JP3400029B2 - Patch - Google Patents

Description

Detailed Description of the Invention

[0001]

The present invention relates to a patch for sticking to the skin surface, which is used for protecting the skin surface and the like, and a drug for transdermal absorption through the skin, which is continuously administered in vivo to treat or prevent various diseases. The present invention relates to a patch for performing.

[0002]

2. Description of the Related Art Non-woven fabrics and plastics are used as various patches such as dressings for protecting damaged parts of the skin surface and patches for administering a drug for treating or preventing diseases through the skin surface into the body. Various so-called adhesive tape-shaped patches in which a plaster is formed on one surface of a support such as a film have been proposed.

Usually, such a patch requires a certain amount of skin adhesive force in order to prevent the patch from falling off the skin surface to which it is first applied. The physical irritation during peeling and removing from the skin surface may cause pain and peeling of the stratum corneum during peeling, which may cause unnecessary irritation or damage to the skin surface and may cause pain to the user. is there.

Therefore, it is necessary to moderately reduce the skin adhesiveness in relation to the reduction of skin irritation, and the skin adhesive force is sacrificed to some extent, or the insufficient skin adhesive force is exceeded by an adhesive sheet prepared separately. I am supplementing with a coat.

On the other hand, other required characteristics of the adhesive patch include cohesiveness of the plaster layer (prevention of adhesive residue phenomenon at the time of peeling removal) and anchoring property between the support and the plaster layer (at the time of peeling removal). If there is a drug for transdermal absorption in the plaster layer, the stability of the drug over time (prevention of drug degradation) and For example, drug release (transdermal absorption). Therefore, it is necessary to study various items when developing a patch.

[0006]

DISCLOSURE OF THE INVENTION In the present invention, an acrylic polymer which has been found in the process of developing a patch having low skin irritation and which has been conventionally used for reducing skin irritation. A study was repeatedly conducted on a patch having a soft feeling in the plaster layer by containing a relatively large amount of an organic liquid component having a plasticizing effect.

As a result, a plaster layer having a good balance between skin adhesiveness and low skin irritation could be obtained. However, the support for laminating the plaster layers has a simple plastic film or a plastic film. In the perforated sheet of the laminated film with the perforated sheet, the content of components constituting the plaster layer varies, and in particular, the organic liquid component in the plaster layer blooms at the laminating interface between the support and the plaster layer. May not have sufficient anchoring power. As a result, it was found that there is a possibility that anchoring and destruction may occur when the patch is applied to the skin surface and then peeled off from the skin surface to cause an adhesive residue phenomenon.

[0008] Improving the anchoring property of such a patch has not been studied so far, but it is an extremely important issue when it is put to practical use.

[0009]

The inventors of the present invention have conducted extensive studies to solve the above-mentioned problems, and as a result, have found that an organic layer that exhibits a plasticizing effect on a plaster layer mainly composed of an acrylic polymer. When a relatively large amount of a liquid component was contained, it was found that a patch having extremely excellent anchoring property can be obtained by setting the laminated structure of the support and the plaster layer in a specific state, and the present invention was completed. Came to do.

That is, according to the present invention, an acrylic polymer obtained by polymerizing an alkyl (meth) acrylate as a main component monomer and an organic liquid component compatible with the acrylic polymer are mixed with the acrylic polymer. 2 for 100 parts by weight
A patch having a plaster layer comprising 5 to 200 parts by weight and subjected to a cross-linking treatment, which is formed on the side of a perforated sheet of a support which is a laminated structure of a non-perforated sheet and a perforated sheet. The sheet is made of a non-woven fabric or a woven fabric having a basis weight of 5 to 30 g / m ² , and the plaster layer is embedded inside the perforated sheet and reaches the laminated interface with the non-perforated sheet. Adhesive force to the Bakelite plate by the paste exposed from the inside of the perforated sheet by peeling off the laminated interface with the perforated sheet (pulling speed: 30
0 mm / min, 24 mm width) is 8 g or more.

