WO2021106782A1 - ロピニロール含有貼付剤の粘着剤層保持力向上方法、及びロピニロール含有保持力改善貼付剤 - Google Patents
ロピニロール含有貼付剤の粘着剤層保持力向上方法、及びロピニロール含有保持力改善貼付剤 Download PDFInfo
- Publication number
- WO2021106782A1 WO2021106782A1 PCT/JP2020/043382 JP2020043382W WO2021106782A1 WO 2021106782 A1 WO2021106782 A1 WO 2021106782A1 JP 2020043382 W JP2020043382 W JP 2020043382W WO 2021106782 A1 WO2021106782 A1 WO 2021106782A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- sensitive adhesive
- pressure
- adhesive layer
- ropinirole
- holding power
- Prior art date
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- 229960001879 ropinirole Drugs 0.000 title claims abstract description 112
- 238000000034 method Methods 0.000 title claims abstract description 39
- 239000000853 adhesive Substances 0.000 title claims abstract description 23
- 150000003839 salts Chemical class 0.000 claims abstract description 66
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims abstract description 44
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- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000001540 sodium lactate Substances 0.000 description 1
- 235000011088 sodium lactate Nutrition 0.000 description 1
- 229940005581 sodium lactate Drugs 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 239000003270 steroid hormone Substances 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 229920006132 styrene block copolymer Polymers 0.000 description 1
- 229920003048 styrene butadiene rubber Polymers 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- KKEYFWRCBNTPAC-UHFFFAOYSA-L terephthalate(2-) Chemical compound [O-]C(=O)C1=CC=C(C([O-])=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-L 0.000 description 1
- 150000003505 terpenes Chemical class 0.000 description 1
- 235000007586 terpenes Nutrition 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- KHPCPRHQVVSZAH-UHFFFAOYSA-N trans-cinnamyl beta-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OCC=CC1=CC=CC=C1 KHPCPRHQVVSZAH-UHFFFAOYSA-N 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 239000002759 woven fabric Substances 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
Classifications
-
- 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
-
- 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
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A61K31/4045—Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
-
- 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
- A61K47/02—Inorganic compounds
-
- 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
-
- 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
- A61K9/7069—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained otherwise than by reactions only involving carbon to carbon unsaturated bonds, e.g. polysiloxane, polyesters, polyurethane, polyethylene oxide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
Definitions
- the present invention relates to a method for improving the adhesive layer holding power of a ropinirole-containing patch and a ropinirole-containing holding power improving patch. More specifically, ropinirole and / or a pharmaceutically acceptable salt and a pressure-sensitive adhesive thereof are used.
- the present invention relates to a method for improving the holding power of the pressure-sensitive adhesive layer of the ropinirole-containing patch contained, and a ropinirole-containing holding power improving patch.
- Ropinirole is known as a useful drug for the treatment of Parkinson's disease, restless legs syndrome, etc.
- ropinirole and / or its use from the viewpoints of reducing the number of administrations, improving compliance, and easiness of administration and discontinuation thereof.
- the transdermal administration of a preparation containing a pharmaceutically acceptable salt has been studied.
- Patent Document 1 describes a percutaneous absorption preparation comprising a support and an adhesive layer containing ropinirole or a pharmaceutically acceptable acid addition salt thereof.
- Patent Document 2 describes a ropinirole-containing patch comprising a support layer and a pressure-sensitive adhesive layer containing a specific amount of ropinirole and / or a pharmaceutically acceptable salt thereof. ing.
- Patent Document 3 includes a support layer and a pressure-sensitive adhesive layer containing a mixture of a pharmaceutically acceptable acid addition salt of ropinirole and potassium hydrogen carbonate. The patch is listed.
- Patent Document 4 describes that the ropinilol free substance plasticizes the pressure-sensitive adhesive base and reduces the cohesive force of the pressure-sensitive adhesive layer. Due to the excellent skin permeability and sufficient tackiness of lopinilol, in a lopinilol-containing patch comprising a support layer and a pressure-sensitive adhesive layer containing lopinilol and / or a pharmaceutically acceptable salt thereof, lopinilol and / Alternatively, it is described that the content of the pharmaceutically acceptable salt thereof and the mass per unit area of the pressure-sensitive adhesive layer are within a specific range, and the pressure-sensitive adhesive layer contains a specific amount of alkali metal hydroxide. In addition, sodium hydroxide and the like are mentioned as the alkali metal hydroxide.
- the patch is for continuously transdermally administering the drug by attaching the pressure-sensitive adhesive layer to the skin, for example, the adhesive force of the pressure-sensitive adhesive layer to the skin (generally, in the 180 ° direction or the 90 ° direction). It is indicated by the force indicated by the peeling force), the cohesive force as described in Patent Document 4, and the tack property (generally, the distance by which the ball is rolled on the surface of the adhesive layer set on the inclined surface (ball tack test).
- Various physical properties such as (degree of stickiness) and holding power (power to resist the force that shifts due to the fluidity of the adhesive) are required.
- a patch containing ropinirole and / or a pharmaceutically acceptable salt thereof and a pressure-sensitive adhesive in the pressure-sensitive adhesive layer retains such physical characteristics. We have found that the force tends to be particularly weak.
- fillers such as calcium carbonate as described in Patent Documents 1 to 4 have been conventionally used, but these fillers are contained in the pressure-sensitive adhesive layer.
- the inventors have also found that ropinirole and / or its pharmaceutically acceptable salt may reduce skin permeability.
- the present invention has been made in view of the above-mentioned problems of the prior art, and is pharmaceutically acceptable of ropinirole and / or its pharmaceutically acceptable salt while maintaining the skin permeability of ropinirole and / or its pharmaceutically acceptable salt.
- a method for improving the holding power of the adhesive layer of a ropinirole-containing patch which can improve the holding power of the pressure-sensitive adhesive layer containing a salt and a pressure-sensitive adhesive, and a ropinirole-containing holding power improving sticking having excellent holding power of the pressure-sensitive adhesive layer.
- the purpose is to provide the agent.
- Patent Document 4 describes a ropinirol-containing patch containing at least one selected and a pressure-sensitive adhesive by further incorporating a sodium salt of carbonate in the pressure-sensitive adhesive layer. It has been found that the holding power of the pressure-sensitive adhesive layer can be sufficiently improved as compared with the case of using such sodium hydroxide.
- the skin permeability of ropinirole and / or its pharmaceutically acceptable salt is lowered.
- the present invention has been completed by finding that the skin permeability can be sufficiently maintained when the sodium salt of carbonic acid is used.
