WO2015133329A1 - 貼付製剤 - Google Patents
貼付製剤 Download PDFInfo
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- WO2015133329A1 WO2015133329A1 PCT/JP2015/055173 JP2015055173W WO2015133329A1 WO 2015133329 A1 WO2015133329 A1 WO 2015133329A1 JP 2015055173 W JP2015055173 W JP 2015055173W WO 2015133329 A1 WO2015133329 A1 WO 2015133329A1
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- patch
- layer
- cover layer
- preparation
- support
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
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- 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
-
- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Definitions
- the present invention relates to a patch provided with a laminated support having good adhesion to an adherend.
- Blended patches are commercially available and used in medical settings. Patches containing these systemically active drugs are characterized by the ability to maintain a constant blood concentration of the drug for a long period of time, so that they can be administered once a day to those that can be administered for a week for longer ones. Has been.
- patches are mainly acrylic pressure-sensitive adhesives, silicone pressure-sensitive adhesives, from the viewpoints of solubility between the drug and the base component, drug release from the base component, stable adhesiveness in long-term administration, and the like.
- it is supplied as a so-called tape agent based on a base such as styrene / isoprene / styrene block copolymer.
- Patent Document 1 a method of fixing the patch with a cover sheet (Patent Document 1) or a reservoir type patch preparation in which the cover sheet and the patch are integrated has been proposed ( Patent Document 2).
- Patent Document 2 a method of fixing the patch with a cover sheet (Patent Document 1) or a reservoir type patch preparation in which the cover sheet and the patch are integrated has been proposed ( Patent Document 2).
- patch preparations comprising these cover sheets are not peeled off or detached from the skin patch site due to their strong adhesive strength, but the patch part or reservoir part is In some cases, it was impossible to follow the movement, and thus the skin and the patch could not be pressed together and stable drug release could not be achieved.
- an object of the present invention is to provide a patch preparation that can stably and continuously administer a drug, particularly a systemically active drug, over a long period of time in order to solve such a conventional problem.
- an adhesive layer containing a drug and a patch layer comprising a patch support, and a laminate comprising a cover layer In a patch preparation with a structure, by adopting a patch preparation in which a buffer material is arranged between the patch support and the cover layer, the pressure-bonding property between the skin and the adhesive plaster improves, and the movement of the skin due to exercise etc.
- the present inventors have found that it is possible to provide a patch preparation that allows a stable drug release by pressing the skin and the adhesive plaster with a certain pressure, thereby completing the present invention.
- a patch preparation comprising a pressure-sensitive adhesive paste containing a drug and a patch support, and a laminated structure comprising a cover layer, the patch support of the patch layer
- a patch preparation characterized in that a cushioning material is disposed between the body and the cover layer, and the cover layer covers the periphery of the patch layer.
- the present invention provides: (2) The patch preparation according to (1) above, wherein a shielding film is further disposed between the cover layer and the buffer material; (3) The patch according to the above (1) or (2), wherein the cushioning material is a nonwoven fabric; (4) The patch preparation according to (2) above, wherein the shielding film is a polyethylene terephthalate (PET) film; (5) The patch preparation according to any one of (1) to (4) above, wherein the size of the cover layer is 150 to 250% of the plane area of the patch layer; It is.
- PET polyethylene terephthalate
- the patch preparation of the present invention is a patch preparation having a laminated structure consisting of a patch layer composed of an adhesive plaster and a patch support mixed with a drug, and a cover layer, and in particular, between the patch support and the cover layer. It is characterized by the fact that a cushioning material is arranged on the surface. By providing such a cushioning material, the pressure-bonding action between the skin application site by the cover layer and the adhesive plaster (patch layer) is enhanced, and the skin is applied with a certain pressure against the movement of the skin due to exercise or the like. A pressure-sensitive adhesive paste is pressed onto the site to enable stable drug release. Therefore, it has an advantage that a constant drug blood concentration can be maintained for a long period of time, particularly as a patch containing a systemically active drug.
- 1 is a schematic cross-sectional view of a patch preparation according to the present invention based on a first embodiment. It is typical sectional drawing based on 2nd embodiment of the medicated patch by this invention.
- 2 is a graph showing the results of Test Example 1- (1) using the patch preparation of the present invention and the patch preparation of a comparative example.
- 3 is a graph showing the results of Test Example 1- (2) -A using the patch preparation of the present invention and the patch preparation of a comparative example.
- 3 is a graph showing the results of Test Example 1- (2) -B using the patch preparation of the present invention and the patch preparation of a comparative example.
- 3 is a graph showing the results of Test Example 1- (3) using the patch preparation of the present invention and the patch preparation of a comparative example.
- the present invention is a patch preparation having a laminate structure comprising a pressure-sensitive adhesive plaster containing a drug and a patch support, and a cover layer, in order from the skin sticking side, as described above.
- a patch preparation is characterized in that a buffer material is disposed between the patch support of the layer and the cover layer, and the cover layer has a size that covers beyond the peripheral edge of the patch layer.
- FIG. 1 is a schematic cross-sectional view based on a first embodiment of a patch preparation according to the present invention.
- the patch preparation 1 of the present invention comprises, in order from the skin sticking side, a patch layer 3 composed of an adhesive plaster 8 and a patch support 7 containing a drug, and a cover layer 2.
- a cover layer 2 composed of the cover support 4 and the cover adhesive 5 and a patch layer 3 composed of the patch support 7 and the adhesive plaster 8.
- a cushioning material 6 is disposed between the adhesive support 7 and the cover adhesive 5 of the cover layer 2, and further includes a release liner 9 that removably attaches to the adhesive plaster 8 and covers them.
- the area of the cover layer 2 is larger than the area of the patch layer 3, and the cover adhesive 5 is left around the patch layer 3 so that the cover layer 2 and the patch layer 3 are pasted.
- the agent layer 3 is laminated.
- the size (area) of the cover layer 2 is preferably 150 to 250% of the plane area of the patch layer 3. If it is less than 150%, the adhesion force to the skin application site is insufficient, and if it exceeds 250%, the application site of the cover layer to the skin becomes large, which is not preferable.
- the patch preparation of the present invention is a rectangle of 61 mm ⁇ 61 mm, the size having a width of about 5 to 15 mm around the four pieces (for example, 71 mm ⁇ 71 mm).
- the buffer material 6 and the patch support 7 may be configured separately, respectively, and like the laminate support described later, the buffer material 6 and the patch support 7 May be configured integrally.
