WO2017061393A1 - Patch adhésif - Google Patents

Patch adhésif Download PDF

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Publication number
WO2017061393A1
WO2017061393A1 PCT/JP2016/079355 JP2016079355W WO2017061393A1 WO 2017061393 A1 WO2017061393 A1 WO 2017061393A1 JP 2016079355 W JP2016079355 W JP 2016079355W WO 2017061393 A1 WO2017061393 A1 WO 2017061393A1
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WO
WIPO (PCT)
Prior art keywords
sensitive adhesive
adhesive layer
pressure
fumarate
patch
Prior art date
Application number
PCT/JP2016/079355
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English (en)
Japanese (ja)
Inventor
佳奈 今村
康也 道中
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
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Application filed by 久光製薬株式会社 filed Critical 久光製薬株式会社
Priority to JP2017544493A priority Critical patent/JP6488021B2/ja
Publication of WO2017061393A1 publication Critical patent/WO2017061393A1/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
    • 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • 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
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone

Definitions

  • the present invention relates to a patch, and more particularly to a patch containing emedastin.
  • Emedastine is 1- (2-ethoxyethyl) -2- (4-methyl-1,4-diazepan-1-yl) -1H-benzimidazole (1- (2-Ethoxyethyl) -2- (4-methyl-1 , 4-diazepan-1-yl) -1H-benzimidazole)).
  • Emedastine is known as a drug having an antiallergic action and an antihistamine action (Japanese Patent Laid-Open No. 58-79983 (Patent Document 1)).
  • emedastine difumarate Emedastine Difumarate, molecular formula: C 17 H 26
  • Oral preparations such as capsules containing N 4 O.2C 4 H 4 O 4 , molecular weight: 534.56 are on the market.
  • Patent Document 2 JP-A-3-83924 discloses parenteral administration agents such as oily ointments, gelling agents, creams, lotions, and sprays using a liquid composition containing emedastin.
  • a patch containing emedastine for example, in International Publication No. 2012/144405 (Patent Document 3), an alkali metal diacetate, emedastine fumarate, and a non-aqueous adhesive base are mixed.
  • a patch comprising a pressure-sensitive adhesive layer formed using the obtained pressure-sensitive adhesive layer composition is disclosed in International Publication No. 2014/057928 (Patent Document 4) with emedastine and / or a pharmaceutically acceptable salt thereof.
  • a patch comprising an adhesive layer containing a rubber-based adhesive and / or a silicone-based adhesive and fumaric acid as a cohesive strength improver for the adhesive layer is described.
  • JP-A-7-33665 discloses an adhesive layer (adhesive layer) comprising an acrylic adhesive base, a silicone adhesive base or a rubber adhesive base and emedastine.
  • JP-A-8-193030 discloses a patch having an adhesive layer containing an acrylic polymer substantially free of acid residues and emedastin. Are described respectively.
  • Patent Document 7 describes a patch comprising a pressure-sensitive adhesive layer containing a basic drug such as fentanyl, oxybutynin and a volatile organic acid. Numerous organic acids or organic acid salts containing sodium fumarate are described as compounds that can be added as needed for the purpose of promoting percutaneous absorption of drugs. However, in Patent Document 7, there is no description regarding emedastine.
  • the acrylic adhesive is mainly used as the adhesive in the patch containing emedastin
  • the present inventors have higher transdermal permeability to emedastin than when the rubber adhesive is simply used.
  • the adhesive layer protrudes from the side surface (that is, end face or cross section) of the patch due to temperature and pressure during storage I found out that the problem occurs.
  • the phenomenon that the pressure-sensitive adhesive layer protrudes is also referred to as “glue protrusion” or “tongue protrusion”, and is covered with the support layer from the side surface of the patch on which the support layer and the pressure-sensitive adhesive layer are laminated.
  • the protruding pressure-sensitive adhesive layer adheres to the inner surface of the packaging material of the patch, making it difficult to take out the patch, or the protruding adhesive layer causes the support of the patch. This causes problems such as contamination of the layers and fingers and difficulty in applying the patch to the target site.
