JP3480984B2 - Medical patch - Google Patents

Description

Description: BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a medical patch, and more particularly to a medical patch having improved adhesiveness between a film-like support (excluding a foam) and a pressure-sensitive adhesive layer. Patch for medical use. Conventionally, medical patches have been used as a means for transdermally administering drugs. For example, such patches have been applied to natural rubber-based, synthetic rubber-based, acrylic-based adhesives and the like. Tape containing transdermally absorbable drug; plaster;
A cataplasm containing a water-soluble polymer such as gelatin, polyacrylate or polyvinyl alcohol and water as a medium and containing a transdermally absorbable drug in the medium is widely used. In these medical patches, it is known that when the pressure-sensitive adhesive layer is formed of a water-containing pressure-sensitive adhesive, it absorbs water evaporating from the skin and lowers skin irritation. However, the pressure-sensitive adhesive layer made of a water-containing pressure-sensitive adhesive hardly exerts a large anchoring effect on a film-like support and has insufficient adhesiveness, so that it is liable to cause interface peeling. there were. For this reason, there have been many cases where a nonwoven fabric is used as a support for a medical patch using a water-containing pressure-sensitive adhesive. However, in the nonwoven fabric support, the water content of the pressure-sensitive adhesive layer is easy to volatilize, and the change in the water content of the pressure-sensitive adhesive layer changes the pressure-sensitive adhesive properties and softness with time, and makes it difficult to control the dose of the drug containing a small amount. There was a problem. As a support for keeping the water content of the pressure-sensitive adhesive layer constant, a laminate in which a film or the like is laminated on a nonwoven fabric has been proposed (Japanese Patent Application Laid-Open No. 63-238017).
No.). However, such a laminated body becomes thick and the flexibility is reduced, so that the usability is deteriorated,
There is a problem that the drug may be dissolved or adsorbed on the nonwoven fabric, which adversely affects the stability and release of the drug. The present invention has been made in view of the above-mentioned drawbacks, and has as its object to provide a pressure-sensitive adhesive layer comprising a water-containing pressure-sensitive adhesive and a film-like support. An object of the present invention is to provide a medical patch having excellent adhesion between a pressure-sensitive adhesive layer and a film-like support by improving an anchoring force (excluding a foam) . The film-like support (excluding foam) used in the present invention has a flexibility and a self-supporting property to a patch, and has a pressure-sensitive adhesive layer. It is preferable to prevent the volatilization and migration of the drug, and as a material of such a film-like support, for example, polyethylene, polypropylene, polybutadiene, ethylene-vinyl acetate copolymer, ethylene-propylene copolymer, ethylene- Polyolefin-based polymers such as alkyl (meth) acrylate copolymers and polybutenes; polystyrene-based copolymers such as styrene-isoprene-styrene block copolymers, styrene-butadiene-styrene block copolymers and hydrogenated products thereof; Vinylidene chloride-based polymers such as polyvinylidene chloride and vinylidene chloride-ethylene copolymer A vinyl chloride (co) polymer such as polyvinyl chloride, vinyl chloride-ethylene copolymer, vinyl chloride-alkyl acrylate copolymer; silicone resin; polyfluoroethylene; polyester such as polyethylene terephthalate, polybutylene terephthalate; A polyurethane;
Polyamide and the like are preferable, and are preferably flexible and capable of following the movement of the human body. The film may be used as a single layer or as a laminate of two or more types. The thickness of the film support is 500 μm.