- the bonding support 7 and the buffer material 6 can be joined by a dry laminating method or a thermal laminating method, but the dry laminating method is preferred.
- FIG. 2 shows a schematic cross-sectional view of the patch preparation according to the present invention based on the second embodiment.
- the patch preparation 11 of the present invention comprises a patch layer 13 composed of an adhesive plaster 19 and a patch support 18 mixed with a drug, and a cover layer 12 in order from the skin sticking side.
- the size of the patch layer 13 including the shielding film 16 covers the peripheral edge of the patch layer 13.
- the patch preparation 11 includes a cover layer 12 composed of a cover support 14 and a cover adhesive 15, and a patch layer 13 composed of a patch support 18 and an adhesive plaster 19.
- the cushioning material 17 and the shielding film 16 are further arranged between the patch support 18 of the patch layer 13 and the cover adhesive 15 of the cover layer 12.
- a release liner 20 is attached so as to be peelable and covers them.
- the area of the cover layer 12 is larger than the area of the patch layer 13, and the cover adhesive 15 is left around the patch layer 13, so that the cover layer 12 and the pressure-sensitive adhesive layer 13 are laminated via a buffer material 17 and a shielding film 16.
- the size (area) of the cover layer 12 is preferably 150 to 250% of the plane area of the patch layer 13 as in the first embodiment.
- the buffer material 17, the shielding film 16 and the patch support 18 may be configured as separate bodies, and buffered like a laminate support described later. You may comprise the material 17, the shielding film 16, and the patch support body 18 as one body.
- the bonding method of the buffer material 17, the shielding film 16, and the patch support 18 can be either a dry lamination method or a thermal lamination method, but the dry lamination method is preferable.
- a drug is added to the adhesive paste constituting the patch layer.
- the drug that can be added is not particularly limited, and a drug capable of transdermal absorption is preferable.
- examples of such drugs include local anesthetics (bupivacaine hydrochloride, mepivacaine hydrochloride, etc.), antiepileptic drugs (sodium valproate, etc.), analgesics (morphine hydrochloride, fentanyl citrate, buprenorphine hydrochloride, etc.), antipyretic analgesics ( Sulpyrine, antipyrine, acetaminophen, etc.), antipsychotics (chlorpromazine hydrochloride, levomepromazine hydrochloride, clocapramine hydrochloride, etc.), depression drugs (imipramine hydrochloride, trazodone hydrochloride, fluvoxamine maleate, etc.), antidementia drugs (donepezil, rivas
- the pressure-sensitive adhesive paste can contain other components such as a base in addition to the drug.
- a rubber polymer such as styrene-isoprene-styrene block copolymer (hereinafter abbreviated as SIS), isoprene, polyisobutylene (hereinafter abbreviated as PIB), styrene-butadiene-styrene block copolymer (hereinafter abbreviated as PIB).
- SBR Styrene-butadiene rubber
- the acrylic polymer may be a copolymer containing at least one (meth) acrylic acid derivative typified by 2-ethylhexyl acrylate, methyl acrylate, butyl acrylate, hydroxyethyl acrylate, 2-ethylhexyl methacrylate and the like. If it does not specifically limit.
- acrylic acid / acrylic acid octyl ester copolymer acrylic acid 2-ethylhexyl / vinyl pyrrolidone copolymer
- acrylic ester-vinyl acetate copolymer 2-ethylhexyl acrylate-2-ethylhexyl methacrylate / dodecyl methacrylate copolymer, methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion, acrylic resin alkanolamine solution
- Acrylic polymer adhesive DURO-TAK acrylic adhesive series (National Starch and Chemical Co., Ltd.), Eudragit series (Higuchi Shokai), etc. can be used.
- silicone polymer examples include silicone rubber such as polyorganosiloxane.
- Two or more of these hydrophobic polymers may be used as a mixture, and the blending amount based on the weight of the total composition of these polymers is determined in consideration of the formation of the adhesive paste and sufficient permeability. 5 to 90% by weight, preferably 10 to 80% by weight, more preferably 10 to 50% by weight.
- the adhesive paste may contain an absorption accelerator.
- Absorption promoters that can be used include fatty acid esters, higher alcohols, surfactants, and the like. Specifically, methyl laurate, hexyl laurate, triethyl citrate, isopropyl myristate, myristyl myristate, octyldodecyl myristate, cetyl palmitate, triacetin, cetyl lactate, lauryl lactate, methyl salicylate, glycol salicylate, ethylene salicylate Glycol, diethyl sebacate, diisopropyl sebacate, medium chain fatty acid triglyceride, lauryl alcohol, stearyl alcohol, isostearyl alcohol, myristyl alcohol, oleyl alcohol, cetanol, glycerol monocaprylate, glycerol monocaprate, glycerol monolaurate, glycerol monooleate , So
- Such an absorption enhancer is based on the weight of the entire composition of the adhesive plaster in consideration of sufficient permeability of the active ingredient as a patch preparation and skin irritation such as redness and edema. About 20% by weight is preferably blended, more preferably 0.05 to 10% by weight, and even more preferably 1 to 10% by weight.
- the adhesive plaster may contain a plasticizer.
- Plasticizers that can be used include petroleum oils (eg, paraffinic process oil, naphthenic process oil, aromatic process oil, etc.), squalane, squalene, vegetable oils (eg, olive oil, camellia oil, tall oil, Peanut oil, castor oil), silicone oil, dibasic acid ester (eg, dibutyl phthalate, dioctyl phthalate, etc.), liquid rubber (eg, polybutene, liquid isoprene rubber), fatty acid esters (isopropyl myristate, hexyl laurate, sebacic acid) Diethyl, diisopropyl sebacate), diethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol and the like. Liquid paraffin, liquid polybutene, or silicone oil is particularly preferable.
- the amount of such plasticizer based on the overall composition of the adhesive plaster maintains sufficient skin permeability and sufficient cohesive strength as a patch preparation.
- the total amount may be 10 to 70% by weight, preferably 10 to 60% by weight, and more preferably 10 to 50% by weight.
- tackifying resins examples include rosin derivatives (eg, rosin, rosin glycerin ester, hydrogenated rosin, hydrogenated rosin glycerin ester, rosin pentaerythrester), and alicyclic saturated hydrocarbon resins (eg, Alcon P100).
- rosin derivatives eg, rosin, rosin glycerin ester, hydrogenated rosin, hydrogenated rosin glycerin ester, rosin pentaerythrester
- alicyclic saturated hydrocarbon resins eg, Alcon P100.