- the method for improving the adhesive layer holding power of the ropinirole-containing patch of the present invention comprises a group comprising a support layer and a pressure-sensitive adhesive layer, and the pressure-sensitive adhesive layer is composed of ropinirole and a pharmaceutically acceptable salt thereof.
- a method for improving the holding power of the pressure-sensitive adhesive layer in a ropinirole-containing patch containing at least one selected type and a pressure-sensitive adhesive is a method of further adding a sodium salt of carbonic acid to the pressure-sensitive adhesive layer.
- the pressure-sensitive adhesive is selected from the group consisting of a rubber-based pressure-sensitive adhesive, an acrylic-based pressure-sensitive adhesive having no carboxy group, and a silicone-based pressure-sensitive adhesive. It is preferably at least one kind.
- the sodium salt of carbonic acid is at least one selected from the group consisting of sodium carbonate and sodium hydrogen carbonate.
- the sodium salt of the carbon dioxide is contained in the pressure-sensitive adhesive layer so that the content thereof is 0.5 to 33% by mass based on the total mass. It is preferable to include it in the pressure-sensitive adhesive layer, and the content of at least one selected from the group consisting of the ropinirole and a pharmaceutically acceptable salt thereof in terms of ropinirole-free form is 1.0 mol. It is also preferable to include it in the pressure-sensitive adhesive layer so as to be 0.1 to 5.0 mol.
- the content in terms of at least one ropinirole-free form selected from the group consisting of the ropinirole and its pharmaceutically acceptable salt is preferably 5 to 30% by mass with respect to the total mass of the pressure-sensitive adhesive layer.
- the ropinirole-containing holding power improving patch of the present invention comprises at least one selected from the group consisting of a support layer and a pressure-sensitive adhesive layer, and the pressure-sensitive adhesive layer consisting of ropinirole and a pharmaceutically acceptable salt thereof. It is a patch containing a sodium salt of carbonic acid and an adhesive.
- a pressure-sensitive adhesive layer containing ropinirole and / or its pharmaceutically acceptable salt and an adhesive while maintaining skin permeability of ropinirole and / or its pharmaceutically acceptable salt. It is possible to provide a method for improving the adhesive layer holding power of a ropinirole-containing patch capable of improving the holding power, and a ropinirole-containing holding power improving patch having an excellent holding power of the pressure-sensitive adhesive layer.
- the method for improving the adhesive layer holding power of a ropinirole-containing patch of the present invention includes a support layer and a pressure-sensitive adhesive layer, and the pressure-sensitive adhesive layer is ropinirole.
- a method for improving the holding power of the pressure-sensitive adhesive layer in a ropinirole-containing patch containing at least one selected from the group consisting of the pharmaceutically acceptable salt and the pressure-sensitive adhesive is a method of further adding a sodium salt of carbonic acid to the pressure-sensitive adhesive layer.
- the ropinirole-containing patch according to the method of the present invention includes a support layer and a pressure-sensitive adhesive layer, and the pressure-sensitive adhesive layer is ropinirole and its pharmaceutical use.
- the support layer according to the present invention is not particularly limited as long as it can support the pressure-sensitive adhesive layer described later, and a known support layer for the patch can be appropriately adopted.
- the material of the support layer according to the present invention include polyolefins such as polyethylene and polypropylene; ethylene-vinyl acetate copolymers, vinyl acetate-vinyl chloride copolymers, polyvinyl chloride and the like; polyamides such as nylon; polyethylene terephthalate. Examples thereof include polyesters such as (PET), polyvinyl terephthalate, and polyethylene naphthalate; cellulose derivatives; synthetic resins such as polyurethane, and metals such as aluminum.
- polyester is preferable from the viewpoint of drug non-adsorption property and drug non-permeability.
- the form of the support layer include films; sheets such as sheets, sheet-like porous bodies, and sheet-like foams; fabrics such as woven fabrics, knitted fabrics, and non-woven fabrics; foils; and laminates thereof. Be done.
- the thickness of the support layer is not particularly limited, but is preferably in the range of 5 to 1000 ⁇ m from the viewpoint of workability and manufacturing ease when the patch is applied.
- the patch according to the present invention may further include a release liner on the surface of the pressure-sensitive adhesive layer opposite to the support layer.
- a release liner include polyolefins such as polyethylene and polypropylene; ethylene-vinyl acetate copolymers, vinyl acetate-vinyl chloride copolymers, polyvinyl chloride and the like; polyamides such as nylon; polyesters such as polyethylene terephthalate; cellulose derivatives; Examples thereof include synthetic resins such as polyurethane, films and sheets made of materials such as aluminum and paper, and laminates thereof.
- release liners are those in which a silicone-containing compound coat, a fluorine-containing compound coat, or the like is subjected to a mold release treatment on the surface on the side in contact with the pressure-sensitive adhesive layer so that the liner can be easily peeled off from the pressure-sensitive adhesive layer. It is preferable to have.
- the pressure-sensitive adhesive layer according to the present invention is at least one selected as a drug from the group consisting of ropinirole and its pharmaceutically acceptable salt (in the present specification, in some cases, “ropinirole and / or its pharmaceutically acceptable salt). It contains "salt to be made”).
- the ropinirole contained in the pressure-sensitive adhesive layer according to the present invention may be a free form (in the present specification, sometimes referred to as "ropinirole-free form") or a pharmaceutically acceptable salt thereof.
- the pharmaceutically acceptable salt of ropinirole may be desalted into a free form during and / or during the production, and one of these may be used alone or 2 It may be a mixture of seeds or more.
- the pharmaceutically acceptable salt of ropinirole is preferably a pharmaceutically acceptable acid addition salt of ropinirole (in the present specification, it is sometimes referred to as "ropinirole acid addition salt").
- the acid of the ropinirol acid addition salt include hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, phosphite, hydrobromic acid, maleic acid, malic acid, ascorbic acid, tartrate acid, and fumaric acid.
- the ropinirol acid addition salt When the ropinirol acid addition salt is contained in the pressure-sensitive adhesive layer as a raw material of the patch according to the present invention, the ropinirol acid addition salt is mixed with the following sodium carbonate of carbonic acid as a weak base at the time of production. By doing so, all or part of the ropinirol acid addition salt is desalted (neutralized) in the pressure-sensitive adhesive layer of the preparation during the production process and / or after production to obtain a ropinirol-free product in a free base state. As a result, when the preparation is applied, a ropinirol-free form having higher tissue absorption can be present in the pressure-sensitive adhesive layer.
