WO2017170933A1 - Produit de type patch adhésif - Google Patents

Produit de type patch adhésif Download PDF

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Publication number
WO2017170933A1
WO2017170933A1 PCT/JP2017/013403 JP2017013403W WO2017170933A1 WO 2017170933 A1 WO2017170933 A1 WO 2017170933A1 JP 2017013403 W JP2017013403 W JP 2017013403W WO 2017170933 A1 WO2017170933 A1 WO 2017170933A1
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WO
WIPO (PCT)
Prior art keywords
patch
packaging bag
layer
resin
sensitive adhesive
Prior art date
Application number
PCT/JP2017/013403
Other languages
English (en)
Japanese (ja)
Inventor
永実子 豊島
Original Assignee
ニチバン株式会社
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by ニチバン株式会社 filed Critical ニチバン株式会社
Priority to CN201780021397.4A priority Critical patent/CN108883025A/zh
Priority to JP2018509465A priority patent/JPWO2017170933A1/ja
Publication of WO2017170933A1 publication Critical patent/WO2017170933A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
    • A61J1/05—Containers specially adapted for medical or pharmaceutical purposes for collecting, storing or administering blood, plasma or medical fluids ; Infusion or perfusion containers
    • A61J1/10—Bag-type containers
    • 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
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/485—Morphinan derivatives, e.g. morphine, codeine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • 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

Definitions

  • the present invention relates to a patch product comprising a transdermal patch and a packaging bag.
  • nalfraphine which is a ⁇ -type opioid receptor agonist compound
  • Pruritus in hemodialysis patients and chronic liver disease patients is not a life-threatening complication, but it occurs frequently during sleep and causes problems in daily life such as causing sleep disorders, and cannot be neglected in maintaining QOL of dialysis patients It is a complication.
  • oral drugs are the most common method, but oral drugs of nalfrafin have insomnia, constipation, and sleepiness as side effects, and the incidence of side effects is dose-dependent.
  • Patent Documents 2 to 4 As means for improving the temporal stability of nalfurafine in these patches, a method using a specific tackifying resin in the adhesive layer (Patent Document 2), a method using a free form of nalfurafine (Patent Document 3), and a free narfrafin A method using a body or a salt thereof and a specific pressure-sensitive adhesive (Patent Document 4) has been proposed.
  • the present invention is a patch product comprising a nalfurafine-containing patch and a packaging bag, thereby improving the aging stability of nalfurafine in the patch by a packaging container containing the nalfurafine-containing patch.
  • the present invention provides a patch product having excellent temporal stability of nalflaphine in a patch.
  • the present inventors have conducted intensive research and studied the configuration of a packaging bag having excellent temporal stability of a patch containing nalfraphine. As a result, the present inventors have found that the above problems can be solved by using means for reducing the oxygen concentration and / or the amount of water in the packaging bag, and have completed the present invention.
  • the present invention A patch product comprising a packaging bag and a nalflaphine-containing patch housed in the packaging bag,
  • the present invention relates to a patch product comprising means for reducing the oxygen concentration and / or the amount of water in the packaging bag.
  • the patch product of the following embodiments is further provided.
  • the packaging bag is selected from the group consisting of a layer formed of a hygroscopic resin and a layer containing an oxygen absorbent.
  • the above-mentioned patch product comprising the above and comprising a laminate of at least two layers.
  • the patch product wherein the inside of the packaging bag is replaced with nitrogen as means for reducing the oxygen concentration and / or the amount of water in the packaging bag.
  • the patch product comprising a layer.
  • a patch in which the patch comprises a support, a nalfurafine-containing pressure-sensitive adhesive layer provided on at least one surface of the support, and a release sheet provided on the nalfurafine-containing pressure-sensitive adhesive layer. Said patch product.
  • the patch product wherein the pressure-sensitive adhesive layer contains a rubber-based pressure-sensitive adhesive and a rosin resin.
  • the patch product, wherein the pressure-sensitive adhesive layer contains a salt of narfrafin and a desalting agent.
  • the present invention also relates to a nalflaphine-containing patch formed from a laminate of at least two layers containing at least one selected from the group consisting of a layer formed from a hygroscopic resin and a layer containing an oxygen absorbent. Related to packaging bags.
  • the present invention can suppress degradation of drug content over time by suppressing the decomposition of nalfrafin by using means for reducing the oxygen concentration and / or the amount of water in the packaging bag containing the nalfurafine-containing patch. There is an effect. Therefore, according to this invention, there exists an effect that the patch product which is excellent in the temporal stability of the narfrafin in a patch can be provided.
  • the packaging bag of the present invention has an effect that the decomposition of chemically unstable compounds can be suppressed. Therefore, the packaging bag of this invention is suitable for the packaging bag which preserve
  • FIG. 1 is a cross-sectional view of a laminate including a layer formed from a hygroscopic resin.
  • FIG. 2 is a cross-sectional view of a laminate including a layer containing an oxygen absorbent.
