WO2004026297A1 - Preparation pour usage externe - Google Patents

Preparation pour usage externe Download PDF

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Publication number
WO2004026297A1
WO2004026297A1 PCT/JP2003/011767 JP0311767W WO2004026297A1 WO 2004026297 A1 WO2004026297 A1 WO 2004026297A1 JP 0311767 W JP0311767 W JP 0311767W WO 2004026297 A1 WO2004026297 A1 WO 2004026297A1
Authority
WO
WIPO (PCT)
Prior art keywords
group
external preparation
mass
salt
polyethylene glycol
Prior art date
Application number
PCT/JP2003/011767
Other languages
English (en)
Japanese (ja)
Inventor
Makoto Kanebako
Masami Serizawa
Ai Hirata
Masayuki Kanishi
Toshio Inagi
Original Assignee
Kowa Co., Ltd.
Nissan Chemical Industries, Ltd.
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
Application filed by Kowa Co., Ltd., Nissan Chemical Industries, Ltd. filed Critical Kowa Co., Ltd.
Priority to JP2004537570A priority Critical patent/JP4630065B2/ja
Priority to AU2003264443A priority patent/AU2003264443A1/en
Publication of WO2004026297A1 publication Critical patent/WO2004026297A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • 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
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4418—Non condensed pyridines; Hydrogenated derivatives thereof having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/10—Anti-acne agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to an external preparation containing sutins or a salt thereof as an active ingredient, which is excellent in transdermal absorbability and excellent in stability over time. Itoda
  • Statins such as pivasbasin and pravastatin are known to have excellent 111 ⁇ 0- (8-reducing enzyme inhibitory activity and to be useful as a therapeutic agent for hyperlipidemia (US Patent No. 5, 856, 336, U.S. Pat. No. 4,346,227), which have already been used or are being developed as orally-administered preparations having good stability such as tablets. It is known that in the acidic region, isomerization, lactonization, decomposition, etc. occur, resulting in extremely unstable conditions, and that a stable preparation cannot be obtained unless the pH is at least 7 (US Pat. No. 5,033) 0,447, U.S. Patent No. 5,180,589, U.S. Patent No. 5,356,896, W097Z 23200).
  • HMG-CoA reductase inhibitors are used in addition to hyperlipidemia, acne, psoriasis, dandruff (US Pat. No. 5,730,992, US Pat. No. 6,126,947), hair growth It was reported to be useful as a local action such as suppression (US Pat. No. 5,840,752), and it was required to be developed as an external preparation.
  • an object of the present invention is to provide a topical sutin-containing preparation having good transdermal absorbability and stability over time. Therefore, the present inventor examined percutaneous absorption in the basic region, which is a stable region of statins, and found that sufficient absorption was not obtained, and the percutaneous absorption of statins was more unstable than in the basic region. It was found to be good in the acidic region, which is the region. Thus, the present inventors have conducted various studies to obtain an external preparation that satisfies both transdermal absorption and stability over time. As a result, even when ethanol, isopropanol, propylene glycol, dipropylene glycol, etc. are combined with statins, lactones are obtained.
  • the composition for external use contains 0.001 to 20% by mass of polyethylene glycol, 20 to 80% by mass of polyethylene glycol and water, and has a pH of 4.0 or more and less than 7.0. Things.
  • the external preparation containing the sutins or a salt thereof as an active ingredient of the present invention is an external preparation that suppresses the production of a lactone, has excellent stability over time, and has excellent transdermal absorbability.
  • the organic group represented by R 1 in the compound represented by the general formula (1) used in the present invention is preferably an organic group having a ring structure which may have a substituent.
  • Examples of the organic group having a ring structure include an indolyl group, an indenyl group, a pyridyl group, a pyropyridyl group, a pyrazopyridyl group, a chenobiridyl group, a pyrimidyl group, a pyrazolyl group, a pyrrolyl group, an imidazolyl group, an indolidyl group, a quinolyl group, Nuff A tyl group, a hexahydronaphthyl group, a cyclohexyl group, a phenylsilylphenyl group, a phenylthienyl group or a phenylfuryl group, particularly a hexahydronaphthyl group, an indolyl group, a pyridyl group, a pyrimidyl group, a pyrrolyl group or a
  • Examples of the substituent which may be substituted on the organic group having such a ring structure include a hydroxy group, a linear, branched or cyclic alkyl group, an alkyloxyalkyl group, an alkylcarbonyloxy group, and an alkyl substituent.
  • alkyl group for R 2 a linear, branched or cyclic alkyl group having 1 to 6 carbon atoms is preferable.
  • Salts of the compound represented by the general formula (1) are physiologically acceptable salts, such as alkali metal salts such as sodium salt and potassium salt, alkaline earth metal salts such as calcium salt and magnesium salt, and phenethylamine salt. And the like, and an organic amine salt or an ammonium salt, etc., and a sodium salt and a calcium salt are more preferable.
  • sutins represented by the general formula (1) and salts thereof those which do not form a lactone are preferable.
  • pravasutin US Pat.
  • the content of the statin or a salt thereof is from 0.001 to 20% by mass, preferably from 0.01 to 10% by mass, particularly preferably from 0.1 to 5% by mass in the total amount of the external preparation.
  • the molecular weight of the polyethylene glycol used in the present invention is preferably from 100 to 60,000, more preferably from 300 to 4000, particularly preferably from 300 to 1500.