Furthermore, the present invention provides a patch in which a transdermal drug (excluding bunitrolol and a pharmacologically acceptable salt of bunitrolol) is further contained in the plaster layer. .

The plaster layer in the patch of the present invention comprises an acrylic polymer obtained by polymerizing an alkyl (meth) acrylate ester as a main component monomer and an organic liquid compatible with the acrylic copolymer. It has a composition containing components and is obtained by crosslinking treatment. In the present invention, an acrylic polymer is used as the polymer constituting the plaster layer, but natural rubber, various synthetic rubbers, silicone-based polymers and other polymers and organic liquid components described below are used. The compatibility is not sufficient, a relatively large amount of the organic liquid component cannot be retained in the plaster layer, and the organic liquid component may be exuded from the plaster layer during storage of the patch, which is not preferable. Further, when the plaster layer is subjected to a crosslinking treatment, it is difficult to adjust the degree of crosslinking. Furthermore, when a transdermal drug is contained in the plaster layer, it is difficult to use because it has selectivity in drug release and stability depending on the drug species.

Examples of the (meth) acrylic acid alkyl ester as a main component monomer for obtaining the above acrylic polymer include butyl ester, pentyl ester, hexyl ester, heptyl ester, octyl ester, nonyl ester and decyl ester. , 40% by weight or more, preferably 50% by weight or more, as the main component monomer, a (meth) acrylic acid alkyl ester having an alkyl group having 4 to 18 carbon atoms, such as undecyl ester, undecyl ester, dodecyl ester, and tridecyl ester. The alkyl group may be linear or branched. These (meth) acrylic acid alkyl esters may be used alone or in combination of two or more during the polymerization. Further, if necessary, the alkyl group has 3 or less carbon atoms (meta).
A lower alkyl ester such as acrylic acid methyl ester, (meth) acrylic acid ethyl ester, or (meth) acrylic acid propyl ester is used as one of the amounts of the (meth) acrylic acid alkyl ester having an alkyl group having 4 to 18 carbon atoms. A copolymer may be used instead of the part.

Further, as the acrylic polymer used in the present invention, a copolymer obtained by copolymerizing the above-mentioned (meth) acrylic acid alkyl ester with a copolymerizable monomer can be used. As such a copolymerizable monomer, a polar monomer or a vinyl-based monomer is used.

Examples of polar copolymerizable monomers include carboxyl group-containing monomers such as (meth) acrylic acid, itaconic acid, maleic acid, maleic anhydride and crotonic acid, styrenesulfonic acid and allylsulfonic acid. , Sulfopropyl (meth) acrylate, (meth) acryloyloxynaphthalene sulfonic acid, sulfoxyl group-containing monomers such as acrylamidomethyl propane sulfonic acid, (meth) acrylic acid hydroxyethyl ester, (meth) acrylic acid hydroxypropyl ester, etc. Hydroxy group-containing monomer, (meth) acrylamide, dimethyl (meth) acrylamide, N-butylacrylamide, N-
Amido group-containing monomers such as methylol (meth) acrylamide and N-methylolpropane (meth) acrylamide, (meth) acrylic acid aminoethyl ester, (meth) acrylic acid dimethylaminoethyl ester, (meth) acrylic acid tert-butyl ester Alkylaminoalkyl group-containing monomers such as aminoethyl ester, (meth) acrylic acid methoxyethyl ester, (meth) acrylic acid alkoxyalkyl ester such as (meth) acrylic acid ethoxyethyl ester, (meth) acrylic acid tetrahydrofurfuryl Alkoxy groups such as esters, methoxyethylene glycol esters of (meth) acrylic acid, methoxydiethylene glycol esters of (meth) acrylic acid, and methoxypolyethylene glycol esters of (meth) acrylic acid Sid bond) containing (meth) acrylic acid esters, include (meth) acrylonitrile, these monomers can be copolymerized in combination one or two or more kinds.

