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WO2004078695A1 - Procede de purification de la crocetine - Google Patents

Procede de purification de la crocetine Download PDF

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Publication number
WO2004078695A1
WO2004078695A1 PCT/JP2004/002693 JP2004002693W WO2004078695A1 WO 2004078695 A1 WO2004078695 A1 WO 2004078695A1 JP 2004002693 W JP2004002693 W JP 2004002693W WO 2004078695 A1 WO2004078695 A1 WO 2004078695A1
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Prior art keywords
crocetin
solvent
purification
crocin
purified
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Ceased
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PCT/JP2004/002693
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English (en)
Inventor
Masahiro Takahashi
Koichi Harada
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Riken Vitamin Co Ltd
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Riken Vitamin Co Ltd
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Publication of WO2004078695A1 publication Critical patent/WO2004078695A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/42—Separation; Purification; Stabilisation; Use of additives
    • C07C51/43—Separation; Purification; Stabilisation; Use of additives by change of the physical state, e.g. crystallisation
    • 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
    • A23L5/00—Preparation or treatment of foods or foodstuffs, in general; Food or foodstuffs obtained thereby; Materials therefor
    • A23L5/40—Colouring or decolouring of foods
    • A23L5/42—Addition of dyes or pigments, e.g. in combination with optical brighteners
    • A23L5/43—Addition of dyes or pigments, e.g. in combination with optical brighteners using naturally occurring organic dyes or pigments, their artificial duplicates or their derivatives
    • A23L5/44—Addition of dyes or pigments, e.g. in combination with optical brighteners using naturally occurring organic dyes or pigments, their artificial duplicates or their derivatives using carotenoids or xanthophylls
    • 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
    • A61K8/36—Carboxylic acids; Salts or anhydrides thereof
    • A61K8/362—Polycarboxylic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • 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
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/42—Separation; Purification; Stabilisation; Use of additives
    • C07C51/47—Separation; Purification; Stabilisation; Use of additives by solid-liquid treatment; by chemisorption

Definitions

  • the present invention relates to a method for the purification of crocetin which is obtained by hydrolysis of crocin existing in a plant extract.
  • Crocin which is extracted from dried fruits of gardenia or fromdried saffron stigma, is digentiobiose ester of crocetin. Crocetin is obtained by hydrolyzing crocin with alkali, etc. to remove digentiobiose of crocin (c.f . , for example, non-patent literature 1 ) .
  • Crocin is water-soluble and used as a primary color component of gardenia yellow for coloring a wide range of foods in Japan.
  • crocetin is insoluble in water and soluble in diluted alkaline water, and thus it has been limitedly used as a coloring agent for Chinese noodle (c.f., for example, patent literature 2) or soft drinks (c.f., for example, patent literature 3), etc.
  • crocetin of high purity prepared not only byhydrolysis of crocin but alsobytheremoval of impurities forpurification is desired.
  • Patent literature 1 Japanese Unexamined Patent Publication No. H07-018194
  • Patent literature 2 Japanese Unexamined Patent Publication No. S54-064652
  • Patent literature 3 Japanese Unexamined Patent Publication No. H06-248193
  • Patent literature 4 Japanese Unexamined Patent Publication No. H05-320036
  • Patent literature 5 Japanese Unexamined Patent Publication No. H07-285846 (Patent literature 6) Japanese Unexamined Patent Publication No. Hll-246396
  • Non-patent literature 2 KON Masayo, "gardenia carotenoidpigment” , Bulletin of FukuokaWomen' s JuniorCollege, 1999, No. 57, p.31-34
  • Non-patent literature 3 KAMIKURAMieko, et al. , "Journal of the Food Hygienic Society of Japan", 1985, 26, No.2, p.151 (Non-patent literature 4) J.Agric.Food Chem. , 1996, 44, No.9, p.2613, left column, line46-61
  • Non-patent literature 5 SpectrochemicaActaPart A, 1998, 54, p.654, left column, lines 16-24 (Non-patent literature 6) J.Food Sci.Technol. , 2001, 38, No.4, p.325, left column, lines 36-42
  • An object of the present invention is to provide an easily operated, industrially advantageous method for the production of crocetin.