  • FIG. 3 shows one embodiment (i) of a patch product comprising a packaging bag, a pouch containing a nalfurafine-containing patch and a hygroscopic agent inside the packaging bag, and a cross section of a laminate constituting the packaging bag. It is a figure which shows figure (ii).
  • FIG. 4 shows another embodiment (i) of a patch product comprising a packaging bag, and a pouch containing a patch and an oxygen absorbent inside the packaging bag, and a cross section of the laminate constituting the packaging bag. It is a figure which shows figure (ii).
  • the present invention relates to a patch product comprising a packaging bag and a nalfurafine-containing patch housed in the packaging bag.
  • the packaging bag used in the present invention includes means for reducing the oxygen concentration in the packaging bag, means for reducing the amount of water, or both means, thereby suppressing the decomposition of nalfrafin and its salts. can do.
  • the means for reducing the oxygen concentration and / or moisture content in the packaging bag is not particularly limited as long as the oxygen concentration and / or moisture content in the packaging bag can be reduced, but the layer formed from a hygroscopic resin.
  • a method of using a packaging bag formed of a laminate of at least two layers including at least one selected from the group consisting of layers containing oxygen absorbent, a hygroscopic agent and / or oxygen absorption in the packaging bag A method of enclosing a pouch containing an agent and a method of replacing the inside of the packaging bag with nitrogen are preferred.
  • at least one selected from the group consisting of a layer formed from a hygroscopic resin and a layer containing an oxygen absorbent is included, at least A method of using a packaging bag formed from a laminate of two or more layers and a method of replacing the inside of the packaging bag with nitrogen are more preferable.
  • a plurality of the above methods can be used in combination as means for reducing the oxygen concentration and / or the amount of water in the packaging bag.
  • Method of using a packaging bag formed from a specific laminate As means for reducing the oxygen concentration and / or moisture content in the packaging bag, at least two layers comprising at least one selected from the group consisting of a layer formed from a hygroscopic resin and a layer containing an oxygen absorbent
  • decomposition disassembly of nalfurafine and its salt can be suppressed.
  • the packaging bag used by this invention is formed from the laminated body of an at least 2 layer or more including 1 or more types chosen from the group which consists of the layer formed from the hygroscopic resin, and the layer containing an oxygen absorber.
  • the configuration is not particularly limited, and for example, the following embodiments (1) and (2) can be taken.
  • the packaging bag has a layer structure formed from a hygroscopic resin.
  • the packaging bag used in the present invention can be formed by laminating at least two layers including a layer formed from a hygroscopic resin by heat-sealing.
  • a sealant layer as an innermost layer of a packaging bag
  • a film or sheet formed from a hygroscopic resin examples of the outer layer may include a laminate in which an air blocking layer is provided, and if necessary, an arbitrary resin film or the like is provided as an outer layer from the air blocking layer (see FIG. 1).
  • the innermost layer of the packaging bag is preferably a heat-sealable layer, that is, a sealant layer.
  • the sealant layer may be formed from a conventionally known sealant resin film. Among them, a layer having a high drug non-adsorption ability in addition to easy heat sealing is preferable.
  • the sealant layer examples include polyethylene resin films such as low density polyethylene (LDPE), linear low density polyethylene (L-LDPE), and high density polyethylene (HDPE); acid-modified polyethylene, polypropylene, acid-modified polypropylene, copolymerization Polyolefin resin films such as polypropylene, ethylene-vinyl acetate copolymer (EVA), ethylene- (meth) acrylic acid ester copolymer, ethylene- (meth) acrylic acid copolymer; polyester such as polyethylene terephthalate (PET)
  • PP unstretched polypropylene resin
  • PE unstretched polyethylene resin
  • Beam is preferable.
  • (meth) acrylic acid represents both acrylic acid and methacrylic acid.
  • the sealant layer has a minimum thickness that can be heat sealed to produce a hermetic packaging bag, and is preferably 10 ⁇ m to 50 ⁇ m, for example, 30 ⁇ m.
  • the film or sheet layer formed from a hygroscopic resin is a film or sheet layer formed from a resin in which a hygroscopic agent is dispersed or contained in the resin to express hygroscopicity.
  • the hygroscopic agent is not particularly limited, and barium oxide, calcium chloride, magnesium sulfate, calcium oxide, calcium sulfate, lithium chloride, lithium perchlorate, alumina, silica gel, zeolite, etc. are used, and one or more may be selected. it can.
  • the resin is not particularly limited, but polyolefin, particularly low density polyethylene (LDPE) is preferable because it is excellent in dispersibility of the hygroscopic agent.
  • Examples of the form of the film or sheet formed from the hygroscopic resin include Moist Catch (registered trademark) (manufactured by Kyodo Printing Co., Ltd.).
  • the layer disposed on the outside of the film or sheet layer formed from the hygroscopic resin is preferably an air blocking layer from the viewpoint of preventing moisture in the air from affecting nalfrafin and its salt.
  • the air barrier layer only needs to be a material that can block the entry of air from the outside of the packaging bag.