m or less, more preferably 40 to 200 μm. Further, on the pressure-sensitive adhesive layer forming surface of the film-like support,
If necessary, a corona discharge treatment, a chemical oxidation treatment, an ozone treatment, or the like may be performed. [0008] In the medical patch of the present invention, a primer layer is provided between the support and the pressure-sensitive adhesive layer. The primer layer is formed from a copolymer containing monoethylenically unsaturated radically polymerizable monomers containing amino groups and alkyl (meth) acrylate as constituents. The amino group-containing monoethylenically unsaturated radically polymerizable monomer is preferably represented by the general formula CH = CR ¹ -CO-A-R ² -NR ³ . In the formula, R ¹ , A, R ² and R ³ are as follows. R ¹ represents a hydrogen atom or an alkyl group, and is preferably a methyl group. A represents an oxygen atom or an imino group, preferably -NH-. R ² is a linear or branched alkylene, preferably an alkylene having 2 to 8 carbon atoms. R ³ represents a hydrogen atom or an organic residue having up to 22 carbon atoms, preferably an alkyl group, an aryl group or an aralkyl group. The monoethylenically unsaturated radical polymerizable monomer containing a tertiary amino group includes, for example, dimethylaminoethyl (meth) acrylate, diethylaminoethyl (meth) acrylate, dibutylaminoethyl (meth) acrylate, morpholinoethyl (Meth) acrylate, piperidinoethyl (meth) acrylate,
Dimethylamino-2-propyl (meth) acrylate,
Dimethylaminoneopentyl (meth) acrylate, dimethylaminoethyl (meth) acrylamide, diethylaminoethyl (meth) acrylamide, dibutylaminoethyl (meth) acrylamide, morpholinoethyl (meth) acrylamide, piperazinoethyl (meth) acrylamide, dimethylamino-2- Propyl (meth) acrylamide, dimethylamino neopentyl (meth) acrylamide and the like. The amount of the amino group-containing monoethylenically unsaturated radically polymerizable monomer in the above copolymer is as follows:
When the amount is reduced, the hydrophilicity is reduced and the adhesiveness with the water-containing adhesive is not improved. When the amount is increased, the high adhesiveness with the hydrophobic support is not obtained. Is preferred. The amino group of the monoethylenically unsaturated radically polymerizable monomer may be used as a quaternary ammonium salt with hydrochloric acid or the like, if necessary. The (meth) acrylic acid alkyl ester is preferably one having 1 to 18 carbon atoms.
Methyl (meth) acrylate, ethyl (meth) acrylate, n-butyl (meth) acrylate, n-hexyl (meth) acrylate, n-octyl (meth) acrylate,
Examples thereof include 2-ethylhexyl (meth) acrylate and n-dodecyl (meth) acrylate. Other copolymerizable monomers may be added to the above copolymer as long as the hydrophilicity and flexibility of the primer layer are not impaired. Examples of such a copolymerizable monomer include (meth) acrylamide, (meth) acrylic acid, hydroxyalkyl (meth) acrylate, polyalkylene glycol (meth) acrylate, ethylene, vinyl acetate, and vinyl propion. And N-vinyl-2-pyrrolidone. The content of these copolymerizable monomers is preferably less than 20% by weight in the copolymer constituting components. The above copolymer can be produced by a conventionally known method, for example, polymerization in water or an organic solvent, emulsion polymerization in an aqueous phase (a copolymer in an acid form has a water-soluble property). Lower). Since the copolymer is obtained as a solution or an aqueous dispersion, it is formed into a powder by, for example, spray drying. As the molecular weight of the copolymer decreases, the moldability deteriorates, and as the molecular weight increases, the processability decreases.
