WO2019111897A1 - Remède contre la dermatite - Google Patents

Remède contre la dermatite Download PDF

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Publication number
WO2019111897A1
WO2019111897A1 PCT/JP2018/044566 JP2018044566W WO2019111897A1 WO 2019111897 A1 WO2019111897 A1 WO 2019111897A1 JP 2018044566 W JP2018044566 W JP 2018044566W WO 2019111897 A1 WO2019111897 A1 WO 2019111897A1
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WIPO (PCT)
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formula
salt
integer
astaxanthin derivative
dermatitis
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PCT/JP2018/044566
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English (en)
Japanese (ja)
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康弘 西田
郁 小林
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アスタファーマシューティカルズ株式会社
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Publication of WO2019111897A1 publication Critical patent/WO2019111897A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/225—Polycarboxylic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Definitions

  • the present invention relates to a remedy for dermatitis containing an astaxanthin derivative.
  • Atopic dermatitis is a chronic disease that develops in the background of atopic predisposition, so it is necessary to use drugs continuously, but on the other hand, topical steroids have sharp sharpness of clinical effect, skin thinning Because it has local side effects such as swelling and atrophy, full moon-like face, flushing, hirsutism and skin tears, it is not always easy to apply to patients with highly absorbable drugs, patients with weak skin, children and women There is a problem that is not.
  • atopic dermatitis is a chronic disease as described above, the steroid external preparation is used for a long period of time, and the steroid external preparation becomes difficult to be effective, which may result in a state of so-called steroid resistance. Sudden discontinuation of the drug may cause you to suffer from the phenomenon of rebound which exacerbates the symptoms even before external use.
  • Patent Documents 1 and 2 provide steroid compounds of the formula (I) with extremely few side effects.
  • a steroid compound is a compound obtained by converting a steroid to dessiclesonide and adding a sugar substituted to a unexpectedly bulky functional group, and has a stronger anti-inflammatory effect in external administration than existing steroid drugs, Not only systemic side effects but also local side effects are reduced (Patent Document 2, paragraphs 0006 to 0011).
  • the main object of the present invention is to provide a remedy for dermatitis which can be replaced by a steroid and has a definite therapeutic effect on dermatitis.
  • trans-astaxanthin derivatives represented by the formula (I), their geometric isomers, mixtures of these geometric isomers, their optical isomers The inventors have found that the isomers or their salts have an excellent therapeutic effect on dermatitis, and completed the present invention.
  • the present invention provides the following inventions [1] to [4].
  • n 1 , n 2 are the same or different and each represents an integer of 1 to 6).
  • trans-astaxanthin derivative represented by the above formula (I), a geometric isomer thereof, a mixture of these geometric isomers, an optical isomer thereof or a salt thereof for the preparation of a therapeutic agent for dermatitis.
  • a dermatitis characterized by administering an effective amount of the trans-astaxanthin derivative represented by the above formula (I), its geometric isomer, a mixture of these geometric isomers, their optical isomers or their salts Treatment method.
  • the trans-astaxanthin derivative represented by the formula (I) of the present invention is various animals such as humans, dogs, cats and horses in general.
  • the astaxanthin derivative represented by the formula (I) its geometric isomer, a mixture of those geometric isomers, an optical isomer thereof, or a salt thereof
  • the composition is excellent as an agent for treating dermatitis.
  • the agent for treating dermatitis comprises, as an active ingredient, the trans-astaxanthin derivative represented by the above formula (I), its geometric isomer, a mixture of these geometric isomers, their optical isomer or a salt thereof .
  • Dermatitis includes atopic dermatitis, contact dermatitis, drug-related eczema dermatitis, photo eczema rash, eczema dermatitis such as primary irritation dermatitis, urticaria, erythema, psoriasis, Lichen planus, pemphigus, pemphigus, eczema-like dermatitis and the like are included, and the remedy for dermatitis of the present invention is particularly useful for the treatment of atopic dermatitis.
  • Subjects that may be treated according to the present invention include, but are not limited to, warm-blooded animals including humans such as dogs, cats, cows, pigs, horses, sheep, goats, monkeys, rabbits, rats or mice.