  • a soft metal foil such as an aluminum foil (hereinafter also referred to as AL)
  • AL aluminum deposition
  • silica deposition alumina deposition
  • a vapor deposition layer such as silica alumina binary vapor deposition can be employed.
  • the packaging bag has a layer structure containing an oxygen absorbent.
  • the packaging bag used in the present invention can be formed by laminating at least two laminated bodies including a layer containing an oxygen absorbent by heat fusion. And as said laminated body, for example, from a sealant layer as an innermost layer of a packaging bag, a film or sheet layer containing an oxygen absorbent as a layer outside the sealant layer, and a film or sheet layer containing an oxygen absorbent Examples of the outer layer include an air barrier layer, and if necessary, a laminate in which an arbitrary resin film or the like is disposed as an outer layer from the air barrier layer (see FIG. 2).
  • the innermost layer of the packaging bag is preferably a heat-sealable layer, that is, a sealant layer.
  • a sealant layer the sealant layer shown in the above (1) can be used.
  • the oxygen absorbent is not particularly limited, but in addition to inorganic oxides, mixtures made of electrolytes, reducing inorganic salts, polyphenols, reducing sugars, reducing agents, unsaturated fatty acid compounds, unsaturated organic compounds Examples thereof include a compound, a thermoplastic polymer, a composition containing an oxygen absorption promoting substance, or a mixed system thereof.
  • Oxygard registered trademark
  • Oxycatch registered trademark
  • AGELESS OMAC Mitsubishi Gas Chemical Co., Ltd.
  • the layer disposed on the outside of the film or sheet layer containing the oxygen absorbent is preferably an air blocking layer from the viewpoint of preventing moisture in the air from affecting nalfrafin and salts thereof.
  • the air blocking layer the air blocking layer shown in the above (1) can be used.
  • the packaging bag used in the present invention includes a layer formed from a hygroscopic resin and / or a layer containing an oxygen absorbent from the viewpoint of further suppressing the decomposition of nalfurafine and its salt.
  • a heat-sealing layer is disposed between at least two laminates.
  • the heat-fusible layer is made of a heat-fusible resin that melts and heat-fuses by heating, and heats between laminates including a layer formed from a hygroscopic resin and / or a layer containing an oxygen absorbent. To be fused.
  • the heat-sealable resin is not particularly limited as long as it is a heat-sealable resin.
  • polyethylene polypropylene, ethylene-vinyl acetate copolymer, ethylene-methacrylic acid copolymer, ethylene-methacrylic acid ester copolymer
  • examples thereof include a polymer, an ethylene-acrylic acid copolymer, and an ethylene-acrylic acid ester copolymer.
  • the packaging bag used in the present invention is composed of a laminate of at least two layers including at least one selected from the group consisting of a layer formed from a hygroscopic resin and a layer containing an oxygen absorbent.
  • the laminated body only needs to have the above-described laminated structure, and may have a laminated structure including an arbitrary resin film or the like as necessary.
  • arbitrary resin film etc. polyolefin-type resin films, such as a polyethylene film, a polypropylene film, a polymethylpentene film, etc.
  • Vinyl resin film such as vinyl film, polyvinylidene chloride film, polyvinyl alcohol film, polystyrene film, polyacrylonitrile film, ionomer film
  • polyester resin film such as polyethylene terephthalate film
  • polyamide resin film such as nylon film
  • Cellulosic resin films polycarbonate resin films; and laminated films thereof.
  • the above-mentioned resin films and their laminated films are laminated with soft aluminum foil (hereinafter sometimes abbreviated as AL).
  • AL soft aluminum foil
  • examples thereof include a film and a pigment-added resin film obtained by adding a black pigment or the like to the above-described resin film.
  • these resin films, laminated films, etc. can be used in various combinations as a laminate.
  • the packaging bag may be formed from a laminate including an ethylene-vinyl alcohol copolymer (hereinafter also referred to as EVOH) or a cyclic polyolefin film (hereinafter also referred to as COC).
  • EVOH ethylene-vinyl alcohol copolymer
  • COC cyclic polyolefin film
  • a specific laminated structure of a preferable laminate used in the packaging bag used in the present invention is formed from the innermost layer of the packaging bag from polyethylene (PE) / hygroscopic resin. Or a layer containing an oxygen adsorbent / AL / polyester.
  • the laminate can be produced by dry lamination, extrusion lamination, or coextrusion lamination, and the thickness of the laminate can be about 10 ⁇ m to 100 ⁇ m.
  • Each layer is laminated directly or via an adhesive or the like. When the layers are bonded with an adhesive, it is desirable to use an adhesive with little drug adsorption.
  • an isocyanate such as toluene diisocyanate (TDI) or diphenylmethane diisocyanate (MDI) can be used as an adhesive, or a polyurethane adhesive containing a polyol or the like can be used.
  • the package is formed to be slightly larger than the patch containing nalflavine.