- the content of ropinilol and / or a pharmaceutically acceptable salt thereof according to the present invention (content of ropinilol-free form or pharmaceutically acceptable salt content of ropinilol, or pharmaceutically acceptable form of ropinilol-free form and ropinilol. If any of the salts allowed in the above is contained, the total content thereof, the same shall apply hereinafter) is the total mass of the pressure-sensitive adhesive layer (in the present specification, "the total weight of the pressure-sensitive adhesive layer" in terms of ropini roll-free form.
- Mass is the total mass of the pressure-sensitive adhesive layer in the patch after production (after the sodium salt of carbon dioxide is contained), more preferably the total mass of the pressure-sensitive adhesive layer composition described below minus the mass of the solvent. It is preferably 5 to 30% by mass, more preferably 5 to 25% by mass, further preferably 5 to 20% by mass, and 5 to 15% by mass. Is even more preferable, and 5 to 13.2% by mass is particularly preferable.
- the skin permeability of the ropinirole and / or its pharmaceutically acceptable salt tends to decrease, while when the upper limit is exceeded, the absolute amount in the pressure-sensitive adhesive layer increases, so that the pressure-sensitive adhesive layer composition is spread during the formation of the pressure-sensitive adhesive layer. It tends to be difficult to obtain a uniform preparation.
- the pressure-sensitive adhesive layer according to the present invention contains a pressure-sensitive adhesive.
- the pressure-sensitive adhesive according to the present invention include rubber-based pressure-sensitive adhesives, acrylic-based pressure-sensitive adhesives, silicone-based pressure-sensitive adhesives, and the like, and one of these may be used alone or in combination of two or more. ..
- the pressure-sensitive adhesive according to the present invention is preferably at least one selected from the group consisting of a rubber-based pressure-sensitive adhesive, an acrylic-based pressure-sensitive adhesive having no carboxy group, and a silicone-based pressure-sensitive adhesive, and at least one of them. It is more preferable to contain a rubber-based pressure-sensitive adhesive.
- the content of the pressure-sensitive adhesive is 10 to 90 with respect to the total mass of the pressure-sensitive adhesive layer. It is preferably by mass, preferably 17 to 85% by mass, and even more preferably 20 to 70% by mass.
- Examples of the rubber-based pressure-sensitive adhesive according to the present invention include natural rubber and synthetic rubber, and from the viewpoint that they tend to be superior in the cohesive force of the pressure-sensitive adhesive layer and the skin permeability of ropinilol, the styrene-isobutylene-styrene block co-weight.
- the "synthetic rubber having no hydroxyl group and carboxy group” has substantially no hydroxyl group and carboxy group, preferably the content of the hydroxyl group and the carboxy group in the molecule is 3% by mass. Indicates synthetic rubber that is less than%.
- the content thereof is the total mass of the pressure-sensitive adhesive layer.
- it is preferably 10 to 55% by mass, and more preferably 15 to 35% by mass.
- acrylic pressure-sensitive adhesive examples include those listed as pressure-sensitive adhesives in the "Pharmaceutical Additives Dictionary 2016 (edited by the Japan Pharmaceutical Additives Association)", and one of these is used alone. Although it may be a combination of two or more kinds, it is preferably an acrylic pressure-sensitive adhesive having no carboxy group, and more preferably an acrylic pressure-sensitive adhesive having no functional group.
- the "acrylic pressure-sensitive adhesive having no carboxy group” and the “acrylic pressure-sensitive adhesive having no functional group” have substantially no carboxy group and functional group, respectively, preferably a polymer. It shows an acrylic polymer in which the contents of a carboxy group and a functional group (including a carboxy group) are less than 3% by mass, respectively.
- acrylic pressure-sensitive adhesive having no carboxy group examples include -2-ethylhexyl acrylate / vinylpyrrolidone copolymer, -2-ethylhexyl acrylate / -2-ethylhexyl methacrylate / dodecyl methacrylate copolymer, and acrylic.
- Copolymer 2-hydroxypropyl (meth) acrylate copolymer, 3-hydroxypropyl (meth) acrylate copolymer, 4-hydroxybutyl copolymer (meth) acrylate, -2-ethylhexyl acrylate.
- acrylic pressure-sensitive adhesives having a hydroxy group such as vinyl acetate, hydroxyethyl acrylate, and glycidyl methacrylate copolymer, and one of them may be used alone or in combination of two or more. ..
- acrylic pressure-sensitive adhesive having no carboxy group commercially available ones may be appropriately used.
- acrylic pressure-sensitive adhesive having no carboxy group commercially available ones may be appropriately used.
- MAS 811 and MAS 683 manufactured by Cosmed Pharmaceutical Co., Ltd.
- Duro-Tak registered trademark acrylic pressure-sensitive adhesive series.
- 87-900A, 87-901A, 87-9301, 87-4098, 87-9008, 87-9805 (manufactured by Henkel); GMS 3083, GMS 3253 of GELVA® acrylic adhesive series (manufactured by Henkel) , GMS3235 and the like, and Duro-Tak (registered trademark) acrylic adhesive series (manufactured by Henkel) 87-202A, 87-2287, 87-2516, 87-2510, 87-4287, 87-2525, 87-201A, 87-202A, 87-208A, 87-502A, 87-503A, 87-504A; GELVA (registered trademark) acrylic adhesive series (manufactured by Henkel) GMS 788, GMS 737, etc.
- the contained acrylic polymer or the like can be appropriately used.
- the pressure-sensitive adhesive layer according to the present invention contains the acrylic pressure-sensitive adhesive
- its content is the total mass of the pressure-sensitive adhesive layer.
- it is preferably 10 to 90% by mass, more preferably 20 to 85% by mass, and even more preferably 20 to 70% by mass.
- the content of the acrylic pressure-sensitive adhesive is less than the lower limit, the cohesive force of the pressure-sensitive adhesive layer tends to decrease, while when it exceeds the upper limit, the skin permeability of ropinirole tends to decrease. It is in.
- the silicone-based pressure-sensitive adhesive includes MQ (polydimethylsiloxane), VMQ (polymethylvinylsiloxane), in the ASTM standard (ASTM D 1418).
- MQ polydimethylsiloxane
- VMQ polymethylvinylsiloxane
- ASTM standard ASTM D 1418
- silicone rubber represented by PMQ (polymethylphenylsiloxane) and PVMQ (polyphenylvinylmethylsiloxane)
- a silicone resin other than silicone rubber such as polyditrimethylsilylsiloxane.