  • the compound according to formula (I), its geometric isomer, a mixture of these geometric isomers and optical isomers thereof have a common salt-forming reaction with a basic substance or a basic compound desired from having a carboxyl group in the molecule
  • a pharmaceutically acceptable salt can be formed by Such salts include, for example, alkali metal salts such as sodium salts, potassium salts and lithium salts; alkaline earth metal salts such as calcium salts and magnesium salts, amino acids such as lysine salts, ornithine salts and arginine salts Salts can be mentioned, among which lysine salts can be mentioned as preferred.
  • the double bond part in the medium chain carbon chain part in the astaxanthin basic skeleton can take on the structure of trans and cis geometric isomers in terms of chemical structure.
  • the active ingredient according to the present invention not only the trans form of formula (I) but also cis forms represented by the following formula (Ia) and formula (Ib) are also active ingredients of the dermatitis remedy according to the present invention It can be mentioned.
  • the therapeutic agent for dermatitis of the present invention comprises as an active ingredient a mixture of trans form of formula (I) and cis form which is its geometric isomer in various mixing ratios and a mixture of trans form and cis form.
  • the compound of the formula (I), its geometric isomer and a mixture of these geometric isomers may include the optical isomer (IA) represented by the following, and its enantiomer and a mixture thereof, All diastereomers are also included as an active ingredient of the dermatitis therapeutic agent according to the present invention.
  • the compounds of the trans form of the above-mentioned formula (IA) are preferred. Further, among the trans compounds of the above formula (IA), compounds in which m 1 and m 2 each represent an integer of 1 and n 1 and n 2 each represent an integer of 3 are preferable.
  • an optically active trans-astaxanthin derivative represented by the formula (IA) or a salt thereof is more preferable, and an optically active cis-astaxanthin derivative corresponding to the optically active trans-astaxanthin derivative represented by the formula (IA) More preferred is a highly pure optically active trans-astaxanthin derivative substantially free of a salt or a salt thereof.
  • containing the active ingredient of the dermatitis therapeutic agent according to the present invention in "high purity" means that the purity of the active ingredient is at least 95% or more, preferably 98% or more.
  • the desired optically active trans-astaxanthin derivative of the formula (IA) can be produced by removing the protecting group of the compound of the formula (II) which is a starting compound.
  • the elimination reaction may be a conventional elimination reaction of a protecting group, and specifically, an elimination reaction with an acid can be mentioned.
  • a protecting group a tertiary butyl group, a trimethylsilyl group, a tetrahydropyranyl group etc. can be mentioned, A tertiary butyl group, a trimethylsilyl group etc. can be mentioned as a suitable thing.
  • the compound of formula (IA) can be produced by reacting the compound of formula (II) with an acid in an inert solvent.
  • the solvent used is not particularly limited as long as it is inert to the reaction, and examples thereof include aliphatic hydrocarbons such as hexane, heptane, ligroin and petroleum ether; aromatics such as benzene, toluene and xylene Hydrocarbons; Halogenated hydrocarbons such as chloroform, methylene chloride, 1,2-dichloroethane and carbon tetrachloride; Nitriles such as acetonitrile and propionitrile; ethyl formate, isopropyl formate, isobutyl formate, ethyl acetate, Organic acid esters such as isobutyl acetate and butyl acetate; ethers such as diethyl ether, diisopropyl ether, tetrahydro
  • the acid which can be used is not particularly limited as long as it is used as an acid in a usual reaction, and, for example, inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, perchloric acid and phosphoric acid; acetic acid, formic acid Organic acids such as boric acid, methanesulfonic acid, p-toluenesulfonic acid, camphorsulfonic acid, trifluoroacetic acid, trifluoromethanesulfonic acid; zinc chloride, tin tetrachloride, boron trichloride, boron trifluoride, boron tribromide Or a acidic ion exchange resin, preferably an inorganic or organic acid, most preferably hydrochloric acid, acetic acid, formic acid and trifluoroacetic acid.
  • inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, perchloric acid and phosphoric acid
  • acetic acid
  • the reaction temperature varies depending on the raw material compound to be reacted, the acid used, the solvent and the like, but is usually ⁇ 20 ° C. to 150 ° C., preferably 0 ° C. to 100 ° C.
  • the reaction time varies depending on the raw material compound, the solvent, the reaction temperature and the like, but is usually 30 minutes to 10 days, and preferably 30 minutes to 5 days.
  • the amount of the solvent used may be 10 to 50 times, preferably 30 times the volume of the weight of the compound of formula (II).