- aliphatic hydrocarbon resins for example, Quinton B170, manufactured by Nippon Zeon
- terpene resins for example, Clearon P-125, manufactured by Yasuhara Chemical
- maleic resin examples include rosin derivatives (eg, rosin, rosin glycerin ester, hydrogenated rosin, hydrogenated rosin glycerin este
- the blending amount of such a tackifying resin based on the entire composition of the adhesive plaster is 5 to 70% by weight, preferably 5% in consideration of sufficient adhesive strength as a patch preparation and irritation to the skin upon peeling. It can be ⁇ 60 wt%, more preferably 10 ⁇ 50 wt%.
- an antioxidant can be blended in the adhesive plaster as necessary.
- tocopherols and their ester derivatives ascorbic acid, ascorbic acid stearate, nordihuman logayaretinic acid, dibutylhydroxytoluene (hereinafter abbreviated as BHT), butylhydroxyanisole and the like are desirable.
- filler calcium carbonate, magnesium carbonate, silicate (eg, aluminum silicate, magnesium silicate, etc.), silicic acid, barium sulfate, calcium sulfate, calcium zincate, zinc oxide, titanium oxide and the like are desirable.
- silicate eg, aluminum silicate, magnesium silicate, etc.
- silicic acid barium sulfate, calcium sulfate, calcium zincate, zinc oxide, titanium oxide and the like are desirable.
- crosslinking agent examples include thermosetting resins such as amino resins, phenol resins, epoxy resins, alkyd resins, and unsaturated polyesters, isocyanate compounds, blocked isocyanate compounds, organic crosslinking agents, and inorganic crosslinking agents such as metals or metal compounds. desirable.
- ethyl paraoxybenzoate ethyl paraoxybenzoate, propyl paraoxybenzoate, butyl paraoxybenzoate and the like are desirable.
- ultraviolet absorbers such as p-aminobenzoic acid derivatives, anthranilic acid derivatives, salicylic acid derivatives, amino acid compounds, dioxane derivatives, coumarin derivatives, imidazoline derivatives, and pyrimidine derivatives are desirable.
- Such antioxidants, fillers, cross-linking agents, preservatives, ultraviolet absorbers, etc. are preferably 10% by weight or less, more preferably 5% by weight or less, and particularly preferably 5% by weight or less, based on the total weight of the adhesive plaster composition. Preferably it can mix
- a stretchable or non-stretchable support can be used.
- a film such as cloth, nonwoven fabric, polyurethane, polyester, polyvinyl acetate, polyvinylidene chloride, polyethylene, polyethylene terephthalate (hereinafter abbreviated as PET), aluminum foil, or a composite material thereof is selected.
- PET polyethylene terephthalate
- the thickness is preferably 4 to 75 ⁇ m.
- the patch preparation of the present invention is characterized in that a buffer material is disposed between the patch layer and the cover layer.
- a cushioning material any cushioning material may be used, and examples thereof include urethane sheets, nonwoven fabrics, rubber sponges, and plastic foams, but nonwoven fabrics are particularly preferable.
- the basis weight is preferably about 30 to 150 g / m 2 , more preferably 50 to 100 g / m 2 .
- a shielding film may be further provided between the cushioning material disposed on the patch layer and the cover layer.
- the shielding film is provided in order to reinforce the adhesiveness between the cover layer and the patch layer including the buffer material.
- the adhesive component contained in the cover adhesive is transferred to the adhesive plaster. There is also an action of preventing the above and an action of preventing the components of the adhesive plaster from shifting to the cover adhesive.
- a sheet-like material such as polyurethane, polyester, polyvinyl acetate, polyvinylidene chloride, polyethylene, PET, and aluminum foil can be preferably used, and PET is particularly preferable.
- the thickness of the shielding film is preferably 4 to 75 ⁇ m.
- the cover layer in the patch preparation of the present invention comprises a cover support and a cover adhesive, and has an action of firmly fixing the patch layer to the skin.
- the constituent material of the cover support can be selected from, for example, cloth, non-woven fabric, polyurethane, polyester, polyvinyl acetate, polyvinylidene chloride, polyethylene, PET, aluminum, or a composite material thereof. Of these, non-woven fabric or PET is preferably used. In the case of a nonwoven fabric, those having a basis weight of 30 to 150 g / m 2 are used, and preferably 50 to 100 g / m 2 .
- the base component used for the cover adhesive is not particularly limited as long as it is a biocompatible material capable of bonding the skin and the patch preparation.
- a pressure-sensitive adhesive is preferable, and polyacrylate, polydimethylsiloxane, polyisobutylene, or a combination thereof is more preferable.
- the release liner protects the adhesive plaster until the patch preparation is applied to the skin, and the drug contained in the adhesive plaster does not change, and is coated with silicon so that it can be easily peeled off. If it is what is, it will not specifically limit. Specific examples thereof include a silicon film coated with a polyethylene film, a polyethylene terephthalate film or a polypropylene film.
- a method for producing a patch preparation provided by the present invention will be described.
- a paste solution obtained by mixing the material constituting the adhesive paste with an appropriate organic solvent such as toluene is applied onto a liner, and the paste solution is dried at about 60 to 100 ° C. Get the body.
- an adhesive preparation is laminated on the patch support side of the patch support / buffer material (laminate support) prepared in advance to prepare an intermediate preparation (patch layer + laminate support).
- the base component used for the cover adhesive is mixed with an appropriate organic solvent such as toluene, and the resulting mixed solution is applied to a plastic sheet such as a PET film.
- cover layer original Dry to the extent that it is laminated on a cover support such as a non-woven fabric to obtain a cover layer original.
- the obtained cover layer original fabric is punched into a desired size, the plastic sheet is peeled off, and laminated on the laminate support side of the intermediate preparation to obtain a patch preparation.
- Laminate support 1 A PET film (thickness: 12 ⁇ m) as a patch support and a non-woven fabric (weight per unit: 100 g / m 2 ) as a buffer material were laminated to prepare.
- Laminate support 2 A PET film (thickness: 12 ⁇ m) as a patch support, a non-woven fabric (weight per unit: 50 g / m 2 ) as a buffer material, and a PET film (thickness: 12 ⁇ m) as a shielding film were laminated in this order.