Examples of vinyl monomers include vinyl acetates such as vinyl acetate and vinyl propionate, N-vinyl-2-pyrrolidone, methylvinylpyrrolidone, vinylpyridine, vinylpiperidone, vinylpyrimidine, vinylpiperazine and vinyl. Pyrazine, vinylpyrrole, vinylimidazole, vinylcaprolactam,
Examples thereof include vinyl monomers having a nitrogen atom-containing heterocyclic ring such as vinyl oxazole, and these monomers can be used alone or in combination of two or more kinds thereof to be copolymerized.

The polar monomer and the vinyl-based monomer may be used alone or in combination of two or more, and may be copolymerized with the above (meth) acrylic acid alkyl ester. These copolymerizable monomers may be used. Among them, a carboxyl group-containing monomer, a hydroxy group-containing monomer, which has a functional group serving as a cross-linking point when a cross-linking treatment is performed, and from the viewpoint of improving the cohesive force by increasing the glass transition temperature of the acrylic polymer, It is preferable to polymerize a monomer, an amide group-containing monomer, a (meth) acrylic acid alkoxyalkyl ester, and an alkoxy group (or an oxide bond in a side chain) -containing (meth) acrylic acid ester as a copolymerization component. Further, from the viewpoint of improving cohesive force and improving drug solubility when a drug is contained, it is preferable to copolymerize vinyl esters and vinyl monomers having a nitrogen atom-containing heterocycle.

The amount of the above-mentioned copolymerizable polar monomer and / or vinyl-based monomer is adjusted so that the cohesive force of the acrylic polymer-based plaster layer is adjusted or a drug is contained. Although it can be optionally set by adjusting the solubility of the above, the copolymerization amount is usually 50% by weight or less, preferably 2 to 40% by weight.

The organic liquid component contained in the plaster layer of the patch of the present invention together with the acrylic polymer exhibits a function of plasticizing the plaster layer by being compatible with the acrylic polymer. In the present invention, by plasticizing the plaster layer, it is possible to give a soft feeling to the skin when applied to the skin surface, and to further impart a suitable cohesive force by performing a crosslinking treatment, and after use It is possible to reduce skin irritation as much as possible at the time of peeling and removing.

In order to exert such an action, the content of the organic liquid component is 25 to 200 parts by weight, preferably 40 to 180 parts by weight, particularly preferably 60 to 100 parts by weight with respect to 100 parts by weight of the acrylic polymer. It is desirable to set it in the range of 180 parts by weight. If the content of the organic liquid component is too small, a sufficient plasticizing effect cannot be exerted, and reduction in skin irritation cannot be expected so much. On the other hand, if the content of the organic liquid component is too high, the plaster layer will be plasticized too much and the cohesive force will decrease. Shows a tendency to increase sex.

As such an organic liquid component, it is liquid at room temperature and is compatible with the above acrylic polymer, and specifically, ethylene glycol, diethylene glycol, triethylene glycol, propylene glycol, polyethylene glycol, Glycols such as polypropylene glycol, olive oil, castor oil, squalene, oils and fats such as lanolin, ethyl acetate, ethyl alcohol, dimethyldecyl sulfoxide, methyl octyl sulfoxide, dimethyl sulfoxide, dimethylformamide, dimethylacetamide, dimethyllaurylamide, dodecyl. Organic solvents such as pyrrolidone and isosorbitol, liquid surface-active agents, hydrocarbons such as liquid paraffin, ethoxylated stearyl alcohol, glycerin ester, fluorine Ester, isopropyl myristate, isotridecyl myristate, diethyl sebacate, ethyl laurate, N-methylpyrrolidone, ethyl oleate, oleic acid, diisopropyl adipate, isopropyl palmitate, octyl palmitate, 1,3-butanediol Examples thereof include organic compounds that are liquid at room temperature, and one or more of these are compounded and used. Among these, isopropyl myristate, diethyl sebacate, octyl palmitate, ethyl oleate, diethyl phthalate, diisopropyl adipate, from the viewpoint of reducing skin irritation and promoting percutaneous absorption when a drug is contained. It is preferable to use one or a combination of liquid substances such as fatty acid esters such as, fatty acids such as monocapric acid and oleic acid, and surfactants such as sorbitan monocaprylate.

