WO2014057928A1 - 貼付剤 - Google Patents
貼付剤 Download PDFInfo
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- WO2014057928A1 WO2014057928A1 PCT/JP2013/077328 JP2013077328W WO2014057928A1 WO 2014057928 A1 WO2014057928 A1 WO 2014057928A1 JP 2013077328 W JP2013077328 W JP 2013077328W WO 2014057928 A1 WO2014057928 A1 WO 2014057928A1
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- Prior art keywords
- pressure
- sensitive adhesive
- adhesive layer
- patch
- mass
- Prior art date
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- 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
- 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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
- A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
- A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
- A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
- A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
- A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
- A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
- A61K9/7061—Polyacrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
Definitions
- the present invention relates to a patch, and more particularly to a patch containing emedastine.
- Emedastine is 1- (2-ethoxyethyl) -2- (hexahydro-4-methyl-1H-1,4-diazepin-1-yl) -1H-benzimidazole (1- (2-Ethoxyethyl) -2- (hexahydro) -4-methyl-1H-1,4-diazine-1-yl) -benzimidazole).
- Emedastine is known as a drug having an inhibitory action on histamine release and an antihistaminic action and having an antiallergic effect.
- emedastine difumarate Emedastine Difumarate, molecular formula: C 17 H 26 N 4 O ⁇ 2C
- Oral preparations such as capsules containing 4 H 4 O 4 and a molecular weight of 534.56 are on the market.
- JP-A-3-83924 Patent Document 1 describes parenteral administration agents such as oily ointments, gelling agents, creams, lotions and sprays using a liquid composition containing emedastin.
- Patent Document 1 describes parenteral administration agents such as oily ointments, gelling agents, creams, lotions and sprays using a liquid composition containing emedastin.
- patches containing emedastin include, for example, an adhesive comprising an acrylic adhesive base, a silicone adhesive base, or a rubber adhesive base and emedastine in JP-A-7-33665 (Patent Document 2).
- An adhesive comprising an acrylic adhesive base is described.
- JP-A-8-193030 describes a patch comprising a pressure-sensitive adhesive layer containing an acrylic polymer and emedastine. Has been.
- Patent Document 4 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 4, there is no description regarding emedastine.
- JP-A-3-83924 Japanese Unexamined Patent Publication No. 7-33665 JP-A-8-193030 International Publication No. 2005/115355
- the present inventors have not sufficiently cohesive force of the adhesive layer, so that the adhesive is peeled off. It has been found that the problem that the adhesive layer remains on the skin occurs.
- the release of emedastine from the adhesive layer is lower than when other adhesives are used. It has been found that the absorbability decreases.
- the present invention has been made in view of the above-mentioned problems of the prior art, and an object of the present invention is to provide a patch excellent in the cohesiveness of the pressure-sensitive adhesive layer and the release of emedastin.
- the present inventors have found that in a patch comprising a support layer and an adhesive layer, a rubber-based adhesive and / or a silicone-based adhesive and an alkali metal fumarate salt Surprisingly, the alkali metal fumarate acts as a cohesive force improver for the pressure-sensitive adhesive layer, and emedastine and / or a pharmaceutically acceptable salt thereof is contained in the pressure-sensitive adhesive layer in combination. It has been found that a pressure-sensitive adhesive layer having excellent cohesiveness can be obtained even when contained. Further, the present inventors have found that such a patch is also excellent in the release of emedastine from the pressure-sensitive adhesive layer, and can increase the transdermal absorption of emedastine.
- fillers such as titanium oxide, zinc oxide, and silicate compounds, plasticizers and tackifiers were used as additives to improve the cohesive strength of the adhesive layer, and also promoted percutaneous absorption of drugs.
- a number of compounds such as those described in Patent Document 4 were known as additives intended to be used, but the present inventors have disclosed that emedastine and / or a pharmaceutically acceptable salt thereof, By combining the rubber-based pressure-sensitive adhesive and / or the silicone-based pressure-sensitive adhesive and the alkali metal fumarate, it is possible to exert both the cohesive force improving effect of the pressure-sensitive adhesive layer and the emedastine releasing effect. As a result, the present invention has been completed.
- the patch of the present invention is a patch comprising a support layer and an adhesive layer
- the adhesive layer is at least one selected from the group consisting of emedastine and pharmaceutically acceptable salts thereof. It contains at least one pressure-sensitive adhesive selected from the group consisting of drugs, rubber-based pressure-sensitive adhesives, and silicone-based pressure-sensitive adhesives, and an alkali metal fumarate salt as a cohesive strength improver for the pressure-sensitive adhesive layer.
- the alkali metal fumarate is preferably at least one selected from the group consisting of monosodium fumarate, disodium fumarate and monopotassium fumarate.
- the content of the alkali metal fumarate is preferably 1 to 10% by mass in the pressure-sensitive adhesive layer.
- the pressure-sensitive adhesive layer contains a styrene block copolymer or a mixture of a styrene block copolymer and polyisobutylene as the pressure-sensitive adhesive, and liquid paraffin is used. It is preferable to further contain the styrene-based block copolymer so that the mass ratio (the styrene-based block copolymer mass / the liquid paraffin mass) is less than 1.5.
- 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 pharmaceutically acceptable salts thereof, It contains at least one pressure-sensitive adhesive selected from the group consisting of a rubber-based pressure-sensitive adhesive and a silicone-based pressure-sensitive adhesive, and an alkali metal fumarate as a cohesive strength improver for the pressure-sensitive adhesive layer.
- 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, polybutylene terephthalate, and polyethylene naphthalate; synthetic resins such as polyolefins such as polyethylene and polypropylene; and metals such as aluminum.
- Examples of the form include films; sheets such as foam sheets and microporous sheets; fabrics such as woven fabrics, knitted fabrics and nonwoven fabrics; foils; and laminates thereof.
- a polyester film is preferable from the viewpoint of excellent flexibility and drug impermeability in a sustained-release patch applied for several days.