  • the present inventors had conducted intensive investigations to solve the above mentioned problems and, as a result, they have found that a desired crocetin of high purity canbe effectivelypreparedwhen crocetin containing impurities , which is obtained by hydrolysis of crocin existing in a plant extract, is treated with a specific organic solvent. Based on this finding, the present inventors have achieved the present invention.
  • the present invention relates to the following (1) to (9).
  • a method for the purification of crocetin which comprises the steps of (a) treating crocetin obtained by hydrolysis of crocin, which exists in a plant extract, with lower alcohol or a mixed solvent containing 50% by volume or more of lower alcohol; and (b) removing a soluble component in the solvent.
  • a method for the purification of crocetin which comprises the steps of (a) treating crocetin obtained by hydrolysis of crocin, which exists in a plant extract, with lower alcohol or a mixed solvent containing 50% by volume or more of lower alcohol to remove a soluble component in the solvent; and (b) crystallizing the above treated crocetin from an aprotic solvent which can crystallize crocetin.
  • a cosmetic product or pharmaceutical composition which comprises the purified crocetin described in the above
  • Crocin which is ayellow carotenoid pigment , is contained in dried fruits of gardenia (rubiaceae) (Gardenia augusta ERRIL var. grandiflora HORT., Gardenia jasminoides ELLIS) and dried saffron stigma, and the fruits of gardenia are preferably used as an industrial material to obtain crocin.
  • crocin is extracted frompulverized, driedfruits of gardeniawithwater or an alcohol or a mixture thereof .
  • water is pre erable as an extracting solvent, the extraction rate is low.
  • amixture ofwater andan alcohol is usedfor industrial purposes .
  • the alcohol include ethanol, methanol and the like, among which methanol is preferably used.
  • the preferable mixing ratio of an alcohol relative to the mixture of the alcohol and water is, for example, not less than 50% by volume.
  • the extract is collected all together and filtered through filter paper or filter cloth optionally using a filter aid such as diatomite .
  • the filtrate is concentrated to recover alcohol, whereby a concentrate can be obtained.
  • an iridoid glycoside such as geniposide, etc. from the extract of gardenia by absorbent resin treatment or membrane separation treatment, etc.
  • Absorbent resin treatment is carried out in such a manner that acolumnis filledwithaporous absorbent andthe concentrate which is diluted to the appropriate concentration is supplied to the column.
  • a pigment solution i.e. the above diluted concentrate containing crocin
  • impurities are washed out with water or a mixture of a dilute alcohol and water.
  • the pigments were desorbed i.e. eluted by 50 to 70 % by volume of alcohol and the eluted solution is concentrated to give a concentrate in which geniposide is significantly reduced.
  • Examples of the alcohol include a lower alcohol having 1 to 4 carbon atoms such as methanol, ethanol, propanol, isopropanol, n-butanol, i-butanol, sec-butanol, tert-butanol, etc., among which ethanol is preferably used.
  • Examples of the porous absorbent include Amberlite XAD-4, Jlmberlite XAD-7 (Trademark: Organo Corporation), Diaion HP-20, HP-21, HP-40 (Trademark: Mitsubishi Chemical Corporation), and the like.
  • Membrane separation treatment is carried out by, for example, pouring the concentrate which is diluted to the appropriate concentration onto ultrafiltration membrane modules with a molecular weight cutoff of 2,000 to 20,000. Impurities permeate the membrane together with water, and pigments including crocin are concentrated. These procedures are repeated, while supplying water, until the desired degree of purity is obtained. Lastly, the liquid is separated and concentrated to prepare a concentrate in which geniposide is significantly reduced.
  • Concentration is carried out according to a common method by using a condensing vessel, which usually results in a concentrate havingmoisture content of about 10 to 80 % byweight , preferably about 15 to 40 % byweight with the color value (E 10% ⁇ cra ) of about 100 to 650, preferably about 400 to 600.