- a silicone resin other than the silicone rubber is mixed, it is preferably 0.1 to 20% by mass with respect to the total mass of the silicone-based pressure-sensitive adhesive.
- silicone-based adhesives commercially available ones may be appropriately used.
- the following model numbers BIO-PSA7-410X, BIO-PSA7-420X , BIO-PSA7-430X, BIO-PSA7-440X, BIO-PSA7-450X, BIO-PSA7-460X (each X is 1 or 2 independently), BIO-PSA AC7-4201, BIO-PSA AC7-4301, BIO-PSA AC7-4302, MD7-4502, MD7-4602, 7-9700, MG7-9800, MG7-9850; Silicone provided by BIO-PSA 7-4560, which is a hot melt silicone adhesive.
- a system adhesive or the like can be used as appropriate.
- the silicone-based pressure-sensitive adhesive for example, when it has a methyl group, the hydrogen atom of the methyl group is dehydrogenated by blending a peroxide to crosslink the methyl groups.
- a cross-linking agent composed of a SiH group-containing siloxane compound is bonded to crosslink the vinyl groups; when it has a hydroxyl group (that is, when it has a silanol group), the silanol is subjected to dehydration condensation. It may be one in which the bases are crosslinked.
- the content thereof is the total mass of the pressure-sensitive adhesive layer.
- it is preferably 10 to 90% by mass, more preferably 20 to 85% by mass, and even more preferably 20 to 70% by mass.
- the content of the silicone-based pressure-sensitive adhesive is less than the lower limit, the cohesive force of the pressure-sensitive adhesive layer tends to decrease, while when it exceeds the upper limit, the skin permeability of ropinirole tends to decrease. It is in.
- the pressure-sensitive adhesive layer according to the present invention includes drugs other than ropinirole and pharmaceutically acceptable salts thereof, as long as the effects of the present invention are not impaired; absorption promoters (transdermal absorption promoters); adsorbents. , Additives such as tackifiers, plasticizers, solubilizers, fillers, stabilizers, preservatives and the like may be further contained.
- drugs other than the lopinilol and its pharmaceutically acceptable salts include, for example, non-steroidal anti-inflammatory analgesics (diclofenac, indomethacin, ketoprofen, fervinac, loxoprofen, ibuprofen, flurubiprofen, thiaprofen, acemetacin, selegiline).
- non-steroidal anti-inflammatory analgesics include, for example, non-steroidal anti-inflammatory analgesics (diclofenac, indomethacin, ketoprofen, fervinac, loxoprofen, ibuprofen, flurubiprofen, thiaprofen, acemetacin, selegiline).
- Agents (dylthiazem, nicardipine, nilvadipine, metoprol, bisoprol, trandrapril, etc.), anti-Parkinson agents (pergolide, bromocryptin, selegiline, etc.), bronchial dilators (turobterol, isoproterenol, salbutamol, etc.), antiallergic agents (ketotiphen, ketotiphen, etc.) Loratazine, azerastin, terphenazine, cetilidine, acitazanolast, etc.), local anesthetics (lydocaine, dibucain, etc.), anesthetic analgesics (morphine, etc.
- absorption enhancer examples include isopropyl myristate, isopropyl palmitate, lauryl alcohol, hexyl laurate, myristyl alcohol, oleyl alcohol, isostearyl alcohol, octyldodecanol, benzyl alcohol, glycerin monooleate (GMO), and propylene.
- Glycerol monolaurate (PGML), polyoxyethylene sorbitan monooleate (Tween 80), polyoxyethylene sorbitan triste alert (Tween 65), polyoxyethylene sorbitan monoste alert (Tween 60), polyoxyethylene sorbitan monolaurate (Tween 20) , Lauric acid diethanolamide (LADA) and the like, and one of these may be used alone or in combination of two or more.
- the adsorbent examples include hygroscopic inorganic and / or organic substances, and more specifically, minerals such as talc, kaolin, and bentonite; fumed silica (Aerodil (registered trademark), etc.), hydrous silica. Silicon compounds such as zinc oxide, metal compounds such as dry aluminum hydroxide gel; weak acids such as lactic acid and acetic acid; sugars such as dextrin; polyvinylpyrrolidone, aminoalkylmethacrylate copolymers, crospovidone, carboxyvinyl polymers and butylmethacrylatemethylmethacrylate copolymers And the like, and one of them may be used alone or two or more thereof may be used in combination.
- the tackifier is blended mainly for the purpose of enhancing the adhesive strength of the pressure-sensitive adhesive.
- a tackifier include rosin-based resin, terpene-based resin, petroleum-based resin (aliphatic saturated hydrocarbon resin, etc.), phenol-based resin, and xylene-based resin, and one of them.
- the seeds may be used alone or in combination of two or more.
- the content thereof in the case of two or more types, the total content thereof
- it is more preferably 10 to 80% by mass and further preferably 20 to 60% by mass with respect to the total mass of the pressure-sensitive adhesive layer.
- the plasticizer is mainly blended for the purpose of adjusting the adhesive physical properties of the pressure-sensitive adhesive layer, the flow characteristics in the production of the pressure-sensitive adhesive layer, the transdermal absorption characteristics of the drug, and the like.
- plasticizers include silicone oils; paraffinic process oils such as liquid paraffin, petroleum oils such as naphthenic process oils and aromatic process oils; squalane, squalane; olive oil, camellia oil, castor oil, and tall.
- Vegetable oils such as oil and lacquer oil; dibasic acid esters such as dibutylphthalate and dioctylphthalate; liquid rubbers such as liquid polybutene and liquid isoprene rubber; diethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol and the like. One of them may be used alone or two or more of them may be used in combination.
- the plasticizer is preferably at least one selected from the group consisting of silicone oil, liquid paraffin, and liquid polybutene.
- the adhesive strength as a patch becomes better as the content (the total content of two or more kinds thereof). From this viewpoint, it is more preferably 5 to 60% by mass, and further preferably 7 to 40% by mass, based on the total mass of the pressure-sensitive adhesive layer.
- the solubilizer is formulated mainly for the purpose of promoting the dissolution of the drug.
- examples of such a solubilizer include organic acids such as acetic acid, aliphatic alcohols, and surfactants, and one of these may be used alone or in combination of two or more.
- the solubilizer is preferably at least one selected from the group consisting of organic acids and aliphatic alcohols.
- the filler is blended mainly for the purpose of adjusting the adhesive force and holding force of the pressure-sensitive adhesive layer.