- 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 may have a structure in which the pressure-sensitive adhesive layer is laminated on both surfaces of the support layer, but from the viewpoint that it can be produced by a simpler process, the support
- the pressure-sensitive adhesive layer is preferably laminated on one surface of the body layer.
- 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.
- Such a release liner layer is not particularly limited, and any known release liner layer of a patch can be appropriately employed.
- a film made of a material such as polyester, polypropylene, polyethylene, paper, and the laminate thereof are used. It is preferable that the resin is subjected to a release treatment such as a silicone coat so that it can be easily peeled off. Further, 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 is at least one selected from the group consisting of at least one drug selected from the group consisting of emedastine and pharmaceutically acceptable salts thereof, a rubber-based pressure-sensitive adhesive, and a silicone-based pressure-sensitive adhesive. It contains a seed adhesive and an alkali metal fumarate salt as a cohesive strength improver for the adhesive layer.
- 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 emedastin as a drug.
- emedastin may be a free base, a pharmaceutically acceptable salt of emedastin, or a mixture thereof, but from the viewpoint that the release from the adhesive layer is further improved. It is preferably contained in the pressure-sensitive adhesive layer in a free base state.
- Examples of the pharmaceutically acceptable salt of emedastine include acid addition salts of emedastin.
- the acid include monobasic acids such as hydrochloric acid, hydrobromic acid, and methanesulfonic acid; fumaric acid, maleic acid, citric acid, and the like.
- examples thereof include polybasic acids such as acid and tartaric acid.
- fumaric acid from the viewpoint that the following fumarate alkali metal salt can be produced in the pressure-sensitive adhesive layer when it is contained in combination with a basic compound containing an alkali metal in the pressure-sensitive adhesive layer. It is preferable.
- the content of emedastine and the pharmaceutically acceptable salt thereof according to the present invention varies depending on the purpose of treatment and cannot be generally stated. It is preferable that it is mass%. Further, from the viewpoint that the cohesiveness of the pressure-sensitive adhesive layer and the release of emedastin are more excellent, it is more preferably 0.1 to 20% by mass in the pressure-sensitive adhesive layer.
- 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
- the 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 40% by mass, and more preferably 20% by mass or less in the pressure-sensitive adhesive layer from the viewpoint that the cohesiveness of the pressure-sensitive adhesive layer and the release of emedastin are more excellent.
- the pressure-sensitive adhesive layer according to the present invention contains at least one pressure-sensitive adhesive selected from the group consisting of a rubber-based pressure-sensitive adhesive and a silicone-based 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.).
- Examples of the rubber pressure-sensitive adhesive according to the present invention include styrene such as styrene-isoprene-styrene block copolymer (SIS), styrene-butadiene-styrene block copolymer, and styrene-ethylene / butylene-styrene block copolymer. Natural rubber; polyisobutylene (PIB); polyisoprene. One of these may be used alone, or two or more may be used in combination.
- SIS styrene-isoprene-styrene block copolymer
- PIB polyisobutylene
- One of these may be used alone, or two or more may be used in combination.
- the rubber-based pressure-sensitive adhesive according to the present invention includes a styrene block copolymer or a styrene block. It is preferably a mixture of a copolymer and polyisobutylene, more preferably a styrene-isoprene-styrene block copolymer, or a mixture of a styrene-isoprene-styrene block copolymer and polyisobutylene.
- the mixture of the styrenic block copolymer and polyisobutylene has a mass ratio of styrene block copolymer to polyisobutylene (mass of styrenic block copolymer: mass of polyisobutylene) of 1: 5.
- mass ratio of styrene block copolymer to polyisobutylene mass of polyisobutylene
- it is ⁇ 5: 1.
- styrene block copolymer and / or natural rubber as the rubber-based pressure-sensitive adhesive
- at least one selected from the group consisting of softeners is further added to the pressure-sensitive adhesive layer.
- These tackifiers and softeners may be added even when other rubber adhesives or the following silicone adhesives are used.
- the content thereof is preferably 10 to 99% by mass and more preferably 15 to 95% by mass in the pressure-sensitive adhesive layer. preferable.
- the content of the rubber-based pressure-sensitive adhesive is less than the lower limit, the adhesiveness of the patch to the skin tends to decrease.
- a polymer having an organopolysiloxane skeleton is preferably used as the silicone pressure-sensitive adhesive according to the present invention.
- the polymer having an organopolysiloxane skeleton has a hydroxyl group (for example, a silanol group)
- the capping with the trimethylsilyl group includes an embodiment in which the terminal silanol group of the polymer having an organopolysiloxane skeleton is endcapped with a trimethylsilyl group.
- Examples of such a polymer having an organopolysiloxane skeleton include polydimethylsiloxane (polymer represented by MQ in the case of ASTM D-1418), polymethylvinylsiloxane (polymer represented by VMQ in the representation of ASTM D-1418, etc.) ), Polymethylphenylsiloxane (polymer represented as PVMQ in the display by ASTM D-1418), and the like.
- One of these may be used alone, or two or more may be used in combination.
- BIO-PSA 7 series for example, BIO-PSA 7-410X, BIO-PSA 7-420X, BIO-PSA 7-430X manufactured by Dow Corning, etc. are commercially available. What is currently used may be used as appropriate. Among these, BIO-PSA 7-4201 and BIO-PSA 7-4202 are preferable.
- the content thereof is preferably 10 to 99% by mass, more preferably 15 to 95% by mass in the pressure-sensitive adhesive layer. preferable.
- the content of the silicone pressure-sensitive adhesive is less than the lower limit, the adhesiveness of the patch to the skin tends to decrease.
- the total content is preferably 10 to 99% by mass in the adhesive layer. 15 to 95% by mass is more preferable.
- the pressure-sensitive adhesive layer according to the present invention may further contain another pressure-sensitive adhesive such as an acrylic pressure-sensitive adhesive such as a (meth) acrylic acid ester copolymer, if necessary.
