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WO2008075665A1 - Préparation absorbable par voie transdermique et feuille adhésive destinée à être appliquée sur la peau - Google Patents

Préparation absorbable par voie transdermique et feuille adhésive destinée à être appliquée sur la peau Download PDF

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Publication number
WO2008075665A1
WO2008075665A1 PCT/JP2007/074280 JP2007074280W WO2008075665A1 WO 2008075665 A1 WO2008075665 A1 WO 2008075665A1 JP 2007074280 W JP2007074280 W JP 2007074280W WO 2008075665 A1 WO2008075665 A1 WO 2008075665A1
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WO
WIPO (PCT)
Prior art keywords
sensitive adhesive
pressure
adhesive composition
skin
polymer
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/JP2007/074280
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English (en)
Japanese (ja)
Inventor
Shuhei Taniguchi
Masaoki Goto
Yoichi Matsumura
Masao Sato
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Kaneka Corp
Original Assignee
Kaneka Corp
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Filing date
Publication date
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Priority to JP2008550148A priority Critical patent/JPWO2008075665A1/ja
Publication of WO2008075665A1 publication Critical patent/WO2008075665A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • 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
    • A61K31/12—Ketones
    • A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
    • 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
    • A61K9/7069—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained otherwise than by reactions only involving carbon to carbon unsaturated bonds, e.g. polysiloxane, polyesters, polyurethane, polyethylene oxide
    • 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
    • A61P17/18—Antioxidants, e.g. antiradicals

Definitions

  • the present invention relates to a treatment for a diseased part of the body or a transdermal absorption preparation for administering a physiologically active substance to the circulatory system or skin, and an adhesive sheet applied to the skin surface to protect or treat the skin surface.
  • the present invention relates to a transdermally absorbable preparation excellent in solubility, skin adhesive properties and skin fixability of a physiologically active substance regardless of the type of the physiologically active substance.
  • an adhesive base for this transdermally absorbable preparation As an adhesive base for this transdermally absorbable preparation, a highly safe and well-balanced adhesive property and a good release of a physiologically active substance are required. It is known that the release of a physiologically active substance from a carrier for holding a physiologically active substance is an important factor particularly in a percutaneous absorption preparation intended for systemic action.
  • an adhesive composition layer of a transdermal absorption preparation an acrylic adhesive is used and a transdermal absorption accelerator is added, or the skeleton is modified! (Patent Document 1). There is a problem with safety such as lowering or strong skin irritation.
  • silicone elastomers are known to be effective as bases for implantable and transdermally absorbable preparations that are particularly safe! (Patent Document) 2).
  • silicone adhesives have the following problems: the bioactive substances have low solubility and cannot maintain the necessary concentration of bioactive substances! /, And! /.
  • the pressure-sensitive adhesive sheet for application to the skin is required to maintain a balance between skin adhesive force and skin irritation.
  • Patent Document 1 JP 2004-97730
  • Patent Document 2 JP-A-60-169414
  • Patent Document 3 JP-A-3-220120
  • Patent Document 4 JP 2000-44904 A
  • Patent Document 5 Japanese Patent Laid-Open No. 56-150007
  • Patent Document 6 Japanese Patent Laid-Open No. 58-103311
  • the object of the present invention is to provide skin with less skin irritation than conventional transdermal absorption preparations.
  • a percutaneous absorption preparation that has good wettability and familiarity to skin, has sufficient adhesive strength to the skin, can contain a sufficient amount of a physiologically active substance, and has a good release of the physiologically active substance. It is to provide.
  • Another object of the present invention is to provide an adhesive sheet that reduces the amount of liquid components mixed, suppresses the blooming of organic liquid components, and reduces the skin irritation associated with peeling and exfoliation of the skin.
  • the present invention is as follows.
  • the pressure-sensitive adhesive composition layer is made of a polyether polymer having a siloxane bond, A transdermally absorbable preparation, wherein at least one layer of the agent composition layer contains a physiologically active substance.
  • the pressure-sensitive adhesive composition layer comprises
  • a transdermally absorbable preparation characterized by curing a pressure-sensitive adhesive composition, and containing a physiologically active substance in at least one layer of the pressure-sensitive adhesive composition layer.
  • transdermal absorption preparation according to any one of [1] to [3], wherein the pressure-sensitive adhesive composition layer contains a transdermal absorption enhancer.
  • bioactive substance is dissolved in the polymer (A), mixed with the compound (B) and the catalyst (C), and then cured, [1] to [5] ] /, How to make any transdermal preparation.
  • a pressure-sensitive adhesive sheet for skin application wherein a pressure-sensitive adhesive composition layer is formed on a support, the pressure-sensitive adhesive composition layer comprising
  • a pressure-sensitive adhesive sheet for application to the skin which is obtained by curing a mixture of force.
  • the hydrosilylation catalyst (C) is a platinum monobutylsiloxane complex
  • the content ratio of the polymer (A) and the organic liquid component (D) is 1.0: 0.001; 1.0: 1.5, [8] [; 12], the slippery adhesive sheet.
  • the skin irritation is small compared with the conventional ones, the wettability to the skin, the familiarity is good, and the adhesive strength is sufficient. Good long-term fixation to the skin. Further, according to the transdermally absorbable preparation of the present invention, a sufficient amount of a physiologically active substance can be contained, and good release properties can be obtained.
  • At least one pressure-sensitive adhesive composition layer is provided on a support.
  • the support used in the transdermally absorbable preparation of the present invention is not particularly limited as long as it can hold the pressure-sensitive adhesive composition before being cured, but a physiologically active substance contained in the pressure-sensitive adhesive composition, etc. Is preferably lost from the back through the support and does not cause a decrease in content.
  • urethane polymers such as polyether urethane, amide polymers such as polyether amide, acrylic polymers such as polyacrylate, polyethylene, polypropylene, ethylene polymers such as olefin copolymer, Examples thereof include ester polymers such as ether polyester.
  • fluorine-based polymers such as polytetrafluoroethylene, silicon-based polymers such as polydimethylsiloxane and polydiphenylsiloxane, finalenes such as polychlorinated butyl, polyvinylidene chloride, and polybutyl alcohol, or the above polymer materials
  • silicon-based polymers such as polydimethylsiloxane and polydiphenylsiloxane
  • finalenes such as polychlorinated butyl, polyvinylidene chloride, and polybutyl alcohol
  • foam sheets such as foam sheets, non-woven fabrics, and metal foils.
  • each layer may be made of the same material or different types of materials.
  • a non-woven fabric that has moisture permeability is preferably used.
  • the thickness of the substrate is not particularly limited and can be appropriately selected depending on the purpose and application, and 10 to 5000 111 is exemplified. If the thickness of the support is greater than 5000 am, the followability to the skin is reduced and the skin becomes easy to peel off, which is not preferable because the physical irritation to the skin becomes stronger.