  • the amount of the acid used is usually 5 to 50 times by mole, preferably 10 to 30 times by mole, as long as it is an inorganic acid relative to the compound of the formula (II) which is the raw material, an organic acid
  • the molar amount is usually 100 to 1000 times, preferably 200 to 600 times.
  • the product obtained by the above deprotection reaction can contain geometric isomers such as the above 9-cis form and 13-cis form, so that separation and purification means such as column chromatography, reprecipitation and crystallization can be obtained.
  • separation and purification means such as column chromatography, reprecipitation and crystallization.
  • the same geometric isomer can be separated and removed, and the objective optically active trans-astaxanthin derivative of the formula (IA) can be isolated and manufactured with high purity.
  • the separated cis-form can be isolated and obtained by appropriately combining the purification and separation methods as described above.
  • Representative cis-forms used in this production method are the compounds of the formulas (IAa) and (IAb) as described above, which may be used as sole raw material compounds, as a mixture of cis-forms, or in excess of cis-forms.
  • the desired optically active trans-astaxanthin derivative of the formula (IA) can be produced by dissolving it in an inert solvent as a mixture with the trans form and reacting it with a conversion reagent such as iodine. .
  • the solvent to be used is not particularly limited as long as it is inert to the reaction, and examples thereof include tetrahydrofuran, ethyl acetate, acetonitrile, acetone, water and the like.
  • Preferred examples of the conversion reagent include iodine.
  • the reaction temperature varies depending on the raw material compound to be reacted, the conversion reagent to be used, the solvent and the like, but is usually ⁇ 20 ° C. to 150 ° C., preferably 10 ° C. to 100 ° C.
  • the reaction time varies depending on the raw material compound, the solvent, the reaction temperature and the like, but is usually 30 minutes to 10 days, and preferably 30 minutes to 5 days.
  • the amount of the solvent used is usually 10 times to 50 times the used weight of the compound of formula (IAa) or formula (IAb), preferably 30 times the volume.
  • the amount of conversion reagent used may be usually 0.01 times or more by mole, preferably 0.1 times or more by mole, of the compound of the formula (IAa) or formula (IAb) as a raw material.
  • (2A) A method for directly binding the entire side chain moiety to 3S, 3'S-astaxanthin
  • R means a protecting group (eg, tertiary butyl group).
  • a compound of formula (II) is obtained by dissolving 3S, 3'S-astaxanthin in an inert solvent and then reacting the compound of formula (III) corresponding to the side chain moiety in the compound of formula (I) in the presence of a condensing reagent. Can be manufactured.
  • the solvent examples include organic solvents such as methylene chloride, chloroform and carbon tetrachloride.
  • the condensation reagent those used in ordinary condensation reactions can be used, and as a specific example, water-soluble carbodiimide hydrochloride (eg, 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride) And N, N-diisopropylcarbodiimide, carbonyldiimidazole, dicyclohexylcarbodiimide and the like.
  • the amount of the condensation reagent used is usually at least 2 times the molar amount, preferably 2.5 times to 20 times the molar amount of the raw material 3S, 3'S-astaxanthin.
  • the compound of the formula (III) corresponding to the side chain moiety may be used usually in a 2-fold molar amount or more, preferably 2.5-fold molar to 20-fold molar amount with respect to 3S, 3'S-astaxanthin.
  • the reaction temperature varies depending on the raw material compound to be reacted, the condensation reagent to be used, the solvent and the like, but is usually ⁇ 20 ° C. to 150 ° C., preferably ⁇ 10 ° C. to 100 ° C.
  • the reaction time varies depending on the raw material compound, the solvent, the reaction temperature and the like, but is usually 30 minutes to 10 days, and preferably 30 minutes to 5 days.
  • the amount of the solvent used is usually 10 to 50 times the used weight of 3S, 3'S-astaxanthin, preferably 30 times the volume.
  • the compound of the formula (II) obtained can be usually purified and isolated by appropriately combining purification means such as column chromatography, reprecipitation, recrystallization and the like.
  • the whole side chain part can be manufactured by the following method.
  • R means a protecting group (eg, a tertiary butyl group).
  • the desired compound of formula (III) can be produced by sequentially reacting the compound of formula (IV) with the compound of carbonyldiimidazole (V) and the compound of formula (VII).