  • the area of the patch can be determined as appropriate, but it is preferably 1 cm 2 to 25 cm 2 in view of minimizing the amount of the drug volatilized in the packaging material and adhering to the support as much as possible and considering the ease of application. is there.
  • the laminated body which comprises the packaging bag used by this invention when the plastic laminate film raw material containing aluminum is employ
  • Method of enclosing a pouch in a packaging bag As a means for reducing the oxygen concentration and / or the amount of water in the packaging bag, a method of enclosing a pouch containing a hygroscopic agent, a pouch containing an oxygen absorbent, or both in the packaging bag.
  • the pouch containing the hygroscopic agent and / or the oxygen absorbent enclosed in the packaging bag can suppress the decomposition of nalfurafine and its salt.
  • the following embodiments (3) and (4) can be taken as a form in which a pouch containing a hygroscopic agent and / or an oxygen absorbent is enclosed in the packaging bag.
  • a nalfrafin-containing patch (hereinafter also simply referred to as a patch) 3 and a pouch 4 containing a hygroscopic agent inside the packaging bag [FIG. i) See.
  • the atmosphere inside the packaging bag is omitted.
  • the packaging bag include a sealant layer as the innermost layer of the packaging bag, an air barrier layer as an outer layer from the sealant layer, and an optional resin film as a layer outside the air barrier layer as necessary. Can be mentioned [see FIG. 3 (ii)].
  • the innermost layer of the packaging bag is preferably a heat-sealable layer, that is, a sealant layer.
  • a sealant layer the sealant layer shown in the above (1) can be used.
  • the layer disposed on the outer side of the sealant layer is preferably an air barrier layer from the viewpoint of preventing moisture in the air from affecting nalflavine and its salt.
  • the air blocking layer the air blocking layer shown in the above (1) can be used.
  • the arbitrary resin films etc. which were mentioned above can be used for arbitrary resin films.
  • the pouch containing the hygroscopic agent is not particularly limited as long as the hygroscopic agent can absorb moisture inside the packaging bag.
  • the hygroscopic agent mentioned in the above (1) may be a nonwoven fabric or the like. It is preferable to cover it with a bag or to add a hygroscopic agent to a nonwoven fabric or the like to form a sheet.
  • the patch product 10 includes the packaging bag 2 and the pouch 5 containing the patch 3 and the oxygen absorbent inside the packaging bag [see FIG. 4 (i). In FIG. 4, the atmosphere inside the packaging bag is omitted. ].
  • the packaging bag include a sealant layer as the innermost layer of the packaging bag, an air barrier layer as an outer layer from the sealant layer, and an optional resin film as a layer outside the air barrier layer as necessary. Can be mentioned [see FIG. 4 (ii)].
  • the innermost layer of the packaging bag is preferably a heat-sealable layer, that is, a sealant layer.
  • a sealant layer the sealant layer shown in the above (1) can be used.
  • the layer disposed on the outer side of the sealant layer is preferably an air barrier layer from the viewpoint of preventing moisture in the air from affecting nalflavine and its salt.
  • the air blocking layer the air blocking layer shown in the above (1) can be used.
  • the arbitrary resin films etc. which were mentioned above can be used for arbitrary resin films.
  • the pouch containing the oxygen absorbent is not particularly limited as long as the oxygen absorbent can reduce the oxygen concentration in the packaging bag.
  • the agent is preferably covered with a non-woven fabric to form a bag.
  • a known method can be used, for example, a method of injecting nitrogen after evacuating the inside of the packaging bag.
  • the method for producing the patch product of the present invention is not particularly limited.
  • the patch product is selected from the group consisting of a layer formed from a hygroscopic resin used in the packaging bag used in the present invention and a layer containing an oxygen absorbent.
  • One or more of the laminates containing at least two layers are framed larger than the size of the patch, and three sides are bonded together by heat fusion to form a bag, and after the patch is sealed, the remaining one side
  • the patch product of the present invention can be obtained by heat-sealing and encapsulating.
  • preferable laminates used for packaging bags are frames larger than the size of the patch, and three sides are bonded together by heat fusion to form a bag, After enclosing a pouch containing a hygroscopic agent and / or an oxygen absorbent, the remaining one side is heat-sealed and encapsulated, whereby the patch product of the present invention can be obtained.
  • the moisture content or oxygen content in the packaging bag is preferably low, and the moisture concentration or oxygen concentration in the packaging bag can be lowered by a known method.
  • the moisture content and residual oxygen concentration inside the packaging bag can be reduced by substituting and filling the atmosphere inside the packaging bag with a vacuum gas packaging machine or the like.
  • the state of the atmosphere in this step can be measured by measuring the moisture content or oxygen content with a measuring device installed in the step of performing nitrogen substitution, or by using a measuring device that can be directly enclosed in a packaging bag. With the measuring device that can be directly enclosed in the packaging bag, the moisture content and oxygen concentration in the packaging bag can be measured over time for the patch product.
  • the preferable moisture content (concentration) in the packaging bag in the patch product is not more than the amount of moisture corresponding to a relative humidity of 25% at 25 ° C., and the residual oxygen concentration is not more than 10% by volume.