  • the thickness of the support is as thin as 10 m! /, Which is preferable from the viewpoint of durability! /. From the viewpoint of irritation to the skin and durability, 10 to 2000 111 force ⁇ preferably, more preferably (between 10 and; 1000 m.
  • the pressure-sensitive adhesive composition laminated on the support comprises (A) a polyether polymer having at least one alkenyl group at the terminal, (B) in the molecule;! -10 hydrosilyl groups. It is obtained by curing a pressure-sensitive adhesive composition comprising a compound having (C) a hydrosilylation catalyst.
  • the polymer (A) is a polyether polymer having at least one alkenyl group at the terminal.
  • the alkenyl group is not particularly limited as long as it is a group containing a carbon-carbon double bond active for hydrosilylation reaction.
  • the alkenyl group is preferably an aliphatic unsaturated hydrocarbon group having 2 to 20 carbon atoms, more preferably 2 to 6 carbon atoms (for example, a vinylol group, an arinole group, a methyl butyl group, a propenyl group, a butyr group).
  • Group pentyl group, hexenyl group, etc.
  • a cyclic unsaturated carbon having 3 to 20 carbon atoms, more preferably 3 to 6 carbon atoms.
  • Hydrogenated group eg, cyclopropenyl group, cyclobutyl group, cyclopentyl group, cyclohexenyl group, etc.
  • Methacryl group and the like can be mentioned.
  • Preferable alkenyl groups include those represented by the following formulas (1) and (2) from the viewpoint of easy synthesis reaction.
  • R 1 and R 2 are a hydrogen atom or a hydrocarbon group having 1 to 10 carbon atoms, preferably a hydrogen atom or a methyl group:
  • the polymer (A) has an average of at least 1, preferably 15, more preferably ;! to 3, more preferably 12 alkenyl groups in one molecule.
  • Polymer (A) l If the average number of alkenyl groups in the molecule is less than 1, the curability is insufficient, and if the number of alkenyl groups in the molecule is too large, the network structure becomes dense. For this reason, the adhesive properties tend to deteriorate.
  • the polyoxyalkylene type polymer which consists of a repeating unit represented by these is mentioned.
  • R 3 is a divalent alkylene group.
  • the main chain of the preferred polymer (A) is polyoxypropylene (that is, the above R 3 — is —CH 2 CH 3 (CH 2) —) because of its adhesive properties, skin irritation and wettability to the skin. Moreover, it is preferable also from the point of workability
  • the polyether polymer may be composed of one type of repeating unit or may be composed of a plurality of repeating units.
  • the polyether polymer may be a linear polymer or a branched polymer.
  • the polymer (A) other than the alkenyl group is composed of a polyether skeleton, but may contain other structural units.
  • the total of the polyether skeletons in the polymer (A) is preferably 80% by weight or more, and more preferably 90% by weight or more.
  • the molecular weight of the polymer (A) (from a number average of 3000 50,000 is preferred ⁇ , 6000 is preferred over 50,000 000 ⁇ , 10000) because good adhesive properties with good workability at room temperature are obtained. —3 0000 force S Particularly preferred, when the number average molecular weight is less than 3000, the resulting cured product is brittle. Conversely, if the number average molecular weight exceeds 50,000, the viscosity tends to increase and workability tends to decrease.
  • the molecular weight is a polystyrene-equivalent number average molecular weight measured by GPC.
  • the bonding mode of the alkenyl group to the polyether polymer is not particularly limited, and examples thereof include a direct bond of an alkenyl group, an ether bond, an ester bond, a carbonate bond, a urethane bond, and a urea bond.
  • the production method of the polymer (A) is not particularly limited, and examples thereof include a method of introducing an alkenyl group after obtaining a polyether polymer.
  • various known production methods can be applied to the polyether polymer, and a commercially available polyether polymer may be used.
  • a method for introducing an alkenyl group into a polyether polymer is also known.
  • a monomer having an alkenyl group eg, allylglycidyl ether
  • a monomer for synthesizing a polyether polymer are used.
  • a method of copolymerization or a functional group is previously introduced into a desired portion (end of main chain, etc.)!
  • a functional group eg, hydroxyl group, alkoxide group
  • Examples thereof include a method of reacting a compound having both a reactive functional group and an alkenyl group (eg, acrylic acid, methacrylic acid, butyl acetate, acrylic acid chloride, etc.).
  • the compound (B) is a compound having an average of two or more hydrosilyl groups in one molecule.
  • a hydrosilyl group means a group having a Si—H bond.
  • the chemical structure of the compound (B) other than the hydrosilyl group is not particularly limited.
  • the number average molecular weight of the compound (B) calculated from the SiH group value obtained by titration is preferably 400 to 3000, more preferably 500 to 1000. This is because if the number average molecular weight is too low, it tends to be difficult to obtain a cured product that easily volatilizes during heat-curing, and if it is too high, the curing rate tends to be slow.
  • the number of hydrosilyl groups contained in one molecule of the compound (B) is 1 to 10 and preferably 2 to 8. If the average number of hydrosilyl groups is 2 or more, a plurality of polymer (A) molecules can be cross-linked during curing, exhibiting a cohesive force preferable as a percutaneous absorption preparation, and affixed to the skin. When peeled off, adhesive residue or the like hardly occurs. However, if the number of hydrosilyl groups is too large, the cross-linking becomes too dense, resulting in a transdermal absorption preparation such as skin adhesive strength and tackiness. Kimono properties tend to decrease.
  • the density of the cross-linking affects the density between the polymer parts as the main chain of the polymer (A), and also affects the moisture permeability of the entire transdermally absorbable preparation. Therefore, the number of hydrosilyl groups in compound (B) should be selected in consideration of the balance with adhesive properties.
  • Compound (B) may be used alone or in combination of two or more.
  • the compound (B) is preferably compatible with the polymer (A).
  • suitable compounds (B) include organohydrogensiloxanes modified with organic groups.
  • a typical example of the organohydrogensiloxane is a compound represented by the following formula (3).
  • the value of a in the above formula (3) matches the number of hydrosilyl groups in the molecule.
  • the value of a + b is not particularly limited but is preferably 2-50.
  • R is a hydrocarbon group having 2 to 20 carbon atoms in the main chain.
  • the compound of the above formula (3) can be obtained by modifying R of unmodified methylnodrosilicone and introducing R. Unmodified methylnodogen silicone corresponds to the compound in which R is all H in the above (3). “Silicon market prospect” published by CMC Co., Ltd. As described in "I", it is used as a raw material for various modified silicones.
  • Organic compounds for the introduction of R include ⁇ -olefin, styrene, ⁇ -methylstyrene, allylalkyl ethereol, arinoleanoleno quinenole estenole, arino refeno enole ethenore, arino refino eno estenore.
