WO2010098230A1 - Préparation transdermique - Google Patents

Préparation transdermique Download PDF

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Publication number
WO2010098230A1
WO2010098230A1 PCT/JP2010/052249 JP2010052249W WO2010098230A1 WO 2010098230 A1 WO2010098230 A1 WO 2010098230A1 JP 2010052249 W JP2010052249 W JP 2010052249W WO 2010098230 A1 WO2010098230 A1 WO 2010098230A1
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WO
WIPO (PCT)
Prior art keywords
citalopram
preparation
transdermal administration
skin irritation
triamcinolone acetonide
Prior art date
Application number
PCT/JP2010/052249
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English (en)
Japanese (ja)
Inventor
昭雄 竹内
健治 新
Original Assignee
久光製薬株式会社
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 久光製薬株式会社 filed Critical 久光製薬株式会社
Priority to JP2011501555A priority Critical patent/JP5740300B2/ja
Publication of WO2010098230A1 publication Critical patent/WO2010098230A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
    • A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
    • A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
    • A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
    • 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
    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants
    • 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 a transdermal administration preparation that absorbs citalopram through the skin.
  • Citalopram is a drug classified as a selective serotonin reuptake inhibitor (SSRI) and is used as a drug to improve major depressive disorder, neurotic disorder, acute stress disorder, eating disorder, etc. (Patent Documents 1 to 3). As the administration method, oral administration is common. It is known that citalopram has R and S optical isomers.
  • SSRI selective serotonin reuptake inhibitor
  • Patent Document 3 discusses administration of an antidepressant such as SSRI by transdermal administration, and citalopram is mentioned as an example of an antidepressant.
  • citalopram when citalopram is administered transdermally, there is a problem that strong skin irritation occurs as a side effect. Therefore, in order to provide a citalopram-containing transdermal absorption preparation with little skin irritation that can actually be used at the treatment site, a citalopram-containing patch capable of long-term administration has been demanded.
  • Patent Document 5 discloses that skin irritation is reduced by administering an irritating drug together with a lactone compound having a hydroxyl group.
  • a lactone compound having a hydroxyl group there is room for improvement in skin irritation of a citalopram-containing preparation. There is.
  • Patent Document 6 discloses that a skin irritation reducing component (hydroquinone glycoside, pantethine, tranexamic acid, lecithin, etc.) can be blended with a patch containing fluvoxamine or fluvoxamine maleate as SSRI.
  • a skin irritation reducing component hydroquinone glycoside, pantethine, tranexamic acid, lecithin, etc.
  • Patent Document 4 discloses adding hydrocortisone to a preparation containing fluoxetine, which is an example of SSRI, in order to reduce skin irritation.
  • an object of the present invention is to provide a preparation for transdermal administration which is excellent in skin absorbability of citalopram and has excellent safety by reducing skin irritation caused by citalopram.
  • the present inventors formulated various skin irritation reducing components and anti-inflammatory agents in preparations showing a tendency to show primary skin irritation (Primary Skin Irritation) containing citalopram or a salt thereof, and have an effect on skin irritation. As a result of the investigation, it was found that specific anti-inflammatory steroids effectively reduce the skin irritation of citalopram.
  • the present invention is a transdermal administration preparation for reducing skin irritation caused by citalopram, comprising at least one drug selected from the group consisting of citalopram and a pharmaceutically acceptable salt thereof, triamcinolone acetonide,
  • a transdermal administration preparation containing at least one steroid selected from the group consisting of flumethasone pivalate, alcromethasone propionate, clobetasone butyrate, hydrocortisone butyrate, dexamethasone and prednisolone valerate acetate.
  • the steroid agent is preferably triamcinolone acetonide because of its excellent synergistic effect with the above drugs.
  • the content of triamcinolone acetonide can be 0.005 to 0.5% by mass based on the total mass (based on the total amount of the preparation for transdermal administration).
  • Sitalopram is preferably S-form, that is, escitalopram, among optical isomers.
  • Oxalate is excellent as a pharmaceutically acceptable salt of escitalopram, and a patch can be applied as a dosage form of a transdermal preparation.
  • a patch can be applied as a dosage form of a transdermal preparation.
  • it is preferable to contain a styrene-isoprene-styrene block copolymer.