  • the present invention has been made in view of the above-described problems of the prior art, and provides a patch in which adhesive sticking out of the pressure-sensitive adhesive layer is sufficiently suppressed and the skin permeability and stability of emedastin are excellent. With the goal.
  • an acrylic adhesive in an adhesive patch comprising a support layer and an adhesive layer, emedastine and / or a pharmaceutically acceptable salt thereof, an acrylic adhesive
  • the present inventors have found that by incorporating fumarate in the pressure-sensitive adhesive layer, even if the content of the acrylic pressure-sensitive adhesive is large, the sticking out of the pressure-sensitive adhesive layer is sufficiently suppressed.
  • the present inventors have found that such a patch is also excellent in skin permeability and stability of emedastin, and have completed the present invention.
  • the patch of the present invention is a patch comprising a support layer and an adhesive layer
  • the pressure-sensitive adhesive layer contains at least one drug selected from the group consisting of emedastine and a pharmaceutically acceptable salt thereof, an acrylic pressure-sensitive adhesive, and a fumarate; and
  • the acrylic pressure-sensitive adhesive content is 30 to 98% by mass in the pressure-sensitive adhesive layer.
  • the number of moles converted to fumaric acid of the fumarate relative to 1 mole converted to the emedastine free form of the emedastine and pharmaceutically acceptable salt thereof is 0.1-4. .3 moles are preferred.
  • the content of the fumarate is preferably 0.5 to 35% by mass in the pressure-sensitive adhesive layer.
  • the fumarate is preferably an alkali metal fumarate, and the fumarate is monosodium fumarate, disodium fumarate, monopotassium fumarate, difumarate. It is preferably at least one selected from the group consisting of potassium, magnesium fumarate, and calcium fumarate.
  • the drug is an emedastine free form.
  • the patch of the present invention is a patch comprising a support layer and an adhesive layer, wherein the adhesive layer is at least one drug selected from the group consisting of emedastine and a pharmaceutically acceptable salt thereof. , An acrylic adhesive, and a fumarate.
  • the support layer according to the present invention is a layer that physically supports the pressure-sensitive adhesive layer and protects the pressure-sensitive adhesive layer from an external environment.
  • a support layer is not particularly limited, and any known support layer for a patch can be appropriately employed.
  • the material of the support layer include polyesters such as polyethylene terephthalate (PET), polybutylene terephthalate, and polyethylene naphthalate; polyolefins such as polyethylene and polypropylene; synthetic resins such as nylon and polycarbonate; and metals such as aluminum.
  • Examples of the form of the support layer include films; sheets such as foam sheets and porous sheets; fabrics such as woven fabrics, knitted fabrics and nonwoven fabrics; foils; and laminates thereof. Among these, a polyester film is preferable from the viewpoint of excellent flexibility and drug impermeability.
  • the thickness of the support layer is not particularly limited, but is usually preferably about 2 to 300 ⁇ m.
  • the patch of the present invention preferably has a structure in which the pressure-sensitive adhesive layer is laminated on one surface of the support layer. Moreover, it is more preferable that a release liner layer for protecting the pressure-sensitive adhesive layer is further laminated on the surface of the pressure-sensitive adhesive layer opposite to the support layer until the adhesive is used.
  • the release liner layer is not particularly limited, and any known release liner layer for patches can be appropriately employed. Polyesters such as polyethylene terephthalate (PET), polybutylene terephthalate, polyethylene naphthalate; polyethylene, polypropylene Polyolefins such as: films made of paper and the like, and laminates thereof.
  • PET polyethylene terephthalate
  • polybutylene terephthalate polyethylene naphthalate
  • polyethylene polypropylene Polyolefins
  • films made of paper and the like and laminates thereof.
  • a release liner layer a surface in contact with the pressure-sensitive adhesive layer is preferably coated with a silicone compound or a fluorine compound so that it can be easily peeled off from the pressure-sensitive adhesive layer.
  • a polyethylene terephthalate film coated with a compound is preferred.
  • the thickness of the release liner layer is not particularly limited, but it is usually preferably about 2 to 300 ⁇ m.