  • crocetin can be obtained by hydrolysis of the said extract, the said concentrate or the concentrate, in which geniposide is significantly reduced.
  • the concentrate is subjected to hydrolysis after, if desired, diluted with water to the appropriate concentration.
  • Hydrolysis is carried out by the action of an acid, an alkali oran appropriatehydrolase.
  • the acid include hydrochloric acid, sulfuri ⁇ acid, phosphoric acid, etc.
  • the alkali include sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, etc.
  • An example of the hydrolase includes ⁇ -glucosidase, etc.
  • an alkali is preferably used for hydrolysis .
  • the method may follow a common method and is not particularly limited.
  • the reaction solution may or may not be stirred, or may or may not be heated, while preferably it is stirred and heated to proper temperature to accelerate the reaction.
  • an appropriate amount of an aqueous solution of an inorganic acid such as hydrochloric acid, sulfuric acid, phosphoric acid, etc. or an aqueous solution of an organic acid such as citric acid, etc. is added to the reaction solution to adjust the pH to about 4.0 or lower.
  • the reaction solution is added to an aqueous solution of an inorganic acid such as hydrochloric acid, sulfuric acid, phosphoric acid, etc. or an aqueous solution of an organic acid such as citric acid, etc. to adjust the pH to about 4.0 or lower, preferably about 3.0 or lower, so that crocetin is precipitated.
  • a mixture containing crocetin is filtered through filter paper or filter cloth to collect paste-like solidsubstance containingcrocetin.
  • crocetin is precipitated upon initiation of the reaction and becomes a suspension.
  • the mixture containing crocetin is filtered through filter paper or filter cloth to collect paste-like solid substance containing crocetin.
  • Crocetin thus obtained has a relatively low purity, because it includes materials other than crocetin such as lipid and its decomposition products, polyphenols (e.g. chlorogenic acid) or saccharides (e.g. glucose, gentiobiose) which are generated by hydrolysis and not completely removed by water washing. Therefore, it is not appropriate to use such crocetin as it is in cosmetic products, skin cosmetics, foods, health foods or pharmaceutical compositions.
  • the present invention relates to a method for preparing crocetin of high purity by further treating the said crocetin with a specific solvent .
  • the said crocetin is treated with a lower alcohol.
  • the lower alcohol include one member or a mixture of two or more members selected from the group of lower alcohols having 1 to 4 carbon atoms such as methanol, ethanol, propanol, isopropanol, n-butanol, i-butanol, sec-butanol, tert-butanol, etc. , among which methanol is preferably used.
  • the amount of methanol is about 1 to 2000 parts by volume, preferably about 10 to 250 parts by volume, more preferably about 10 to 40 parts by volume relative to 1 part by weight of crocetin.
  • a mixture of the said crocetin and methanol is stirred at about 30 to 65 °C, preferably at about 45 to 50 °C for about 0.5 to 1 hour under gentle reflux. Then the mixture is cooled to room temperature and filtered through filter paper or filter cloth.
  • the filtering method includes suction filtration, pressure filtration or centrifugal separation, etc. Crocetin remaining on filter paper or filter cloth is collected, and the filtrate containing soluble impurities inmethanol is discarded.
  • the said crocetin maybe treatedwith amixed solvent containing about 50% byvolume or more, preferably about 70% by volume or more of lower alcohol .
  • Examples of the solvent to be mixedwith the lower alcohol include solvents having high compatibility with lower alcohol such as water, saturatedorunsaturatedaliphatic alcohols , ketones (e.g. acetone, ethylmethylketone) , ethers (e.g. diethyl ether) , ethyl acetate, and the like.
  • solvents having high compatibility with lower alcohol such as water, saturatedorunsaturatedaliphatic alcohols , ketones (e.g. acetone, ethylmethylketone) , ethers (e.g. diethyl ether) , ethyl acetate, and the like.