  • the moisture content of the patch can be measured with an infrared moisture meter.
  • the rate of change after storage in a constant temperature room at 60 ° C. for 1 month is: It is preferably 20 to 70%, particularly preferably 25 to 50%.
  • packaging bag that is, a narfrafin formed from a laminate of at least two layers including at least one selected from the group consisting of a layer formed from a hygroscopic resin and a layer containing an oxygen absorbent.
  • Packaging bags for containing patches are also the subject of the present invention.
  • the patch includes a support, a nalfurafine-containing pressure-sensitive adhesive layer provided on at least one surface of the support, and a release sheet provided on the nalfurafine-containing pressure-sensitive adhesive layer.
  • Examples of the support used for the patch in the patch product of the present invention include flexible supports such as films, nonwoven fabrics, Japanese paper, cotton cloth, knitted fabrics, woven fabrics, and laminate composites of nonwoven fabrics and films. These supports are preferably made of a flexible material that can adhere to the skin and can follow the movement of the skin, and a material that can suppress the occurrence of skin irritation after being applied for a long time. Examples of the material of these supports include polyethylene, polypropylene, polyethylene terephthalate, and the like. There is no restriction
  • the pressure-sensitive adhesive constituting the pressure-sensitive adhesive layer is not particularly limited, and rubber-based pressure-sensitive adhesive, acrylic pressure-sensitive adhesive, silicone pressure-sensitive adhesive, urethane pressure-sensitive adhesive, hydrocolloid-based Although an adhesive etc. are mentioned, Especially preferably, it is a rubber-type adhesive.
  • the pressure-sensitive adhesive layer may have a single-layer structure or a multilayer structure. In the case where the pressure-sensitive adhesive layer has a multilayer structure, the narfrafin may be contained in one or more of them.
  • the pressure-sensitive adhesive layer comprises (a) an elastomer, (b) one or more tackifiers selected from terpene resins and rosin resins, (c) at least one of nalflavine and salts thereof, and ( d) It contains a desalting agent and further contains other components as required.
  • the pressure-sensitive adhesive layer in the patch in the patch product of the present invention is composed of a non-aqueous system, and water is not intentionally added in the manufacturing process.
  • (A) Elastomer There is no restriction
  • examples thereof include SIS5002 (manufactured by JSR Corporation) and quinac 3520 (manufactured by Nippon Zeon Corporation), which are styrene-isoprene-styrene block copolymers.
  • the said elastomer may be used individually by 1 type, and may use 2 or more types together.
  • the content of the elastomer in the pressure-sensitive adhesive layer can be appropriately selected according to the purpose, but is preferably 15% by mass or more, more preferably 20% by mass or more, and further preferably 30% by mass or more. Moreover, 60 mass% or less is preferable, 50 mass% or less is more preferable, and 40 mass% or less is further more preferable.
  • Tackifier There are no particular limitations on the tackifier as long as it improves tackiness, but it is preferable to contain one or more tackifiers selected from terpene resins and rosin resins.
  • the terpene resin include ⁇ -pinene resin, ⁇ -pinene resin, terpene-phenol resin, aromatic modified terpene resin, hydrogenated terpene resin and the like.
  • rosin resin examples include rosins such as gum rosin, tall oil rosin, and wood rosin; hydrogenated rosin, disproportionated rosin, polymerized rosin, modified rosin such as maleated rosin; rosin glycerin ester, hydrogenated rosin ester, hydrogenated Rosin ester such as rosin glycerin ester; and the like.
  • tackifier examples include YS resin PX1150N (manufactured by Yasuhara Chemical Co., Ltd.) and Pine Crystal KE-311 (manufactured by Arakawa Chemical Industries, Ltd.). The said tackifier may be used individually by 1 type, and may use 2 or more types together. Moreover, you may combine the tackifier selected from the said terpene resin and the said rosin resin. In particular, rosin resin is preferable from the viewpoint of stability of narfrafin.
  • nalflaphine and its salt As the above-mentioned nalfurafine, a free form of nalfurafine can be used, but it is preferably blended in the pressure-sensitive adhesive layer as a salt of nalfurafine.
  • the salt of narfrafin is converted into a free form by a desalting agent described later.
  • the salt of nalfurafine is not particularly limited as long as it is a pharmaceutically acceptable salt, but an acid addition salt of nalfurafine is preferable from the viewpoint of skin permeability.
  • the acid addition salt include hydrochloride, acetate, maleate, and oxalate. Among these, nalfrafin hydrochloride is preferable from the viewpoint of skin permeability.
  • the nalflaphine salt may be used alone or in combination of two or more.