  • Polyethylene dalicol is known to oxidize formaldehyde, an impurity at the time of production, and decrease the pH over time. Therefore, the peroxide value (POPOV) is preferably 5 meq / kg or less, particularly preferably 1 meq / kg or less, and the formaldehyde concentration is preferably 5 ppm or less, particularly preferably 2 ppm or less.
  • the content of polyethylene glycol is important from the viewpoint of the stability of the statins with time, and is 20 to 80% by mass, preferably 25 to 75% by mass, particularly 30 to 70% by mass in the total amount of the external preparation. Is preferred. Polyethylene glycol content If the content is less than 20% by mass, the effect of inhibiting the formation of lactones of the quinones is low, and if the content exceeds 80% by mass, it becomes difficult to adjust the pH of the external preparation.
  • Water is contained in the balance amount in the total amount of the external preparation, but it is preferably contained in an amount of 10 to 75% by mass, more preferably 20 to 70% by mass, particularly preferably 25 to 65% by mass.
  • the pH of the external preparation of the present invention is 4.0 or more and less than 7.0, preferably 4.0 to 6.7, more preferably 4.5 to 6.7.
  • 7.0 preferably 4.0 to 6.7
  • 4.5 to 6.7 For pH measurement, mix 1 part by weight of the external preparation and 9 parts by weight of water, shake thoroughly, and measure at pH 25 ° C overnight.
  • pH adjuster examples include phosphoric acid, acetic acid, boric acid, lactic acid, succinic acid, citric acid, tartaric acid, phthalic acid and salts thereof such as alkali metals, glycine, sodium hydroxide and the like.
  • Britton-Robinson Buffer, Clark-Lubs Buffer, Koltov Buffer examples include phosphoric acid, acetic acid, boric acid, lactic acid, succinic acid, citric acid, tartaric acid, phthalic acid and salts thereof such as alkali metals, glycine, sodium hydroxide and the like.
  • various optional ingredients that are acceptable as pharmaceutical additives can be added to the external preparation of the present invention as needed.
  • examples thereof include a solvent and polyethylene.
  • examples include water-soluble polymers other than glycols, stabilizers, and bases.
  • the solvent examples include monohydric alcohols such as benzyl alcohol, stearyl alcohol, and oleyl alcohol, polyhydric alcohols such as concentrated glycerin, 1,3-butylene glycol, 21-ethyl-1,3-hexanediol, and polypropylene glycol 2000. Alcohol.
  • water-soluble polymer examples include celluloses such as hydroxyethylcellulose and hydroxypropylcellulose; sucrose;) polysaccharides such as 3-cyclodextrin; sugar alcohols such as sorbitol and mannitol; and polyvinyl alcohol. And synthetic polymers such as polyvinylpyrrolidone.
  • Stabilizers include methyl paraoxybenzoate, propyl paraoxybenzoate Phenolic substances such as chlorobutanol, phenylethyl alcohol, etc., antioxidants such as vitamin E, butylhydroxyanisole, tocopherol acetate, propyl gallate, 2-mercaptobenzimidazole, etc. And reducing agents such as ascorbic acid, sodium bisulfite and sodium thiosulfate.
  • Examples of the base include polyacrylic acid (sodium), carboxyvinyl polymer, gelatin, starch, ester gum, alicyclic saturated hydrocarbon resin, dimethylpolysiloxane, styrene / isoprene / styrene block copolymer, and the like.
  • the form of the present invention is not limited as long as it is an external preparation, and examples thereof include night creams, gels, creams, lotions, sprays, ointments and the like.
  • the pH of the prepared external preparation (immediately after production) and the lactone production rate after storage at 60 ° C for 3 days were measured by the following methods.
  • Lactone formation rate measurement Lactone formation after storage of external preparations at 60 ° C for 3 days The percentage was measured by the following method.
  • Lactone formation rate () (L / (P + L)) X 100 (1)
  • Table 1 shows the measurement results.
  • Example 1 The external preparation of Example 1 containing polyethylene glycol was stable because lactone formation was inhibited and isopropanol was used instead of polyethylene glycol.
  • the external preparations containing alcohols such as Comparative Example 1), ethanol (Comparative Example 2), propylene glycol (Comparative Example 3), and dipropylendalcol (Comparative Example 4) did not inhibit the formation of lactone bodies. It was unstable.
  • Table 2 shows the measurement results of pH and lactone formation rate. ⁇
  • Table 3 shows the measurement results of the pH and the lactone formation rate.
  • Table 4 shows the measurement results of the pH and the lactone formation rate.
  • the topical formulation containing pitapastatin has a molecular weight of 300, 150, 400
  • the lactone formation rate was suppressed and stable when stored under conditions of 60 for 3 days.
  • Example 8 the external preparations produced in Example 8 and Comparative Example 7 were used.
  • Britton-Robinson Buffer pH 6.0 was used for the reception solution.
  • the permeable membrane used was an abdominal extirpated Hiff (hereinafter abbreviated as “Hif”) of a Wistar rat (male, 8 weeks old).
  • the Hiff surface was placed on the permeation portion of a vertical diffusion cell (Franz cell) with the donor side facing one side, and filled with 1 mL of the donor solution and 3 OmL of the receptor solution.
  • Receptor solution was maintained at a constant temperature (3 '2 0 ⁇ , a transmission experiment was performed in order to prevent evaporation of water during the experiment, Donna.
  • a 0.5 mL receptor solution was taken from the mouth, and 0.5 mL of a new receptor solution was replenished.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Dermatology (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Emergency Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