- Laminate support 3 A PET film (thickness: 12 ⁇ m) as a patch support, a non-woven fabric (weight per unit: 100 g / m 2 ) as a buffer material, and a PET film (thickness: 12 ⁇ m) as a shielding film were laminated in this order.
- Laminate support 4 A PET film (thickness: 4 ⁇ m) as a patch support, a non-woven fabric (weight per unit: 50 g / m 2 ) as a buffer material, and a PET film (thickness: 4 ⁇ m) as a shielding film were laminated in this order.
- Laminate support 5 A PET film (thickness: 4 ⁇ m) as a patch support, a non-woven fabric (weight per unit: 100 g / m 2 ) as a buffer material, and a PET film (thickness: 4 ⁇ m) as a shielding film were laminated in this order.
- Laminate support 6 A PET film (thickness: 16 ⁇ m) as a patch support, a non-woven fabric (weight per unit: 50 g / m 2 ) as a buffer material, and a PET film (thickness: 16 ⁇ m) as a shielding film were laminated in this order.
- Laminate support 7 A PET film (thickness: 16 ⁇ m) as a patch support, a non-woven fabric (weight per unit: 100 g / m 2 ) as a buffer material, and a PET film (thickness: 16 ⁇ m) as a shielding film were laminated and produced in this order.
- a cover adhesive was applied on a plastic sheet (PET film) as a cover layer original fabric, and after removing the solvent by drying, a cover support was bonded and prepared.
- Cover layer fabric As a cover adhesive, 67 parts of Duro-Tak (registered trademark) 87-4287 and 33 parts of Eudragit E100 (registered trademark) were dissolved and mixed in toluene, applied onto a PET film, and the solvent was removed by drying. Then, it bonded together with the nonwoven fabric (weight per unit: 80g / m ⁇ 2 >) as a cover support body, and produced the cover original fabric.
- Duro-Tak registered trademark
- Eudragit E100 registered trademark
- Donepezil and lauryl alcohol were previously dissolved in toluene, and then mixed with the remaining components dissolved in toluene to prepare an adhesive paste solution.
- the addition amount of toluene added 50 weight part with respect to 100 weight part of plaster components.
- Example 1 After applying the above-prepared pressure-sensitive adhesive body solution onto a release film (release liner), the solvent is removed by drying, and the laminate support 1 is bonded together, and then punched out to a size of 61 mm ⁇ 61 mm An intermediate preparation (patch layer + buffer material) was prepared. Separately, the cover layer original fabric prepared in advance above is punched into a size of 71 mm ⁇ 71 mm, the PET film is peeled off, and pasted into the intermediate preparation (patch layer + buffer material) prepared in the above, Example 1 A patch preparation was obtained.
- Examples 2 to 7 In accordance with the method described in Example 1 above, a pre-prepared pressure-sensitive adhesive solution was applied onto a release film (release liner), and then the solvent was removed by drying to obtain a laminate support 2 (Example 2), laminate. Pasting with support 3 (Example 3), laminate support 4 (Example 4), laminate support 5 (Example 5), laminate support 6 (Example 6) and laminate support 7 (Example 7) After being combined, each was punched out to a size of 61 mm ⁇ 61 mm to prepare an intermediate preparation (patch layer + buffer material + shielding film).
- the cover layer original fabric prepared in advance is punched into a size of 71 mm ⁇ 71 mm, the PET film is peeled off, and the intermediate preparation (patch layer + buffer material + shielding film) prepared by punching out is pasted and carried out, respectively.
- the patch preparations of Examples 2 to 7 were obtained.
- Comparative Example 1 (Patch with no cushioning material) : After the pre-prepared pressure-sensitive adhesive solution is applied onto a release film (release liner), the solvent is removed by drying, and it is attached to a PET film (thickness: 16 ⁇ m) as a patch support, which is 61 mm ⁇ 61 mm. Punched to size, an intermediate preparation (PET film + plaster) was prepared. Next, separately, the cover layer raw fabric prepared in advance is punched into a size of 71 mm ⁇ 71 mm, the release film is peeled off, and pasted together with the intermediate preparation (PET film + plaster) punched out above, and the adhesive preparation of Comparative Example 1 Got.
- compositions of the patches of Examples 1 to 7 and the patch of Comparative Example 1 are summarized in Table 2 below.
- Test Example 1 Contact pressure measurement
- the patch preparation of the present invention is a patch preparation having a laminated structure comprising a patch layer composed of an adhesive plaster body and a patch support, and a cover layer containing the drug.
- a patch layer composed of an adhesive plaster body and a patch support, and a cover layer containing the drug.
- the buffer material between the body and the cover layer By providing the buffer material between the body and the cover layer, the pressure-bonding property between the skin application site by the cover layer and the adhesive layer of the patch layer is improved.
- each skin patch preparation of Examples 1 to 7 and Comparative Example 1 and a commercially available patch preparation (Comparative Example 2) described later were used, and bioskin was used as an adherend by the following test method.
- Contact pressure measurement using artificial skin manufactured by BEAULAX, CO., LTD.
- Comparative Example 2 As a patch preparation of Comparative Example 2, a commercially available buprenorphine-containing tape (Norspan Tape: registered trademark, percutaneous absorption type / sustained pain treatment agent / Hisamitsu Pharmaceutical Co., Ltd.) was used.
- Nespan Tape registered trademark, percutaneous absorption type / sustained pain treatment agent / Hisamitsu Pharmaceutical Co., Ltd.
- Test Example 1- (1) And a basis weight of 50 g / m 2 nonwoven as a buffer material, a comparison of contact pressure when using the 100 g / m 2 nonwoven fabric. Examination with each patch preparation of Example 2, Example 3, and Comparative Example 1.
- Test Example 1- (2) -A Comparison of contact pressure due to difference in thickness between the patch support and the shielding film (comparison when using a non-woven fabric having a basis weight of 50 g / m 2 as a buffer). Examination with each patch preparation of Example 4, Example 6, Comparative Example 1 and Comparative Example 2.
- Test Example 1- (2) -B Comparison of contact pressure due to difference in thickness between the patch support and the shielding film (comparison when using a non-woven fabric with a basis weight of 100 g / m 2 as a buffer). Examination with each patch preparation of Example 5, Example 7, Comparative Example 1 and Comparative Example 2.
- Test Example 1- (3) Comparison of contact pressure with and without shielding film. Examination with each patch preparation of Example 1, Example 3, and Comparative Example 1.