  • Etc The number of hydrosilyl groups in the molecule after modification can be adjusted by the amount of the organic compound added for modification.
  • the ratio of the amount of the polymer ( ⁇ ) to the compound ( ⁇ ) in the pressure-sensitive adhesive composition for forming the pressure-sensitive adhesive composition layer is such that the compound ( ⁇ ) Expressed by the total amount of derived hydrosilyl groups.
  • the total amount of alkenyl groups in the pressure-sensitive adhesive composition depends on the size of the total amount of hydrosilyl groups per mole. Considering the balance between imparting appropriate tackiness and reducing the adhesive residue, etc., the total amount of hydrosilyl groups per mol of alkenyl groups is preferably 0.;! To 5.0 mol, more preferably (It is mono 0.4-4.
  • the hydrosilylation catalyst that is the catalyst (C) is not particularly limited, and any catalyst that promotes the hydrosilylation reaction can be used. Specifically, chloroplatinic acid, platinum-vinylsiloxane complexes (for example, platinum-1,3, divinyl-1,1,3,3, -tetramethyldisiloxane complexes are platinum 1,3,5,7 tetravinyl 1 , 3, 5, 7 tetramethylcyclotetrasiloxane complexes), platinum-olefin complexes (e.g.
  • Etc. are exemplified.
  • platinum 1,3-divinyl-1,1,2 which is more preferable than platinum bullysiloxane complex which is preferable platinum complex catalyst which does not contain a conjugate base of strong acid as a ligand.
  • a 3, 3, —tetramethyldisiloxane complex or a white gold 1,3,5,7-tetravinyl-1,3,5,7-tetramethylcyclotetrasiloxane complex is particularly preferred.
  • the amount of the catalyst (C) is not particularly limited, but is preferably 10—sio— 1 mol, more preferably 10—with respect to 1 mol of the total amount of alkenyl groups of the polymer (A). 6 ⁇ ; a 10-2 mol. Within the above range, it is easy to achieve an appropriate curing rate, stable curability, and necessary pot life.
  • the organic liquid component (D) is preferably contained in the pressure-sensitive adhesive composition layer. Addition of organic liquid components reduces pain and skin irritation when peeling adhesive tape for skin application and transdermal absorption preparation from the skin surface, and improves diffusion of bioactive substances by plasticizing the adhesive. In some cases, it may contribute to improving the release of physiologically active substances on the skin surface.
  • the organic liquid component used in the present invention is not particularly limited, but is preferably a component having compatibility with each component and capable of being uniformly dissolved and dispersed in the pressure-sensitive adhesive composition layer.
  • an organic liquid component a ) Polyhydric alcohols such as ethylene glycol, diethylene glycol, dipropylene glycol, propylene glycol, polyethylene glycol, polypropylene glycol, butanediol, triethylene glycol, glycerol;
  • Oils such as olive oil, camellia oil, soybean oil, castor oil, lanolin;
  • fatty acids such as oleic acid
  • Organic solvents such as ethanol, ethyl acetate, dimethyl sulfoxide, isosorbitol, dimethyldecyl sulfoxide, methyloctyl sulfoxide, dimethylformamide, dimethylacetamide, N-methinorepyrrolidone, dodecinorepyrrolidone;
  • Organic liquid components include fatty acid esters because of excellent diffusibility of physiologically active substances.
  • the content of these organic liquid components is not particularly limited.
  • a polymer (A ) For a weight of 1 is 0.001-1.5, preferably ⁇ is 0.001-1.0.
  • the content of the liquid component is outside this weight ratio, practical skin adhesion and low skin irritation cannot be obtained, and the release of the physiologically active substance is not sufficient.
  • the percutaneous absorption enhancer used in the present invention improves the solubility of the physiologically active substance in the pressure-sensitive adhesive, or acts on the skin surface to cause keratin softening, keratin penetration, pore opening. By fulfilling functions such as porosity, the transdermal absorbability of physiologically active substances can be improved.
  • the percutaneous absorption enhancer used in the present invention is not particularly limited, but is preferably one that can be uniformly dispersed in the pressure-sensitive adhesive layer.
  • those that act as a transdermal absorption enhancer may be used alone or mixed with other transdermal absorption enhancers to exhibit both characteristics. Even if you use it, it ’s powerful and fun.
  • transdermal absorption enhancer examples include, for example, monovalent or polyhydric alcohols, monovalent or divalent carboxylic acids, hydroxycarboxylic acids, esters, pyrrolidone derivatives, surfactants, Hydrocarbons, monocyclic monoterpenes, urea derivatives, specific compounds, etc. are used
  • the monohydric alcohol is preferably an alcohol having 18 or less carbon atoms from the viewpoint of promoting transdermal absorption.
  • polyhydric alcohol examples include ethylene glycol, diethylene glycol, dipropylene glycol, propylene glycol, polyethylene glycol, polypropylene glycol, butanediol, triethylene glycol, and glycerin.
  • the monovalent carboxylic acid is preferably a carboxylic acid having 20 or less carbon atoms from the viewpoint of promoting transdermal absorption.
  • a carboxylic acid having 20 or less carbon atoms from the viewpoint of promoting transdermal absorption.
  • Aliphatic monocarboxylic acids such as formic acid and linolenic acid can be mentioned.
  • divalent carboxylic acid examples include oxalic acid, malonic acid, succinic acid, dartaric acid, pimelic acid, suberic acid, adipic acid, sebacic acid, phthalic acid, isophthalic acid, terephthalic acid, and the like.
  • hydroxycarboxylic acid examples include malic acid and tartaric acid.
  • esters composed of the monovalent and polyhydric alcohols and monovalent and divalent carboxylic acids or hydroxycarboxylic acids are preferably used.
  • Examples of the pyrrolidone derivatives include 1-dedecylazacycloheptane-2-one, 1-geranylazacycloheptane 2-one, 1-arnesylazacycloheptane 2-one 2 pyrrolidone, 1-methyl 2 Pyrrolidone, 5 Methyl 2 Pyrrolidone, 1,5 Methyl-2 Pyrrolidone, 1-Ethyl 2 Pyrrolidone, 2 Pyrrolidone 1-5 Carboxylic acid.
  • a noionic surfactant a cationic surfactant, a cationic surfactant, or an amphoteric surfactant is used.
  • nonionic surfactant examples include polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monopalmitate, sorbitan monolaurate, sorbitan alkyl esters such as sorbitan monopalmitate; polyoxyethylene lauryl ether nore, Poly oxyethylene hexenoredecinoleateolate, etc.