Further, in the present invention, a crosslinking treatment is carried out in order to enhance the internal cohesive force of the plaster layer and to impart an appropriate soft feeling, skin adhesiveness and cohesiveness to the skin. That is, by applying the patch of the present invention to the skin surface by forming the plaster layer as a crosslinked structure, cohesive failure does not occur inside the plaster layer even if shear stress is applied from the outside, and moreover, skin adhesion It becomes a viscoelastic body having a creep property capable of exerting force.

Examples of such crosslinking treatment include physical crosslinking by irradiation with radiation such as ultraviolet irradiation or electron beam irradiation, polyisocyanate compound, organic peroxide, organic metal salt, metal alcoholate, metal chelate compound, melamine. Chemical crosslinking treatment using a crosslinking agent such as a derivative or a polyfunctional compound can be adopted. When radiation or organic peroxide is used among these crosslinking means, a decomposition reaction may occur depending on the drug species, and also highly reactive isocyanates, metal salts and organic compounds used for ordinary crosslinking reaction. With metal salts, the viscosity of the solution may increase after compounding, resulting in poor workability. It is also possible to preliminarily copolymerize a polyfunctional monomer such as diacrylate with an acrylic polymer as an adhesive, but depending on the type, the solution viscosity during coating may increase. , Handle with care.

Therefore, in the present invention, among these cross-linking agents, metal alcoholates made of titanium or aluminum, metal chelate compounds, and polyfunctional isocyanates (particularly trifunctional isocyanates) are preferable from the viewpoints of reactivity and handleability. Is. These cross-linking agents do not cause a thickening phenomenon of the solution until coating and drying, and are extremely excellent in workability. These cross-linking agents are usually blended in the range of about 0.05 to 5 parts by weight with respect to 100 parts by weight of the acrylic polymer. Even when the acrylic polymer constituting the plaster layer does not have a functional group that reacts with the cross-linking agent, by subjecting it to an alkali treatment or the like before the cross-linking treatment, a structure capable of cross-linking treatment is obtained. It can be modified.

If necessary, an antioxidant, various pigments, various fillers, a percutaneous absorption enhancer, a stabilizer, a drug dissolution aid, a drug dissolution inhibitor, etc. are added to the plaster layer having the above structure. 2-5 with 100 parts by weight of the acrylic polymer
It can be blended in the range of about 0 parts by weight.

In the patch of the present invention, the transdermal drug (excluding bunitrolol and a pharmacologically acceptable salt of bunitrolol) is contained in the adhesive layer in a dissolved or dispersed state. Thus, the patch can be used for the purpose of treating and / or preventing various diseases.

As the drug to be contained, specifically, corticosteroids, analgesic and anti-inflammatory agents, hypnotic sedatives, tranquilizers, antihypertensive agents, antihypertensive agents, antihypertensive diuretics, antibiotics, anesthetics, antibacterial agents, antifungal agents. , Vitamins, coronary vasodilators, antihistamines, antitussives, sex hormones, antidepressants, cerebral circulation improvers, antiemetics, antitumor agents, biomedicals, etc.
Two or more of these drugs may be used in combination, if desired.

The content of these drugs can be appropriately set depending on the type of drug and the purpose of administration, but it is usually contained in the plaster at about 1 to 40% by weight, preferably about 2 to 30% by weight. If the content is less than 1% by weight, it is not possible to expect a drug release in an amount effective for treatment or prevention, and if it exceeds 40% by weight, there is a limit to the treatment or prevention effect and it is economically disadvantageous.