- Test Example 2 Sticking test : For each of the patch preparations of Examples 2 to 5 and Comparative Example 1, each placebo preparation containing no drug was prepared and applied to the upper arm of 4 adult subjects. The presence or absence of floating was observed.
- each patch preparation of the present invention exhibited a high skin adhesion rate as compared with the patch preparation of the comparative example.
- a patch preparation having a laminated structure in which a cover layer is provided on a patch, wherein a buffer material is disposed between the patch support and the cover layer, whereby the skin patch site and the patch by the cover layer are provided.
- the adhesive preparation of the adhesive layer of the layer is improved, and the adhesive preparation is attached to the skin application site with a certain pressure so that the adhesive preparation can be stably released. Therefore, the medicinal effect is enormous in that it can maintain a constant drug blood concentration for a long period of time, particularly as a patch containing a systemically active drug.
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Abstract
Description
これらの全身作用性の薬物を配合した貼付剤は、一定の薬物血中濃度を長期間維持できるという特徴があるため、1日1回投与できるものから、長いものでは1週間投与できるものまで開発されている。
一方、貼付剤自体の粘着力を強化して、皮膚からの剥がれを極力防止することにより、安定的な薬物血中濃度の維持を目指した試みも多く見られるが、皮膚の可動部分に対する粘着力は不十分であり、また粘着力を過度に強化した場合には、皮膚面からの剥離時に痛みを伴い、皮膚刺激性の原因となる可能性も指摘されているため、単純に膏体部分の粘着力を強化することのみでは、貼付期間中の薬物の安定的な経皮吸収を維持するのは難しいものである。
しかしながら、これらのカバーシートを具備した貼付製剤は、カバーシート自体はその強力な粘着力により皮膚貼付部位からの剥離、および脱落することはないものの、貼付剤部分、あるいはリザーバー部分は、貼付部位の動きに追従することができず、そのため皮膚と貼付剤が圧着できずに安定的な薬物放出ができない場合があった。
(1)皮膚貼着側から順に、薬物を配合した粘着膏体及び貼付剤支持体からなる貼付剤層、並びにカバー層からなる積層構造の貼付製剤であって、前記貼付剤層の貼付剤支持体とカバー層との間に緩衝材を配し、カバー層が貼付剤層の周縁部を超えてカバーする大きさであることを特徴とする貼付製剤。
(2)カバー層と緩衝材との間に、更に遮蔽フィルムを配したことを特徴とする上記(1)に記載の貼付製剤;
(3)緩衝材が不織布である上記(1)又は(2)に記載の貼付剤;
(4)遮蔽フィルムが、ポリエチレンテレフタレート(PET)フィルムである上記(2)に記載の貼付製剤;
(5)カバー層の大きさが、貼付剤層の平面積に対して150~250%の大きさである上記(1)~(4)のいずれかに記載の貼付製剤;
である。
かかる緩衝材を配したことにより、カバー層による皮膚貼付部位と粘着膏体(貼付剤層)との圧着作用が増強され、運動等による皮膚の動きに対しても一定の圧力を持って皮膚貼付部位に粘着膏体が圧着し、安定的な薬物の放出を可能とするものである。
したがって、特に全身作用性の薬物を配合した貼付剤として、一定の薬物血中濃度を長期間維持できるという利点を有する。
図1は、本発明による貼付製剤の第一の実施形態に基づく、模式的断面図である。
図1に示されるように、本発明の貼付製剤1は、皮膚貼着側から順に、薬物を配合した粘着膏体8及び貼付剤支持体7からなる貼付剤層3、並びにカバー層2からなる積層構造の貼付製剤であって、貼付剤層3の貼付剤支持体7とカバー層2との間に緩衝材6を配置し、カバー層2が緩衝材6を含めた、貼付剤層3の周縁部を超えてカバーする大きさで構成されている。
この場合のカバー層2の大きさ(面積)は、貼付剤層3の平面積に対して150~250%の大きさであるのが好ましい。
150%未満であると、皮膚貼付部位に対する貼着力が不十分であり、また250%を超えると、カバー層の皮膚に対する貼着部位が大きくなり、好ましいものではない。
例えば、後記する実施例からも判明するように、本発明の貼付製剤が61mm×61mmの矩形である場合には、その4片の周囲に5~15mm程度の幅を有する大きさ(例えば、71mm×71mm)とすればよい。
図2に示されるように、本発明の貼付製剤11は、皮膚貼着側から順に、薬物を配合した粘着膏体19及び貼付剤支持体18からなる貼付剤層13、並びにカバー層12からなる積層構造の貼付製剤であって、貼付剤層13の貼付剤支持体18とカバー層12との間に緩衝材17、並びに、更に遮蔽フィルム16を配置し、カバー層12が、緩衝材17及び遮蔽フィルム16を含めた貼付剤層13の周縁部を超えてカバーする大きさで構成されている。
この場合のカバー層12の大きさ(面積)は、第一の実施態様と同様に、貼付剤層13の平面積に対して150~250%の大きさであるのが好ましい。