  • Poly oxyethylene alcohol quinoleic tere Fatty acid amides such as lauric acid diethanolamide, tetraoleic acid polyoxyethylene sorbite, polyoxyethylene fatty acid Examples thereof include amides and alkylaminoxides.
  • anionic surfactant examples include those having at least one of a carboxylic acid group, a sulfonic acid group, a sulfate ester group and a phosphate ester group in the molecule.
  • Examples of those having a carboxylic acid group include, for example, fatty acid sarcophagus, ether carboxylic acid (salt), carboxylates such as condensates of amino acids and fatty acids, and the like; For example, alkyl sulfonate, sulfosuccinic acid, ester sulfonate, alkyl allyl and alkyl naphthalene sulfonate, N-acyl sulfonate, etc .; those having a sulfate ester group include, for example, sulfated oil, ester sulfate, ether Sulfates, alkylaryl ether sulfates, amide sulfates, etc .; those having a phosphate ester group include, for example, alkyl phosphates, amide phosphates, ether phosphates, alkyl phosphates, Each is listed.
  • Examples of the cationic surfactant include fatty acid amines, alkyl quaternary ammonium salts, aromatic quaternary ammonium salts, pyridinium salts, imidazolium salts and the like.
  • amphoteric surfactants include sulfobetaine, aminocarboxylate, imidazoline derivatives, etc., in addition to force lupoxybetaine such as lauryldimethylaminoacetic acid betaine.
  • hydrocarbon examples include liquid paraffin, squalane, squalene, and the like.
  • Examples of the monocyclic monoterpenes include P-menthane, limonene, ⁇ -terbinene, and terpino.
  • Len 1-menthol, 1-strength nore-p-onole, ⁇ -terhineol 1-mentholone, d-carbon, cineol, and urea derivatives include urea, allantoin and the like.
  • Examples of the specific compound include panthenol, tocopherol, tocopheryl acetate, tocopheryl linoleate, crotamiton, pyrothiodecane, polybylpyrrolidone, and EDTA.
  • transdermal absorption enhancers can be mixed and used as necessary.
  • the content of the percutaneous absorption enhancer is not particularly limited.
  • the content of the percutaneous absorption enhancer is 0.0001-1.5, preferably ⁇ is 0. 001-1. 0. If the content of the percutaneous absorption accelerator is outside this weight ratio, practical skin adhesion and low skin irritation may not be obtained, and the release of bioactive substances may not be achieved. But it may not be enough.
  • the pressure-sensitive adhesive composition layer in the transdermally absorbable preparation and the adhesive sheet for skin application of the present invention is obtained by curing the above-mentioned pressure-sensitive adhesive composition.
  • curing refers to heating the pressure-sensitive adhesive composition mixed with the polymer material to cause the polymer (A) and the compound (B) to undergo a hydrosilylation reaction by heating.
  • Examples of the curing condition include leaving it to stand at 40 to 180 ° C.-ei for 60 minutes. If you want to cure more completely, you can leave it at 40-80 ° C for several days.
  • the viscosity upon curing is preferably 10-; lOOOPa's. This viscosity can be controlled by the ratio of the amounts of components (A) to (C) and the type and amount of storage stabilizer for compound (B) described above.
  • the pressure-sensitive adhesive composition for forming the pressure-sensitive adhesive composition layer may contain components other than the above (A) to (D) and the percutaneous absorption enhancer. These components include tackifiers, storage stabilizers for compound (B), and other components.
  • tackifier examples include phenol resin, modified phenol resin, terpene phenol resin, xylene phenol resin, cyclopentagen monophenol resin, xylene resin, petroleum resin, phenol-modified petroleum resin, rosin ester resin, low molecular weight polystyrene. Resin, terpene resin and the like. When these are used in order to improve the adhesive properties, they may be used alone or in combination of two or more. When these tackifiers are used, the amount used is preferably 10 to 100 parts by weight, more preferably 15 to 50 parts by weight with respect to 100 parts by weight of the total amount of the polymer (A) and the compound (B). Part. If the amount used is too large, the moisture permeability of the pressure-sensitive adhesive composition layer decreases, which is preferable! /.
  • Examples of the storage stabilizer for the compound (B) include compounds containing an aliphatic unsaturated bond, organophosphorus compounds, organosulfur compounds, nitrogen-containing compounds, tin compounds, and organic peroxides.
  • the power S that can include refumarate, jetinoremalate, dimethyl maleate, 2-pentenenitrile, 2,3 dichro
  • Storage stabilizer suppresses conversion of hydrosilyl group (Si H group) to Si OH group in compound (B) (due to standing for a long time or mixing of moisture), improving the pot life of coating Can be made.
  • the pressure-sensitive adhesive composition for forming the pressure-sensitive adhesive composition layer includes a water-soluble organic polymer and a water-absorbent for improving the water resistance, sweat resistance, water absorption and the like of the pressure-sensitive adhesive composition layer.
  • Polymers may be added, and other plasticizers, softeners, fillers, pigments, surfactants, ultraviolet absorbers, antioxidants, antibacterial agents, and the like may also be added. At this time, it is preferable not to use organic solvents, but it is not to deny their use!
  • the physiologically active substance in the present invention is not particularly limited and can be used. Specific examples of the physiologically active substance include the following compounds.
  • ⁇ -adrenergic agonists such as albuterol, bumpterol, vitorte Ronole, Carbuteronole, Clenbuteronole, Chlorprenalin, Denonomine, Dioxededrine, Dopexamine, Ephedrine, Epinephrine, Etafedrine, Ethylnorepinephrine, Fuenoteronole, Formoteronole, Hexoprenaline, Evotrenaline, Provoline Monore, Mabuteronorole, Metaproterenol, Methoxyphenamine, Oxipheudrin, Pinole Buteronorenore, Pre-Nanoterero Norre, Pro Power Teronol, Protokironole, Reproterol, Limitero Noreno, Litodolin, Soterenore, Terbuterol and Xamoterol
  • Adrenergic blocking agents such as acebutolol, alprenolol, ammos laronore, arochinoronore, atenololinore, befnoronore, betaxolonore, benontronore, bisoproronole, bopindronore, f, cumolono Behuetoronore, Fu, Furoronole, Pu, Nitroronore, Buplanolo Monore, Butidoline Hydrochloride, Butofiroro Norole, Carazolol, Force Noor Theoronole, Force Nole Bejiro Nore, Serif.
  • Adrenergic blocking agents such as acebutolol, alprenolol, ammos laronore, arochinoronore, atenololinore, befnoronore, betaxolonore, benontronore, bisoproron
  • Rollo Nore Setamoronore, Chlorano Ronore, Gileno Ronore, Eno Rono Norole, Esmolono, Indeno Ronore, Labeta Ronore, Levov, Noro Nonore, Mepindronore, Metiplano Roole, Meproro Ronore, Mopro Rono Leo Oxyprenololeno, penbutronole, pindronore, practolo nore, pronetaro nore, propranolo nore, sotaronore, snorffinaronore, talino ronore, tenoreta ronore, timolo ronore, and triprolonore.