  • nalflavine As content in the said adhesive layer of the salt of the said nalfurafine, 0.1 mass% or more is preferable, and 0.2 mass% or more is more preferable. Moreover, 5.0 mass% or less is preferable at the point of skin permeability and skin irritation, 4.0 mass% or less is more preferable, and 3.0 mass% or less is further more preferable. Even when a free form of nalfurafine is used in place of the nalflaphine salt, an amount similar to the content of the nalfurafine salt can be added to the pressure-sensitive adhesive layer. In the present invention, when it is described as nalflavine, it refers to both a free form of nalflaphine and a pharmaceutically acceptable salt thereof unless otherwise specified.
  • the desalting agent is not particularly limited as long as it converts the salt of nalflaphine into a free form, and can be appropriately selected according to the purpose.
  • monoethanolamine e.g., monoethanolamine , Sodium bicarbonate, and a polymer compound having an amino group are preferred.
  • the content of the desalting agent can be appropriately selected according to the purpose, but in terms of skin irritation and skin permeability, the content is 5 mol or more with respect to 1 mol of the salt of narfrafin. Preferably, it is 10 mol or more. Moreover, it is preferable that it is 30 mol or less, and it is more preferable that it is 25 mol or less.
  • As a blending method of the desalting agent it may be performed once during the production process or may be performed in several steps.
  • the content in the pressure-sensitive adhesive layer is preferably 0.01% by mass or more, more preferably 0.1% by mass or more, and further preferably 0.3% by mass or more. . Moreover, 10 mass% or less is preferable, 5.0 mass% or less is more preferable, and 1.0 mass% or less is further more preferable.
  • polymer compound having an amino group in terms of skin permeability, dialkyl (meth) acrylate (methyl or ethyl) aminoalkyl (methyl or ethyl) and alkyl (meth) acrylate (methyl, ethyl, Propylene or butyl), copolymers composed of monomer units selected from monohydroxyalkyl (meth) acrylates (ethyl, propyl or butyl) and combinations thereof are preferred.
  • Examples of such a polymer compound having an amino group include Eudragit (registered trademark) EPO (manufactured by Evonik), which is a methyl methacrylate-butyl methacrylate-dimethylaminoethyl methacrylate copolymer.
  • the desalting agent is a polymer compound having an amino group
  • 1.0% by mass or more is preferable in the pressure-sensitive adhesive layer, and 2.0% by mass or more is more preferable.
  • 40 mass% or less is preferable in the said adhesive layer at the point of skin permeability and skin irritation.
  • the said desalting agent may be used individually by 1 type, and may use 2 or more types together.
  • the average thickness of the pressure-sensitive adhesive layer can be appropriately selected according to the purpose, but is preferably 5 ⁇ m to 500 ⁇ m, more preferably 10 ⁇ m to 300 ⁇ m, and further preferably 20 ⁇ m to 200 ⁇ m.
  • the pressure-sensitive adhesive layer may further contain other additives such as other drugs, softeners, antioxidants, absorption accelerators, inorganic fillers, ultraviolet absorbers and antioxidants.
  • the release sheet used for the patch in the patch product of the present invention is preferably a material that is difficult to absorb and adsorb the drug in the pressure-sensitive adhesive layer.
  • a polyester film having a silicone treatment on one or both sides silicone Examples include treated polyethylene laminate fine paper, silicone-treated glassine paper, and the like.
  • the method for producing the patch in the patch product of the present invention is not particularly limited and can be appropriately selected according to the purpose.
  • an adhesive containing an elastomer, a tackifier, a salt of nalfrafin, and a desalting agent examples thereof include a method of preparing an agent composition and coating it on a support, and a method of applying the support onto a release sheet and then bonding the support.
  • nalfurafine hydrochloride was used as all nalflaphine.
  • Example 1 As the elastomer, styrene-isoprene-styrene block copolymer (SIS; trade name “SIS5002”, manufactured by JSR Corporation) 7.97% by mass, styrene-isoprene-styrene block copolymer (SIS; trade name “Quintac”) 3520 ", manufactured by Nippon Zeon Co., Ltd.) 23.9% by mass, as the tackifier, terpene resin (trade name” YS Resin PX1150N “, Yashara Chemical Co., Ltd.) 19.1% by mass, and as the softener, liquid paraffin (Trade name “Hycol M352”, manufactured by Kaneda Co., Ltd.) 48.48% by mass, nalflaphine hydrochloride 0.25% by mass dissolved in an appropriate amount of methanol as the salt of nalfurafine, and monoethanol as the desalting agent 0.3% by weight of amine is present so that
  • the solvent (toluene) was added to prepare a pressure-sensitive adhesive composition was mixed until uniform.
  • the obtained pressure-sensitive adhesive composition was coated on a silicone-treated polyester film (average thickness 75 ⁇ m) as a cover material (release sheet) to an average thickness of 30 ⁇ m to form a pressure-sensitive adhesive layer.
  • a polyester film was laminated as a support on this pressure-sensitive adhesive layer, and cut into a size of 7.5 cm 2 to prepare patch 1.
  • the patch product 1 was produced as follows, and the stability test with time shown below was performed to evaluate the stability of the drug in the patch. The evaluation results are shown in Table 1.