また、この第二の実施態様の貼付製剤においても、緩衝材17、遮蔽フィルム16及び貼付剤支持体18とは、別体としてそれぞれ構成してもよく、後記するラミネート支持体のように、緩衝材17、遮蔽フィルム16と貼付剤支持体18の三者を一体として構成してもよい。緩衝材17、遮蔽フィルム16、及び貼付剤支持体18の接合方法はドライラミネート法でもサーマルラミネート法でも可能であるが、ドライラミネート法が好ましい。
添加できる薬物は特に限定されず、経皮吸収可能な薬物が好ましい。そのような薬物としては、例えば、局所麻酔剤(塩酸ブピバカイン、塩酸メピバカイン等)、抗てんかん薬(バルプロ酸ナトリウム等)、鎮痛剤(塩酸モルヒネ、クエン酸フェンタニル、塩酸ブプレノルフィン等)、解熱鎮痛剤(スルピリン、アンチピリン、アセトアミノフェン等)、抗精神病薬(塩酸クロルプロマジン、塩酸レボメプロマジン、塩酸クロカプラミン等)、うつ病治療薬(塩酸イミプラミン、塩酸トラゾドン、マレイン酸フルボキサミン等)、抗認知症薬(ドネペジル、リバスチグミン、ガランタミン臭化水素酸塩、塩酸メマンチン等)、抗不安薬(ジアゼパム、アルプラゾラム、クエン酸タンドスピロン等)、精神安定剤(塩酸ヒドロキシジン等)、脳機能賦活薬(塩酸チアプリド、酒石酸プロチレリン等)、脳循環改善薬(イソソルビド、ペントキシフィリン、塩酸ファスジル等)、パーキンソン病治療剤(塩酸ベンゼラジド、塩酸アマンタジン、塩酸タリペキソール等)、筋弛緩剤(塩酸エピリゾン、塩酸チザニジン、塩酸トルペリゾン等)、消化性潰瘍治療薬(臭化ブチルスコポラミン、塩酸ピレンゼピン、臭化チメピジウム等)、抗ヒスタミン薬(マレイン酸クロルフェニラミン、塩酸プロメタジン、塩酸セチリジン等)、化学伝達物質遊離抑制薬(フマル酸エメダスチン、トシル酸スプラタスト、塩酸エピナスチン等)、心疾患治療薬(アミノフィリン、塩酸ジルチアゼム、ニコランジル、塩酸プロプラノロール、塩酸イソプレナリン、リン酸ジソピラミド、塩酸プロカインアミド等)、高血圧治療薬(カプトプリル、マレイン酸エナラプリル、塩酸アモスラロール、塩酸プラゾシン、ウラピジル、塩酸クロニジン等)、血管拡張薬(塩酸トラゾリン等)、血管収縮薬(メチル硫酸アメジニウム、塩酸エチレフリン、塩酸フェニレフリン、塩酸ミドドリン等)、高脂血症治療薬(プラバスタチンナトリウム、フルバスタチンナトリウム、セリバスタチンナトリウム等)、鎮咳・去痰薬(臭化水素酸デキストロメトルファン、塩酸ホミノベン、アセチルシステイン等)、喘息治療薬(塩酸クレンブテロール、臭化水素酸フェノテロール、塩酸プロカテロール等)、H2遮断薬(塩酸ラニチジン、塩酸ロキサジンアセテート等)、プロトンポンプインヒビター(オメプラゾール、ランソプラゾール、ラベプラゾール等)、制吐剤(塩酸グラニセトロン、塩酸アザセトロン、塩酸オンダンセトロン、塩酸ラモセトロン等)、非ステロイド性抗炎症剤(ロキソプロフェンナトリウム、フルルビプロフェン、ジクロフェナクナトリウム、塩酸チアラミド等)、抗リュウマチ剤(ブシラミン、ペニシラミン等)、泌尿器疾患用薬(塩酸オキシブチニン、塩酸タムスロシン、塩酸プロピベリン等)、β遮断薬(フマル酸ビソプロロール、塩酸ベタキソロール等)が挙げられる。
その配合量は、薬物によって異なるが、粘着膏体全体の重量に対して5~30重量%、好ましくは5~20重量%、より好ましくは10~20重量%である。
粘着膏体に配合する基剤としては、ゴム系高分子、アクリル系高分子、あるいはシリコーン系高分子が好ましく用いられる。
ゴム系高分子としては、スチレン-イソプレン-スチレンブロック共重合体(以下、SISと略記する)、イソプレン、ポリイソブチレン(以下、PIBと略記する)、スチレン-ブタジエン-スチレンブロック共重合体(以下、SBSと略記する)、スチレン-ブタジエンゴム(以下、SBRと略記する)等が挙げられる。
具体的には、例えば、医薬品添加物辞典2007(日本医薬品添加剤協会編集)に粘着剤として収載されているアクリル酸・アクリル酸オクチルエステル共重合体、アクリル酸2-エチルヘキシル・ビニルピロリドン共重合体溶液、アクリル酸エステル-酢酸ビニルコポリマー、アクリル酸2-エチルヘキシル-メタクリル酸2-エチルヘキシル・メタクリル酸ドデシル共重合体、アクリル酸メチル-アクリル酸2-エチルヘキシル共重合樹脂エマルジョン、アクリル樹脂アルカノールアミン液に含有するアクリル系高分子等の粘着剤、DURO-TAKアクリル系粘着剤シリーズ(ナショナルスターチアンドケミカル社製)、オイドラギットシリーズ(樋口商会)等が使用できる。
具体的には、ラウリン酸メチル、ラウリン酸ヘキシル、クエン酸トリエチル、ミリスチン酸イソプロピル、ミリスチン酸ミリスチル、ミリスチン酸オクチルドデシル、パルミチン酸セチル、トリアセチン、乳酸セチル、乳酸ラウリル、サリチル酸メチル、サリチル酸グリコール、サリチル酸エチレングリコール、セバシン酸ジエチル、セバシン酸ジイソプロピル、中鎖脂肪酸トリグリセリド、ラウリルアルコール、ステアリルアルコール、イソステアリルアルコール、ミリスチルアルコール、オレイルアルコール、セタノール、グリセリンモノカプリレート、グリセリンモノカプレート、グリセリンモノラウレート、グリセリンモノオレート、ソルビタンモノラウレート、ソルビタンモノオレエート、ショ糖モノラウレート、ポリソルベート20、プロピレングリコールモノラウレート、ポリエチレングリコールモノラウレート、ポリエチレングリコールモノステアレート、ラウロマクロゴール、HCO-60、ラウリン酸ジエタノールアミド、N-メチル-2-ピロリドン、クロタミトン、ジメチルスルホキシドが挙げられるが、好ましくはクエン酸トリエチル、ミリスチン酸イソプロピル、乳酸セチル、オレイルアルコール、ソルビタンモノオレエート、ポリエチレングリコールモノステアレート、ラウロマクロゴール、N-メチル-2-ピロリドン及びトリアセチン等を挙げることができる。
このような吸収促進剤は、貼付製剤としての充分な主薬の透過性、及び発赤、浮腫等の皮膚刺激性等を考慮して、粘着膏体の組成全体の重量に基づいて、0.01~20重量%程度配合することが好ましく、さらに好ましくは0.05~10重量%、より好ましくは1~10重量%である。
使用され得る粘着付与樹脂としては、ロジン誘導体(例えば、ロジン、ロジングリセリンエステル、水添ロジン、水添ロジングリセリンエステル、ロジンのペンタエリストールエステル等)、脂環族飽和炭化水素樹脂(例えばアルコンP100、荒川化学工業社製)、脂肪族系炭化水素樹脂(例えばクイントンB170、日本ゼオン社製)、テルペン樹脂(例えばクリアロンP-125、ヤスハラケミカル社製)、マレイン酸レジン等が挙げられる。