  • the compound of formula (IV) is an intermediate compound of formula (VI) by reacting carbonyldiimidazole (V) in the presence or absence of a reagent such as a base in an inert solvent.
  • a reagent such as a base in an inert solvent.
  • the desired compound of formula (III) can be produced by reacting the compound of formula (VII) with trimethylsilyl chloride in the presence of a reagent such as a base and then reacting with the compound of formula (VI) .
  • organic solvents such as chloroform and methylene chloride can be exemplified as the solvent, and the amount of these organic solvents used is usually 5 times the used weight of the compound of the formula (IV)
  • a volume of 30 to 30 volumes, preferably 15 volumes, may be used.
  • the basic reagent those used for ordinary condensation reactions can be used, and specific examples can include triethylamine, N, N-diisopropylethylamine, pyridine, N, N-dimethylaminopyridine and the like.
  • the reaction temperature varies depending on the raw material compound to be reacted, the reagent used, the solvent and the like, but is usually ⁇ 20 ° C.
  • reaction time varies depending on the raw material compound, the solvent, the reaction temperature and the like, but is usually 15 minutes to 10 days, and preferably 30 minutes to 2 days can be mentioned.
  • organic solvents such as chloroform, methylene chloride, pyridine and the like can be mentioned as solvents for reacting trimethylsilyl chloride and the compound of formula (VII).
  • the amount used is usually 5 times to 50 times the volume, preferably 20 times the volume of the used weight of the compound of the formula (VII).
  • the base those used for ordinary condensation reactions can be used, and specific examples can include triethylamine, N, N-diisopropylethylamine, pyridine, N, N-dimethylaminopyridine and the like.
  • the amount of the base or reagent used is usually at least 2 moles, preferably 2.5 to 5.0 moles, per mole of the compound of the formula (VI) as the raw material.
  • the reaction temperature varies depending on the raw material compound to be reacted, the reagent used, the solvent and the like, but is usually ⁇ 20 ° C. to 100 ° C., and preferably 0 ° C. to 30 ° C.
  • the reaction time varies depending on the raw material compound, the solvent, the reaction temperature and the like, but is usually 15 minutes to 5 days, and preferably 30 minutes to 2 days can be mentioned.
  • the compound of formula (VI) is added and reacted at a reaction temperature which varies depending on the starting compound to be reacted, the reagent to be used, the solvent and the like, but is usually -20 ° C to 150 ° C, preferably 10 ° C. To 60 ° C.
  • the reaction time varies depending on the raw material compound, the solvent, the reaction temperature and the like, but is usually 30 minutes to 10 days, and preferably 30 minutes to 4 days.
  • R means a protecting group (eg, tertiary butyl group or trimethylsilyl group).)
  • the side chain part (VIII) obtained by reacting the compound represented by the general formula (VII) with carbonyldiimidazole (V) is bound to 3S, 3'S-astaxanthin, This can then be achieved by coupling part (XI) of the side chain part to the obtained product (IX).
  • reaction temperature varies depending on the raw material compound to be reacted, the reagent to be used, the solvent and the like, but is usually ⁇ 20 ° C. to 150 ° C., preferably ⁇ 10 ° C. to 100 ° C.
  • the reaction time varies depending on the raw material compound, the solvent, the reaction temperature and the like, but is usually 30 minutes to 10 days, and preferably 30 minutes to 5 days.
  • bases include triethylamine, N, N-diisopropylethylamine, pyridine, N, N-dimethylaminopyridine and the like.
  • the compound of the formula (IX) can be produced by reacting the resulting part of the side chain part (VIII) with 3S, 3'S-astaxanthin in the same manner as in the reaction of 2A above. .
  • the step of obtaining the target general formula (II) can be achieved by reacting the compound having the general formula (IX) obtained above with the general formula (XI).
  • This reaction is carried out according to the method for producing the above general formula (VIII).
  • the reaction temperature varies depending on the raw material compound to be reacted, the reagent to be used, the solvent and the like, but is usually ⁇ 20 ° C. to 100 ° C., preferably 0 ° C. to 40 ° C.
  • the reaction time varies depending on the raw material compound, the solvent, the reaction temperature and the like, but is usually 30 minutes to 10 days, and preferably 30 minutes to 30 hours.