  • patch products 1-6 were prepared using a packaging bag using a laminate in which PAN (polyacrylonitrile) was disposed as the innermost layer and AL was disposed as the air barrier layer. It was used for.
  • Patches 7-9 use packaging bags obtained using moist catch (manufactured by Kyodo Printing Co., Ltd., sealant layer / moisture absorbing layer / aluminum / PET), and patches 10-12 use oxycatch (Kyodo Printing Co., Ltd.)
  • Patch products 7 to 12 were produced using packaging bags obtained using PE (sealant layer) / oxygen absorbing layer / aluminum / PET (manufactured by the company) and subjected to the following tests.
  • the patch was housed in each packaging bag, the inside of the bag was purged with nitrogen, the packaging bag was sealed by heat sealing, and stored at 60 ° C.
  • the content of nalflaphine in the patch was quantified by high performance liquid chromatography.
  • the nalfuraffin content after 3 months with respect to the nalfurafine content at the start of storage was calculated as a percentage and used as the drug residual rate (%).
  • Example 2 In Example 1, 0.05% by mass of BHT was added as an antioxidant, and the same method as in Example 1 except that the amount of the softening agent was changed from 48.48% by mass to 48.43% by mass. A patch 2 and a patch product 2 were prepared and evaluated.
  • Example 3 In Example 1, instead of 19.1% by mass of “YS Resin PX1150N”, which is a terpene resin as the tackifier, “Pine Crystal KE-311 (ultra-light rosin ester)” (Arakawa Chemical) A patch 3 and a patch product 3 were prepared and evaluated in the same manner as in Example 1 except that 19.1% by mass (manufactured by Kogyo Co., Ltd.) was used.
  • Example 4 In Example 3, the desalting agent was 3.2% by mass of “Eudragit EPO” (manufactured by Evonik), which is a polymer compound containing an amino group instead of 0.3% by mass of monoethanolamine, and as an antioxidant.
  • the patch 4 and the patch product 4 were prepared in the same manner as in Example 3 except that 0.05% by mass of BHT was added and the amount of the softening agent was changed from 48.48% by mass to 45.53% by mass. Were made and evaluated.
  • Example 5 In Example 4, except that the antioxidant was not added and the amount of the softening agent was changed from 45.53 mass% to 45.58 mass%, the patch 5 and the patch were prepared in the same manner as in Example 4. Product 5 was made and evaluated.
  • Example 5 is the same as Example 5 except that nalfurafine hydrochloride is a free form of nalfurafine, no desalting agent is added, and the amount of the softening agent is changed from 45.58% by mass to 48.78% by mass.
  • a patch 6 and a patch product 6 were prepared and evaluated in the same manner.
  • Example 7 In Example 4, except that the packaging material was changed to a moist catch (made by Kyodo Printing Co., Ltd.) including a layer formed of a hygroscopic resin, the patch 7 and the patch product 7 were prepared in the same manner as in Example 4. Prepared and evaluated.
  • Example 8 In Example 5, except that the packaging material was changed to a moist catch (made by Kyodo Printing Co., Ltd.) including a layer formed from a hygroscopic resin, patch 8 and patch product 8 were produced in the same manner as in Example 5. And evaluated.
  • a moist catch made by Kyodo Printing Co., Ltd.
  • Example 9 In Example 2, instead of 19.1% by mass of “YS Resin PX1150N”, which is a terpene resin as the tackifier, “Pine Crystal KE-311 (ultra-light rosin ester)” (Arakawa Chemical) Kogyo Kogyo Co., Ltd. was used in the same manner as in Example 2 except that the product was changed to 19.1% by mass and the packaging material was changed to a moist catch (manufactured by Kyodo Printing Co., Ltd.). In addition, a patch product 9 was prepared and evaluated.
  • Example 10 In Example 4, the patch 10 and the patch product 10 were produced in the same manner as in Example 4 except that the packaging material was changed to Oxycatch (produced by Kyodo Printing Co., Ltd.) including a layer containing an oxygen absorbent. And evaluated.
  • Oxycatch produced by Kyodo Printing Co., Ltd.
  • Example 11 In Example 5, the patch 11 and the patch product 11 were produced in the same manner as in Example 5 except that the packaging material was changed to oxy catch (manufactured by Kyodo Printing Co., Ltd.) including a layer containing an oxygen absorbent. And evaluated.
  • oxy catch manufactured by Kyodo Printing Co., Ltd.
  • Example 12 In Example 2, instead of 19.1% by mass of “YS Resin PX1150N”, which is a terpene resin as the tackifier, “Pine Crystal KE-311 (ultra-light rosin ester)” (Arakawa Chemical) Kogyo Kogyo Co., Ltd., except that the packaging material was changed to 19.1% by mass and the packaging material was changed to Oxycatch (manufactured by Kyodo Printing Co., Ltd.). A patch product 12 was prepared and evaluated.