  • the pressure-sensitive adhesive layer according to the present invention contains at least one drug selected from the group consisting of emedastine and a pharmaceutically acceptable salt thereof, an acrylic pressure-sensitive adhesive, and a fumarate.
  • the thickness of such a pressure-sensitive adhesive layer is not particularly limited, but is usually preferably about 20 to 300 ⁇ m.
  • the pressure-sensitive adhesive layer according to the present invention contains at least one drug selected from the group consisting of emedastine and pharmaceutically acceptable salts thereof as a drug.
  • Emedastine has the following formula:
  • Such emedastin may be an emedastin free form (free base), a pharmaceutically acceptable salt of emedastin, or a mixture thereof, but it has a higher release property from the adhesive layer. From the viewpoint of improving, it is preferable that at least a part of the pressure-sensitive adhesive layer is contained in the form of an emedastin free body.
  • the above-mentioned emedastine free form is produced from a pharmaceutically acceptable salt of emedastin during and / or after production even if it is added as the free form during the manufacture of the patch. It may be contained in the agent.
  • a method for producing emedastin free form from a pharmaceutically acceptable salt of emedastin include, for example, the pressure-sensitive adhesive layer or the pressure-sensitive adhesive layer composition forming the pressure-sensitive adhesive layer. Examples thereof include a method in which the emedastine salt and a desalting agent are blended and the emedastine salt is desalted to obtain a free form thereof.
  • Examples of the pharmaceutically acceptable salt of emedastine include an acid addition salt of emedastin, and the acid includes monobasic acids such as hydrochloric acid, hydrobromic acid, methanesulfonic acid, and phosphoric acid; fumaric acid, Examples thereof include polybasic acids such as maleic acid, citric acid, and tartaric acid.
  • fumaric acid is preferable from the viewpoint that the following fumarate can be produced in the pressure-sensitive adhesive layer when the pressure-sensitive adhesive layer contains the desalting agent in combination.
  • the content of emedastine and the pharmaceutically acceptable salt thereof according to the present invention varies depending on the purpose of treatment, and thus cannot be generally specified.
  • release of emedastin The content in terms of body is preferably 1 to 20% by mass.
  • the content of emedastine and its pharmaceutically acceptable salt is more preferably in the pressure-sensitive adhesive layer,
  • the content in terms of the free form of emedastin is 2 to 20% by mass and 2.5 to 17% by mass.
  • the pressure-sensitive adhesive layer according to the present invention may further contain a drug other than emedastine within a range that does not impair the effects of the present invention.
  • drugs include, but are not limited to, antiemetics (eg, granisetron, azasetron, ondansetron, ramosetron, etc.), therapeutic drugs for frequent urination in overactive bladder (eg, oxybutynin, tolterodine, etc.), Angiotensin converting enzyme inhibitors (eg, captopril, delapril, etc.), Ca antagonists (eg, nifedipine, etc.), coronary vasodilators (eg, diltiazem, nicorandil, etc.), local anesthetics (eg, lidocaine, procaine, etc.), Thymus hormones (eg, serum thymic factor), muscle relaxants (eg, tizanidine, eperisone, d
  • a drug other than emedastine is further contained in the pressure-sensitive adhesive layer, its content varies depending on the purpose of treatment, and thus cannot be generally specified, but usually in the pressure-sensitive adhesive layer.
  • the content is preferably 0.1 to 20% by mass, and more preferably 10% by mass or less in the pressure-sensitive adhesive layer from the viewpoint that the adhesive layer has a suppression effect of sticking out and the skin permeability of emedastin is excellent. .
  • the pressure-sensitive adhesive layer according to the present invention contains an acrylic pressure-sensitive adhesive as a pressure-sensitive adhesive.
  • the pressure-sensitive adhesive means that it exhibits adhesiveness at the temperature at which the patch is applied (preferably 0 ° C. to 50 ° C., more preferably 10 ° C. to 40 ° C., more preferably 15 ° C. to 40 ° C.).
  • acrylic pressure-sensitive adhesive examples include a homopolymer having a (meth) acrylic acid alkyl ester as a monomer, and a copolymer of (meth) acrylic acid alkyl ester as a main monomer and other comonomers.
