 1999-06-16 2000-12-21 Merck Patent Gmbh Obtention d'isoquercetine a partir de pates bioflavonoidiques
EP1127572A3 (fr) * 2000-02-25 2003-05-02 Basf Aktiengesellschaft Utilisation de flavones dans le traitement de maladies induites par cyclooxygenase-2
EP1055413A3 (fr) * 1999-05-22 2003-06-11 Beiersdorf Aktiengesellschaft Combinations de filtres photoprotecteurs sulfonés et de dérivés de la flavone et/ou de la flavanone, en particulier de flavonoides, et compositions cosmétiques les contenant
EP1055412A3 (fr) * 1999-05-22 2003-06-18 Beiersdorf Aktiengesellschaft Compositions photoprotectrices cosmétiques et/ou dermatologiques contenant des dérivés de la flavone et/ou de la flavanone, en particulier des flavonoides et du benzotriazol
EP1055411A3 (fr) * 1999-05-22 2003-06-18 Beiersdorf Aktiengesellschaft Compositions photoprotectrices cosmétiques ou dermatologiques contenant des dérivés de la flavone et/ou de la flavanone, en particulier des flavonoides et de la s-triazine
JP2004051637A (ja) * 2002-07-18 2004-02-19 Merck Patent Gmbh 光防御剤
WO2006105843A3 (fr) * 2005-04-05 2007-03-29 Merck Patent Gmbh Procede pour la dissociation de rutinosides
US10639294B2 (en) 2018-10-02 2020-05-05 Janssen Pharmaceutica Nv Pharmaceutical compositions comprising a hydroxyethylquercetin glucuronide metabolite
US11304968B2 (en) 2018-11-16 2022-04-19 Janssen Pharmaceutica Nv Pharmaceutical compositions comprising a hydroxyethylquercetin glucuronide

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CN101985439B (zh) * 2010-11-18 2012-05-09 桂林市三棱生物制品有限公司 从毛冬青地上部分分离提取98%槲皮素的工艺
JP2016013075A (ja) * 2014-07-01 2016-01-28 イビデン株式会社 ケルセチン含有抽出物
CN105412074A (zh) * 2015-12-24 2016-03-23 厦门大学 槲皮素在制备预防及治疗与ApoE蛋白水平有关疾病的药物中的应用

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FR5072M (fr) * 1965-10-25 1967-05-16
US4603046A (en) * 1985-08-23 1986-07-29 Charles Of The Ritz Group Ltd. Improved sunscreen or sunblock composition
JPH01308476A (ja) * 1988-06-06 1989-12-13 Showa Denko Kk 紫外線吸収剤
JPH03255013A (ja) * 1990-03-01 1991-11-13 San Ei Chem Ind Ltd 化粧料
JP3477628B2 (ja) * 1995-06-19 2003-12-10 アサヒビール株式会社 ホップ苞より得られるポリフェノール製剤とその製造法

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1055413A3 (fr) * 1999-05-22 2003-06-11 Beiersdorf Aktiengesellschaft Combinations de filtres photoprotecteurs sulfonés et de dérivés de la flavone et/ou de la flavanone, en particulier de flavonoides, et compositions cosmétiques les contenant
EP1055412A3 (fr) * 1999-05-22 2003-06-18 Beiersdorf Aktiengesellschaft Compositions photoprotectrices cosmétiques et/ou dermatologiques contenant des dérivés de la flavone et/ou de la flavanone, en particulier des flavonoides et du benzotriazol
EP1055411A3 (fr) * 1999-05-22 2003-06-18 Beiersdorf Aktiengesellschaft Compositions photoprotectrices cosmétiques ou dermatologiques contenant des dérivés de la flavone et/ou de la flavanone, en particulier des flavonoides et de la s-triazine
WO2000076992A1 (fr) * 1999-06-16 2000-12-21 Merck Patent Gmbh Obtention d'isoquercetine a partir de pates bioflavonoidiques
US6683164B1 (en) 1999-06-16 2004-01-27 Merck Patent Gmbh Recovery of isoquercetin from bioflavanoid pastes
EP1127572A3 (fr) * 2000-02-25 2003-05-02 Basf Aktiengesellschaft Utilisation de flavones dans le traitement de maladies induites par cyclooxygenase-2
JP2004051637A (ja) * 2002-07-18 2004-02-19 Merck Patent Gmbh 光防御剤
WO2006105843A3 (fr) * 2005-04-05 2007-03-29 Merck Patent Gmbh Procede pour la dissociation de rutinosides
US10639294B2 (en) 2018-10-02 2020-05-05 Janssen Pharmaceutica Nv Pharmaceutical compositions comprising a hydroxyethylquercetin glucuronide metabolite
US11304968B2 (en) 2018-11-16 2022-04-19 Janssen Pharmaceutica Nv Pharmaceutical compositions comprising a hydroxyethylquercetin glucuronide

Also Published As

Publication number Publication date
CN1325452A (zh) 2001-12-05
WO2000026399A3 (fr) 2000-08-10
KR20010080347A (ko) 2001-08-22
AU1036600A (en) 2000-05-22
EP1124980A2 (fr) 2001-08-22
BR9914811A (pt) 2001-07-03
JP2002528132A (ja) 2002-09-03
CA2348728A1 (fr) 2000-05-11

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