- an acrylic pressure-sensitive adhesive such as a (meth) acrylic acid ester copolymer
- the alkali metal fumarate described later exhibits a function as a cohesive strength improver when the rubber-based pressure-sensitive adhesive and / or the silicone-based pressure-sensitive adhesive is used.
- these other pressure-sensitive adhesives are contained in the pressure-sensitive adhesive layer according to the present invention.
- the content thereof is preferably 10% by mass or less, and more preferably substantially not contained.
- the emedastine and / or a pharmaceutically acceptable salt thereof, the rubber-based pressure-sensitive adhesive and / or the silicone-based pressure-sensitive adhesive, and an alkali metal fumarate are combined and contained in the pressure-sensitive adhesive layer.
- the present inventors have found out. Therefore, it is possible to more reliably apply the patch of the present invention to the target skin, and on the other hand, it is possible to sufficiently suppress the adhesive layer from remaining on the skin when peeling off. It becomes.
- alkali metal fumarate examples include monosodium fumarate, disodium fumarate, monopotassium fumarate, and dipotassium fumarate.
- the cohesiveness of the pressure-sensitive adhesive layer and the release of emedastine From the viewpoint that the properties tend to be further improved, it is preferably at least one selected from the group consisting of monosodium fumarate, disodium fumarate and monopotassium fumarate, and disodium fumarate. More preferred.
- the alkali metal fumarate according to the present invention is one that is added as the compound at the time of production, and is produced during and / or after the production and contained in the pressure-sensitive adhesive layer. May be.
- the method for containing such an alkali metal fumarate salt in the pressure-sensitive adhesive layer include, for example, the fumarate according to the present invention in the pressure-sensitive adhesive layer composition for forming the pressure-sensitive adhesive layer at the time of producing a patch.
- the method further comprises adding the free base of emedastine and the alkali metal fumarate to the pressure-sensitive adhesive layer.
- the content of the alkali metal fumarate salt according to the present invention is preferably 0.1 to 15% by mass, more preferably 1 to 10% by mass in the pressure-sensitive adhesive layer.
- the content of the alkali metal fumarate is less than the lower limit, the cohesiveness of the pressure-sensitive adhesive layer tends not to be sufficiently improved.
- the content exceeds the upper limit streaking is caused in the production process. There is a tendency for problems to occur.
- the rubber-based pressure-sensitive adhesive is used as the pressure-sensitive adhesive
- the content of the alkali metal fumarate is preferably 0.1 to 15% by mass in the pressure-sensitive adhesive layer. More preferably, it is more preferably 2 to 5% by mass.
- the silicone-based pressure-sensitive adhesive is used as the pressure-sensitive adhesive, the content of the alkali metal fumarate is preferably 0.1 to 15% by mass in the pressure-sensitive adhesive layer. More preferably, it is more preferably 3 to 10% by mass.
- the pressure-sensitive adhesive layer according to the present invention may further contain additives such as the tackifier, the softener, the solubilizer, the filler, and the stabilizer as long as the effects of the present invention are not impaired. Good.
- additives such as the tackifier, the softener, the solubilizer, the filler, and the stabilizer as long as the effects of the present invention are not impaired.
- the tackifier in the case of using a styrene block copolymer and / or natural rubber as the pressure-sensitive adhesive, at least one selected from the group consisting of the tackifier and the softener is further contained. It is preferable.
- tackifier examples include rosin resin, rosin ester resin, terpene resin, terpene phenol resin, C5 petroleum resin, C5 / C9 petroleum resin, DCPD (dicyclopentadiene) petroleum resin, coumarone / indene resin, Examples include alicyclic saturated hydrocarbon resins and those added with hydrogen, and one of these may be used alone or two or more of them may be used in combination.
- the content thereof is preferably 70% by mass or less in the pressure-sensitive adhesive layer.
- softener examples include petroleum oil (eg, paraffinic process oil, naphthenic process oil, aromatic process oil, etc.), squalane, squalene, vegetable oil (eg, olive oil, camellia oil, castor oil, tall oil, Peanut oil, etc.), silicone oil, dibasic acid esters (eg, dibutyl phthalate, dioctyl phthalate, etc.), liquid rubber (eg, polybutene, liquid isoprene rubber, etc.), liquid fatty acid esters (eg, isopropyl myristate, hexyl laurate) , Diethyl sebacate, diisopropyl sebacate, etc.), diethylene glycol, polyethylene glycol, glycol salicylate, propylene glycol, dipropylene glycol, triacetin, triethyl citrate, crotamiton, etc.
- petroleum oil eg, paraffinic process oil, naphthenic process oil, aromatic process oil, etc
- Be used one by itself may be used in combination of two or more.
- liquid paraffin, liquid polybutene, isopropyl myristate, diethyl sebacate, and hexyl laurate are preferable, and liquid paraffin is more preferable.
- silicone adhesive when using the said silicone adhesive as said adhesive, silicone oil is preferable.
- the content thereof is preferably 50% by mass or less in the pressure-sensitive adhesive layer.
- the solubilizer depends on the type of solute to be dissolved, but for example, fatty acids (eg, capric acid, oleic acid, linoleic acid, etc.), fatty acid esters (eg: isopropyl myristate, isopropyl palmitate, etc.), Fatty acid derivatives (eg, propylene glycol monolaurate, diethanolamide laurate), fatty acid glycerol esters (eg: glycerol monolaurate, glycerol monooleate), polyhydric alcohol esters of fatty acids (eg: sorbitan monolaurate), Aliphatic alcohols (eg, octyldodecanol, isostearyl alcohol, oleyl alcohol, etc.), polyhydric alcohols (eg, propylene glycol, dipropylene glycol, polyethylene glycol, etc.), pyrrolidone derivatives (eg, N-methyl-2-) Rolidone, etc.