  • Analgesics such as chlorobutanol; narcotic analgesics such as alfentanil, allylprozin, alphaprozin, anileridine, benzylmorphine, benzitolamide, buprenorphine, butorphanol, cloutazen, codine, methylcodine bromide, Codin phosphate, codin sulfate, desomorphin, dextromoramide, dezocine, dianpromide, dihydrocodine, dihydrocodine enol acetate, dihydromorphine, dimenoxadol, dimethylepheptanol, dimethylthianbutene, dioxaphethyl butyrate, dipipanone utazene , Fentanyl, hydrocodone, hydromorphone, hydroxypentidine, isomethadone, ketobemidone, levorfano monole, oral fentanyl, hydroco
  • Anti-anginal drugs such as acebutolol, alprenolol, amaminodarone, amlodipine, alotinoronole, atenololenore, beprizinore, benotronolore, bukumoronore, buetoronore, pu, fulleronole, pu, nitroronole, , Pranolo nore, carozolo nore, canolete chin nore, force nore veiro ronore, seriprolonore, cineno zet maleate, dinorethiazem, enonolol, ferrodipine, galopamil, imolamine, indenolol, isosorbide ristromepine reprodine , Nadro Ichinole, Nikanorepine, 2 Fedipine, 2 Fenaronore, Ninorevadipine, Niplageronor
  • Antiarrhythmic drugs for example, acebutol, asecaine, adenosine, ajmarin, alpenolone, amiodarone, amoproxan, apuridine, arochinoronore, atenololone, bevantolol, bretyrimole tosylate, bubumolonore, bufetrolol, bunaphtholol, bunaphtholol , Butidoline hydrochloride, butobenzine, capobenic acid, carazolone, carteololole, cifenline, chloranolore, disopyramide, encainide, esmolol, flecainide, galopamil, hydroquinidine, indecainide, indenolol, ipirato bromide, cadmium bromine Metibra Noro-no-re, Mexiletine, Moricidin, Nadox
  • Antidepressants bicyclic systems such as vinedarin, caloxazone, citalopram, dimetazan, i Ndalpine, fencamine, indeloxazine hydrochloride, nefobum, nomifensine, oxytributane, oxypertin, paroxetine, sertraline, thiazesim, trazodone and zometapine; And phenelzine; pyrrolidone series such as cotinine, oral lysiprin and rolipram; tetracyclic systems such as maprotiline, metralindole, mianserin and oxaprotilin.
  • Tricyclic systems such as azinazolam, amitoliptyline, amitriptyline, amoxapine, buttriptyline, clomipramine, dexipitrine, desipramine, dibenzepine, dimetracrine, docepine, doxepin, fluacidin, imipramine, imipramine N-oxide, iprin Oral fepramine, melitracene, metapramine, nonoretriptyline, noxiptylline, obipramol, pizotirin, puvisepine, protriptyline, quinupramine, tianeptine and trimipramine; and others such as adrafiel, benactidine, bupropion, butacetin, danol , Acedarmic acid deanol, acetoamide benzoic acid dianol, dioxadrole, etoperidone, pheno-remamate, Xetine,
  • Antiestrogens such as dermadinone acetate, ethamoxytriphetol, tamoxifen and toremifene.
  • Anti-gonadotropins such as danazol, gestrinone and paroxypropion.
  • Antihypertensive agents allylethanolamine derivatives, such as amothralol, bufura ronore, gireno ronore, labetaro nore, pronetaronore, sotaroronole and snorefinarol; allylooxypropanolamine derivatives such as acebutolol, alprenolol Nore, Arachino Ronore, Ateno Ro Nore, Betaxo Ronole, Benon Thoro Nore, Bisopro Roh Nore, Boppin Roh Nore, Pu, Nitro Ro Nore, Pu, Plano Roan Nore, Pu, Tofiro Ronore, Carazo Ronore, Canole Tesoro Lore, Power Nore Loro Nore, Seta Moronore, Eno Noro Nore, Nendoro Monore, Mepindronore, Metibranolo Norre, Metoprolonore, Moprolonore,
  • Derivatives such as clodidine, lofexidine, phentolamine, thiamenidine and tronidine; quaternary ammonium compounds, azamethonium bromide, chlorisondamine chloride, hexamethonium, bis (methyl sulfate) pentacinium, pentamethonium bromide, Pentritium tartrate, phenactodium chloride and trimethydinum methosulfate; quinazoline derivatives such as alfuzosin, bunazosin, doxazosin, prazosin, terazosin and trimazosin; reserpine derivatives, vietaserpine, deservidin, resinpine, resorpine and retainn sulfonamide derivatives, e.g., ambuside, clopamide, furosemide, in Dapamido, quinethazone, tripamide and xipamide; and others such as,
  • Anti-inflammatory (non-steroidal) agents aminoaryl carboxylic acid derivatives such as fenfenamic acid, ethoenamate, flufenamic acid, isonyxin, meclofenamic acid, mefanamic acid, diflumic acid, tanolenifnoremate, telophenamate and tolfenam Acid; allylic acetic acid derivatives such as acemetacin, alclofenac, amphenac, bufae exac, synmethacin, clopilac, diclofenac sodium, etodolac, felubinac, fenclofenac, fenclolac, fenclozic acid, fenthiazac, gnorecamecin , Ibufenac, Indomethacin, Isofezolac, Isoxepak, Ronazolac, Methiazine acid, Oxamethasine, Progourmet Tacin, Sulind
  • Antitumor agents 2 Aminolevulinic acid and alkylating agents: alkyl sulfonates such as busulfan, improsulfan and piperosulfan; aziridines such as benzodeva, carboquan, meledepa and uredeno; ethyleneimine and methylmelamines such as , Altretamine, triethylenemelamine, triethylenephosphoramide, triethylenphosphoramide and trimethylolomelamine; nitrogen mustard systems such as chlorambucil, chlornafazine, cyclophosphamide, estramustine, ifosfamide, Mechlorethamine, mechlorethamine hydrochloride, melphalan, nobenbiquine, phenesterin, prednisotin, trophosphamide and uracil mustard; nitrosourea For example, force noremustine, chlorozotocin, hotemustine, mouth mucin, dimustine and rani
  • Antiparkinson agents such as amantadine, benserazide, bietanautin, biperidene, bromocriptine, budipine, carbidono, deprenyl, dexetimide, dietadine, droxidopa, etopropazine, ethylbenzhydramine, lepodopa, naxagolide, Noregolide, pyroheptin, pridinol, prodipine, tenoledaride, tigloidin, and trihexyphenidyl hydrochloride.