L'invention concerne une préparation pour usage externe caractérisée en ce qu'elle comprend : de 0,001 à 20 % en poids d'un composé de statine représenté par la formule générale suivante (1), dans laquelle R1 représente un groupe organique ; X représente -CH2CH2- ou -CH=CH- et R2 représente hydrogène ou alkyle ; de 20 à 80 % en poids de polyéthylène glycol ; et de l'eau. Cette préparation est également caractérisée en ce qu'elle présente un pH de 4,0 à 7,0, à l'exclusion de 7,0. Cette préparation, qui contient, comme principe actif, le composé statine ou un sel de ce dernier, est inhibée de façon qu'elle ne produise pas une lactone. Enfin, cette préparation présente une stabilité à long terme et une capacité d'absorption percutanée excellentes.
PCT/JP2003/011767 2002-09-20 2003-09-16 Preparation pour usage externe WO2004026297A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
JP2004537570A JP4630065B2 (ja) 2002-09-20 2003-09-16 外用剤
AU2003264443A AU2003264443A1 (en) 2002-09-20 2003-09-16 Preparation for external use

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US41202702P 2002-09-20 2002-09-20
US60/412,027 2002-09-20

Publications (1)

Publication Number Publication Date
WO2004026297A1 true WO2004026297A1 (fr) 2004-04-01

Family

ID=32030785

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2003/011767 WO2004026297A1 (fr) 2002-09-20 2003-09-16 Preparation pour usage externe

Country Status (3)

Country Link
JP (1) JP4630065B2 (fr)
AU (1) AU2003264443A1 (fr)
WO (1) WO2004026297A1 (fr)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006001251A1 (fr) * 2004-06-24 2006-01-05 Kowa Co., Ltd. Composition d'atorvastatine a usage externe
JP2010126478A (ja) * 2008-11-27 2010-06-10 Kowa Co 貼付剤
WO2012056509A1 (fr) * 2010-10-25 2012-05-03 興和株式会社 Composition pharmaceutique
JP4981194B2 (ja) * 2010-10-25 2012-07-18 興和株式会社 医薬組成物
JP2020070251A (ja) * 2018-10-30 2020-05-07 花王株式会社 オートファジー抑制剤
US12023318B2 (en) 2018-08-29 2024-07-02 Ucl Business Ltd Therapy for Inflammatory Linear Verrucous Epidermal Nevus (ILVEN)