  • the mixture of the said crocetin and the mixed solvent containing 50% by volume or more of lower alcohol is stirred at a temperature below the boiling point of the mixed solvent for 0.5 to 1 hour preferably under gentle reflux. Then the mixture is cooledto room temperature and filtered through filter paper or filter cloth. Crocetin remaining on filter paper or filter cloth is collected, and the filtrate containing soluble impurities in the mixed solvent is discarded.
  • the said crocetin which is a hydrolysis product of crocin, is subjected to crystallization procedure in an aprotic solvent which can crystallize crocetin such as dimethylformamide, dimethylsulfoxide, dimethylacetamido, N-methyl-2-pyrrolidone, acetonitorile, ⁇ -butyrolactone, hexamethylphosphoric triamide, sulfolane, 1 , 3-dimethyl-2-imidazolidinone,
  • an aprotic solvent which can crystallize crocetin such as dimethylformamide, dimethylsulfoxide, dimethylacetamido, N-methyl-2-pyrrolidone, acetonitorile, ⁇ -butyrolactone, hexamethylphosphoric triamide, sulfolane, 1 , 3-dimethyl-2-imidazolidinone,
  • N-methylcaprolactam Preferably dimethylformamide, dimethylsulfoxide or a mixture thereof, more preferably dimethylformamide is used.
  • Those aprotic solvents may be used independently or as a mixed solvent of one or more of them.
  • the said aprotic solvents may be mixed with a nonpolar solvent or other solvents as long as the mixture can crystallize crocetin. Examples of such nonpolar solvent include benzene, toluene, hexane, etc., and examples of such other solvents include water, methanol, ethanol, chloroform, etc.
  • the crystallization method may follow a common method and is not particularly limited. That is, the amount of the solvent used may be any amount that can produce a saturated solution at a temperature at which crocetin dissolves, and for example the amount of dimethylformamide relative to 1 part by weight of crocetin is about 10 to 40 parts by volume, preferably about 15 to 20 parts by volume.
  • the mixed solution of the said crocetin and dimethylformamide is heated to between room temperature and 100 °C, preferably about between 50 °C and 80 °C, and stirred for about 0.5 to 1 hour to dissolve crocetin.
  • the solution may be concentrated preferably under vacuum after dissolution.
  • the solution is gradually cooled to room temperature (about 1 °C to 30 °C) or lower after impurities, if present, are removed from the solution by filtration.
  • the solution is allowed to stand calmly preferably at the original temperature to form crystals , then the mixed solution containing formed crocetin crystals is filtered through filter paper or filter cloth. Crocetin remaining on filter paper or filter cloth is collected, and the filtrate containing soluble impurities in dimethylformamide is discarded.
  • dimethylsulfoxide is used, crystals are occasionally not precipitated depending on the amount of the solvent used even if the solution is cooled to room temperature. In such a case, crystals may be precipitated by, for example, adding the appropriate amount of water.
  • resulting crocetin crystals arewashedwithmethanolorethanol, preferablyethanol.
  • the amount of ethanol is about 5 to 80 parts by volume, preferably about 10 to 40 parts by volume relative to 1 part by weight of crocetin crystals. Solvents such as dimethylformamid adhered to the surface of crocetin crystals are removed by washing with ethanol, whichmakes it easier to remove solvents in the finishing operation .
  • the purified crocetin obtained in the first method may be used as starting material in place of the said crocetin.
  • Use of the purified crocetin increases the possibility of obtaining crocetin crystals of higher purity.
  • crocetin with the purity of about 70 % by weight or more, often about 80 % by weight or more can be obtained by the first method
  • crocetin with the purity of about 90 % by weight or more, often about 95 % by weight or more can be obtained by the second method.
  • the color value of the purified crocetin of high purity prepared with crystallization step is measured by the below-mentioned method to result in the value 35,700, based on which the above purity is calculated.
  • Crocetin has been reported to show not only actions on skinas asinglet oxygenscavenger, collagenproduction stimulant and skin immunostimulator as described above, but also physiological actions suchas cholesterol lowering effect , tumor growth inhibiting effect , hepatotoxicity inhibitory effect , etc. Therefore, the purified crocetin of the present invention is useful as a pharmaceutical composition or cosmetic product or skin cosmetics.