  • (meth) acrylic acid refers to acrylic acid and methacrylic acid.
  • Examples of the main monomer ((meth) acrylic acid alkyl ester) include butyl (meth) acrylate, isobutyl (meth) acrylate, hexyl (meth) acrylate, octyl (meth) acrylate, and (meth) acrylic acid 2- Examples thereof include ethylhexyl and decyl (meth) acrylate, and one of these may be used alone or two or more thereof may be combined.
  • Examples of the comonomer include hydroxyalkyl (meth) acrylate, ethylene, propylene, styrene, vinyl acetate, N-vinyl-pyrrolidone, acrylic amide, and the like. It may be a combination of the above.
  • acrylic pressure-sensitive adhesives examples include acrylic acid / octyl acrylate ester copolymers, 2-ethylhexyl acrylate, and the like that are listed in the “Pharmaceutical Additives Dictionary 2007 (edited by Japan Pharmaceutical Additives Association)”.
  • Vinyl pyrrolidone copolymer solution acrylic ester / vinyl acetate copolymer, 2-ethylhexyl acrylate / 2-ethylhexyl methacrylate / dodecyl methacrylate copolymer, methyl acrylate / 2-ethylhexyl acrylate copolymer resin emulsion, acrylic resin Examples include acrylic polymers contained in the alkanolamine liquid, and one of these may be used alone or two or more of them may be combined.
  • acrylic pressure-sensitive adhesive commercially available products such as DURO-TAK acrylic pressure-sensitive adhesive series (manufactured by Henkel) and Eudragit series (manufactured by Higuchi Trading Co., Ltd.) may be used.
  • the acrylic pressure-sensitive adhesive includes a crosslinked type having a crosslinked structure in which polymers are crosslinked and a non-crosslinked type having no crosslinked structure.
  • the present inventors have a tendency that adhesive protrusion is more noticeable, but a fumarate is combined and contained in the pressure-sensitive adhesive layer.
  • the fumarate functions as a fluidization inhibitor of the acrylic pressure-sensitive adhesive, and paste sticking is sufficiently suppressed. I found out.
  • the acrylic pressure-sensitive adhesive according to the present invention is not particularly limited. However, from the viewpoint of particularly suppressing the sticking out of the pressure-sensitive adhesive layer, it may be a non-functional group or an OH group. It is particularly preferable that it has an OH group.
  • the content of the acrylic pressure-sensitive adhesive according to the present invention is 30% by mass or more in the pressure-sensitive adhesive layer.
  • the acrylic pressure-sensitive adhesive content in the pressure-sensitive adhesive layer is particularly preferably 30 to 98% by mass, preferably 30 to 97% by mass, 35 to 98% by mass, 35 to 97% by mass, More preferred are 50 to 98% by mass, 50 to 97% by mass, 60 to 98% by mass, 60 to 97% by mass, and 75 to 95% by mass.
  • the content of the acrylic pressure-sensitive adhesive is less than the lower limit, the skin permeability of emedastine tends to decrease, or the adhesive force and cohesive force of the pressure-sensitive adhesive layer tend to decrease.
  • the amount of the acrylic adhesive tends to be more prominent when the content of the acrylic adhesive is increased. Even when the content of the acrylic pressure-sensitive adhesive is not less than the above lower limit, the paste is sufficiently suppressed.
  • the pressure-sensitive adhesive layer according to the present invention includes, as necessary, a styrene-based block copolymer; a natural rubber; a polyisobutylene; a rubber-based pressure-sensitive adhesive such as polyisoprene; and a silicone-based pressure-sensitive adhesive such as organopolysiloxane (silicone).
  • Other pressure-sensitive adhesives may further be contained, but when these other pressure-sensitive adhesives are contained in the pressure-sensitive adhesive layer according to the present invention, they become difficult to be compatible with the acrylic pressure-sensitive adhesive.
  • the content thereof is preferably 60% by mass or less, and preferably 10% by mass or less in the pressure-sensitive adhesive layer. More preferably not.
  • the pressure-sensitive adhesive layer according to the present invention further contains a fumarate.