  • Antiprostatic hypertrophy agents for example, guestnolone caproate, mepaltricin.
  • Antipsychotics butyrophenones, eg, benperidol, bromperidol, oral peridonole, funoreanisone, neuroperidonole, menoleperone, moperon, pinonperone, superon, timiperone and trifluperidol; phenothiazines For example, acetophenazine, butaperazine, force norefenadine, chronoreproetadine, chronorepromazine, crospydazine, methoxypromazine, metofenazet, oxaflumazine, perazine, pericazine, permethazine, penolefenadine, piperacetazine, pipothiazine, Perazine, promazine, sulforidazine, thiopropazate, thioridazine, trifluoperazine and triflupromazine; thioxanthen
  • Antispasmodic drugs such as alibendol, ambusetamide, aminopromazine, apoat mouthpin, methylbebonium sulfate, vietamiberin, butavelin, butohoutu bromide, N-butylscopolammonium bromide, caro Verin, symtropium bromide, cinnamedrine, talepopride, fluoric acid quine, hydrochloric acid quine, cycloiodide iodide, difumeline, diisopromine, dioxafethyl butyrate, diponium bromide, drofenine, bromide mepronium, ethaverin, fetalamine, fenalamide, Berin, fenpiplan, fenpiberin bromide, fentonium bromide, flavoxate, furopropion, darconic acid, guaiacamine
  • Anti-anxiety drugs arylpiperazines such as buspirone, gepirone and ipsapirone; benzodiazepine derivatives such as alprazolam, bromazepam, force mazepam, clonoresidazepoxide, clobazam, chlorazepate, cothiazebam, cloxazolam , Diazenome, ethinole oral frazepate, etizolam, funoreidazepam, funoretazolam, funoretopram zepam, halazebam, ketazolam, lorazepam, loxapine, medazepam, metaclazebam, mexazolam, zezepamopam, zezepamopam, zezepamopam, zezepamopam
  • cyclalbamate emyl strength, hydroxyphenamate, meprobamate, fen
  • Calcium regulators such as calciphediol, calcitonin, calcitrione, clodronic acid, dihydrotaxosterol, elcatonin, etidronic acid, ipriflavone
  • Cardiotonic agents such as acephylline, acetyl digititoxin, 2-amino-4-picoline, anrinone, benfurosyl semisuccinate, bucladecin, selvage mouth, camphoramide, conbalatoxin, simarin, denopamine , Deslanoside, ditalin, digitalis, digitoxin, digoxin, dobutamine, dopamine, dopexamine, enoximone, erythrookn, phenalkamine, guitarine, gitoxin, glycosamine, heptaminol, hydrastinine, ibopamine, lantodinoline, lantodisino, rietholine Vine, Oxifedrine, Prenalterol, Prosilaridin, Reciprochogenin, Silarene, Silarenin, Stroke Fantin, Sulmazonole, Theobromine and Samoteroru.
  • Chelating agents such as defelodimine, dithiocarb sodium, calcium sodium edetate, disodium edetate, sodium edetate, trisodium edetate, penicillamine, trisodium calcium pentenoate, pentectic acid , Sushi mail and trientin.
  • Dopamine receptor agonists such as bromocriptine, dopexamine, fenoldopam, ibopamine, lisuride, naxagolide and pergolide.
  • Enzyme inducer for example, flumesinol.
  • Estrogens Non-steroidal estrogens such as benzestrone, bropalo estrone, chlorotrianicene, genestrone, getinorestino lestrone, dipropionate getinorestino lestrone, dimestrone, phosfe Stranole, hexestroleol, metallestritol and metestrone, and steroidal estrogens such as colpolmon, conjugated estrogen hormone, ethylenin, equilin, estradiol, estradiol benzoate, 17 / 3-estradiol cypionate, estrio 1 Norest Estrone, Ettinorest Radio 1 Norst, Mestranol, Mexestrone, Mitatorie Diol, clobetasone butyrate, quinestradiol and quinestrol.
  • steroidal estrogens such as benzestrone, bropalo estrone, chlorotrianicene, genestrone, getinorestin
  • Darcocorticoids such as 21-acetoxyprefunenolone, alclomethasone, algestone, amicinonide, beclomethasone, betamethasone, budesonide, chloroprednisone, clobetasole, pu, oral betazone, croconoletron, Cloprednenole, Conoleticosterone, Cortisone, Cortivazole, Deflazacort, Desonide, Desoxymethazone, Dexamethasone, Diflorazone, Diflucortron, Diflupredonate, Enoxolone, Fluazaconoleto, Fluchlorosonide, Flumethonolide, Flunosolito Nido, fluocortin butyl, fluoreoconoretron, fluorometron, fluperolone acetate, fluprednidene acetate, fluprednisolone, fluland lenoli , Formocortal, no, no
  • Mineralcorticoids such as aldosterone, deoxycorticosterone, deoxycorticosterone acetate, and flucortisone.
  • Monoamine oxidase inhibitors such as deprenyl, iproclozide, ipronid azide, isocarboxazide, mokuguchibemid, octomoxine, noregilin, phenelzine, phenoxypropazine, bivalylbenzhydrazine, prodipine, Troxaton and tranylcypromine.
  • Muscle relaxants skeletal
  • afroqualone alchlorium, atracacrylic besylate, noclofen, benzocamine, benzoquinone chloride, C-carepsin, calisop oral doll, chlormezanone, strength Chlorphenesin rubamate, chlorproetadine, clozo Oxazone, clare, cyclalbamate, cyclobenzaprine, dantrolene, decamethonium bromide, diazepam, eperisone, camdinium bromide, flumetramide, triethogallium iodide, hexacarbaline bromide, hexafluorenium bromide, idrosilamide, Methyl lauexium, leptodactylin, memantine, mefenesin, mefenoxalone, methaxalone, metcarbamol, methocrine io
  • Narcotic antagonists such as amifenazole, cyclazocine, levalorphan, clawide, nalmuphen, nalorphine, narolphine dinicotinate, naloxone and naltrexone.
  • Progestogens such as, for example, arlinolestrenole, anastrone, chlormadinone acetate, dermadinone acetate, demegestone, desogestrel, dimethisterone, diddrogesterone, ethisterone, ethinodiol, full mouth gestone, guest den, caproic acid Guest Nolone, haloprogesterone, 17 hydroxy 16 methylene progesterone, 17 ⁇ -hydroxyprogesterone, caproic acid 17 ⁇ hydroxygesterone, linestrenol, medlogestone, medroxyprogesterone, megestrol acetate, melengestrol, noregetindrone, Norethinodrel, Norgesterone, Norgestimate, Norgestrel, Noregestrienone, Norevinisterone, Pentagestrone, Progesterone, Promeg Ton,
  • Vasodilators coronary arteries
  • Bronchodilators Ephedrine derivatives, such as albuterol, bumpterol, vitonoletero nore, canolebutero nore, clenbuteronole, clonoleprenalin, dioxededrine, ephedrine, epinifrin, eprodinole, etafedrin, etyl Pinephrine, fenoterone, hexoprenalin, isoetarine, isoproterenol, mabuteronorenore, metaproterenorole, N-methylephedrine, pyrbuteronole, protellonore, protokironole, lef.