  • the crocetin of the present invention maybe usedas ayellowpigment in food including confectioneries , noodles, dairy products, fish paste, pickled vegetables, vinegaredfood, Neri-yokan (thick sweet bean jelly) , Mizu-yokan (soft sweet bean jelly) , Uiro (sweet steamed rice paste) , boiled beans, Neri-uni(paste of seasoned sea-urchin eggs), Furikake (seasoned fish and vegetable flakes), etc.
  • Known pharmaceutical carriers escipients or other additives to be used with crocetin may be chosen by those skilled in the art depending on the types and purposes of the use. More specifically, excipients, disintegrators, binding agents, surfactants, emulsifiers, plasticizers, wetting agents, lubricants, sugars, pH regulators, preservatives, flavoring agents, coloring agents or the like may be exemplified in the case of pharmaceutical compositions or cosmetic products , and various nutrients , vitamins, flavoring agents, coloring agents , antioxidants , flavoring materials for chocolate, cheese, etc., artificial sweeteners or the like may be exemplified in the case of foods or health foods .
  • compositions of the present invention may be administered orally in the form of syrup, powder, granule, pill, tablet, hard capsule, soft capsule or may be administered parenterally in the form of suppository, parenteral injection, infusion, etc., depending on the method and root of administration.
  • crocetin may be appropriately added to produce a cosmetic product in the form of cream, lotion, ointment, liquid formulation, paste, etc.
  • crocetin When crocetin is appliedto foodorhealth food, itmaybe provided in the form of granule, tablet, chewing gum, candy, jelly, beverage, etc. , though the form is not limited to those mentioned above.
  • crocetin With regard to the intake of crocetin, it is advisable to adjust the dosage of crocetin as an active ingredient in a range of about 0.1 mg to 500 mg, preferably about 1 mg to 300 mg, more preferably about 2 mg to 100 mg per a day per a human adult considering the absorption rate in the case of oral formulations , though the intake cannot be generalized because it depends on sex, age, health condition, etc. of those who take crocetin. In the case of parenteral formulations such as injections or infusions, it is advisable to adjust the dosage of crocetin in a range of about 0.1 mg to 100 mg, preferably about 0.1 mg to 50 mg, more preferably about 0.5 mg to 10 mg per a day per a human adult.
  • crocetin is contained in an amount of about 0.001 to 10 % by weight relative to the whole weight of the skin cosmetics.
  • crocetin in the case of food or health food, it is generally advisable to add crocetin in an amount of about 0.00003 to 10 % by weight, preferably about 0.01 to 5 % by weight, relative to the whole weight of the food or health food.
  • compositions, skin cosmetics, cosmeticproducts, foods orhealthfoodswhichcontain crocetin may be administered, used or taken one to several times a day.
  • Color value was measured by the method mentioned below according to "Food Additives Other Than Chemically Synthesized Compounds, voluntary standards (second edition), gardenia yellow” Japan Food Additives Association.
  • the sample is precisely measured in such a way that the measured absorbance thereof falls between 0.3 and 0.7, and then dissolved in Kolthoff buffer (50mM Na 2 CO 3 -50mM Na 2 B0 7 , pHlO.0) to accurately prepare 500 ml of the solution.
  • supersonic treatment is applied for the dissolution.
  • the solution (10 mL) is exactly measured and Kolthoff buffer (50mM Na 2 C0 3 -50mM Na 2 B 4 0 7 , pH 10.0) is added thereto to prepare 50 mL of a test solution.
  • the resulting concentrate was mixed with 40 % by weight of sodium hydroxide solution (17 g) , and the mixed solution was subjected to hydrolysis reaction at 50 °C for 3.5 hours while stirring. After the reaction, the reaction mixture was added to 4 % by weight of aqueous phosphoric acid solution (420 ml) to make it acidic and allowed to stand at room temperature for about 3 hours . The precipitated deposits were collected by centrifugation at 10,000 x g for 10 minutes, and twice subjected to washing with 100 ml of water and the centrifugation. The resulting paste-like solid substance was vacuum-dried at 50 °C for 8 hours to give about 1.2 g of crocetin. The color value (E 10% ⁇ cm ) of the crocetin was about 12,500.