The weight average molecular weight is preferably 1 × 10 ^{4 to} 3 × 10 ⁶ . If necessary, a crosslinking agent such as a polyfunctional isocyanate compound, a polyfunctional epoxy compound, a melamine resin, or an organic or inorganic peroxide may be added to the copolymer. Further, if necessary, photocrosslinking or radiation crosslinking may be performed. As a method for forming the primer layer, for example, a method in which the above copolymer is dissolved in a solvent for volatility such as methanol, coated with a bar coater, a gravure coating machine or the like, and dried. . The thickness of the primer layer is preferably 0.1 to 5 μm because the effect of improving the anchoring property cannot be obtained even if the primer layer becomes thinner or thicker. The water-containing pressure-sensitive adhesive layer used in the present invention is formed from a water-containing pressure-sensitive adhesive which is a main component thereof. Examples of the water-containing pressure-sensitive adhesive include proteins such as gelatin; polysaccharides such as agar, mannan and alginic acid; cellulose derivatives such as carboxymethylcellulose and methylcellulose; poly (meth) acrylic acid (salt) and (meth) acrylic acid -(Meth) acrylic polymers such as (meth) acrylic acid alkyl ester copolymer, 2-hydroxyethyl (meth) acrylate and carboxyvinyl polymer; polyvinylpyrrolidone, polyvinyl alcohol, partially saponified polyvinyl alcohol, acetalized polyvinyl alcohol Polyvinyl alcohols such as polyethylene glycol, polypropylene glycol, ethylene-
Polyalkylene glycols such as propylene glycol copolymer; polyvinyl alkyl ethers such as polyvinyl methyl ether and polyvinyl ethyl ether; acrylamides such as polyacrylamide, dimethylaminoethyl acrylamide, diacetone acrylamide; polyvinyl acetamide, tragacanth gum, locust bean gum and the like And one or more of these gums are used. Further, a crosslinked product of these metal salts or a crosslinking agent may be used. The content of the water-containing pressure-sensitive adhesive in the water-containing pressure-sensitive adhesive layer is preferably 0.1 to 90% by weight, more preferably 5 to 70% by weight. In order to impart plasticity to the water-containing pressure-sensitive adhesive layer, glycerin, ethylene glycol, propylene glycol, 1,3-butanediol,
One or more polyhydric alcohols such as sorbitol, maltitol, and polyethylene glycol may be contained. The content of these is preferably 1 to 70% by weight,
More preferably, it is 5 to 60% by weight. When the water content of the water-containing pressure-sensitive adhesive layer is low, sufficient adhesive force cannot be obtained, and when the water content is high, it is difficult to maintain the shape of the adhesive. Is 1 to 50% by weight. In order to enhance the solubility of the drug, the water-containing pressure-sensitive adhesive layer is used to emulsify with a dissolving agent such as n-butyl stearate, isopropyl myristate, isopropyl palmitate, or water in the pressure-sensitive adhesive layer. May be added. Further, a tackifier, a stabilizer, an antioxidant, a filler, and the like may be added to the water-containing pressure-sensitive adhesive layer as needed. A medical patch can be obtained by adding a drug to the water-containing pressure-sensitive adhesive layer. The drug is not particularly limited, and examples thereof include anti-inflammatory analgesics such as methyl salicylate and indomethacin; anti-inflammatory agents; coronary vasodilators;
Tranquilizer; antihypertensive, antibiotic; antibacterial; antihistamine. The content of the drug in the water-containing pressure-sensitive adhesive layer is preferably from 1 to 30% by weight. As a method for forming the above-mentioned water-containing pressure-sensitive adhesive layer, a conventionally known method for producing a pressure-sensitive adhesive tape can be used. For example, a method in which a water-containing pressure-sensitive adhesive is directly applied to a primer layer on a support. A water-containing pressure-sensitive adhesive is once applied on a flat endless belt having a peelable surface and dried to form a pressure-sensitive adhesive layer, and then the pressure-sensitive adhesive layer is pressure-bonded onto a primer layer of a support on which a primer layer has been formed. Transfer method. When the water-containing pressure-sensitive adhesive layer has a small thickness, it cannot contain a required amount of a drug. When the water-containing pressure-sensitive adhesive layer has a large thickness, the drug contained in the pressure-sensitive adhesive layer in the vicinity of the support does not sufficiently diffuse. Since the utilization rate decreases, 30 to 1,000 μm
Is preferred. When the patch of the present invention is used as a medical patch, a release paper may be laminated on the pressure-sensitive adhesive layer to protect the pressure-sensitive adhesive layer. As such a release paper, a polyethylene terephthalate film, a polyethylene-coated high-quality paper, a polypropylene film, or the like, which is subjected to a silicon treatment, is used. Release paper thickness is 30
0 μm or less, more preferably 10 to 200 μm
m. In the medical patch of the present invention, the primer component is provided on the support, so that the hydrophobic component of the primer adheres to the support surface and the hydrophilic component adheres to the water-containing pressure-sensitive adhesive layer. Therefore, the support and the pressure-sensitive adhesive layer are firmly adhered to each other via the primer layer. Next, an embodiment of the present invention will be described. Example 1 A 50 μm-thick ethylene-vinyl acetate copolymer film support was coated on a dimethylaminoethyl methacrylate-methyl methacrylate-butyl methacrylate (weight ratio 1: 2: 1) copolymer (Rohm Pharma Co., Ltd.). A 10% by weight methanol solution of “EUDRAGIT E-100” manufactured by Co., Ltd. was applied to a thickness of 1 μm after drying, and dried at 60 ° C. for 3 minutes to form a primer layer.