The patch of the present invention comprises the above-mentioned plaster layer laminated and formed on one side of a support, and a non-porous sheet and a perforated sheet laminated structure is used as the support. The plaster layer is formed on the side of the perforated sheet of this laminate, and the plaster layer is embedded inside the perforated sheet and the embedded plaster reaches the lamination interface with the non-perforated sheet. I am trying. The degree of embedding of the plaster is such that the laminate interface between the non-perforated sheet and the perforated sheet in the support is forcibly peeled off as described in the examples below, and the bakelite by the plaster exposed from the inside of the perforated sheet. Adhesive force to plate (pull speed 300mm /
Min., 24 mm width) is preferably 5 g or more, and more preferably 8 g or more, from the viewpoint of practical anchorage. The non-perforated sheet means a sheet that is not subjected to an intentional perforation means such as a perforation treatment or a foaming treatment. It means a sheet having voids communicating with the front and back surfaces.

Examples of the material for the non-porous sheet include polyester, nylon, saran, polyethylene, polypropylene, polyvinyl chloride, polyvinylidene chloride, ethylene / ethyl acrylate copolymer, ethylene / vinyl acetate copolymer, ethylene / vinyl. Various plastics such as alcohol copolymer, polytetrafluoroethylene, surlyn, polyurethane, rayon, vinylon, acryl, acetate and triacetate, and metal foil can be used, and a single layer sheet or a laminated sheet made of these may be used. Of these non-perforated sheets, those in which the organic liquid component in the plaster layer and the drug for percutaneous absorption do not penetrate, that is, so-called strike-through is preferable, and a sheet made of polyester, polytetrafluoroethylene, polyethylene, polypropylene or the like is used. Is desirable.

On the other hand, as the perforated sheet, a sheet, paper, woven cloth, non-woven cloth, knitted cloth or the like obtained by perforating the non-perforated sheet or subjecting it to continuous foaming treatment can be used. Among these perforated sheets, in order to sufficiently embed the plaster layer, it is preferable to use a perforated sheet made of non-woven fabric or woven fabric, and in this case, the basis weight is 5 to 30 g /
m ^2, it is preferred from the viewpoint of improving anchoring property between the plaster layer in particular employed ones 8 to 20 g / m ^2.

The support used for the patch of the present invention is a laminate of the above-mentioned non-porous sheet and perforated sheet, and the lamination method is not particularly limited, and the extrusion molding method, thermocompression bonding method, polyester type A bonding method using a known adhesive such as an adhesive is adopted. The thickness of the resulting support is not particularly limited, considering the flexibility when the patch of the present invention is applied to the skin surface and the anchoring property of the plaster layer and the perforated sheet, the thickness of the non-porous sheet is 0.5 to 50 μm, preferably 1 to 25 μm, the thickness of the perforated sheet is 10 to 50
0 μm, preferably about 10 to 200 μm, and the total thickness of the support is 11 to 550 μm, preferably 15
It is set to about 225 μm. The thickness of the plaster layer is difficult to express because it is embedded in the perforated sheet, but the thickness of the plaster layer obtained by subtracting the thickness of the support from the total thickness of the patch is 30 to
The thickness is set to 200 μm, preferably 40 to 180 μm, and particularly preferably 50 to 150 μm.

The patch of the present invention forms the plaster layer on the side of the perforated sheet in such a support, and the formed plaster layer is embedded inside the perforated sheet and laminated with the non-perforated sheet. It reaches the interface (the surface of the adhesive layer when the non-perforated sheet and the perforated sheet are bonded together with an adhesive). As a method for forming the plaster layer on the surface of the support,
A method in which a solution of the plaster component is directly applied to the perforated sheet side of the support and dried (direct copying method), or a solution of the plaster component is previously applied to the separator surface and dried to form a plaster layer. Then, there is a method (transfer method) in which this is attached to the side of the perforated sheet of the support and pressure transfer is performed. When the cohesive force of the plaster layer is relatively small, the plaster layer is embedded inside the perforated sheet even by the transfer method, but in order to make sure that the plaster layer is embedded inside the perforated sheet to improve the anchoring force, It is preferable to use the copying method.