  • the method for producing a compound having the general formula (XI) can be achieved according to the method for synthesizing t-butyl ester of generally known amino acid when (1) R is a t-butyl group, (2) When R is a trimethylsilyl group, it can be achieved by reacting a compound having the general formula (X) with trimethylsilyl chloride in the presence of a base in an inert solvent (to form a compound of the general formula (III) It can be achieved according to the method).
  • the reaction of (2) can be achieved according to generally known methods for silylation of hydroxyl and carboxyl groups.
  • R in the general formula (XI) is a trimethylsilyl group
  • the trimethylsilyl group can be easily eliminated by using water or weakly acidic water for post-treatment of the reaction to generate the general formula (II). .
  • the desired product of the formula (II) can be produced by appropriately combining and using the obtained purification means such as ordinary column chromatography, reprecipitation, recrystallization and the like.
  • the compound of the formula (I) according to the present invention can be administered as an external preparation, an oral preparation or an injection, preferably It is good to administer by external preparation.
  • the external preparation can typically be administered in the form of an ointment, a solution, a lotion, a liniment, a gel, an aerosol, a plaster, a patch, a cream and the like.
  • These external preparations include pharmaceutically acceptable additives such as solubilizers, bases, emulsifiers, wetting agents, stabilizers, stabilizers, dispersants, plasticizers, pH adjusters, absorption accelerators, gels.
  • the component for external use may be blended with ingredients such as a preservative, a preservative, a filler, a preservative, a preservative, a pigment, a fragrance, a refreshing agent, a thickener, an antioxidant, a skin lightening agent and an ultraviolet light absorber.
  • Oral agents or injections can be prepared by using conventional formulation techniques.
  • the oral preparation may be administered in any form such as tablets, capsules, granules, powders and the like, and is appropriately mixed with pharmaceutically acceptable excipients, disintegrants, binders and other pharmaceutical additives, It can be produced by using conventional formulation techniques.
  • the injection can be produced by a usual formulation technique, using an appropriate combination of a pharmaceutically acceptable osmotic pressure regulator, a stabilizer, a solubilizer, a pH regulator and the like.
  • the compound of the formula (I) according to the present invention when the compound of the formula (I) according to the present invention, its geometric isomer, a mixture of these geometric isomers, their optical isomers or a salt thereof is administered as an external preparation or an oral preparation, the external preparation of the present invention Alternatively, the number and frequency of administration of the oral preparation can be appropriately selected depending on the condition to be treated, dosage form, administration route, patient's age, body weight, sex or general health condition, and base, etc.
  • the daily dose when applied to a warm-blooded animal having a weight of about 70 kg, the daily dose is 0.01 to 500 mg, preferably 1 to 100 mg, more preferably 5 to 20 mg once or more, for example, 1 to 6 times a day It may be administered by
  • the compound of the formula (I) according to the present invention, its geometric isomer, a mixture of these geometric isomers, their optical isomers or a salt thereof is administered as an injection, it is usually 5 per day for adults.
  • 0.about.80.0 mg may be administered intravenously, and may be increased or decreased appropriately according to the symptoms.
  • the compounds of the formula (I) according to the present invention, their geometric isomers, mixtures of their geometric isomers, their optical isomers or their salts are particularly problematic in terms of safety within the above-mentioned dose range. Absent.
  • Model preparation NC / Nga; slc mice were prepared, and skin inflammation was caused by intradermally administering a mite antigen-administered solution to the right auricle of the mouse under isoflurane inhalation anesthesia.
  • the mite antigen administration was performed on days 0, 3, 7, 10 and 14 when the first administration day was day 0.
  • the resulting solution was washed with a mixture of hydrochloric acid (5.66 kg) and 20% brine (106 kg).
  • the aqueous layer was extracted with ethyl acetate (57.4 kg), and the organic layer and the extract were combined.
  • the resulting solution was washed with 20% brine (100 kg), dried over anhydrous magnesium sulfate and concentrated under reduced pressure.
  • Ethyl acetate (14.4 kg) was added and stirred to a homogeneous solution at 45-55 ° C.
  • the solution was cooled to 20-30 ° C., n-heptane (108.7 kg) was added dropwise, and after confirming the precipitation of crystals, the solution was stirred for 1 hour.
  • the precipitated crystals were collected by filtration to give the title compound (7.98 kg, purity 99.2%) as white crystals.