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996008248A1 (fr) * 1994-09-13 1996-03-21 Ramot University Authority For Applied Research And Industrial Development Ltd. Composition pour le traitement d'affections de la peau
EP0738510A2 (fr) * 1995-04-20 1996-10-23 L'oreal Utilisation d'un inhibiteur d'hmg coenzyme A reductase pour lutter contre le vieillissement de la peau
WO1997026874A1 (fr) * 1996-01-23 1997-07-31 Novartis Ag Utilisation des derives de la fluvastatine dans les maladies de la peau et compositions topiques a base de ces derives
WO2000002541A1 (fr) * 1998-07-09 2000-01-20 Lts Lohmann Therapie-Systeme Ag Emplatre transdermique contenant au moins un principe actif influant sur le taux de lipides sanguins
WO2001039770A1 (fr) * 1999-11-29 2001-06-07 L'oreal UTILISATION D'INHIBITEURS D'HMG CoA-REDUCTASE POUR LE TRAITEMENT DE LA SEBORRHEE
US20020055533A1 (en) * 2000-09-01 2002-05-09 Sankyo Company, Limited Pharmaceutical composition

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IL121565A (en) * 1995-12-22 2002-02-10 Kowa Co Stabilized pharmaceutical preparations containing derivatives of acid (E) -3,5-DIHYDROXY-7- [4 (-4) -FLUOROPHENYL-2 (CYCLOPROPYL-QUINOLIN-3 (-YL] -6-HEPTENOIC
JP2002145774A (ja) * 2000-09-01 2002-05-22 Sankyo Co Ltd 医薬組成物

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996008248A1 (fr) * 1994-09-13 1996-03-21 Ramot University Authority For Applied Research And Industrial Development Ltd. Composition pour le traitement d'affections de la peau
EP0738510A2 (fr) * 1995-04-20 1996-10-23 L'oreal Utilisation d'un inhibiteur d'hmg coenzyme A reductase pour lutter contre le vieillissement de la peau
WO1997026874A1 (fr) * 1996-01-23 1997-07-31 Novartis Ag Utilisation des derives de la fluvastatine dans les maladies de la peau et compositions topiques a base de ces derives
WO2000002541A1 (fr) * 1998-07-09 2000-01-20 Lts Lohmann Therapie-Systeme Ag Emplatre transdermique contenant au moins un principe actif influant sur le taux de lipides sanguins
WO2001039770A1 (fr) * 1999-11-29 2001-06-07 L'oreal UTILISATION D'INHIBITEURS D'HMG CoA-REDUCTASE POUR LE TRAITEMENT DE LA SEBORRHEE
US20020055533A1 (en) * 2000-09-01 2002-05-09 Sankyo Company, Limited Pharmaceutical composition

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006001251A1 (fr) * 2004-06-24 2006-01-05 Kowa Co., Ltd. Composition d'atorvastatine a usage externe
JPWO2006001251A1 (ja) * 2004-06-24 2008-04-17 興和株式会社 アトルバスタチン外用剤組成物
JP4579920B2 (ja) * 2004-06-24 2010-11-10 興和株式会社 アトルバスタチン外用剤組成物
JP2010126478A (ja) * 2008-11-27 2010-06-10 Kowa Co 貼付剤
WO2012056509A1 (fr) * 2010-10-25 2012-05-03 興和株式会社 Composition pharmaceutique
WO2012057103A1 (fr) * 2010-10-25 2012-05-03 興和株式会社 Composition pharmaceutique
JP4981194B2 (ja) * 2010-10-25 2012-07-18 興和株式会社 医薬組成物
US12023318B2 (en) 2018-08-29 2024-07-02 Ucl Business Ltd Therapy for Inflammatory Linear Verrucous Epidermal Nevus (ILVEN)
JP2020070251A (ja) * 2018-10-30 2020-05-07 花王株式会社 オートファジー抑制剤
JP7156907B2 (ja) 2018-10-30 2022-10-19 花王株式会社 オートファジー抑制剤

Also Published As

Publication number Publication date
AU2003264443A1 (en) 2004-04-08
JPWO2004026297A1 (ja) 2006-01-12
AU2003264443A8 (en) 2004-04-08
JP4630065B2 (ja) 2011-02-09

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