  • the present invention further provides a method of administering citalopram, particularly a method of reducing side effects caused by citalopram.
  • the method of the present invention comprises at least one drug selected from the group consisting of citalopram and pharmaceutically acceptable salts thereof, triamcinolone acetonide, flumethasone pivalate, alcromethasone propionate, clobetasone butyrate, hydrocortisone butyrate, dexamethasone and And a step of administering to a patient a transdermal preparation containing at least one steroid selected from the group consisting of prednisolone valerate.
  • the method of the present invention it is possible to avoid side effects such as nausea, diarrhea, and digestive tract disorders caused by oral administration of citalopram, and to reduce skin irritation caused by transdermal administration of citalopram, so that the administration method of citalopram is excellent in safety. Can provide.
  • the transdermal administration formulation of the present invention is excellent in skin absorbability of citalopram, and is excellent in safety by reducing skin irritation caused by citalopram. Therefore, according to the preparation for transdermal administration of the present invention, skin irritation caused by citalopram is remarkably reduced and the absorption of citalopram is excellent even when the preparation is applied for a long time in anticipation of systemic pharmacological effects. .
  • the drug used in the present invention is citalopram (1- (4-fluorophenyl) -1- [3- (dimethylamino) propyl] -1,3-dihydroisobenzofuran-5-carbonitrile) or a pharmaceutical thereof Is an acceptable salt.
  • Citalopram has two optical isomers, R-form and S-form, but “citalopram” in this specification is any mixture of R-form and S-form, R-form, or S-form unless otherwise specified. Means.
  • Examples of the pharmaceutically acceptable salt of citalopram include citalopram hydrobromide, citalopram hydrochloride, citalopram oxalate, etc. Among them, citalopram hydrobromide is particularly preferable.
  • citalopram S-form which is an optical isomer, that is, escitalopram (Escitalopram; (S) -1- (4-fluorophenyl) -1- [3- (dimethylamino) propyl] -1,3-dihydroiso Benzofuran-5-carbonitrile) is preferably used, and pharmaceutically acceptable salts thereof include escitalopram oxalate.
  • the compounding amount of the above drug in the preparation is preferably 0.01 to 20% by mass, more preferably 1 to 10% by mass, based on the total mass of the transdermal preparation as citalopram. Within this range, a sufficient amount of drug for treatment can be absorbed through the skin and a preparation with less skin irritation can be obtained.
  • total mass basis of transdermal administration formulation means the total mass basis when the transdermal administration formulation is an ointment, gel, cream, liquid, etc. When the preparation is a patch, it means the total mass standard of the adhesive layer.
  • steroid agent steroid external preparation
  • a drug classified as medium (IV group) on the classification (IV class) indicating the strength of the external steroid agent is used. That is, at least one steroid agent selected from the group consisting of triamcinolone acetonide, flumetasone pivalate, alcromethasone propionate, clobetasone butyrate, hydrocortisone butyrate, dexamethasone and prednisolone acetate valerate is used.
  • Such steroids also reduce side effects derived from steroids compared to strong steroids (I-III).
  • the blending amount of the steroid used in the present invention into the transdermal preparation varies depending on each steroid, but is blended in the range of 0.001% to 3% by mass based on the total mass of the transdermal preparation.
  • the content is 0.01% by mass to 0.5% by mass.
  • it is the compounding quantity in an external preparation.
  • triamcinolone acetonide is 0.01 mass% to 0.2 mass%
  • flumethasone pivalate is 0.01 mass% to 0.05 mass%
  • alcromethasone propionate is 0.05 mass% to 0.2 mass%
  • 0.01% to 0.1% by weight of clobetasone butyrate 0.01% to 0.2% by weight of hydrocortisone butyrate
  • prednisolone acetate valerate Is preferably from 0.05% by mass to 0.5% by mass.
  • the classification of the strength of the anti-inflammatory action of the steroid can be determined according to the method (particularly ointment) described in Journal of Japanese Dermatological Association, 110 (7), 1099-1104, 2000.
  • Triamcinolone acetonide is particularly preferable as the steroid used in the present invention because the skin irritation suppressing effect is high even at low concentrations.
  • the amount of triamcinolone acetonide is 0.005% by mass to 0.5% by mass based on the total mass of the preparation for transdermal administration.