抗酸化剤としては、トコフェロール及びこれらのエステル誘導体、アスコルビン酸、アスコルビン酸ステアリン酸エステル、ノルジヒトログアヤレチン酸、ジブチルヒドロキシトルエン(以下、BHTと略記する)、ブチルヒドロキシアニソール等が望ましい。
遮蔽フィルムは、カバー層と、緩衝材を含めた貼付剤層との接着性を強化するために設けられる。また、貼付剤支持体が不織布、あるいは織布等、通気性の高い素材であり、かつ緩衝材が不織布である場合には、カバー粘着剤に含有される粘着剤成分が粘着膏体に移行するのを防止する作用、及び粘着膏体の成分がカバー粘着剤に移行するのを防止する作用もある。
そのような遮蔽フィルムとしては、ポリウレタン、ポリエステル、ポリ酢酸ビニル、ポリ塩化ビニリデン、ポリエチレン、PET、アルミニウム箔等のシート状物を好ましく使用することができ、特にPETが好ましい。
また遮蔽フィルムの厚みは4~75μmであるのが好ましい。
カバー支持体の構成材料としては、例えば、布、不織布、ポリウレタン、ポリエステル、ポリ酢酸ビニル、ポリ塩化ビニリデン、ポリエチレン、PET、アルミニウム等のフィルム、またはそれらの複合素材から選択することができる。なかでも、不織布あるいはPETが好ましく使用される。不織布の場合、その目付が30~150g/m2のものが使用され、好ましくは50~100g/m2である。
そのような具体例としては、ポリエチレンフィルム、ポリエチレンテレフタレートフィルムまたはポリプロピレンフィルムをシリコンコートしたものが挙げられる。
先ず、粘着膏体を構成する材料を、トルエン等の適当な有機溶媒と混合して得られる膏体溶液を、ライナー上に塗布し、膏体溶液を60~100℃程度で乾燥させて粘着膏体を得る。
次にあらかじめラミネートして作製した貼付剤支持体/緩衝材(ラミネート支持体)の貼付剤支持体側に、粘着膏体をラミネートし、中間製剤(貼付剤層+ラミネート支持体)を作製する。
次に、カバー粘着剤に使用する基剤成分をトルエン等の適当な有機溶媒等と混合して、得られた混合溶液をPETフィルム等のプラスチックシートに塗布し、その混合溶液を60~80℃程度で乾燥させ、不織布等のカバー支持体にラミネートし、カバー層原反を得る。
得られたカバー層原反を所望のサイズに打ち抜き、そのプラスチックシートを剥がし、中間製剤のラミネート支持体側にラミネートし、貼付製剤を得る。
以下の積層構造を有する、貼付剤支持体/緩衝材からなるラミネート支持体、または、貼付剤支持体/緩衝材/遮蔽フィルムからなるラミネート支持体を作製した。
貼付剤支持体としてのPETフィルム(厚み:12μm)、及び緩衝材としての不織布(目付:100g/m2)をラミネートし、作製した。
ラミネート支持体2:
貼付剤支持体としてのPETフィルム(厚み:12μm)、緩衝材としての不織布(目付:50g/m2)、および遮蔽フィルムとしてのPETフィルム(厚み:12μm)を、この順にラミネートし、作製した。
ラミネート支持体3:
貼付剤支持体としてのPETフィルム(厚み:12μm)、緩衝材としての不織布(目付:100g/m2)、および遮蔽フィルムとしてのPETフィルム(厚み:12μm)を、この順にラミネートし、作製した。
ラミネート支持体4:
貼付剤支持体としてのPETフィルム(厚み:4μm)、緩衝材としての不織布(目付:50g/m2)、および遮蔽フィルムとしてのPETフィルム(厚み:4μm)を、この順にラミネートし、作製した。
ラミネート支持体5:
貼付剤支持体としてのPETフィルム(厚み:4μm)、緩衝材としての不織布(目付:100g/m2)、および遮蔽フィルムとしてのPETフィルム(厚み:4μm)を、この順にラミネートし、作製した。
ラミネート支持体6:
貼付剤支持体としてのPETフィルム(厚み:16μm)、緩衝材としての不織布(目付:50g/m2)、および遮蔽フィルムとしてのPETフィルム(厚み:16μm)を、この順にラミネートし、作製した。
ラミネート支持体7:
貼付剤支持体としてのPETフィルム(厚み:16μm)、緩衝材としての不織布(目付:100g/m2)、および遮蔽フィルムとしてのPETフィルム(厚み:16μm)を、この順にラミネートし、作製した。
カバー層原反として、プラスチックシート(PETフィルム)上に、カバー粘着剤を塗工して、溶媒を乾燥除去後、カバー支持体を貼り合わせ作製した。
カバー粘着剤としてDuro-Tak(登録商標)87-4287を67部、およびオイドラギットE100(登録商標)33部をトルエンに溶解、混合し、PETフィルム上に塗工して、溶媒を乾燥除去した。その後、カバー支持体としての不織布(目付:80g/m2)と貼り合せて、カバー原反を作製した。
下記の表1処方に基づく、薬物(ドネペジル)含有の粘着膏体溶液を調製した。
なお、トルエンの添加量は、膏体成分100重量部に対し、50重量部添加した。
上記で予め調製した粘着膏体溶液を、剥離フィルム(剥離ライナー)上に塗工後、溶媒を乾燥除去し、上記のラミネート支持体1と貼り合わせた後、それを61mm×61mmのサイズに打ち抜き、中間製剤(貼付剤層+緩衝材)を作製した。
別に、上記で予め作製したカバー層原反を71mm×71mmのサイズに打ち抜き、そのPETフィルムを剥がし、上記で打ち抜いて作成した中間製剤(貼付剤層+緩衝材)と貼り合わせて、実施例1の貼付製剤を得た。
上記の実施例1に記載の方法に準じ、予め調製した粘着膏体溶液を、剥離フィルム(剥離ライナー)上に塗工後、溶媒を乾燥除去し、ラミネート支持体2(実施例2)、ラミネート支持体3(実施例3)、ラミネート支持体4(実施例4)、ラミネート支持体5(実施例5)、ラミネート支持体6(実施例6)及びラミネート支持体7(実施例7)と貼り合わせた後、それぞれを61mm×61mmのサイズに打ち抜き、中間製剤(貼付剤層+緩衝材+遮蔽フィルム)を作製した。
次いで、予め作製したカバー層原反を71mm×71mmのサイズに打ち抜き、そのPETフィルムを剥がし、上記で打ち抜いて作成した中間製剤(貼付剤層+緩衝材+遮蔽フィルム)と貼り合わせて、それぞれ実施例2~7の貼付製剤を得た。
予め調製した粘着膏体溶液を剥離フィルム(剥離ライナー)上に塗工後、溶媒を乾燥除去し、貼付剤支持体としてのPETフィルム(厚み:16μm)と貼り合わせて、それを61mm×61mmのサイズに打ち抜き、中間製剤(PETフィルム+膏体)を作製した。
次いで、別に、予め作製したカバー層原反を71mm×71mmのサイズに打ち抜き、その剥離フィルムを剥がし、上記で打ち抜いた中間製剤(PETフィルム+膏体)と貼り合わせて、比較例1の貼付製剤を得た。
本発明の貼付製剤は、薬物を配合する粘着膏体及び貼付剤支持体からなる貼付剤層、並びにカバー層からなる積層構造の貼付製剤であって、特に貼付剤支持体とカバー層との間に緩衝材を配したことにより、カバー層による皮膚貼付部位と貼付剤層の粘着膏体との圧着性が向上する。