  • the water content of each patch was measured. Specifically, the patch 7 or the patch 13 was accommodated in each packaging bag, the inside of the bag was purged with nitrogen, the packaging bag was sealed by heat fusion, and stored at 60 ° C. At the start of storage and 1 month after the start of storage, the amount of water in the patch was quantified with an infrared moisture meter (AD-4715, A & D). The water content after one month with respect to the water content in the preparation at the start of storage was calculated as a percentage and used as the water content change rate (%). The infrared moisture meter was measured by assuming that the drying temperature was 100 ° C., the monitoring time was 300 seconds, and the amount of change in the measured value was 0.05% or less within the monitoring time as the final measured value.
  • AD-4715, A & D infrared moisture meter
  • the patches 1 to 12 (Examples 1 to 12) It was found that the configuration realized a patch product with good drug stability.
  • the patch products 10 to 12 using oxycatch as a packaging material showed a very good result that the drug residual amount in the patches 10 to 12 was 96% or more even when stored at 60 ° C. for 3 months. Met.
  • the adhesive layer of the patch from the patches 4, 5, 7, 8, 10-11, styrene-isoprene-styrene block copolymer (SIS), rosin resin as the tackifier, and desalting agent
  • SIS styrene-isoprene-styrene block copolymer
  • rosin resin as the tackifier
  • desalting agent As a result, it has been found that a composition containing an amino group-containing polymer compound is preferable.
  • the patch product 7 using the moist catch has a moisture decrease rate (%) of 37% when stored for one month at 60 ° C.
  • the moisture reduction rate of the agent 13 was 11%. This is because moisture in the packaging material is reliably absorbed by using a packaging bag formed of a laminate of at least two layers including a laminate including a layer formed of a hygroscopic resin. Was confirmed.

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  • Packages (AREA)
  • Medical Preparation Storing Or Oral Administration Devices (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Cette invention concerne un produit de type patch adhésif comprenant un sachet d'emballage et un patch adhésif contenant une nalfurafine à l'intérieur dudit sachet d'emballage, et qui permet d'obtenir une excellente stabilité de la nalfurafine dans le temps résultant de l'utilisation d'un moyen capable de réduire la concentration d'oxygène et/ou la teneur en humidité à l'intérieur dudit sachet d'emballage.
PCT/JP2017/013403 2016-03-31 2017-03-30 Produit de type patch adhésif WO2017170933A1 (fr)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019171333A1 (fr) 2018-03-08 2019-09-12 Victoria Link Ltd Traitement de maladies démyélinisantes

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005072716A1 (fr) * 2004-01-30 2005-08-11 Hisamitsu Pharmaceutical Co., Inc. Sachet d'emballage contenant du plâtre
WO2006114868A1 (fr) * 2005-04-20 2006-11-02 Nichiban Co., Ltd. Preparation medicinale pour une absorption percutanee
WO2010123103A1 (fr) * 2009-04-24 2010-10-28 久光製薬株式会社 Sac de conditionnement contenant un timbre adhésif et procédé de stockage du timbre adhésif
JP2012158718A (ja) * 2011-02-02 2012-08-23 Toyo Seikan Kaisha Ltd 吸湿性樹脂組成物及び吸湿性多層容器
JP2014196279A (ja) * 2013-03-29 2014-10-16 三笠製薬株式会社 ナルフラフィン含有経皮吸収貼付剤
WO2015025767A1 (fr) * 2013-08-21 2015-02-26 久光製薬株式会社 Patch adhésif
WO2015025766A1 (fr) * 2013-08-21 2015-02-26 久光製薬株式会社 Patch adhésif

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005072716A1 (fr) * 2004-01-30 2005-08-11 Hisamitsu Pharmaceutical Co., Inc. Sachet d'emballage contenant du plâtre
WO2006114868A1 (fr) * 2005-04-20 2006-11-02 Nichiban Co., Ltd. Preparation medicinale pour une absorption percutanee
WO2010123103A1 (fr) * 2009-04-24 2010-10-28 久光製薬株式会社 Sac de conditionnement contenant un timbre adhésif et procédé de stockage du timbre adhésif
JP2012158718A (ja) * 2011-02-02 2012-08-23 Toyo Seikan Kaisha Ltd 吸湿性樹脂組成物及び吸湿性多層容器
JP2014196279A (ja) * 2013-03-29 2014-10-16 三笠製薬株式会社 ナルフラフィン含有経皮吸収貼付剤
WO2015025767A1 (fr) * 2013-08-21 2015-02-26 久光製薬株式会社 Patch adhésif
WO2015025766A1 (fr) * 2013-08-21 2015-02-26 久光製薬株式会社 Patch adhésif

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
YASUHIDE HORIUCHI: "Seizaika no Science Rinsho de Tsukaiyasui Kusuri o Mezashite Dai 25 Kai Remitch Capsules 2.5µg", PHARMACIA, vol. 48, no. 4, 1 April 2012 (2012-04-01), pages 323 - 325, ISSN: 2189-7026 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019171333A1 (fr) 2018-03-08 2019-09-12 Victoria Link Ltd Traitement de maladies démyélinisantes

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