Furthermore, in the patch of the present invention, it is desirable that the surface of the plaster layer formed on the surface of the support is covered and protected with a known separator until it is used. It is preferable that the liquid components and the drug for transdermal absorption are sterilized and packed so as not to reduce volatilization.

[0035]

EFFECT OF THE INVENTION As described above, the patch of the present invention ensures that a plaster layer containing an acrylic polymer and an organic liquid component and subjected to a crosslinking treatment is embedded in a support having a specific laminated structure. Therefore, it has a good balance between skin adhesiveness (adhesion) and low skin irritation, and is also excellent in anchoring property between the support and the plaster layer.

[0036]

EXAMPLES Examples of the present invention will be shown below and will be described more specifically. In the following, parts and% mean parts by weight and% by weight.

Example 1 Acrylic polymer solution was prepared by copolymerizing 72 parts of acrylic acid 2-ethylhexyl ester, 25 parts of N-vinyl-2-pyrrolidone and 3 parts of acrylic acid in ethyl acetate. In this solution, 50 parts of isopropyl myristate was mixed with 50 parts of the acrylic polymer, and 0.5 part of aluminum tris (acetylacetonate) was added to 1% acetic acid with respect to 100 parts of the acrylic polymer. It was added as an ethyl solution, and ethyl acetate was further added to adjust the coating viscosity to obtain a plaster solution.

The resulting paste solution was dried on the nonwoven fabric side of a support obtained by extrusion-molding a polyester film (2 μm thickness) on a polyester nonwoven fabric (weight per unit area: 12 g / m ² ), and the thickness of the paste layer after drying was 80 μm. Thus coated and dried to form a crosslinked plaster layer.

Next, a polyester separator (thickness of 75 μm) was attached to the surface of the formed plaster layer to obtain the adhesive patch of the present invention.

Example 2 Using an acrylic polymer obtained by polymerizing 97 parts of 2-ethylhexyl acrylate and 3 parts of acrylic acid, 45 parts of isopropyl myristate were mixed with 55 parts of the acrylic polymer, Further, 0.5 part of aluminum tris (acetylacetonate) was mixed with 100 parts of the acrylic polymer to obtain a plaster solution.

The obtained plaster solution was applied onto a polyester separator (thickness: 75 μm) so that the thickness after drying was 80 μm, and dried to form a crosslinked plaster layer in advance.

Then, the obtained plaster layer was attached to the non-woven fabric side of the support used in Example 1 to obtain the adhesive patch of the present invention.

Example 3 A patch of the present invention was obtained in the same manner as in Example 1 except that 1 part of dipropoxy-bis (acetylacetonato) titanium as a crosslinking agent was blended.

Example 4 In Example 1, 40 parts of isopropyl myristate and 10 parts of metoprolol were mixed with 50 parts of the acrylic polymer, and 0.8 parts of aluminum tris was added to 100 parts of the acrylic polymer. A patch containing the drug of the present invention was obtained in the same manner as in Example 1 except that (acetylacetonate) was mixed to prepare a plaster solution.

Example 5 45 parts of the acrylic polymer prepared in Example 2 was mixed with 45 parts of isopropyl myristate and 10 parts of ketoprofen, and 0.3 part of 100 parts of the acrylic polymer was added. A patch containing the drug of the present invention was obtained in the same manner as in Example 2 except that a plaster solution was prepared by adding a trifunctional isocyanate (manufactured by Nippon Polyurethane Company, trade name Coronate HL).