Next, a water-containing adhesive is applied on the primer layer,
After drying, a water-containing pressure-sensitive adhesive layer having a thickness of 200 μm was formed to obtain a medical patch. As the water-containing pressure-sensitive adhesive, polyacrylate 10% by weight, water 50% by weight, glycerin 35
A mixture consisting of 5% by weight and 5% by weight of dried aluminum hydroxide gel was used. Example 2 Example 1 was repeated except that a 50 μm thick polyethylene film was used as a support.
In the same manner as in the above, a medical patch was prepared. Example 3 A medical patch was prepared in the same manner as in Example 1 except that a polyethylene terephthalate film having a thickness of 50 μm was used as a support. Example 4 As a water-containing pressure-sensitive adhesive, a mixture consisting of 20% by weight of polyvinylpyrrolidone, 10% by weight of ethylene glycol, 30% by weight of polyethylene glycol and 40% by weight of ethanol was used.
A medical patch was prepared in the same manner as in Example 1 except that the aqueous pressure-sensitive adhesive layer was formed by drying at 0 ° C. for 3 minutes. Example 5 As a water-containing adhesive, a mixture consisting of 8% by weight of N-vinylacetamide, 1% by weight of dried aluminum hydroxide gel, 40% by weight of glycerin, 1% by weight of tartaric acid and 50% by weight of water was used. Other than using it,
In the same manner as in Example 1, a medical patch was produced. Example 6 As a primer, a copolymer of trimethylammonium methacrylate-ethyl methacrylate-methyl methacrylate (weight ratio 0.2: 1: 2) ("EUDRAGIT" manufactured by Rohm Pharma) was used.
A medical patch was prepared in the same manner as in Example 1 except that a 10 wt% methanol solution of RS POL ") was used. Comparative Example 1 A medical patch was prepared in the same manner as in Example 1 except that no primer was used. Comparative Example 2 A medical patch was prepared in the same manner as in Example 2 except that no primer was used. Comparative Example 3 A medical patch was prepared in the same manner as in Example 3 except that no primer was used. Anchor Force Test of Patches The patches obtained in the above Examples and Comparative Examples were subjected to the following anchor force tests, and the results are shown in Table 1. JI
According to SZ0237, the medical patch is 15m wide
m, cut into a length of 100 mm to give a sample, and this sample was stuck to the center of a stainless steel plate with an acrylic adhesive double-sided tape adhered to the surface, left overnight, and then left at 180 ° constant speed peeling test (peeling speed 100 mm / min, temperature 35 ± 1 ° C., 50% relative humidity), and the peel strength was defined as the anchor force. [Table 1] The constitution of the medical patch of the present invention is as described above, and a monoethylenically unsaturated radical polymerization containing an amino group on a film-like support (excluding a foam). Since a primer layer composed of a copolymer of a functional monomer and an alkyl (meth) acrylate is provided,
While the adhesive strength between the support and the pressure-sensitive adhesive layer is significantly improved,
Demonstrate stable adhesive strength. Therefore, medical patches for various purposes can be easily designed by utilizing the low skin irritation property of the hydrous adhesive.

Claims (1)

(57) [Claim 1] A patch comprising a film-like support (excluding foam) provided with a water-containing pressure-sensitive adhesive layer on one surface, wherein the support and the pressure-sensitive adhesive A medical patch, characterized in that a primer layer comprising a copolymer of a monoethylenically unsaturated radically polymerizable monomer containing an amino group and an alkyl (meth) acrylate ester is provided between the first and second layers. Agent.