- fillers include aluminum hydroxide, calcium carbonate, magnesium carbonate; silicates such as aluminum silicate and magnesium silicate; silicic acid, barium sulfate, calcium sulfate, calcium zincate, zinc oxide, and oxidation. Examples thereof include titanium, and one of these may be used alone or two or more thereof may be used in combination. According to the method of the present invention, since a patch having excellent holding power of the pressure-sensitive adhesive layer can be obtained without blending these fillers, it is not substantially blended from the viewpoint of maintaining the skin permeability of ropinirole.
- the blending amount of the filler (the total blending amount of two or more kinds thereof) is 1% by mass or less with respect to the total mass of the pressure-sensitive adhesive layer. It is preferably 0.1% by mass or less, and more preferably 0.1% by mass or less.
- a component that functions as a desalting agent for a pharmaceutically acceptable acid addition salt of ropinirole other than the following sodium salt of carbonic acid is used as long as the effect of the present invention is not impaired. It may be used further.
- a component include a metal ion-containing desalting agent and a basic nitrogen atom-containing desalting agent, and examples of the metal ion-containing desalting agent include strong bases such as sodium hydroxide and potassium hydroxide. One of these may be used alone or in combination of two or more.
- weak bases such as sodium acetate (including anhydrous sodium acetate), magnesium hydroxide, sodium citrate, and sodium lactate are also components that can function as desalting agents.
- the blending amount of the above components (2 types) in the above cases is preferably 1% by mass or less, more preferably 0.1% by mass or less, based on the total mass of the pressure-sensitive adhesive layer.
- the thickness of the pressure-sensitive adhesive layer according to the present invention is not particularly limited, but is, for example, per unit area of the pressure-sensitive adhesive layer.
- a thickness having a mass of 25 to 250 g / m 2 is preferable, a thickness of 50 to 200 g / m 2 is more preferable, and a thickness of 50 to 150 g / m 2 is further preferable, and the thickness is 50 to 120 g / m 2 .
- the thickness is even more preferable.
- the sticking area of the patch according to the present invention is preferably 1 to 300 cm 2 and more preferably 5 to 30 cm 2.
- the sodium salt of carbonic acid is contained in the pressure-sensitive adhesive layer containing the ropinirole and / or a pharmaceutically acceptable salt thereof and the pressure-sensitive adhesive.
- the "sodium salts of carbonic acid” in the present invention a salt consisting of acid and sodium selected from the group consisting of carbonate and bicarbonate, carbonate ions (CO 3 2-) or bicarbonate ions (HCO 3 - ) And sodium ion (Na + ) are bound to each other. More specific examples of the sodium salt of carbonic acid according to the present invention include sodium carbonate and sodium hydrogen carbonate, and one of them may be used alone or in combination of two or more.
- the content of the sodium salt of carbonic acid with respect to the total mass of the pressure-sensitive adhesive layer is 0.5 to 33% by mass. It is preferable to include it in the pressure-sensitive adhesive layer, more preferably 0.5 to 25% by mass, and further preferably 1 to 20% by mass.
- the content of the sodium salt of carbonic acid in the obtained pressure-sensitive adhesive layer is less than the above lower limit, the effect of improving the holding power of the pressure-sensitive adhesive layer tends not to be sufficiently exerted, while when it exceeds the above-mentioned upper limit, the effect of improving the holding power of the pressure-sensitive adhesive layer tends to be insufficient.
- the cohesive force of the pressure-sensitive adhesive layer tends to decrease.
- the content of the sodium salt of carbonic acid according to the present invention includes the following sodium salt-derived component of carbonic acid in addition to the content of the sodium salt of carbonic acid, the sodium salt of carbonic acid of the component is contained. Includes converted content.
- the content of the sodium salt of carbonic acid with respect to 1.0 mol of the ropinirole and / or its pharmaceutically acceptable salt in terms of ropinirole-free form is carbonic acid or carbonic acid.
- the pressure-sensitive adhesive layer contains 0.1 to 5.0 mol in terms of hydrogen (converted to CO 3 or HCO 3). From the viewpoint of the balance between maintaining sufficient skin permeability of ropinirole and improving the holding power of the pressure-sensitive adhesive layer, it is more preferable to add ropinirole to the pressure-sensitive adhesive layer in an amount of 0.5 to 5.0 mol. It is more preferable to add the content so as to be 1.0 to 5.0 mol.
- the pressure-sensitive adhesive layer in the pressure-sensitive adhesive layer so as to be 0.2 to 4.0 mol, preferably 0.5 to 3.0 mol. It is even more preferable to include it so as to be 1.0 to 2.0 mol, and it is even more preferable to include it so as to be 1.0 to 2.0 mol.
- the content of the sodium salt of carbonic acid in the obtained pressure-sensitive adhesive layer is less than the above lower limit, the skin permeability of ropinirole tends to decrease, while when it exceeds the above-mentioned upper limit, the pressure-sensitive adhesive layer is aggregated. The force tends to decrease.
- the sodium salt of carbon dioxide according to the present invention into the pressure-sensitive adhesive layer, for example, in the method for producing a ropinirole-containing patch, the ropinirole and / or a pharmaceutically acceptable salt thereof, sodium carbonate.
- a salt and the pressure-sensitive adhesive are mixed and the obtained pressure-sensitive adhesive layer composition is molded to obtain the pressure-sensitive adhesive layer.
- the method for producing the ropinirole-containing patch for example, the following production method can be mentioned.
- the ropinirole and / or its pharmaceutically acceptable salt, the sodium carbonate salt, and the pressure-sensitive adhesive, and if necessary, the other drug, the absorption enhancer, the additive, the solvent, and the like. are mixed according to a conventional method to obtain a uniform pressure-sensitive adhesive layer composition.
- the solvent include water, absolute ethanol, toluene, hexane, ethyl acetate, cyclohexane, heptane, butyl acetate, ethanol, methanol, xylene, isopropanol, and a mixture of two or more of these.
- the pressure-sensitive adhesive layer composition is spread on the surface of the support layer (usually on one surface), and if necessary, the solvent is dried and removed to form a pressure-sensitive adhesive layer, which is further required. It is cut into a desired shape according to the above.
- the method for producing the lopinilol-containing patch may further include a step of laminating the release liner on the surface of the pressure-sensitive adhesive layer opposite to the support layer, and the pressure-sensitive adhesive layer composition. Is first spread on one surface of the release liner to form the pressure-sensitive adhesive layer, and then the support layer is laminated on the surface of the pressure-sensitive adhesive layer opposite to the release liner, if necessary.