Example 6 A patch of the present invention was obtained in the same manner as in Example 2, except that isopropyl myristate as the organic liquid component was changed to diethyl sebacate.

Example 7 A patch containing a drug of the present invention was obtained in the same manner as in Example 4, except that the amount of the acrylic polymer was 40 parts and the amount of isopropyl myristate was 50 parts. It was

Example 8 In Example 5, 30 parts of isopropyl myristate as an organic liquid component and 15 parts of diethyl sebacate were used.
Further, the amount of trifunctional isocyanate is 0.3
A patch containing the drug of the present invention was obtained in the same manner as in Example 5 except that the amount was changed to 5 parts.

Example 9 A patch of the present invention containing a drug was prepared in the same manner as in Example 4, except that 25 parts of isopropyl myristate and 15 parts of diethyl sebacate were further added as an organic liquid component in Example 4. I got an agent.

Comparative Example 1 The plaster solution obtained in Example 1 was applied onto a polyester separator (thickness: 75 μm) so that the thickness after drying was 80 μm, and dried to form a crosslinked plaster layer in advance. did.

Next, the obtained plaster layer was attached to the nonwoven fabric side of the support used in Example 1 to prepare a patch.

Comparative Example 2 In Comparative Example 1, 1 part was added to 100 parts of the acrylic polymer.
A patch was prepared in the same manner as in Comparative Example 1 except that part of titanium acetoacetonate was added.

Comparative Example 3 A patch was prepared in the same manner as in Comparative Example 1 except that diethyl sebacate was used instead of isopropyl myristate as the organic liquid component in Comparative Example 1.

Comparative Example 4 Example 1 was repeated except that 10 parts of metoprolol was mixed with 90 parts of the acrylic polymer prepared in Example 1 to prepare a plaster solution, and no crosslinking agent was added thereto. A patch containing a drug was prepared in the same manner as in (the plaster layer did not contain an organic liquid component and was not crosslinked).

Comparative Example 5 A patch containing a drug was prepared in the same manner as in Comparative Example 4 except that 15 parts of metoprolol was added to 85 parts of the acrylic polymer in Comparative Example 4 (the organic liquid component was contained in the plaster layer. Not contained and not crosslinked).

Comparative Example 6 The plaster solution obtained in Example 1 was applied onto a polyester support film (non-porous, 25 μm thick) so that the thickness after drying was 80 μm, and dried to crosslink the plaster. The layers were pre-formed.

Next, the obtained plaster layer was attached to one surface of a polyester separator (thickness: 75 μm) to prepare a patch.

Comparative Example 7 40 parts of isopropyl myristate and 10 parts of metoprolol were mixed with 50 parts of the acrylic polymer obtained in Example 1, and 0.8 part was added to 100 parts of the acrylic polymer. Aluminum tris (acetylacetonate) is mixed to form a paste solution, and this solution is dried on a polyester separator (75 μm thick) to a thickness of 80 μm.
m was applied and dried to form a crosslinked plaster layer in advance.

Then, the obtained plaster layer was attached to the non-woven fabric side of the support used in Example 1 to prepare a patch containing a drug.

Comparative Example 8 In Comparative Example 7, 50 parts of the acrylic polymer was added to 40 parts,
A patch containing a drug was prepared in the same manner as in Comparative Example 7 except that isopropyl myristate was changed to 50 parts.

Comparative Example 9 A patch containing a drug was prepared in the same manner as in Comparative Example 7 except that 40 parts of isopropyl myristate was changed to 40 parts of diethyl sebacate in Comparative Example 7.

Comparative Example 10 In Comparative Example 7, 25 parts of isopropyl myristate as an organic liquid component and 15 parts of diethyl sebacate were used.
A patch containing a drug was obtained in the same manner as in Comparative Example 7 except that parts were further compounded.

The following characteristics of the patches obtained in Examples and Comparative Examples were evaluated. The results are shown in Table 1.