  • the blending amount of triamcinolone acetonide is more preferably 0.01% by mass to 0.1% by mass.
  • the preparation for transdermal administration of the present invention can further contain additives such as a basic compound, a plasticizer, an absorption accelerator, and an organic acid as necessary.
  • an acid addition salt is used as a pharmaceutically acceptable salt of citalopram
  • a basic compound examples include low molecular compounds containing basic nitrogen (triethanolamine, diisopropanolamine, diethanolamine, etc.), and high molecular compounds containing basic nitrogen (aminoalkyl methacrylate copolymer E, polyvinyl acetal diethylaminoacetate, Polyvinyl pyridine, etc.) and basic alkali metal salts (sodium acetate, potassium acetate, sodium borate, sodium carbonate, trisodium citrate, sodium silicate, sodium hydroxide, potassium hydroxide, etc.).
  • sodium acetate, sodium carbonate, sodium hydroxide, and potassium hydroxide are preferable, and sodium hydroxide and potassium hydroxide are particularly preferable.
  • the transdermal administration preparation of the present invention can further contain a transdermal absorption enhancer as necessary.
  • the transdermal absorption enhancer is not particularly limited as long as it can absorb the necessary amount for treatment from the skin, but 0.5 to 20% by mass based on the entire preparation is blended.
  • Such an absorption promoter may be any compound that has been conventionally recognized as having an effect of promoting absorption into the skin, such as fatty acids, fatty alcohols, fatty acid esters or ethers having 6 to 20 carbon atoms, aromatic organic acids, Aromatic alcohols, aromatic organic acid esters, or ethers (they may be saturated or unsaturated, and may be cyclic, linear or branched), lactic acid esters, and acetic acid esters , Monoterpene compounds, azone, azone derivatives, glycerol fatty acid esters, sorbitan fatty acid esters (Span system), polysorbate (Tween system), polyethylene glycol fatty acid esters, polyoxyethylene hydrogenated castor oil system ( HCO), sugar fatty acid esters, fatty acid alkylolamide, etc. It is.
  • caprylic acid caproic acid, lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, lauryl alcohol, myristyl alcohol, oleyl alcohol, Stearyl alcohol, cetyl alcohol, methyl laurate, hexyl laurate, diethanolamide laurate, isopropyl myristate, diethyl sebacate, diisopropyl adipate, propylene glycol monolaurate, N-methyl-2-pyrrolidone, pyrothiodecane, l-menthol , D-limonene.
  • Such absorption promoters can be used alone or in admixture of two or more.
  • the plasticizer is not particularly limited as long as it is a compound having plasticity.
  • petroleum oil paraffinic process oil, naphthenic process oil, aromatic process oil, etc.
  • squalane squalene
  • plant system Oil oil, camellia oil, castor oil, tall oil, peanut oil
  • silicon oil dibasic acid ester (dibutyl phthalate, dioctyl phthalate, etc.)
  • liquid rubber polybutene, liquid isoprene rubber
  • liquid fatty acid esters myristic acid
  • diethylene glycol polyethylene glycol, glycol salicylate, propylene glycol, dipropylene glycol, triacetin, triethyl citrate, Tamiton and the like.
  • plasticizers can be used alone or in admixture of two or more.
  • an antioxidant an ultraviolet absorber, and a crystallization inhibitor can be used.
  • the antioxidant include tocopherol and their ester derivatives, ascorbic acid, ascorbic acid stearate, nordi. Human log ayaretic acid, dibutylhydroxytoluene (BHT), butylhydroxyanisole and the like are preferable.
  • the ultraviolet absorber p-aminobenzoic acid derivatives, anthranilic acid derivatives, salicylic acid derivatives, coumarin derivatives, amino acid compounds, imidazoline derivatives, pyrimidine derivatives, dioxane derivatives and the like are desirable.
  • the crystallization inhibitor polyvinylpyrrolidone or the like is desirable.
  • the preparation for transdermal administration of the present invention is not particularly limited as long as it is a dosage form capable of supplying a drug for a period required for treatment, and patches, ointments, gels, creams, liquids and the like can be used.
  • a dosage form capable of supplying an effective amount of a drug for a long time a patch is mentioned as a dosage form suitable for the present invention.