- the filler examples include inorganic compounds such as silica, aluminum oxide, aluminum hydroxide, zinc oxide, titanium oxide, talc, clay, kaolin, glass, barium sulfate, calcium carbonate, hydroxyapatite, ceramics; cellulose, silk, polyester , Polyolefin, polyacrylic acid ester, polymethacrylic acid ester, polystyrene, and the like, and one of these may be used alone, or two or more may be used in combination.
- inorganic compounds such as silica, aluminum oxide, aluminum hydroxide, zinc oxide, titanium oxide, talc, clay, kaolin, glass, barium sulfate, calcium carbonate, hydroxyapatite, ceramics
- the stabilizer examples include tocopherol and tocopherol ester derivatives, ascorbic acid, ascorbic acid stearyl ester, nordihydroguaiaretic acid, dibutylhydroxytoluene (BHT), butylhydroxyanisole, and the like.
- BHT dibutylhydroxytoluene
- One kind may be used alone, or two or more kinds may be used in combination.
- the content thereof is preferably 30% by mass or less in the pressure-sensitive adhesive layer, and is 20% by mass or less. More preferred is 10% by mass or less.
- the pressure-sensitive adhesive layer according to the present invention is a rubber-based pressure-sensitive adhesive from the viewpoint that the cohesive force improving effect of the pressure-sensitive adhesive layer and the effect of improving emedastine release are exhibited by the configuration of the present invention. preferable.
- a styrene block copolymer preferably styrene-isoprene-styrene block copolymer
- a styrene block copolymer preferably styrene-isoprene-styrene block copolymer
- poly It is particularly preferable that a mixture with isobutylene is contained and liquid paraffin is contained as the softening agent.
- the compounding ratio of the rubber-based pressure-sensitive adhesive and liquid paraffin in this case is the mass ratio of styrene block copolymer to liquid paraffin (mass of styrene block copolymer / mass of liquid paraffin). It is preferably less than 5, more preferably 0.5 to 1.25.
- mass ratio is less than the lower limit, the adhesiveness of the pressure-sensitive adhesive layer tends to be reduced.
- the upper limit is exceeded, the cohesive force of the pressure-sensitive adhesive layer is not required even in the configuration of the present invention. Since it becomes large to some extent, there is a tendency that the effect of improving the cohesive force by the configuration of the present invention is not exhibited any more.
- the patch of the present invention is not particularly limited and can be produced by a conventionally known method.
- a pressure-sensitive adhesive, an alkali metal fumarate salt, a solvent, and, if necessary, a pressure-sensitive adhesive layer composition containing the additive are prepared, and this is formed on one surface of the support layer at a desired thickness.
- coating and removing the said solvent is mentioned.
- the solvent is not particularly limited and can be appropriately selected according to the type of drug or adhesive used, alkali metal fumarate, etc., for example, lower alcohols such as methanol, ethanol, isopropanol, toluene, xylene, Examples include pentane, n-hexane, cyclohexane, heptane, octane, methyl acetate, ethyl acetate, propyl acetate, methyl butyrate, ethyl butyrate, and propyl butyrate.
- lower alcohols such as methanol, ethanol, isopropanol, toluene, xylene
- Examples include pentane, n-hexane, cyclohexane, heptane, octane, methyl acetate, ethyl acetate, propyl acetate, methyl butyrate, ethyl butyrate, and prop
- the alkali metal fumarate added to the pressure-sensitive adhesive layer composition is preferably pulverized.
- the alkali metal fumarate instead of the pressure-sensitive adhesive layer composition, emedastine fumarate, the rubber-based pressure-sensitive adhesive, and / or the silicone-based
- a pressure-sensitive adhesive a basic compound containing an alkali metal, a solvent, and a composition containing the additive as necessary, the alkali metal fumarate can be contained in the obtained pressure-sensitive adhesive layer. .
- the release liner layer is further provided as a patch of the present invention
- the pressure-sensitive adhesive layer composition is first applied on one surface of the release liner layer to form the pressure-sensitive adhesive layer
- the patch of the present invention can also be obtained by laminating the support layer on the surface of the adhesive layer opposite to the release liner layer.
- each of the obtained patches was cut into a size of 2.5 cm ⁇ 2.5 cm, and the release liner layer was peeled off and attached to a rotating cylinder of an elution tester so that the adhesive layer was on the outside. Thereafter, a round bottom flask containing 900 ml of purified water was attached to a dissolution tester, the temperature was set to 32 ° C., and the rotating cylinder was immersed in the purified water of the round bottom flask.
- D v represents the formulation diffusion coefficient
- C v0 represents the initial emedastine amount
- L v denotes the thickness of the adhesive layer.
- Reference Examples 4 to 11 Patches of Reference Examples 4 to 11 were obtained in the same manner as Reference Example 1 except that the composition of the pressure-sensitive adhesive layer composition was changed to the composition shown in Table 2. In addition, for each patch of Reference Examples 4 to 11, a patch containing no disodium fumarate was prepared and used as a reference preparation. The patches obtained in Reference Examples 4 to 11 were compared with the reference preparation. The cohesive strength improving effect was evaluated. The obtained results are shown in Table 2 together with the composition of each pressure-sensitive adhesive layer composition (excluding toluene). In Reference Examples 10 to 11, since the adhesive layer remaining ratio in the reference preparation was 2% or less, the evaluation of the cohesive strength improvement effect was D.
- Example 1 First, 16.7 parts by mass of styrene-isoprene-styrene block copolymer (SIS, rubber adhesive), 7.1 parts by mass of polyisobutylene (PIB, rubber adhesive), alicyclic saturated hydrocarbon resin (Arcon) P100, Arakawa Chemical Industries, Inc., tackifier) 52.4 parts by mass, liquid paraffin (softener) 19.0 parts by mass, and pulverized disodium fumarate 2 parts by mass in toluene, rubber adhesive A composition containing the agent was obtained. Then, a methanol solution of 2.8 parts by mass of emedastine (free base) was added to the composition and further stirred to obtain a pressure-sensitive adhesive layer composition.