  • the present inventors combine the emedastine and / or a pharmaceutically acceptable salt thereof, the acrylic pressure-sensitive adhesive, and the fumarate to form the pressure-sensitive adhesive layer. It was found that the sticking out of the paste was sufficiently suppressed.
  • a filler or tackifier such as silica or talc is added as a fluidization inhibitor of an acrylic pressure-sensitive adhesive instead of fumarate, emedastin Skin permeability tends to decrease.
  • the fumarate has the following formula:
  • the metal examples include lithium (Li), sodium (Na), potassium (K), calcium (Ca), magnesium (Mg), and the like. It may be a combination.
  • the fumarate according to the present invention includes at least one fumarate selected from the group consisting of monosodium fumarate, disodium fumarate, monopotassium fumarate, dipotassium fumarate, magnesium fumarate, and calcium fumarate.
  • An acid alkali metal salt is preferred.
  • Such a fumarate may be added as the compound at the time of manufacture of the patch, or may be generated during and / or after manufacture and contained in the pressure-sensitive adhesive layer.
  • Examples of the method for containing such a fumarate in the pressure-sensitive adhesive layer include, for example, using an emedastine acid addition salt as the emedastine salt, and 0.5 to 4 equivalents relative to the acid-base equivalent of the emedastine acid addition salt.
  • Examples thereof include a method in which a desalting agent (more preferably 1 to 2 equivalents) is added to desalt the emedastine acid addition salt to produce an emedastin free form and a fumarate salt in the pressure-sensitive adhesive layer.
  • a desalting agent for example, 4 mol in the case of sodium hydroxide
  • emedastine difumarate + sodium tetrahydroxide Emedastine free form + disodium 2 fumarate + 4H 2 O
  • the method of desalting emedastine fumarate as described above to form emedastine free form and disodium fumarate in the pressure-sensitive adhesive layer can be mentioned.
  • the content of the fumarate according to the present invention is preferably 0.5 to 35% by mass, more preferably 1 to 35% by mass in the pressure-sensitive adhesive layer, and 1 to 20% by mass. More preferably, they are 1 to 18% by mass, 1 to 15% by mass, and 1 to 13% by mass.
  • the content (concentration) of the fumarate is less than the lower limit, the effect of suppressing the adhesive paste from the pressure-sensitive adhesive layer tends to decrease.
  • the number of moles converted to fumaric acid of the fumarate (hereinafter referred to as “fumedic acid”) relative to the number of moles of 1 converted to the emedastine free form of the emedastine and its pharmaceutically acceptable salt.
  • the number of moles of “fumaric acid” is preferably 0.1 to 4.3 mol, preferably 0.3 to 4.3 mol, 0.5 to 4.3 mol, 0.5 to 3 mol. 0.7 to 3 mol, 0.7 to 2.7 mol, 1 to 2.7 mol, and 1 to 2.4 mol are more preferable.
  • the concentration and the number of moles of fumarate in the pressure-sensitive adhesive layer are not particularly limited from the viewpoint that the adhesive layer is particularly prevented from sticking and the skin permeability and stability of emedastin are sufficient. It is particularly preferable that the above condition is satisfied.
  • the content of the fumarate is preferably 0.5 to 35% by mass, and the number of moles of fumaric acid is preferably 0.1 to 4.3 mol.
  • the content of the fumarate is 1 to 35% by mass (more preferably 1 to 20% by mass, 1 to 18% by mass, 1 to 15% by mass), and the number of moles of fumaric acid is 0.3%.
  • the content of the fumarate is 1 to 13% by mass, and the number of moles of fumaric acid is 0.5 to 4.3 mol (more preferably 0.3 mol). 5 to 3 mol, 0.7 to 3 mol, 0.7 to 2.7 mol, 1 to 2.7 mol, and 1 to 2.4 mol) are more preferable.
  • the pressure-sensitive adhesive layer according to the present invention may further contain a salt produced by the desalting agent and / or the desalting agent as long as the effects of the present invention are not impaired.
  • the desalting agent include metal ion-containing desalting agents such as sodium hydroxide, lithium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, and alkali metal salts of organic acids; ammonia and the like.