  • a patch containing substantially no water is particularly preferable from the viewpoint of excellent stability of the drug in the preparation.
  • “Contains substantially no water” means that the preparation is composed of a non-aqueous material. However, it is permissible for the preparation to contain a trace amount of water of 1% by mass or less derived from the raw material or the production environment.
  • a patch having a non-aqueous adhesive layer has a relatively strong adhesive force and therefore has good adhesion to the skin. Also, compared with a patch having an aqueous adhesive layer, the patch absorbs the skin of the drug. Can be increased.
  • the patch using the non-aqueous adhesive layer of the present invention has less skin irritation and excellent treatment. There is an effect.
  • the patch When the dosage form is a patch, the patch preferably has a configuration having an adhesive layer on a support, and may have a release liner on the adhesive layer.
  • Base materials used for the adhesive layer include styrene-isoprene-styrene block copolymer (SIS), isoprene rubber, polyisobutylene (PIB), styrene-butadiene-styrene block copolymer (SBS), and styrene-butadiene rubber.
  • SBR polyacrylate copolymers
  • polyacrylate copolymers at least two copolymers of 2-ethylhexyl acrylate, vinyl acetate, methacrylate, methoxyethyl acrylate, and acrylic acid
  • adhesives for drugs used It is possible to select appropriately in consideration of solubility in water. Moreover, it is also possible to mix and use these adhesives.
  • a tackifier such as rosin, terpene, or petroleum resin may be used in combination.
  • the support used for the patch is not particularly limited, but a non-stretchable or stretchable material such as a polymer film, a woven fabric or a non-woven fabric can be used and provided on the support. It is preferable that the material does not adsorb or permeate the drug contained in the adhesive layer.
  • a non-stretchable or stretchable material such as a polymer film, a woven fabric or a non-woven fabric can be used and provided on the support. It is preferable that the material does not adsorb or permeate the drug contained in the adhesive layer.
  • polyethylene terephthalate, polyurethane, polyethylene, polypropylene, rayon, cotton, and an aluminum sheet can be mentioned, and these may be laminated and used.
  • the release liner used for the patch is not particularly limited as long as it protects the adhesive surface during the period until the patch is used, but polyolefin, polyester, ethylene-vinyl acetate copolymer, paper, etc. Can be mentioned. Among these, polyethylene, polypropylene, and polyethylene terephthalate can be preferably used.
  • the surface may be subjected to a release treatment with silicone or fluorine, or may be provided with a cut such as a back crack, a half cut, or a perforation.
  • the adhesion area of the preparation preferably to 10 ⁇ 60cm 2.
  • the preparation for transdermal administration of the present invention can contain a conventional base depending on the dosage form even in a dosage form other than the patch.
  • a liquid preparation it contains a lower alcohol, a polyhydric alcohol, water and the like. be able to.
  • an oily base, a higher alcohol, a fatty acid ester, a polyhydric alcohol and derivatives thereof, a surfactant, a gelling agent, water and the like can be included.
  • part means part by mass.
  • a drug was added to a mixed solution of 65 parts of SIS, 35 parts of PIB, 180 parts of tackifier, 40 parts of liquid paraffin and toluene (solvent) prepared using a mixer to obtain an adhesive solution. This is spread on a release-treated film, and the solvent is dried and removed to form an adhesive layer. Then, a support is placed on the adhesive layer, and the adhesive layer is pressure-transferred to transfer the transdermal patch. An agent was obtained.
  • Each formulation used in the following test examples was formulated with 8.0% of escitalopram oxalate as a drug according to the above general method and a predetermined amount of the additives described in each of the examples and comparative examples. (Containing SIS, PIB, tackifier, and liquid paraffin in the composition ratio described in the above production method) were blended so that the entire preparation was 100%.
  • Test Example 1 Effect of additive on primary skin irritation of preparation containing escitalopram oxalate ⁇ Test method>
  • the back of the rabbit was depilated and various test preparations containing the additives shown in Table 1 were applied for 24 hours.
  • the skin redness 25 hours after administration was measured using a color difference meter.
  • the test results are shown in Table 1.
  • Test Example 2 Effect of steroid agent on primary skin irritation of preparation containing escitalopram oxalate ⁇ Test method>
  • the back of the rat was depilated and various test preparations containing the steroids listed in Table 2 were affixed.