- SIS styrene-isoprene-styrene block copolymer
- PIB polyisobutylene
- alicyclic saturated hydrocarbon resin Arcon
- liquid paraffin softener
- the obtained pressure-sensitive adhesive layer composition was applied on one surface of a release-treated polyethylene terephthalate film (release liner layer) and then dried at 80 ° C. to form a pressure-sensitive adhesive layer having a thickness of 100 ⁇ m.
- a patch was obtained by laminating a polyethylene terephthalate film (support layer) on the surface of the pressure-sensitive adhesive layer opposite to the release liner layer.
- Examples 2 to 3 Comparative Example 1 Except that disodium fumarate was 5 parts by mass (Example 2) or 10 parts by mass (Example 3), and the addition amount of each compound was changed to the amount shown in Table 3 according to this, it was the same as Example 1. Thus, patches of Examples 2 to 3 were obtained. Further, the patch (reference preparation) of Comparative Example 1 was obtained in the same manner as in Example 1 except that disodium fumarate was not used and the addition amount of each compound was changed to the amount shown in Table 3 accordingly. It was. Next, cohesiveness evaluation tests were conducted for Examples 1 to 3 and Comparative Example 1, and the adhesive strength of the patches obtained in Examples 1 to 3 was compared with that of the patch (reference formulation) obtained in Comparative Example 1. Each improvement effect was evaluated.
- Comparative Example 2 A pressure-sensitive adhesive layer composition containing an acrylate pressure-sensitive adhesive obtained by stirring 95 parts by mass of an acrylate pressure-sensitive adhesive solution (Duro-Tak 87-2516, manufactured by Henkel) and 5 parts by mass of pulverized disodium fumarate in toluene
- a patch of Comparative Example 2 was obtained in the same manner as Example 1 except that was used.
- a patch was prepared in the same manner as above except that disodium fumarate was not used and the amount of the acrylate pressure-sensitive adhesive solution added was 100 parts by mass.
- standard formulation was evaluated. The obtained results are shown in Table 4 together with the composition of the pressure-sensitive adhesive layer composition (excluding toluene).
- Comparative Examples 3 to 7 Patches of Comparative Examples 3 to 7 were obtained in the same manner as Comparative Example 2 except that the composition of the pressure-sensitive adhesive layer composition was changed to the composition shown in Table 4, respectively.
- a patch containing no disodium fumarate was prepared and used as a reference formulation.
- the patches obtained in Comparative Examples 3-7 were compared with the above-mentioned reference formulation. The cohesive strength improving effect was evaluated. The obtained results are shown in Table 4 together with the composition of each pressure-sensitive adhesive layer composition (excluding toluene).
- Duro-Tak 87-2194, Duro-Tak 87-4098, Duro-Tak 87-2051, Duro-Tak 87-202A and Duro-Tak 87-235A are all acrylate adhesives manufactured by Henkel. Indicates a solution.
- the alkali metal fumarate acts as a cohesive strength improver for the pressure-sensitive adhesive layer containing the rubber-based pressure-sensitive adhesive, and exhibits excellent cohesiveness in the pressure-sensitive adhesive layer. It was confirmed that In addition, as is apparent from the results shown in Tables 3 to 4 and FIG. 1, the adhesive patch of the present invention exhibits excellent cohesiveness of the pressure-sensitive adhesive layer and also excellent emedastin release properties. Was confirmed.
- a composition containing styrene-isoprene-styrene block copolymer, polyisobutylene, alicyclic saturated hydrocarbon resin, liquid paraffin, and ground sodium hydroxide was mixed with a methanol solution of emedastine difumarate. Evaluation of the patch obtained in the same manner as in Example 1 except that the pressure-sensitive adhesive layer composition obtained above was used, and the results were the same as those in Examples 1 to 3.
- Example 4 First, 76.3 parts by mass of silicone adhesive (BIO-PSA 7-4202, manufactured by Dow Corning), 17.5 parts by mass of silicone oil (softener, 350-CST, manufactured by Dow Corning), and pulverization 3.2 parts by mass of disodium fumarate was stirred in toluene to obtain a composition containing a silicone-based pressure-sensitive adhesive. Subsequently, a methanol solution of 3.0 parts by mass of emedastine (free base) was added to the composition and further stirred to obtain a pressure-sensitive adhesive layer composition. The obtained pressure-sensitive adhesive layer composition was applied on one surface of a release-treated polyethylene terephthalate film (release liner layer), and then dried at 80 ° C.
- silicone adhesive BIO-PSA 7-4202, manufactured by Dow Corning
- silicone oil softener, 350-CST, manufactured by Dow Corning
- pulverization 3.2 parts by mass of disodium fumarate was stirred in toluene to obtain a composition
- a patch was obtained by forming and laminating a polyethylene terephthalate film (support layer) on the surface of the pressure-sensitive adhesive layer opposite to the release liner layer.
- Examples 5 to 7, Comparative Example 8 The disodium fumarate is 4.0 parts by mass (Example 5), 6.0 parts by mass (Example 6) or 10 parts by mass (Example 7), respectively.
- the patches of Examples 5 to 7 were obtained in the same manner as in Example 4 except that the amount shown in 5 was used. Further, the patch (reference preparation) of Comparative Example 8 was obtained in the same manner as in Example 4 except that disodium fumarate was not used and the addition amount of each compound was changed to the amount shown in Table 5 accordingly. It was. Next, a cohesiveness evaluation test was conducted for Examples 4 to 7 and Comparative Example 8, and the adhesive strength of the patches obtained in Examples 4 to 7 was compared with the adhesive patch (reference preparation) obtained in Comparative Example 8.