  • Ephedrine derivatives such as albuterol, bumpterol, vitonoletero nore, canolebutero nore, clenbuteronole, clonoleprenalin, dioxededrine,
  • incontinence treatments such as oxiputinine, osteoporosis treatments such as risedronate, antihistamine treatments such as ketofetin acetate, diabetes treatments such as tolptamide, and ventilation treatments such as colchicine.
  • the method for mixing these physiologically active substances into the pressure-sensitive adhesive composition is not particularly limited, but usually the physiologically active substance is dissolved in the polymer (A) and then mixed with the compound (B) and the catalyst (C). However, in order to further improve the solubility of the physiologically active substance, the polymer (A) and the compound (A) and the compound (A) are dissolved after the physiologically active substance is dissolved in the organic liquid component. B) and the catalyst (C) are more preferred to be produced by mixing and curing this! /.
  • the method of laminating the pressure-sensitive adhesive composition layer on the support is not particularly limited.
  • a method in which the pressure-sensitive adhesive composition is applied to one surface of the support and then cured under the above conditions An example is a method in which the support is bonded after the adhesive composition is coated on a sheet (release sheet) previously provided with a release agent and cured.
  • release agents such as silicones, olefins, and fluorines are known as release agents, and can be used appropriately. Of these, olefin-based and solvent-free addition-curable silicone-based release agents are preferred from the standpoints of cost and ensuring releasability.
  • the thickness of the pressure-sensitive adhesive composition layer is not particularly limited, and may be, for example, 10 to 5000 Hm.
  • An oxypropylene polymer glycol having a number average molecular weight of 3000 was obtained by a polymerization method using caustic alkali.
  • propylene oxide was prepared using a double metal cyanide complex catalyst (zinc hexanocobaltate) using the oxypropylene polymer glycol as an initiator.
  • Polymerization was performed to obtain a polymer having a number average molecular weight of 28000.
  • This polymer is converted into a allyl group using 28% methanol solution of sodium methylate and allylic chloride, and then desalted and purified to have approximately two allylic terminus in one molecule.
  • a polyoxyalkylene polymer (polymer (A)) was obtained.
  • the amount of the aryl terminal group of the obtained polymer was 0.12 mmol / g.
  • This pressure-sensitive adhesive composition was applied to a treated surface of a release paper that had been subjected to silicone release treatment at room temperature so that the thickness after curing was 50 m, and cured at 130 ° C for 3 minutes to adhere. An agent layer was formed.
  • a moisture-permeable polyurethane sheet (DSU—214—CDB, SO ⁇ m) (basis weight: 35 g / m 2 ) manufactured by Seadam Co., Ltd. (basis weight: 35 g / m 2 ) as a support is 5 kg / cm. 2.
  • Lamination was performed at a speed of 2 m / min. In this way, a transdermal absorption preparation was prepared.
  • Example 1 and Comparative Examples 1 and 2 were affixed to the skin of the hands of three volunteers and reapplied or smeared every 24 hours. Table 1 shows the results of observing these conditions.
  • a transdermal absorption preparation cut to a width of 20 mm was affixed to the back of a volunteer, and a lkg-weight roller was reciprocated once and pressed. After 6 hours, the percutaneously absorbable preparation was peeled off, and the exfoliated percutaneously absorbable preparation was used to measure the amount of exfoliated corneum.
  • the skin exfoliated from the volunteer's back is immersed in keratin staining solution (Gentian Violetl%, Brilliant GreenO. 5%, distilled water 98.5%) manufactured by Wako Pure Chemical Industries, Ltd. for about 30 minutes to stain skin keratin. I did. Thereafter, the sample was thoroughly washed with distilled water and then dried for 24 hours. The pressure-sensitive adhesive layer surface of the sample after drying was observed using a microscope, image analysis was performed, and the keratin exfoliation area ratio was obtained.
  • the present invention can contain a sufficient amount of a physiologically active substance that is less irritating to the skin than conventional adhesives and creams, and is capable of releasing the physiologically active substance. It is clear to provide a good transdermal absorption formulation.
  • Polymer (A) 4.2 parts by weight of compound (B) per 100 parts by weight of platinum 1,3-divinyl-1,1,3,3-tetramethyldisiloxane complex (3 parts by weight) as a hydrosilylation catalyst 0/0 platinum isopropanol solution) 0.1 part by weight, to give dimethyl 0.03 parts by weight of maleic acid, myristyl phosphate isopropyl 30 parts by weight, the estradiol 1 part by weight were mixed thoroughly adhesive composition.
  • This pressure-sensitive adhesive composition was applied on a polyester film (thickness 25 m) so that the thickness after curing was 50 inches, and then heated at 130 ° C for 5 minutes to obtain the transdermal absorption preparation of the present invention. It was.
  • Example 5 10.7 parts by weight of the compound (B) per 100 parts by weight of the polymer (A), platinum 1,3-divinyl-1,1,3,3-tetramethyldisiloxane complex (3 parts by weight) as a hydrosilylation catalyst % Platinum isopropanol solution) 0.1 part by weight, 0.03 part by weight of dimethyl maleate and 1 part by weight of estradiol were sufficiently mixed to obtain an adhesive composition.
  • This pressure-sensitive adhesive composition was applied on a polyester film (thickness 25 ⁇ m) so that the thickness after curing was 50 ⁇ m, and then heated at 130 ° C. for 5 minutes to obtain the transdermally absorbable preparation of the present invention. Obtained.
  • Table 2 shows the results of adhesion tests on the examples and comparative examples.
  • Each strip-shaped preparation sample cut to a width of 25 mm was affixed to a SUS304 plate, and a rubber roller weighing 2 kg was brought into close contact by reciprocating at a speed of 2 m / min, and then left for 1 hour.
  • the adhesive strength was measured by peeling the tape at a 180 ° angle at a speed of 300 mm / min.
  • the present invention can contain a sufficient amount of a physiologically active substance, and the adhesive strength is controlled by adding an organic liquid component, resulting in low skin irritation! /, An adhesive sheet It is clear that it provides.
  • the release test was performed using a Franz diffusion cell.
  • a permeable membrane As a permeable membrane, a 25111-thick urethane film cut into a circle having a diameter of 3 cm was used, and a 50% ethanol solution was used as a reservoir solution. The sample was cut into a circle with a diameter of 1 cm and used.