  • the skin reaction 25, 48, and 72 hours after administration was evaluated according to the Draize method, and a primary irritation index (Primary Irritation Index, PII) was calculated.
  • the test results are shown in Table 2.
  • Test Example 3 Skin permeability of escitalopram oxalate-containing preparation containing triamcinolone acetonide ⁇ Test method>
  • the dorsal skin of the hairless mouse was peeled off, and attached to a flow-through cell in which warm water of 32 ° C. was circulated around the outer periphery with the dermis side as the receptor side.
  • various test preparations are affixed to the stratum corneum side of the skin, and the receptor solution is sampled up to 24 hours every 2 hours at 5 mL / hr using a phosphate buffer (pH 7.4) as the receptor layer.
  • the drug concentration was measured using high performance liquid chromatography. The maximum value of the skin permeation rate of the drug per hour and the total amount of drug permeation up to 24 hours were calculated from the obtained measured values.
  • the test results are shown in Table 3.
  • the transdermally absorbable preparation of the present invention can be obtained by adding triamcinolone acetonide to escitalopram.
  • the skin irritation of escitalopram was significantly reduced to a very low level without being disturbed.
  • the transdermally absorbable preparation of the present invention is useful because the skin irritation caused by citalopram is remarkably reduced by adding a specific steroid, and an amount of citalopram that can be expected to have a sufficient therapeutic effect can be transdermally administered. is there.

Abstract

La présente invention concerne une préparation transdermique parfaitement sans risque qui permet une excellente absorption percutanée de citalopram, tout en présentant une réduction de l'irritation cutanée due au citalopram. L'invention concerne spécifiquement une préparation transdermique destinée à réduire l'irritation cutanée due au citalopram. Cette préparation transdermique contient au moins un médicament choisi dans un groupe constitué de citalopram et de ses sels pharmaceutiquement acceptables et d'au moins un stéroïde choisi dans un groupe constitué de triamcinolone acétonide, fluméthasone pivalate, alclométasone dipropionate, clobétasone butyrate, hydrocortisone butyrate, dexaméthasone et prednisolone valérate acétate.
PCT/JP2010/052249 2009-02-27 2010-02-16 Préparation transdermique WO2010098230A1 (fr)

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JP2009-046893 2009-02-27

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WO2017037812A1 (fr) * 2015-08-29 2017-03-09 株式会社メドレックス Préparation pharmaceutique sous forme de timbre comprenant un accepteur d'acide
US10016502B2 (en) 2015-08-29 2018-07-10 Medrx Co., Ltd Patch preparation containing an acid scavenger
WO2020158879A1 (fr) 2019-01-31 2020-08-06 久光製薬株式会社 Timbre adhésif

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CN105030733A (zh) * 2015-07-08 2015-11-11 成都易创思生物科技有限公司 一种复方曲安奈德涂膜剂及其制备方法
WO2017037812A1 (fr) * 2015-08-29 2017-03-09 株式会社メドレックス Préparation pharmaceutique sous forme de timbre comprenant un accepteur d'acide
WO2017038768A1 (fr) * 2015-08-29 2017-03-09 株式会社メドレックス Préparation pharmaceutique collante comprenant un capteur d'acide
JP6161142B1 (ja) * 2015-08-29 2017-07-12 株式会社 メドレックス 酸捕捉剤を含有する貼付製剤
CN107921043A (zh) * 2015-08-29 2018-04-17 株式会社梅德瑞科思 含有酸捕捉剂的贴剂
US10016502B2 (en) 2015-08-29 2018-07-10 Medrx Co., Ltd Patch preparation containing an acid scavenger
US10639374B2 (en) 2015-08-29 2020-05-05 Medrx Co., Ltd Patch preparation containing an acid scavenger
CN107921043B (zh) * 2015-08-29 2021-08-10 美德阿利克斯株式会社 含有酸捕捉剂的贴剂
WO2020158879A1 (fr) 2019-01-31 2020-08-06 久光製薬株式会社 Timbre adhésif
CN113382724A (zh) * 2019-01-31 2021-09-10 久光制药株式会社 贴剂
KR20210113308A (ko) 2019-01-31 2021-09-15 히사미쓰 세이야꾸 가부시키가이샤 첩부제
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