その点を実証するために、実施例1~7、および比較例1の各貼付製剤、更に後記する市販の貼付製剤(比較例2)を用い、下記の試験方法により、被着体としてバイオスキン(人工皮膚:BEAULAX, CO., LTD.製)を用いた接触圧力測定を行った。
被着体であるバイオスキンに、φ20mmの受圧センサーを取り付け、なるべく中央部分に受圧センサーが配置されるように、各実施例及び各比較例の製剤を適用した。
φ90mmのシャーレ―を製剤の上に置き、均一に荷重(圧力)が掛かるように500gの分銅を静置した。
圧力が一定になった状態を10秒間維持し、荷重を解除した。
圧力の減衰挙動、および収束値をグラフ化し、比較評価した。なお、事前の検討によって収束点を確認し、6分(480秒)とした。
比較例2の貼付製剤として、市販ブプレノルフィン含有テープ剤(ノルスパンテープ:登録商標、経皮吸収型・持続性疼痛治療剤/久光製薬)を使用した。
試験例1-(1):
緩衝材として目付50g/m2の不織布と、100g/m2の不織布を使用した場合の接触圧の比較。
実施例2、実施例3、比較例1の各貼付製剤での検討。
貼付剤支持体及び遮蔽フィルムの厚み違いによる接触圧の比較(緩衝剤として目付50g/m2の不織布を使用した場合の比較)。
実施例4、実施例6、比較例1、比較例2の各貼付製剤での検討。
貼付剤支持体及び遮蔽フィルムの厚み違いによる接触圧の比較(緩衝剤として目付100g/m2の不織布を使用した場合の比較)。
実施例5、実施例7、比較例1、比較例2の各貼付製剤での検討。
遮蔽フィルムの有無による接触圧の比較。
実施例1、実施例3、比較例1の各貼付製剤での検討。
それぞれの試験結果を、図3~6に示した。
図中の結果から、本発明の各貼付製剤は、比較例の各貼付製剤と比較して被着体への接触圧が高いことが認められた。
したがって、本発明の貼付製剤は、被着体へ高い密着性を示し、運動等による皮膚の動きに対しても一定の圧力を持って皮膚貼付部位において粘着膏体が圧着し、安定的な薬物の放出が行えるものである。
実施例2~5及び比較例1の貼付製剤について、薬物を含有していない各プラセボ製剤を作製し、成人被験者4名の上腕部に貼付し、24時間貼付後の製剤の貼付状態(剥がれ・浮きの有無)を観察した。
貼付剤層における剥がれ、浮きの部分を除いた、皮膚に密着している部分の面積(接着面積)を求め、さらに下記の計算式より貼付後24時間における、貼付剤層の皮膚接着率を算出した。
皮膚接着率=(接着面積/貼付剤層の面積)×100 単位:(%)
その結果を表3に示した。
したがって、特に全身作用性の薬物を配合した貼付剤として、一定の薬物血中濃度を長期間維持できる点で、その医療上の効果は多大なものである。
Claims (5)
- 皮膚貼着側から順に、薬物を配合した粘着膏体及び貼付剤支持体からなる貼付剤層、並びにカバー層からなる積層構造の貼付製剤であって、
前記貼付剤層の貼付剤支持体とカバー層との間に緩衝材を配し、
カバー層が、貼付剤層の周縁部を超えてカバーする大きさである、
ことを特徴とする貼付製剤。 - カバー層と緩衝材との間に、更に遮蔽フィルムを配したことを特徴とする請求項1に記載の貼付製剤。
- 緩衝材が不織布である請求項1又は2に記載の貼付製剤。
- 遮蔽フィルムが、ポリエチレンテレフタレート(PET)フィルムである請求項2に記載の貼付製剤。
- カバー層の大きさが、貼付剤層の平面積に対して150~250%の大きさである請求項1~4のいずれかに記載の貼付製剤。
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EP15758321.2A EP3115044A4 (en) | 2014-03-06 | 2015-02-24 | Patch preparation |
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Cited By (4)
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WO2017164084A1 (ja) * | 2016-03-24 | 2017-09-28 | 株式会社メドレックス | 誤用防止特性を有する貼付製剤 |
JP2020083885A (ja) * | 2018-11-16 | 2020-06-04 | 得生製薬股▲ふん▼有限公司 | 経皮吸収型パッチ |
WO2021079795A1 (ja) | 2019-10-21 | 2021-04-29 | 株式会社メドレックス | 積層型貼付剤 |
US11903939B2 (en) | 2016-03-24 | 2024-02-20 | Medrx Co., Ltd. | Patch preparations with accidental use prevention features |
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- 2015-02-24 EP EP15758321.2A patent/EP3115044A4/en active Pending
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US11903939B2 (en) | 2016-03-24 | 2024-02-20 | Medrx Co., Ltd. | Patch preparations with accidental use prevention features |
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EP3115044A4 (en) | 2017-10-11 |
JP6457486B2 (ja) | 2019-01-23 |
JPWO2015133329A1 (ja) | 2017-04-06 |
US10695335B2 (en) | 2020-06-30 |
US20160367536A1 (en) | 2016-12-22 |
TW201538179A (zh) | 2015-10-16 |
CA2941446C (en) | 2022-09-06 |
TWI648072B (zh) | 2019-01-21 |
CA2941446A1 (en) | 2015-09-11 |
EP3115044A1 (en) | 2017-01-11 |
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