- a manufacturing method may be used in which a patch is obtained by cutting into a predetermined shape accordingly.
- the present invention includes the support layer and the pressure-sensitive adhesive layer as a patch with improved holding power of the pressure-sensitive adhesive layer, and the pressure-sensitive adhesive layer is ropinirole and / or its pharmaceutical. Also provided is a ropinirole-containing holding power improving patch containing the allowable salt, the sodium salt of carbon dioxide, and the pressure-sensitive adhesive.
- the support layer, the pressure-sensitive adhesive layer, ropinirole and / or a pharmaceutically acceptable salt thereof, a sodium carbonate of carbonate, and a pressure-sensitive adhesive thereof are preferred embodiments and contents thereof. Including the amount, it corresponds to the above-mentioned ropinirole-containing patch according to the method of the present invention.
- the ropinirol acid addition salt is contained in the pressure-sensitive adhesive layer as a raw material of the patch, as described above, the ropinirol acid addition salt is made of a sodium salt of carbonic acid, which is also a weak base, during the production process and / or after production. All or part of the adhesive layer of the above-mentioned preparation is desalted. Therefore, the pressure-sensitive adhesive layer in the ropinirol-containing holding power improving patch of the present invention obtained in this case contains at least a mixture of the ropinirol acid addition salt and the sodium salt of carbonic acid in addition to the pressure-sensitive adhesive.
- the mixture may be a ropinirol-free form and a component derived from the sodium salt of carbonic acid (derived from the sodium salt of carbonic acid) as a desalting reaction product of the ropinirol acid addition salt and the sodium salt of carbonic acid. Ingredient) may be contained.
- Examples of the sodium salt-derived component of carbonic acid include carbonic acid, carbonate ion, hydrogen carbonate, hydrogen carbonate ion, sodium ion, and sodium salt, and even if one of these is used alone, it is a combination of two or more. You may.
- the sodium salt may be, for example, hydrochloric acid, sulfuric acid, nitrate, phosphoric acid, or phosphite, although it depends on the acid of the ropinirol acid addition salt or, if necessary, the type of acid that may be contained in the pressure-sensitive adhesive layer. Examples thereof include sodium salts of acids such as acid, odorous acid, maleic acid, malic acid, ascorbic acid, tartaric acid and fumaric acid.
- a ropinirole-containing holding power improving patch it may be packaged (preferably enclosed) in a packaging container from the time of manufacture to the time of use.
- the packaging container is not particularly limited, and a container that can be normally used as a patch packaging container can be appropriately used.
- a plastic packaging bag or a plastic packaging bag on which a metal layer (for example, an aluminum layer) is formed can be used.
- a metal packaging bag (for example, an aluminum packaging bag) or the like is preferably used.
- the packaging body in which the ropinirole-containing holding power improving patch is packaged in the packaging container may further have an oxygen scavenging means.
- an oxygen scavenger using iron powder or an oxygen scavenger containing vitamin C as a main component more specifically, Ageless series (Mitsubishi Gas Chemicals Co., Ltd.)) enclosed in the packaging container. ), Pharmakeep series (manufactured by Mitsubishi Gas Chemical Co., Ltd.), etc.); Layer with oxygen scavenging function (more specifically, powders such as aluminum, zinc, manganese, copper, iron, hydrosulfite, activated carbon, etc. are mixed. Examples thereof include the packaging container provided with the layer and the like.
- ⁇ Skin Permeation Test (In Vitro Hairless Mouse Skin Permeation Test)> First, the skin of the body of the hairless mouse was peeled off to remove fat, and a patch was applied to the epidermis side by cutting into a size of 3.14 cm 2 and removing the release liner. This was set in a flow-through type Franz type permeation test cell so that the dermis side was in contact with the receptor solution, and the cell was filled with the receptor solution (PBS). Next, the receptor solution was sent at a flow rate of about 2.5 ml / hr while circulating warm circulating water around the outer periphery so that the receptor solution was kept at 32 ° C., and the receptor solution was sent every 4 hours for up to 24 hours. Was collected.
- the ropinirole skin permeation amount per unit area of the pressure-sensitive adhesive layer was calculated, and the cumulative ropinirole skin permeation amount from the start of application to 24 hours was defined as the 24 hr cumulative skin permeation amount ( ⁇ g / cm 2 ).
- the patch was cut into a size of 10 mm in width and 50 mm in length to prepare a test piece. Remove the release liner from each test piece to expose the adhesive layer surface, and place it in the center of one end of the stainless steel plate (made of SUS304), which is a test plate, so that the sticking area is 10 mm wide and 25 mm long, 1 kg.
- the roller was reciprocated once and crimped, and the test piece was attached to the test plate. Immediately after crimping with a roller, the test plate is hung so that the length direction of the test piece is in the vertical direction, a weight of 500 g is attached to the free end (lower end) of the test piece, and the temperature is 32 ° C.
- Example 1 First, 15.0 parts by mass of ropinilol hydrochloride, 4.2 parts by mass of sodium hydrogen carbonate (corresponding to 1.0 mol with respect to 1.0 mol of ropinirol hydrochloride), and a styrene-isobutylene-styrene block copolymer. 13.4 parts by mass of (SIS), 9.0 parts by mass of polyisobutylene (PIB), 40.4 parts by mass of alicyclic saturated hydrocarbon resin, and 18.0 parts by mass of liquid paraffin were added to an appropriate amount of solvent (water, methanol). , And toluene) and mixed to obtain a pressure-sensitive adhesive layer composition.
- SIS SIS
- PIB polyisobutylene
- alicyclic saturated hydrocarbon resin 18.0 parts by mass of liquid paraffin
- the obtained pressure-sensitive adhesive layer composition was spread on a release liner (polyester film subjected to a release treatment) to a thickness of 100 g / m 2 , and the solvent was dried and removed for adhesion.
- a drug layer was formed.
- a support layer (polyester film) was laminated on the surface of the obtained pressure-sensitive adhesive layer opposite to the release liner to obtain a patch laminated in the order of support layer / pressure-sensitive adhesive layer / release liner. ..
- Example 1 The patches obtained in Example 1 and Comparative Examples 1 and 2 were subjected to the above-mentioned skin permeation test and retention test, respectively.
- the results are shown in Table 1 below together with the composition of each pressure-sensitive adhesive layer composition (excluding the solvent).
- Table 1 the numerical values in parentheses in the column of ropinirole hydrochloride indicate the parts by mass in terms of ropinirole-free form (hereinafter, the same applies to Tables 2 to 3).