- the alkali metal fumarate also works as a cohesive strength improver for the pressure-sensitive adhesive layer containing the silicone-based pressure-sensitive adhesive, and exhibits excellent cohesiveness in the pressure-sensitive adhesive layer. It was confirmed. Further, as is apparent from the results shown in Table 5 and FIG. 2, in the patch of the present invention, excellent cohesiveness of the pressure-sensitive adhesive layer is exhibited, and the release of emedastin is also excellent. confirmed.
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Abstract
Description
本発明に係る支持体層は、前記粘着剤層を物理的に支持し、外的な環境から前記粘着剤層を保護する層である。このような支持体層としては、特に制限されず、貼付剤の支持体層として公知のものを適宜採用することができる。このような支持体層の材質としては、例えば、ポリエチレンテレフタレート、ポリブチレンテレフタレート、ポリエチレンナフタレート等のポリエステル;ポリエチレン、ポリプロピレン等のポリオレフィンといった合成樹脂や、アルミニウム等の金属が挙げられ、前記支持体層の形態としては、フィルム;発泡シート、微多孔シート等のシート;織布、編布、不織布等の布帛;箔;及びこれらの積層体等が挙げられる。これらの中でも、数日間適用する徐放性の貼付剤において、柔軟性及び薬物非透過性に優れるという観点から、ポリエステルフィルムが好ましい。また、前記支持体層の厚さとしても特に制限されないが、通常2~300μm程度であることが好ましい。
本発明に係る粘着剤層は、エメダスチン及びその薬学的に許容される塩からなる群から選択される少なくとも1種の薬物、ゴム系粘着剤及びシリコーン系粘着剤からなる群から選択される少なくとも1種の粘着剤、並びに前記粘着剤層の凝集力向上剤としてのフマル酸アルカリ金属塩を含有するものである。このような粘着剤層の厚さとしては特に制限されないが、通常20~300μm程度であることが好ましい。
本発明に係る粘着剤層は薬物としてエメダスチンを含有する。このようなエメダスチンとしては、遊離塩基であってもエメダスチンの薬学的に許容される塩であってもそれらの混合物であってもよいが、粘着剤層からの放出性がより向上するという観点から、遊離塩基の状態で前記粘着剤層中に含有されていることが好ましい。
本発明に係る粘着剤層は、粘着剤としてゴム系粘着剤及びシリコーン系粘着剤からなる群から選択される少なくとも1種の粘着剤を含有する。なお、本発明において、粘着剤とは、貼付剤が適用される温度(好ましくは0℃~50℃、より好ましくは10℃~40℃、さらに好ましくは15℃~40℃)において粘着性を発現することが可能な化合物のことをいう。
本発明においては、前記エメダスチン及び/又はその薬学的に許容される塩と前記ゴム系粘着剤及び/又は前記シリコーン系粘着剤とフマル酸アルカリ金属塩とを組み合わせて前記粘着剤層中に含有させることにより、エメダスチンの粘着剤層からの放出性が向上すると共に、フマル酸アルカリ金属塩が前記粘着剤層の凝集力向上剤として機能し、粘着剤層の付着性及び凝集性が著しく向上することを本発明者らは見出した。したがって、本発明の貼付剤を対象の皮膚に貼付する際にはより確実に貼付することが可能となり、他方、剥離する際には皮膚への粘着剤層の残存を十分に抑制することが可能となる。
本発明に係る粘着剤層としては、本発明の効果を阻害しない範囲内において、前記粘着付与剤、前記軟化剤、溶解剤、充填剤、安定化剤等の添加剤がさらに含有されていてもよい。特に、前述のように、前記粘着剤としてスチレン系ブロック共重合体及び/又は天然ゴムを用いる場合においては、前記粘着付与剤及び前記軟化剤からなる群から選択される少なくとも1種がさらに含有されていることが好ましい。
本発明の貼付剤は、特に制限されず、従来公知の方法により製造することができ、例えば、先ず、エメダスチン及び/又はその薬学的に許容される塩、前記ゴム系粘着剤及び/又は前記シリコーン系粘着剤、前記フマル酸アルカリ金属塩、溶剤、並びに必要に応じて前記添加剤を含有する粘着剤層組成物を調製し、これを前記支持体層の一方の面上に所望の厚さで塗布した後に加温して前記溶剤を除去することにより、前記支持体層の一方の面上に前記粘着剤層を形成せしめる方法が挙げられる。
先ず、得られた各貼付剤をそれぞれ1cm×5cmの大きさに切り抜き、剥離ライナー層を剥離して質量を測定した後、ベークライト板に貼付して30分間静置した。その後、30cm/minの速度で貼付剤をベークライト板から剥離し、剥離後の貼付剤の質量を測定して下記式(1):
粘着剤層残り率(%)=[(貼付前の貼付剤質量-剥離後の貼付剤質量)/貼付前の貼付剤質量]×100 ・・・(1)
により粘着剤層残り率(%)を算出した。
凝集力向上率(%)={1+[(貼付剤Yの粘着剤層残り率-貼付剤Xの粘着剤層残り率)/貼付剤Yの粘着剤層残り率]}×100 ・・・(3)
により凝集力向上率(%)を算出し、基準製剤と比較した凝集力向上効果を、凝集力向上率(%)が150%以上の場合をA、凝集力向上率(%)が110%以上150%未満の場合をB、凝集力向上率(%)が110%未満の場合をCとして評価した。なお、貼付剤Yの粘着剤層残り率が2%以下であった場合には、凝集力向上率の値にかかわらず凝集力向上効果の評価はDとした。