  • Dimethylformamide ( 6.5 ml) was added to 0.15 g of purified crocetin obtained in Example 1, then dissolved at 80 °C while stirring. The insoluble substances were filtered through quantitative filter paper No. 5C, and the filtrate was allowed to stand at 10 °C for 3 days. Next, the mother liquor containing formed crocetin crystals was passed through a sintered glass filter No.3, and the crystals were vacuum-dried at 50 °C after washed with 10 ml of methanol to give about 0.09 g of purified crocetin. The color value (E 10% lcm ) of the purified crocetin was about 35,700.
  • Example 4 Melting point determination and elemental analysis of the crystals obtained in Example 4 were carried out by an external institution. The results are shown below. Melting point: 285 °C to 286 °C
  • crocetinofhighpurity is easily prepared in an industrial manner, and it is preferably applied to cosmetic products , skin cosmetics , pharmaceutical compositions and the like.
  • the unpleasant taste and off-flavor of the crocetin are significantly decreased because of the purification, which makes it possible for such crocetin to be used in a broader range of food or health food.

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Abstract

La présente invention concerne un procédé simple et avantageux au plan industriel de fabrication de crocétine. Plus spécifiquement, cette invention concerne un procédé de purification de la crocétine, consistant à traiter de la crocétine obtenue par hydrolyse de crocine présente dans un extrait de plante avec un alcool inférieur ou un solvant mélangé contenant 50 % par volume ou plus d'un alcool inférieur et à extraire un composant soluble du solvant présent dans le solvant. L'invention concerne également un procédé de purification de la crocétine consistant à dissoudre de la crocétine obtenue par hydrolyse de la crocine, laquelle est présente dans un extrait de plante, dans un solvant aprotique qui peut faire se cristalliser la crocétine et la crocétine cristallisante à a partir du solvant. Avec la présente invention, il est possible de fabriquer efficacement une crocétine purifiée recherchée d'une grande pureté. La crocétine purifiée est utilise comme composition pharmaceutique ou produit cosmétique, notamment pour la peau et peut s'utiliser comme additif pour produits alimentaires et produits diététiques.
PCT/JP2004/002693 2003-03-07 2004-03-03 Procede de purification de la crocetine Ceased WO2004078695A1 (fr)

Applications Claiming Priority (2)

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JP2003061550A JP2004269663A (ja) 2003-03-07 2003-03-07 クロセチンの精製方法
JP2003-061550 2003-03-07

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Cited By (15)

* Cited by examiner, † Cited by third party
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CN101811956A (zh) * 2010-04-15 2010-08-25 施冬云 反式西红花酸的制备方法和应用