  • the acid include acetic acid, diacetic acid, propionic acid, butyric acid and the like.
  • the said metal ion containing desalting agent is preferable.
  • the content thereof is preferably 40% by mass or less in the pressure-sensitive adhesive layer, preferably 0.1 to More preferably, the acid-base equivalent converted to a desalting agent is 0.5 to 4 with respect to the acid-base equivalent converted to the acid addition salt of emedastin and its pharmaceutically acceptable salt.
  • the amount is preferably an equivalent amount, more preferably 1 to 2 equivalents.
  • the pressure-sensitive adhesive layer according to the present invention further includes additives such as a tackifier resin, a plasticizer, a transdermal absorption accelerator, a stabilizer, a filler, and a fragrance, as long as the effects of the present invention are not impaired. It may be contained.
  • additives such as a tackifier resin, a plasticizer, a transdermal absorption accelerator, a stabilizer, a filler, and a fragrance, as long as the effects of the present invention are not impaired. It may be contained.
  • the content thereof is preferably 20% by mass or less in the pressure-sensitive adhesive layer, more preferably 0.5 to 20% by mass. Preferably, it is 1 to 15% by mass.
  • the patch of the present invention is not particularly limited and can be produced by a conventionally known method.
  • the emedastine and / or the above-mentioned by roll mixing, Banbury mixer mixing, etc.
  • a pressure-sensitive adhesive layer composition containing the pharmaceutically acceptable salt, the acrylic pressure-sensitive adhesive, the fumarate, and, if necessary, the desalting agent and the additive is prepared.
  • the solvent method first, in the organic solvent, the emedastine and / or pharmaceutically acceptable salt thereof, the acrylic adhesive, the fumarate, and optionally the desalting agent or
  • the pressure-sensitive adhesive layer composition is prepared by mixing the additive, applied to one surface of the release liner layer at a desired thickness, and then the solvent is removed by drying to laminate the support layer. Then, the patch of the present invention can be obtained by appropriately cutting this.
  • the adhesive layer composition is applied on one surface of the support layer to a desired thickness, the solvent is dried and removed, and the release liner layer is laminated as necessary, and this is appropriately cut. By doing so, the patch of the present invention can be obtained.
  • the organic solvent is not particularly limited and can be appropriately selected depending on the type of drug, adhesive, fumarate, etc. used, for example, ethyl acetate, toluene, cyclohexane, hexane, ethanol, methanol, isopropanol, etc. Can be used.
  • emedastin free substance and the fumarate salt are produced during production and / or after production and contained in the pressure-sensitive adhesive layer
  • emedas By using a composition containing chin fumarate, the acrylic pressure-sensitive adhesive, the desalting agent, the organic solvent, and, if necessary, the additive, emedastine free substance and the above-mentioned Fumarate can be included.
  • the patch of the present invention is preferably sealed in a packaging bag.
  • the packaging bag is not particularly limited, and those that can be used as a packaging bag for normal patches can be appropriately used.
  • each aluminum laminate bag is taken out from the chamber and opened, and the adhesive layer protrudes beyond the area covered by the support layer from the side of the patch (The paste protruding part) was removed, and the mass of the patch after the paste protruding part was removed was measured using the electronic balance to obtain a mass of 2. Subsequently, all the remaining pressure-sensitive adhesive layers were also removed from the support layer using a solvent, and the masses of the support layer and the release liner layer were measured using the electronic balance to obtain a mass of 3.
  • ⁇ Skin permeability test> First, the skin on the back of the hairless mouse is peeled off, the patches obtained in each Example and Comparative Example are applied to the epidermis side, and the flow-through type Franz type permeation test cell (the dermis side is the receptor tank side) 3 cm 2 ). Next, the receptor bath was filled with a phosphate buffer solution as a receptor solution, and the receptor solution was sampled every 4 hours up to 24 hours while circulating hot water at 32 ° C. around the permeation test cell.
  • the amount of emedastine in the sampled solution was measured using a high performance liquid chromatography apparatus (manufactured by Shimadzu Corporation, column: ODS column, mobile phase: 3 mM sodium 1-heptanesulfonate-0.1% glacial acetic acid / methanol (45 / 55 (volume ratio)), detection wavelength: 280 nm).