先ず、得られた各貼付剤をそれぞれ2.5cm×2.5cmの大きさに切り抜き、剥離ライナー層を剥離して粘着剤層が外側となるように溶出試験機の回転シリンダーに装着した。その後、900mlの精製水を入れた丸底フラスコを溶出試験機に装着して温度を32℃に設定し、前記丸底フラスコの精製水中に前記回転シリンダーを浸漬した。これを速度50rpmで回転させながら所定時間毎に溶出液10mlをサンプリングし、高速液体クロマトグラフ法により水中に放出されたエメダスチンの質量(水中放出量)を測定して測定開始からT時間後(Tは任意の正の数)の総水中放出量を求め、試験前の粘着剤層中に含有させたエメダスチン質量(初期エメダスチン量)から、下記式(3):
水中放出率(%)=(T時間後の総水中放出量/初期エメダスチン量)×100 ・・・(3)
により測定開始からT時間後の水中放出率(%)を算出した。次いで、上記で得られた各時間における水中放出量について、下記式(4):
によりカーブフィッティングし、製剤中拡散係数(Dv[μm2/hr])を求めた。なお、水中放出率及び/又は製剤中拡散係数が大きい程、粘着剤層からのエメダスチンの放出量が多いことを示し、その分エメダスチンの経皮吸収性が向上するものと認められる。
先ず、スチレン-イソプレン-スチレンブロック共重合体(SIS、ゴム系粘着剤)11.9質量部、ポリイソブチレン(PIB、ゴム系粘着剤)7.1質量部、脂環族飽和炭化水素樹脂(アルコンP100、荒川化学工業社製、粘着付与剤)52.3質量部、流動パラフィン(軟化剤)23.7質量部、及び粉砕したフマル酸二ナトリウム5質量部をトルエン中において攪拌し、粘着剤層組成物を得た。得られた粘着剤層組成物を離型処理が施されたポリエチレンテレフタレートフィルム(剥離ライナー層)の一方の面上に塗布した後、80℃において乾燥させて厚さ100μmの粘着剤層を形成せしめ、前記粘着剤層の前記剥離ライナー層とは反対の面上にポリエチレンテレフタレートフィルム(支持体層)を積層することにより貼付剤を得た。
フマル酸二ナトリウムに代えて粉砕したフマル酸一ナトリウム(参考例2)又はフマル酸一カリウム(参考例3)を用いたこと以外はそれぞれ参考例1と同様にして参考例2~3の貼付剤を得た。また、フマル酸二ナトリウムを用いず、これにあわせて各化合物の添加量をそれぞれ表1に示す量としたこと以外は参考例1と同様にしてフマル酸アルカリ金属塩を含有しない貼付剤(基準製剤)を作製し、これと比較した凝集力向上効果を参考例1~3について評価した。得られた結果を各粘着剤層組成物の組成(トルエンを除く)と共にそれぞれ表1に示す。
粘着剤層組成物の組成をそれぞれ表2に示す組成としたこと以外は参考例1と同様にして参考例4~11の貼付剤を得た。また、参考例4~11の各貼付剤に対してフマル酸二ナトリウムを含有しない貼付剤をそれぞれ作製して基準製剤とし、参考例4~11で得られた貼付剤について、前記基準製剤と比較した凝集力向上効果をそれぞれ評価した。得られた結果を各粘着剤層組成物の組成(トルエンを除く)と共にそれぞれ表2に示す。なお、参考例10~11においては、基準製剤における粘着剤層残り率が2%以下であったため、凝集力向上効果の評価はDとした。
先ず、スチレン-イソプレン-スチレンブロック共重合体(SIS、ゴム系粘着剤)16.7質量部、ポリイソブチレン(PIB、ゴム系粘着剤)7.1質量部、脂環族飽和炭化水素樹脂(アルコンP100、荒川化学工業社製、粘着付与剤)52.4質量部、流動パラフィン(軟化剤)19.0質量部、及び粉砕したフマル酸二ナトリウム2質量部をトルエン中において攪拌し、ゴム系粘着剤を含む組成物を得た。次いで、エメダスチン(遊離塩基)2.8質量部のメタノール溶液を前記組成物中に添加してさらに撹拌し、粘着剤層組成物を得た。得られた粘着剤層組成物を離型処理が施されたポリエチレンテレフタレートフィルム(剥離ライナー層)の一方の面上に塗布した後、80℃において乾燥させて厚さ100μmの粘着剤層を形成せしめ、前記粘着剤層の前記剥離ライナー層とは反対の面上にポリエチレンテレフタレートフィルム(支持体層)を積層することにより貼付剤を得た。
フマル酸二ナトリウムを5質量部(実施例2)又は10質量部(実施例3)とし、これにあわせて各化合物の添加量をそれぞれ表3に示す量としたこと以外は実施例1と同様にして実施例2~3の貼付剤を得た。また、フマル酸二ナトリウムを用いず、これにあわせて各化合物の添加量をそれぞれ表3に示す量としたこと以外は実施例1と同様にして比較例1の貼付剤(基準製剤)を得た。次いで、実施例1~3及び比較例1について凝集性評価試験を行い、実施例1~3で得られた貼付剤について、比較例1で得られた貼付剤(基準製剤)と比較した凝集力向上効果をそれぞれ評価した。得られた結果を各粘着剤層組成物の組成(トルエン、メタノールを除く)と共に表3にそれぞれ示す。また、実施例1~3及び比較例1で得られた貼付剤について、水中放出実験を行った結果を表3及び図1にそれぞれ示す。なお、表3中の水中放出率は、測定開始から24時間後(T=24)の水中放出率である。
アクリレート粘着剤溶液(Duro-Tak 87-2516、ヘンケル社製)95質量部及び粉砕したフマル酸二ナトリウム5質量部をトルエン中において攪拌して得られたアクリレート系粘着剤を含む粘着剤層組成物を用いたこと以外は実施例1と同様にして比較例2の貼付剤を得た。また、フマル酸二ナトリウムを用いず、これにあわせてアクリレート粘着剤溶液の添加量を100質量部としたこと以外は上記と同様にして貼付剤を作製して基準製剤とし、比較例2で得られた貼付剤について、前記基準製剤と比較した凝集力向上効果を評価した。得られた結果を粘着剤層組成物の組成(トルエンを除く)と共に表4に示す。
粘着剤層組成物の組成をそれぞれ表4に示す組成としたこと以外は比較例2と同様にして比較例3~7の貼付剤を得た。また、比較例3~7の各貼付剤に対してフマル酸二ナトリウムを含有しない貼付剤をそれぞれ作製して基準製剤とし、比較例3~7で得られた貼付剤について、前記基準製剤と比較した凝集力向上効果をそれぞれ評価した。得られた結果を各粘着剤層組成物の組成(トルエンを除く)と共にそれぞれ表4に示す。なお、表4中、Duro-Tak 87-2194、Duro-Tak 87-4098、Duro-Tak 87-2051、Duro-Tak 87-202A、Duro-Tak 87-235Aはいずれもヘンケル社製のアクリレート粘着剤溶液を示す。