  • the obtained solution was treated three times with hydrochloric acid (0.3 M, 46.4 kg), 10% saline (45.9 kg), aqueous sodium hydrogen carbonate solution (about 7%, 48.2 kg), 20% saline (45 kg)
  • the extract was successively washed with water, dried over anhydrous magnesium sulfate, and concentrated to dryness under reduced pressure to obtain the title compound (concentrated residue, 3.26 kg, purity 98.1%).
  • the purity of the product is determined by high performance liquid chromatography (column: YMC-TriartC18 ExRS manufactured by YMC Co., Ltd.
  • the precipitated solid was collected by filtration and dried to give the title compound (4.48 g, purity 90.7%) as a dark purple to dark red solid.
  • acetonitrile containing 0.025% trifluoroacetic acid / 0.025% trifluoroacetic acid water 30 to 98 / It was determined using 70-2, flow rate: 1 mL / min, detection wavelength: 474 nm).
  • the optical purity is high performance liquid chromatography (column: YMC, YMC CHIRAL ART Amylase SA (5 ⁇ m, 4.6 mm ID x 250 mm), column temperature: 25 ° C and mobile phase: THF / water / TFA (40:60) : 0.1), flow rate: 1 mL / min, detection wavelength: 474 nm, column retention time: 15.4 minutes (S, S), 17.6 minutes (meso), 20.6 minutes (R, R)) Used to determine.
  • Auricle thickness increase value (4.1) Measurement and calculation of auricle thickness increase value Day 1, 4, 8, 11, 15, 18 and 22 days with the start date of mite antigen administration as day 0 The thickness of the right auricle of the mouse was measured under isoflurane anesthesia respectively. The auricle increase value at each measurement point was calculated by subtracting the initial auricle thickness measurement value at the grouping day from the auricle thickness measurement value at each point.
  • mice under isoflurane anesthesia respectively The skin symptoms shown below in the right auricle of the dog are observed with the naked eye, and their strength is scored as asymptomatic (0 points), mild (1 point), moderate (2 points), severe (3 points) And evaluated. 1) Redness and flushing 2) Skin crust and skin exfoliation 3) Bleeding and clot 4) Hardening
  • Total IgE antibody amount (6.1) Measurement of total IgE antibody amount Heparin from the abdominal vena cava of mice under isoflurane anesthesia 1 hour after the final administration on day 22 with the mite antigen administration day as day 0 Blood was collected using an addition syringe. Plasma was separated from the collected blood by centrifugation, and total IgE was measured by total IgE measurement ELISA.
  • the compound X low dose group showed lower values as compared to the vehicle group at the point of day 22. From the above results, it is inferred that Compound X can be replaced by steroid depending on the dose and have a clear therapeutic effect on atopic dermatitis.

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Abstract

L'invention concerne un nouveau remède contre la dermatite qui contient un dérivé de trans-astaxanthine représenté par la formule (I), un isomère géométrique de celui-ci, un mélange desdits isomères géométriques, un isomère optique ou sel de ceux-ci. (Dans la formule, m1, m2, n1 et n2 peuvent être identiques ou différents et chacun représente un nombre entier de 1 à 6).
PCT/JP2018/044566 2017-12-04 2018-12-04 Remède contre la dermatite WO2019111897A1 (fr)

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JP2017-232349 2017-12-04
JP2017232349A JP2021028301A (ja) 2017-12-04 2017-12-04 皮膚炎治療剤

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WO2019111897A1 true WO2019111897A1 (fr) 2019-06-13

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006022121A (ja) * 2005-07-04 2006-01-26 Yamaha Motor Co Ltd アトピー性皮膚炎抑制剤
WO2015178404A1 (fr) * 2014-05-20 2015-11-26 富士化学工業株式会社 Dérivé de caroténoïde, sel pharmaceutiquement acceptable de ce dernier et ester ou amide pharmaceutiquement acceptable de ce dernier

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006022121A (ja) * 2005-07-04 2006-01-26 Yamaha Motor Co Ltd アトピー性皮膚炎抑制剤
WO2015178404A1 (fr) * 2014-05-20 2015-11-26 富士化学工業株式会社 Dérivé de caroténoïde, sel pharmaceutiquement acceptable de ce dernier et ester ou amide pharmaceutiquement acceptable de ce dernier

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