  • the drug skin permeation rate (Jmax) per hour and the cumulative skin permeation amount up to 24 hours were calculated from the obtained measured values.
  • Example 1 First, 2.83 parts by mass of emedastin free substance, 2.99 parts by mass of disodium fumarate, acrylic adhesive 1 (non-crosslinked polyacrylic acid copolymer having an OH group, DURO-TAK87-2510 (Henkel Corporation) 94.18 parts by mass in ethyl acetate was stirred to obtain a pressure-sensitive adhesive layer composition.
  • the obtained pressure-sensitive adhesive layer composition was applied onto the silicone compound-coated surface of the polyethylene terephthalate film (release liner layer) coated with the silicone compound, then dried to remove the solvent, and the pressure-sensitive adhesive having a thickness of 200 ⁇ m.
  • emedastine fumaric acid
  • emedastine fumaric acid
  • Table 1 the molar ratio of emedastine to fumaric acid (emedastine: fumaric acid) is the fumaric acid of fumarate with respect to 1 mol of mol converted to emedastin free form and / or emedastine free form of emedastine salt.
  • Example 2 to 3 Comparative Examples 1 to 3
  • the patches of Examples 2 to 3 and Comparative Examples 1 to 3 were obtained in the same manner as in Example 1 except that the composition of the adhesive layer was changed to the composition shown in Table 1.
  • acrylic pressure-sensitive adhesive 2 represents a cross-linked polyacrylic acid copolymer having an OH group (solid content of DURO-TAK87-2516 (manufactured by Henkel)).
  • the mass converted into the emedastine free body of emedastine difumarate (10.00 mass parts) is 5.66 mass parts.
  • the results of the paste protrusion evaluation test are shown in Table 1 together with the composition of each patch.
  • the result of the paste protrusion evaluation test in the patches obtained in Examples 1 and 3 and Comparative Examples 1 and 3 shows the result after standing for 1 day
  • the patches obtained in Example 2 and Comparative Example 2 The result of the paste protrusion evaluation test in the preparation shows the result after standing for 7 days.
  • Example 4 to 6 Patches of Examples 4 to 6 and Comparative Examples 4 to 5 were obtained in the same manner as in Example 1 except that the composition of the pressure-sensitive adhesive layer was changed to the composition shown in Table 2.
  • the rubber adhesive is styrene-isoprene-styrene block copolymer (SIS), polyisobutylene (PIB), alicyclic saturated hydrocarbon resin (Arcon P-100, manufactured by Arakawa Chemical Industries). , Shows a mixture containing liquid paraffin in a mass ratio of 17.5: 7.5: 55: 20.
  • Examples 7 to 10 Comparative Example 6
  • the adhesive layers of Examples 7 to 10 were obtained in the same manner as in Example 1 except that the composition of the adhesive layer was as shown in Table 3 and the thickness of the adhesive layer was 50 ⁇ m.
  • the patch of the comparative example 6 was obtained like the comparative example 3 except having made the thickness of the adhesive layer into 50 micrometers.
  • Table 3 shows the results of a stability evaluation test and a skin permeability test for the patches obtained in Examples 7 to 10 and Comparative Example 6, respectively, together with the composition of each patch.
  • the results were the same as the results in Examples 1 to 3 and 5, and the results in Examples 13 to 15 below. Both results were equivalent.
  • Example 11 to 17 Patches of Examples 11 to 17 were obtained in the same manner as in Example 1 except that the composition of the pressure-sensitive adhesive layer was changed to the composition shown in Table 4. Each patch obtained in Examples 11 to 17 was subjected to a paste protrusion evaluation test (1 day standing). The adhesive protrusion improvement rates of Examples 11 to 17 for Comparative Example 3 were calculated in the same manner as the adhesive protrusion improvement rate of Example 1 for Comparative Example 1 described above. Table 4 shows the improvement rate of the obtained paste protrusion together with the composition of each patch. Table 4 also shows the composition of the patches obtained in Example 5 and Comparative Example 3 and the rate of improvement in paste protrusion for reference.