  • a Franz diffusion cell the concentration of the physiologically active substance released from the sample into the reservoir solution was quantified by liquid chromatography. The results are shown in Table 3.
  • the present invention can provide a transdermal absorption preparation having a release characteristic of a physiologically active substance and further having excellent release characteristics by using a transdermal absorption enhancer. Clear power.
  • This pressure-sensitive adhesive composition was applied onto a polyester film (thickness 25, 1 m) so that the thickness after curing was 50, 1 m, and then heated at 130 ° C for 5 minutes to obtain the transdermal structure of the present invention. An absorption formulation was obtained.
  • DURO- TAK387- 2052 (acrylic adhesive, manufactured by NSC) After adding 100 parts by weight of fluorenorebiprofen so that the content of the adhesive composition is 2.5% by weight And sufficiently mixed to obtain a pressure-sensitive adhesive composition.
  • This pressure-sensitive adhesive composition was applied on a polyester film (thickness 25, 1 m) to a thickness of 50, 1 m, and then heated at 130 ° C for 5 minutes to obtain a transdermal absorption preparation.
  • MD7-4502 silicone adhesive, manufactured by Toray Dow Cowing Silicone 100 parts by weight Flurbiprofen was added so that the content of the adhesive composition was 2.5% by weight. Adhesive composition was obtained by mixing thoroughly. This pressure-sensitive adhesive composition was applied on a polyester film (thickness 25 Hm) to a thickness of 50 Hm and then heated at 130 ° C for 5 minutes. Flurbiprofen precipitated in a crystalline state. A uniform formulation could not be obtained.
  • DURO- TAK387- 2052 (acrylic adhesive, manufactured by NSC) To 100 parts by weight, ketoprofen was added so that the content of the adhesive composition was 5.0% by weight, and then mixed well. Thus, a pressure-sensitive adhesive composition was obtained. This pressure-sensitive adhesive composition was applied on a polyester film (thickness 25 m) to a thickness of 50 m, and then heated at 130 ° C. for 5 minutes to obtain a skin-absorbing preparation.
  • ⁇ The physiologically active substance is uniformly dispersed.
  • ⁇ The physiologically active substance is uniformly dispersed but is opaque.
  • Each band-shaped preparation sample cut to a width of 5 mm was affixed to the skin, and a rubber roller having a weight of 2 kg was brought into close contact by reciprocating at a speed of 2 m / min, and then left for 72 hours.
  • Each tape was peeled from the skin at a speed of 300 mm / min at an angle of 180 °, and then the condition of the skin was observed and evaluated as follows.
  • the present invention can contain a sufficient amount of a physiologically active substance that is less irritating to the skin than conventional adhesives, and has a good release of the physiologically active substance. It is clear to provide n

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Abstract

La présente invention concerne une préparation absorbable par voie transdermique comprenant un timbre transdermique adhésif. Ledit timbre transdermique adhésif est caractérisé en ce qu'il comprend un substrat et une couche de composition adhésive formée sur le substrat. Ladite couche de composition adhésive comprend un polymère polyéther présentant une liaison siloxane, et au moins l'une des couches constituant la couche de composition adhésive contient une substance physiologiquement active. Plus spécifiquement, la couche de composition adhésive dans la préparation absorbable par voie transdermique est produite par cuisson d'une composition adhésive comprenant les éléments suivants : (A) un polymère polyéther présentant au moins un groupe alcényle à son extrémité terminale ; (B) un composé présentant 1 à 10 groupes hydroxyles dans la molécule ; et (C) un catalyseur d'hydroxylation. La préparation absorbable par voie transdermique provoque une moindre irritation cutanée comparée à une préparation classique. Elle présente une bonne mouillabilité sur la peau, une bonne conformabilité cutanée et un niveau satisfaisant d'adhérence à la peau. Enfin, elle peut contenir une quantité satisfaisante d'une substance active physiologiquement, et peut libérer ladite substance active physiologiquement de manière satisfaisante.
PCT/JP2007/074280 2006-12-19 2007-12-18 Préparation absorbable par voie transdermique et feuille adhésive destinée à être appliquée sur la peau Ceased WO2008075665A1 (fr)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010013799A1 (fr) * 2008-07-31 2010-02-04 株式会社カネカ Feuille adhésive sensible à la pression devant être collée à la peau
KR102112947B1 (ko) * 2019-01-24 2020-05-19 조시온 기관내 삽관술을 위한 근이완제 조성물

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH04210627A (ja) * 1990-11-30 1992-07-31 Shiseido Co Ltd 外用部材
JPH08245377A (ja) * 1995-03-15 1996-09-24 Yamanouchi Pharmaceut Co Ltd 経皮吸収用製剤
JPH11209271A (ja) * 1998-01-23 1999-08-03 Nitto Denko Corp 経皮吸収製剤
JPH11279060A (ja) * 1998-03-26 1999-10-12 Sankyo Co Ltd 経皮吸収組成物
JP2004067720A (ja) * 2002-08-01 2004-03-04 Nippon Unicar Co Ltd ゲル状粘着剤、医療用品および衛生用品
WO2005011662A1 (fr) * 2003-07-31 2005-02-10 Hisamitsu Pharmaceutical Co., Inc. Patch adhesif
JP2005110875A (ja) * 2003-10-06 2005-04-28 Nitto Denko Corp 皮膚貼付用の粘着シート

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH04210627A (ja) * 1990-11-30 1992-07-31 Shiseido Co Ltd 外用部材
JPH08245377A (ja) * 1995-03-15 1996-09-24 Yamanouchi Pharmaceut Co Ltd 経皮吸収用製剤
JPH11209271A (ja) * 1998-01-23 1999-08-03 Nitto Denko Corp 経皮吸収製剤
JPH11279060A (ja) * 1998-03-26 1999-10-12 Sankyo Co Ltd 経皮吸収組成物
JP2004067720A (ja) * 2002-08-01 2004-03-04 Nippon Unicar Co Ltd ゲル状粘着剤、医療用品および衛生用品
WO2005011662A1 (fr) * 2003-07-31 2005-02-10 Hisamitsu Pharmaceutical Co., Inc. Patch adhesif
JP2005110875A (ja) * 2003-10-06 2005-04-28 Nitto Denko Corp 皮膚貼付用の粘着シート

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010013799A1 (fr) * 2008-07-31 2010-02-04 株式会社カネカ Feuille adhésive sensible à la pression devant être collée à la peau
JPWO2010013799A1 (ja) * 2008-07-31 2012-01-12 株式会社カネカ 皮膚貼付用粘着シート
KR102112947B1 (ko) * 2019-01-24 2020-05-19 조시온 기관내 삽관술을 위한 근이완제 조성물

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