WO2010094745A1 (fr) * 2009-02-18 2010-08-26 Omnica Gmbh Hydrolysat de crocine
CN102432455A (zh) * 2011-12-14 2012-05-02 广西大学 一种制备藏花酸和藏花素的方法
CN103073417A (zh) * 2013-03-04 2013-05-01 苏州衷中医药科技有限公司 高纯度反式西红花酸的制备方法
CN103601764A (zh) * 2013-11-26 2014-02-26 威海东宝制药有限公司 栀子提取物中西红花苷的纯化分离技术
CN103641705A (zh) * 2013-12-02 2014-03-19 威海东宝制药有限公司 一种从栀子果实中提取西红花酸的方法
US9211298B2 (en) 2012-11-16 2015-12-15 Song Gao Compositions containing enriched natural crocin and/or crocetin, and their therapeutic or nutraceutical uses
CN105503968A (zh) * 2015-12-02 2016-04-20 武汉绿孚生物工程有限责任公司 一种从栀子黄色素中分离提纯藏花素和藏花酸的方法
CN108218692A (zh) * 2018-02-26 2018-06-29 南阳泰瑞生物科技股份有限公司 利用栀子果生产藏红花酸的方法
CN109232230A (zh) * 2018-10-31 2019-01-18 湖南中茂生物科技有限公司 一种从新鲜栀子中提取藏红花素的方法
KR20190095050A (ko) * 2018-02-06 2019-08-14 이석렬 크로세틴 제조방법 및 크로세틴을 유효성분으로 포함하는 식욕억제용 건강보조제
WO2021114089A1 (fr) * 2019-12-10 2021-06-17 Hangzhou Menglanruisi Biotechnology Co., Ltd. Procédés d'utilisation de crocétine dans le traitement de tumeurs solides
CN116019802A (zh) * 2023-03-07 2023-04-28 西南交通大学 藏花酸在制备治疗和预防脑缺血性疾病的药物的用途
CN116023255A (zh) * 2021-10-26 2023-04-28 广州博济医药生物技术股份有限公司 西红花酸钠的制备方法
CN117049960A (zh) * 2022-05-04 2023-11-14 鼎赫生物科技股份有限公司 一种番红花酸制备方法及抗氧化之保护眼睛用途

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WO2010094745A1 (fr) * 2009-02-18 2010-08-26 Omnica Gmbh Hydrolysat de crocine
US8569247B2 (en) 2009-02-18 2013-10-29 Omnica Gmbh Hydrolysate of crocin
CN101811956A (zh) * 2010-04-15 2010-08-25 施冬云 反式西红花酸的制备方法和应用
CN101811956B (zh) * 2010-04-15 2013-04-17 施冬云 反式西红花酸的制备方法
CN102432455A (zh) * 2011-12-14 2012-05-02 广西大学 一种制备藏花酸和藏花素的方法
US9211298B2 (en) 2012-11-16 2015-12-15 Song Gao Compositions containing enriched natural crocin and/or crocetin, and their therapeutic or nutraceutical uses
CN103073417B (zh) * 2013-03-04 2015-09-02 苏州衷中医药科技有限公司 高纯度反式西红花酸的制备方法
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CN103601764A (zh) * 2013-11-26 2014-02-26 威海东宝制药有限公司 栀子提取物中西红花苷的纯化分离技术
CN103641705A (zh) * 2013-12-02 2014-03-19 威海东宝制药有限公司 一种从栀子果实中提取西红花酸的方法
CN105503968A (zh) * 2015-12-02 2016-04-20 武汉绿孚生物工程有限责任公司 一种从栀子黄色素中分离提纯藏花素和藏花酸的方法
KR20190095050A (ko) * 2018-02-06 2019-08-14 이석렬 크로세틴 제조방법 및 크로세틴을 유효성분으로 포함하는 식욕억제용 건강보조제
KR102041036B1 (ko) * 2018-02-06 2019-11-05 이석렬 크로세틴 제조방법 및 크로세틴을 유효성분으로 포함하는 식욕억제용 건강보조제
CN108218692A (zh) * 2018-02-26 2018-06-29 南阳泰瑞生物科技股份有限公司 利用栀子果生产藏红花酸的方法
CN109232230A (zh) * 2018-10-31 2019-01-18 湖南中茂生物科技有限公司 一种从新鲜栀子中提取藏红花素的方法
WO2021114089A1 (fr) * 2019-12-10 2021-06-17 Hangzhou Menglanruisi Biotechnology Co., Ltd. Procédés d'utilisation de crocétine dans le traitement de tumeurs solides
CN116023255A (zh) * 2021-10-26 2023-04-28 广州博济医药生物技术股份有限公司 西红花酸钠的制备方法
CN117049960A (zh) * 2022-05-04 2023-11-14 鼎赫生物科技股份有限公司 一种番红花酸制备方法及抗氧化之保护眼睛用途
CN116019802A (zh) * 2023-03-07 2023-04-28 西南交通大学 藏花酸在制备治疗和预防脑缺血性疾病的药物的用途

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