  • Example 18 to 21 The patches of Examples 18 to 21 were obtained in the same manner as in Example 1 except that the composition of the pressure-sensitive adhesive layer was as shown in Table 5 and the thickness of the pressure-sensitive adhesive layer was 50 ⁇ m. Table 5 shows the results of the stability evaluation tests for the patches obtained in Examples 18 to 21 together with the composition of each patch. Table 5 also shows the composition and evaluation results of the patches obtained in Examples 7 to 10 and Comparative Example 6 for reference.
  • Examples 22 to 24, Comparative Examples 7 to 11 Patches of Examples 22 to 24 and Comparative Examples 7 to 11 were obtained in the same manner as in Example 1 except that the composition of the adhesive layer was changed to the composition shown in Table 6.
  • the rubber adhesive is styrene-isoprene-styrene block copolymer (SIS), polyisobutylene (PIB), alicyclic saturated hydrocarbon resin (Alcon P-100, manufactured by Arakawa Chemical Industries). , Shows a mixture containing liquid paraffin in a mass ratio of 17.5: 7.5: 55: 20.
  • Example 22 for Comparative Example 7 Example 23 for Comparative Example 8, Example 24 for Comparative Example 9, and Comparative Example 10 for Comparative Example 10 show the paste protrusion improvement rates, respectively. Calculation was performed in the same manner as the protrusion improvement rate.
  • Table 6 shows the obtained paste protrusion improvement rate together with the composition of each patch. In addition, the composition and evaluation results of the patches obtained in Example 5 and Comparative Example 3 are also shown in Table 6 for reference.

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Abstract

La présente invention concerne un patch adhésif qui comprend une couche de support et une couche adhésive, et : ladite couche adhésive contenant un adhésif acrylique, un sel de fumarate, et au moins un médicament sélectionné dans le groupe constitué par l'émédastine et des sels pharmaceutiquement acceptables de celle-ci; et la teneur de l'adhésif acrylique étant de 30 à 98 % en masse dans la couche adhésive.
PCT/JP2016/079355 2015-10-06 2016-10-03 Patch adhésif WO2017061393A1 (fr)

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JP2017544493A JP6488021B2 (ja) 2015-10-06 2016-10-03 アクリル系粘着剤の流動化抑制方法

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2019094301A (ja) * 2017-11-24 2019-06-20 久光製薬株式会社 貼付剤

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012144405A1 (fr) * 2011-04-18 2012-10-26 久光製薬株式会社 Procédé de fabrication d'une pièce adhésive et pièce adhésive
WO2014057928A1 (fr) * 2012-10-11 2014-04-17 久光製薬株式会社 Timbre transdermique
WO2015115497A1 (fr) * 2014-01-31 2015-08-06 久光製薬株式会社 Ruban adhésif contenant de l'emédastine

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JPS5879983A (ja) * 1981-11-06 1983-05-13 Kanebo Ltd 新規なベンズイミダゾ−ル誘導体、その製造法およびその医薬組成物
JPH0383924A (ja) * 1989-08-28 1991-04-09 Kanebo Ltd 経皮投与用組成物
JPH0733665A (ja) * 1993-05-18 1995-02-03 Kanebo Ltd エメダスチンを含有する粘着性貼付剤
JPH08193030A (ja) * 1995-01-12 1996-07-30 Nitto Denko Corp エメダスチン貼付製剤
RU2543639C2 (ru) * 2009-09-07 2015-03-10 Нипро Пэтч Ко., Лтд. Чрескожно всасывающийся препарат

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012144405A1 (fr) * 2011-04-18 2012-10-26 久光製薬株式会社 Procédé de fabrication d'une pièce adhésive et pièce adhésive
WO2014057928A1 (fr) * 2012-10-11 2014-04-17 久光製薬株式会社 Timbre transdermique
WO2015115497A1 (fr) * 2014-01-31 2015-08-06 久光製薬株式会社 Ruban adhésif contenant de l'emédastine

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2019094301A (ja) * 2017-11-24 2019-06-20 久光製薬株式会社 貼付剤

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