- the patch containing the sodium salt of carbonic acid according to the present invention in the pressure-sensitive adhesive layer for example, Example 1
- the patch containing sodium hydroxide The holding power is significantly improved as compared with the agent (for example, Comparative Example 1), and the improving effect is equivalent to that of the patch containing the above-mentioned calcium carbonate in the pressure-sensitive adhesive layer (for example, Comparative Example 2). Or was excellent.
- Example 2 Each patch was obtained in the same manner as in Example 1 except that the composition of the pressure-sensitive adhesive layer composition was adjusted to the composition shown in Table 2 below.
- the number of moles with respect to 1.0 mol of the ropinirole-free substance is 3.0 mol or Even if it is 5.0 mol (for example, Examples 2 to 3), as in the case of 1.0 mol (for example, Example 1), the pressure-sensitive adhesive while maintaining sufficient skin permeability of ropinirole. It was confirmed that the holding power of the layer could be improved.
- each patch was obtained in the same manner as in Example 1 except that the composition of the pressure-sensitive adhesive layer composition was adjusted to the composition shown in Table 3 below.
- each adhesive is as follows: MAS-811C: Acrylic adhesive with virtually no functional groups (manufactured by Cosmed Pharmaceutical Co., Ltd.), Bio-PSA-7-4202: Bio-PSA-7-4202, Silicone adhesive (manufactured by Dow Corning Toray Specialty Materials Co., Ltd.), Is.
- ropinirole and / or its pharmaceutically acceptable salt is pharmaceutically acceptable by further adding a sodium salt of carbonic acid to the pressure-sensitive adhesive layer containing ropinirole and / or its pharmaceutically acceptable salt and the pressure-sensitive adhesive. It was confirmed that the holding power of the pressure-sensitive adhesive layer can be sufficiently improved while maintaining sufficient skin permeability of the salt.
- ropinirole and / or its pharmaceutically acceptable salt and adhesive while maintaining sufficient skin permeability of ropinirole and / or its pharmaceutically acceptable salt.
- a method for improving the adhesive layer holding power of a ropinirole-containing patch which can improve the holding power of the pressure-sensitive adhesive layer containing and, and a ropinirole-containing holding power improving patch having excellent holding power of the pressure-sensitive adhesive layer. It becomes possible.
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Abstract
Description
炭酸のナトリウム塩を前記粘着剤層にさらに含有せしめる方法である。
炭酸のナトリウム塩を前記粘着剤層にさらに含有せしめる方法である。
先ず、ヘアレスマウス胴体部の皮膚を剥離して脂肪を除去し、表皮側に3.14cm2の大きさに切断して離型ライナーを除去した貼付剤を貼付した。これを真皮側がレセプター液に接するようにフロースルータイプのフランツ型透過試験セルにセットし、前記セルにレセプター溶液(PBS)を満たした。次いで、レセプター溶液が32℃に保温されるように、温めた循環水を外周部に循環させながら約2.5ml/hrの流速でレセプター溶液を送液し、4時間毎に24時間までレセプター溶液を採取した。採取したレセプター溶液中のロピニロール(ロピニロール塩酸塩)の濃度を高速液体クロマトグラフ法により測定し、次式:
ロピニロール皮膚透過量(μg/cm2)={レセプター溶液中のロピニロール濃度(μg/mL)×流量(mL)}/貼付剤面積(cm2)
により、粘着剤層の単位面積あたりにおけるロピニロール皮膚透過量を算出し、貼付開始から24時間までの累積ロピニロール皮膚透過量を24hr累積皮膚透過量(μg/cm2)とした。
先ず、貼付剤を幅10mm、長さ50mmの大きさに裁断して試験片を作製した。各試験片から離型ライナーを除去して粘着剤層面を露出させ、試験板であるステンレス板(SUS304製)の一端の中央に、貼付面積が幅10mm、長さ25mmとなるように置き、1kgのローラを1往復させて圧着して、前記試験片を試験板に貼付した。ローラで圧着後すぐに試験片の長さ方向が鉛直方向となるように試験板を垂下し、上記試験片の自由端(下端)に500gのおもりを取り付け、32℃、65%RHの環境下で、おもりを取り付けてから前記試験片が試験板から剥がれ落ちるまでの経過時間を測定した。当該保持力試験において、上記に示す以外の条件は、JIS規格(JIS-Z-0237:2009)に記載の方法に従って行った。
先ず、ロピニロール塩酸塩15.0質量部、炭酸水素ナトリウム4.2質量部(ロピニロール塩酸塩のモル数1.0モルに対して1.0モルに相当)、スチレン-イソプレン-スチレンブロック共重合体(SIS)13.4質量部、ポリイソブチレン(PIB)9.0質量部、脂環族飽和炭化水素樹脂40.4質量部、及び流動パラフィン18.0質量部を、適量の溶媒(水、メタノール、及びトルエン)に加えて混合し、粘着剤層組成物を得た。次いで、得られた粘着剤層組成物を離型ライナー(離型処理が施されたポリエステル製フィルム)上に100g/m2の厚さになるように展延し、溶媒を乾燥除去して粘着剤層を形成した。得られた粘着剤層の前記離型ライナーと反対の面上に支持体層(ポリエステル製フィルム)を積層し、支持体層/粘着剤層/離型ライナーの順に積層された貼付剤を得た。
粘着剤層組成物の組成を下記の表1に示す組成となるようにしたこと以外は実施例1と同様にして、各貼付剤を得た。
粘着剤層組成物の組成を下記の表2に示す組成となるようにしたこと以外は実施例1と同様にして、各貼付剤を得た。
粘着剤層組成物の組成を下記の表3に示す組成となるようにしたこと以外は実施例1と同様にして、各貼付剤を得た。表3中、各粘着剤は、それぞれ次のとおり:
MAS-811C:官能基を実質的に有さないアクリル系粘着剤(コスメディ製薬株式会社製)、
Bio-PSA-7-4202:Bio-PSA-7-4202、シリコーン系粘着剤(デュポン・東レ・スペシャルティ・マテリアル株式会社製)、
である。
Claims (7)
- 支持体層及び粘着剤層を備え、かつ、前記粘着剤層がロピニロール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種と粘着剤とを含有するロピニロール含有貼付剤において、前記粘着剤層の保持力を向上させる方法であり、