先ず、シリコーン系粘着剤(BIO-PSA 7-4202、ダウ・コーニング社製)76.3質量部、シリコーンオイル(軟化剤、350-CST、ダウ・コーニング社製)17.5質量部、及び粉砕したフマル酸二ナトリウム3.2質量部をトルエン中において攪拌し、シリコーン系粘着剤を含む組成物を得た。次いで、エメダスチン(遊離塩基)3.0質量部のメタノール溶液を前記組成物中に添加してさらに撹拌し、粘着剤層組成物を得た。得られた粘着剤層組成物を離型処理が施されたポリエチレンテレフタレートフィルム(剥離ライナー層)の一方の面上に塗布した後、80℃において20分間乾燥させて厚さ100μmの粘着剤層を形成せしめ、前記粘着剤層の前記剥離ライナー層とは反対の面上にポリエチレンテレフタレートフィルム(支持体層)を積層することにより貼付剤を得た。
フマル酸二ナトリウムをそれぞれ4.0質量部(実施例5)、6.0質量部(実施例6)又は10質量部(実施例7)とし、これにあわせて各化合物の添加量をそれぞれ表5に示す量としたこと以外は実施例4と同様にして実施例5~7の貼付剤を得た。また、フマル酸二ナトリウムを用いず、これにあわせて各化合物の添加量をそれぞれ表5に示す量としたこと以外は実施例4と同様にして比較例8の貼付剤(基準製剤)を得た。次いで、実施例4~7及び比較例8について凝集性評価試験を行い、実施例4~7で得られた貼付剤について、比較例8で得られた貼付剤(基準製剤)と比較した凝集力向上効果をそれぞれ評価した。得られた結果を各粘着剤層組成物の組成(トルエン、メタノールを除く)と共に表5にそれぞれ示す。また、実施例4~7及び比較例8で得られた貼付剤について、水中放出実験を行った結果を表5及び図2にそれぞれ示す。なお、表5中の水中放出率は、測定開始から6時間後(T=6)の水中放出率である。
Claims (4)
- 支持体層及び粘着剤層を備える貼付剤であって、前記粘着剤層がエメダスチン及びその薬学的に許容される塩からなる群から選択される少なくとも1種の薬物、ゴム系粘着剤及びシリコーン系粘着剤からなる群から選択される少なくとも1種の粘着剤、並びに、前記粘着剤層の凝集力向上剤としてのフマル酸アルカリ金属塩を含有することを特徴とする貼付剤。
- 前記フマル酸アルカリ金属塩がフマル酸一ナトリウム、フマル酸二ナトリウム及びフマル酸一カリウムからなる群から選択される少なくとも1種であることを特徴とする請求項1に記載の貼付剤。
- 前記フマル酸アルカリ金属塩の含有量が前記粘着剤層中において1~10質量%であることを特徴とする請求項1又は2に記載の貼付剤。
- 前記粘着剤層が、前記粘着剤としてスチレン系ブロック共重合体又はスチレン系ブロック共重合体とポリイソブチレンとの混合物を含有しており、かつ、流動パラフィンを前記スチレン系ブロック共重合体との質量比(スチレン系ブロック共重合体の質量/流動パラフィンの質量)が1.5未満となるようにさらに含有するものであることを特徴とする請求項1~3のうちのいずれか一項に記載の貼付剤。
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EP13845905.2A EP2907515B1 (en) | 2012-10-11 | 2013-10-08 | Skin patch |
ES13845905T ES2710548T3 (es) | 2012-10-11 | 2013-10-08 | Parche transdérmico |
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JP2015157256A (ja) * | 2014-02-25 | 2015-09-03 | 株式会社鶴見製作所 | 固液分離装置 |
WO2016140087A1 (ja) * | 2015-03-02 | 2016-09-09 | 久光製薬株式会社 | 貼付剤 |
WO2017061393A1 (ja) * | 2015-10-06 | 2017-04-13 | 久光製薬株式会社 | 貼付剤 |
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EP3391884B1 (en) * | 2015-12-10 | 2024-04-10 | KM Transderm Ltd. | Transdermally absorbable preparation |
US11202764B2 (en) * | 2017-04-25 | 2021-12-21 | Hisamitsu Pharmaceutical Co., Inc. | Patch |
CN112823793A (zh) * | 2019-11-20 | 2021-05-21 | 成都康弘药业集团股份有限公司 | 一种含有多奈哌齐的透皮贴剂及其制备方法 |
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CN104703607B (zh) | 2016-11-23 |
JP5925903B2 (ja) | 2016-05-25 |
US9789188B2 (en) | 2017-10-17 |
EP2907515B1 (en) | 2019-01-02 |
TWI592171B (zh) | 2017-07-21 |
EP2907515A1 (en) | 2015-08-19 |
KR101902612B1 (ko) | 2018-09-28 |
US20150250877A1 (en) | 2015-09-10 |
TW201420134A (zh) | 2014-06-01 |
CN104703607A (zh) | 2015-06-10 |
ES2710548T3 (es) | 2019-04-25 |
JPWO2014057928A1 (ja) | 2016-09-05 |
EP2907515A4 (en) | 2016-05-04 |
KR20150065850A (ko) | 2015-06-15 |
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