<Skin patch test> The patches obtained in the examples and comparative examples were 5 cm ² (22.5 mm x 22.5 mm).
It was cut into pieces and attached to the skin of the human upper arm for 24 hours. In the case of a patch containing a drug for transdermal absorption, the amount transferred to the skin was calculated from the difference in the drug content before and after application. Further, when the patch was peeled from the skin surface, the remaining of the plaster layer on the skin surface (residual residue due to anchorage destruction) was visually observed.

<Confirmation Test for Embedding in Perforated Sheet> It is confirmed that the plaster layer is embedded inside the perforated sheet in the patch and reaches the laminating interface with the non-perforated sheet. Therefore, the separator was peeled from the patches obtained in Examples and Comparative Examples, and a 12 μm thick polyester film (without peeling treatment) was stuck and laminated instead.

Next, this was cut into a strip having a width of 24 mm, and only the non-perforated sheet was forcibly peeled off to expose the laminated interface with the perforated sheet.

The exposed perforated sheet surface of the adhesive patch cut into strips was applied to a bakelite plate, and the roller having a load of 300 g was used to make one reciprocating press contact and then 300 m in the 180 ° direction.
The patch was peeled off at a speed of m / min, and the adhesive force at that time was measured.

[0068]

[Table 1]

As is clear from the results shown in Table 1, the patch of the present invention has a suitable skin adhesive force and good anchoring property, and moreover, a patch containing a transdermal drug in a plaster layer. Has proved to be a useful patch with a high skin transfer rate. In particular, in the patches of Comparative Examples 1 to 3 and Comparative Examples 7 to 10, the plaster layer was not sufficiently embedded inside the perforated sheet,
There was a practical problem in terms of anchoring property and adhesive residue.

[Brief description of drawings]

FIG. 1 is a cross-sectional view showing an example of the patch of the present invention, which is an example in which a woven cloth is used as a perforated sheet of a support.

[Explanation of symbols]

1 Non-perforated sheet 2 perforated sheet 3 plaster layer

─────────────────────────────────────────────────── ─── Continuation of the front page (56) References JP-A-2-212419 (JP, A) JP-A-5-65224 (JP, A) (58) Fields investigated (Int.Cl. ⁷ , DB name) A61K 9/00-9/72 CA (STN) WPI (DIALOG)

Claims (4)

(57) [Claims] 1. An acrylic polymer obtained by polymerizing an alkyl (meth) acrylate as a main component monomer, and an organic liquid component compatible with the acrylic polymer ,
25 to 200 parts by weight per 100 parts by weight of acrylic polymer
A patch comprising a part, which is a cross-linked plaster layer, is formed on the side of a perforated sheet of a support which is a laminated structure of a non-perforated sheet and a perforated sheet, and the perforated sheet has a basis weight. Quantity 5
It is composed of a non-woven fabric or woven fabric of 30 g / m ² , and the plaster layer is embedded inside the perforated sheet and reaches the lamination interface with the non-perforated sheet, and the lamination interface between the non-perforated sheet and the perforated sheet. Adhesive force to the bakelite plate by the paste that is peeled off and exposed from the inside of the perforated sheet (pulling speed 300 mm / min,
A patch having a width of 24 mm) of 8 g or more. 2. An acrylic polymer comprising a (meth) acrylic acid alkyl ester having an alkyl group having 4 to 18 carbon atoms and a polar monomer and / or vinyl monomer copolymerizable therewith. The patch according to claim 1, which is a copolymer. 3. The patch according to claim 1, wherein the cross-linking treatment is carried out by adding a cross-linking agent consisting of one kind selected from metal alcoholates, metal chelates and polyfunctional isocyanates. 4. The patch according to claim 1, wherein the plaster layer further contains a drug for percutaneous absorption (excluding bunitrolol and a pharmacologically acceptable salt of bunitrolol).