炭酸のナトリウム塩を前記粘着剤層にさらに含有せしめる、ロピニロール含有貼付剤の粘着剤層保持力向上方法。 - 前記粘着剤が、ゴム系粘着剤、カルボキシ基を有しないアクリル系粘着剤、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種である、請求項1に記載のロピニロール含有貼付剤の粘着剤層保持力向上方法。
- 前記炭酸のナトリウム塩が、炭酸ナトリウム及び炭酸水素ナト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、請求項1又は2に記載のロピニロール含有貼付剤の粘着剤層保持力向上方法。
- 前記炭酸のナトリウム塩を、前記粘着剤層の全質量に対する含有量が0.5~33質量%となるように前記粘着剤層に含有せしめる、請求項1~3のうちのいずれか一項に記載のロピニロール含有貼付剤の粘着剤層保持力向上方法。
- 前記炭酸のナトリウム塩を、前記ロピニロール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種のロピニロールフリー体換算での含有量1.0モルに対する含有量が0.1~5.0モルとなるように前記粘着剤層に含有せしめる、請求項1~4のうちのいずれか一項に記載のロピニロール含有貼付剤の粘着剤層保持力向上方法。
- 前記ロピニロール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種のロピニロールフリー体換算での含有量を前記粘着剤層の全質量に対して5~30質量%とする、請求項1~5のうちのいずれか一項に記載のロピニロール含有貼付剤の粘着剤層保持力向上方法。
- 支持体層及び粘着剤層を備え、かつ、前記粘着剤層がロピニロール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種と炭酸のナトリウム塩と粘着剤とを含有する、ロピニロール含有保持力改善貼付剤。
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KR1020227016613A KR20220084145A (ko) | 2019-11-26 | 2020-11-20 | 로피니롤 함유 첩부제의 점착제층 유지력 향상 방법, 및 로피니롤 함유 유지력 개선 첩부제 |
CN202080081516.7A CN114727986A (zh) | 2019-11-26 | 2020-11-20 | 含罗匹尼罗的贴附剂的粘合剂层保持力提升方法及含罗匹尼罗的保持力改善的贴附剂 |
EP20894038.7A EP4066829A4 (en) | 2019-11-26 | 2020-11-20 | METHOD FOR IMPROVING THE BONDING RESISTANCE OF ADHESIVE LAYER FOR TRANSDERMAL PATCH COMPRISING A ROPINIROLE, AND TRANSDERMAL PATCH WITH IMPROVED BONDING RESISTANCE COMPRISING A ROPINIROLE |
JP2021510258A JP7202450B2 (ja) | 2019-11-26 | 2020-11-20 | ロピニロール含有貼付剤の粘着剤層保持力向上方法、及びロピニロール含有保持力改善貼付剤 |
US17/779,885 US20230015492A1 (en) | 2019-11-26 | 2020-11-20 | Method for improving holding power of adhesive agent layer of ropinirole-containing patch, and ropinirole-containing patch with improved holding power |
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EP (1) | EP4066829A4 (ja) |
JP (1) | JP7202450B2 (ja) |
KR (1) | KR20220084145A (ja) |
CN (1) | CN114727986A (ja) |
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Citations (6)
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JP2008266175A (ja) * | 2007-04-18 | 2008-11-06 | Hisamitsu Pharmaceut Co Inc | 貼付剤及びその製造方法 |
WO2010134433A1 (ja) | 2009-05-21 | 2010-11-25 | 久光製薬株式会社 | 経皮吸収製剤 |
WO2012165254A1 (ja) | 2011-05-31 | 2012-12-06 | 久光製薬株式会社 | ロピニロール含有貼付剤及びその包装体 |
WO2012165253A1 (ja) | 2011-05-31 | 2012-12-06 | 久光製薬株式会社 | ロピニロール含有貼付剤及びその包装体 |
WO2018155390A1 (ja) | 2017-02-24 | 2018-08-30 | 久光製薬株式会社 | 貼付剤及びその包装体 |
JP2019525932A (ja) * | 2016-07-27 | 2019-09-12 | コリウム インターナショナル, インコーポレイテッド | 炭酸水素ナトリウムのin situ変換で促進されたアミン薬物の経皮送達 |
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JP2015151370A (ja) * | 2014-02-14 | 2015-08-24 | 日東電工株式会社 | 貼付製剤 |
KR101937073B1 (ko) | 2015-04-15 | 2019-01-09 | 히사미쓰 세이야꾸 가부시키가이샤 | 로피니롤 함유 첩부제 |
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2020
- 2020-11-20 EP EP20894038.7A patent/EP4066829A4/en active Pending
- 2020-11-20 JP JP2021510258A patent/JP7202450B2/ja active Active
- 2020-11-20 US US17/779,885 patent/US20230015492A1/en active Pending
- 2020-11-20 WO PCT/JP2020/043382 patent/WO2021106782A1/ja unknown
- 2020-11-20 CN CN202080081516.7A patent/CN114727986A/zh active Pending
- 2020-11-20 KR KR1020227016613A patent/KR20220084145A/ko not_active Application Discontinuation
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Patent Citations (6)
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JP2008266175A (ja) * | 2007-04-18 | 2008-11-06 | Hisamitsu Pharmaceut Co Inc | 貼付剤及びその製造方法 |
WO2010134433A1 (ja) | 2009-05-21 | 2010-11-25 | 久光製薬株式会社 | 経皮吸収製剤 |
WO2012165254A1 (ja) | 2011-05-31 | 2012-12-06 | 久光製薬株式会社 | ロピニロール含有貼付剤及びその包装体 |
WO2012165253A1 (ja) | 2011-05-31 | 2012-12-06 | 久光製薬株式会社 | ロピニロール含有貼付剤及びその包装体 |
JP2019525932A (ja) * | 2016-07-27 | 2019-09-12 | コリウム インターナショナル, インコーポレイテッド | 炭酸水素ナトリウムのin situ変換で促進されたアミン薬物の経皮送達 |
WO2018155390A1 (ja) | 2017-02-24 | 2018-08-30 | 久光製薬株式会社 | 貼付剤及びその包装体 |
Non-Patent Citations (1)
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US20230015492A1 (en) | 2023-01-19 |
TWI815062B (zh) | 2023-09-11 |
CN114727986A (zh) | 2022-07-08 |
KR20220084145A (ko) | 2022-06-21 |
JP7202450B2 (ja) | 2023-01-11 |
EP4066829A4 (en) | 2023-12-27 |
JPWO2021106782A1 (ja) | 2021-12-02 |
EP4066829A1 (en) | 2022-10-05 |
TW202131916A (zh) | 2021-09-01 |
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