TW201542249A - Bisoprolol-containing patch preparation - Google Patents

Abstract

The present invention pertains to a bisoprolol-containing patch preparation containing a support body and an adhesive layer laminated to one surface of the support body and containing an adhesive agent and free bisoprolol, the stress relaxation percentage of the adhesive layer being 20-90%, and the shear stress of the adhesive layer being 1.0-6.5 N/30 mm width. The bisoprolol-containing patch preparation has suppressed peeling during use, has superior skin adhesiveness, and suppresses skin irritation during delamination. As the adhesive agent, a rubber-based adhesive is preferable, and a polyisobutylene and/or styrene-isoprene-styrene block copolymer is more preferable.

Description

Attachment preparation containing bisoprolol

The present invention relates to a Pisoplot-containing patch preparation for the sustained absorption of Pisopproin into the living body through the skin surface.

Bisoppro, a highly selective antagonist of the sympathetic β 1 receptor, is used to improve essential hypertension, angina, and arrhythmia, with its fumarate as a lozenge Oral administration. However, when administered orally, there is a lack of pharmacological effects, and there are shortcomings such as sudden changes in blood concentration after administration, which are prone to side effects. In order to improve this phenomenon, in recent years, attention has been paid to transdermal drug preparations.

Such a transdermal administration preparation can, for example, avoid drug metabolism and various side effects caused by the first passage of the liver, and can continue to administer the drug for a long period of time. Among them, from the viewpoint of easy administration of the drug and strict control of the amount of the drug to be administered, the development of the patch containing the drug in the adhesive is in full swing. In this case, various developments of the percutaneous absorption preparation of Bisopoul have been made in recent years.

The transdermal administration preparation generally includes a support body composed of a woven fabric, a non-woven fabric, a plastic film, and the like, and an adhesive layer laminated on the support and containing a drug, and usually has a layer peeled off on the adhesive layer. The form of the liner is provided.

Recently, there have been proposals for the characteristics of transdermal drug preparations: the purpose of improving the comfort when attached to the skin, or reducing the skin irritation caused by the peeling of the stratum corneum during peeling, so that the adhesive layer contains a large amount of liquid components and is carried out. Cross-linking treatment to form a gel-like adhesive Agent layer (Patent Document 1). Such a gel-like adhesive layer can alleviate and disperse the stress applied to the skin surface at the time of peeling while maintaining a high adhesiveness to the skin surface to which it is attached. Therefore, these adhesive layers are preferably used as a transdermal absorption preparation in order to make physical irritations to the skin less and to cause peeling of the stratum corneum.

However, the percutaneous absorption preparation obtained by laminating the gel-like adhesive layer on the support has a tendency to lower the adhesion to the skin surface (sweat resistance) in the summer when the sweating is severe. In particular, there is a case where the skin adhesion force at the peripheral portion of the percutaneous absorption preparation is lowered, and the peripheral portion is easily picked up.

[Previous Technical Literature] [Patent Literature]

Patent Document 1: Japanese Patent Laid-Open No. Hei 6-23029

The present invention has been made in view of the above circumstances, and an object to be solved is to provide a Bisopprox-containing patch preparation which can suppress skin squeezing during use, has excellent skin adhesion, and can suppress skin irritation at the time of peeling.

The inventors of the present invention have intensively studied to solve the above problems, and as a result, have found that the adhesive layer containing Pisopoulo can satisfy the specific stress relaxation rate and specific shear stress, and can be relaxed and dispersed when attaching/detaching the skin surface. The stress is excellent in skin adhesion and the irritation at the time of peeling can be reduced, and the present invention has been completed.

That is, the present invention is as follows.

[1] A bisopprox-containing patch preparation comprising: a support; and a laminate The adhesive layer of the above-mentioned support body and containing the free type of Bisopoulol and the adhesive; wherein the stress relaxation rate of the adhesive layer is 20 to 90%, and the shear stress of the adhesive layer is 1.0 to 6.5. N/30mm wide.

[2] The Pisoppro-containing patch preparation according to the above [1], wherein the stress relaxation rate of the adhesive layer is 40 to 90%, and the shear stress of the adhesive layer is 1.0 to 4.0 N/ 30mm wide.

[3] The Pisoppro-containing patch preparation according to the above [1] or [2], wherein the adhesive contains a rubber-based adhesive.

[4] The Pisoppro-containing patch preparation according to the above [3], wherein the rubber-based adhesive is a polyisobutylene and/or a styrene-isoprene-styrene block copolymer.

[5] The Pisoppro-containing patch preparation according to the above [4], wherein the polyisobutylene has a polyisobutylene having a viscosity average molecular weight of 40,000 to 5,500,000.

[6] The Pisoppro-containing patch preparation according to the above [4], wherein the polyisobutylene contains a first polyisobutylene (a) having a viscosity average molecular weight of 1,800,000 to 5,500,000, and a viscosity average molecular weight of 40,000 to 85,000. The second polyisobutylene (b) and the blending ratio (a: b) of the first polyisobutylene (a) and the second polyisobutylene (b) are 1:0.1 to 1:3 by weight.

[7] The Pisoppro-containing patch preparation according to the above [4], wherein the styrene-isoprene-styrene block copolymer-based styrene ratio is less than 30% by weight.

[8] The Pisoppro-containing patch preparation according to the above [4] or [7], wherein the content of the styrene-isoprene-styrene block copolymer in the adhesive layer is 5 ~50% by weight.

The Bisopprox-containing patch preparation of the present invention has less peeling at the peripheral end portion of the preparation during attachment, can exhibit excellent skin adhesion, and can alleviate skin irritation caused by exfoliation of the stratum corneum during peeling. .

1‧‧‧Support

2‧‧‧Adhesive layer

3‧‧‧Release liner

10‧‧‧ Attachment (test piece)

21‧‧‧ Rubber board

31‧‧‧Clamping Department

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a schematic cross-sectional view showing an embodiment of a patch preparation of the present invention.

Fig. 2 is a plan view showing a state in which the release liner 3 is peeled off from the patch preparation shown in Fig. 1 and placed on a tensile tester.

Figure 3 is a cross-sectional view taken along line III-III of Figure 2;

Fig. 4 is a schematic plan view showing the attachment preparation of the tensile tester shown in Fig. 2 as it changes in the shearing direction.

Fig. 1 is a schematic cross-sectional view showing an embodiment of a Bisoppro-containing patch preparation (hereinafter referred to as "adhesive preparation") of the present invention. The patch preparation 10 shown in Fig. 1 includes a support 1 and an adhesive layer 2 laminated on one surface of the support 1 and a release liner 3 laminated on the adhesive layer 2. Further, the release liner 3 may not be provided. Adhesive layer 2 contains free type of bisopprox and an adhesive.

"Free type Bisopoul" means the free base of Pisopoul. In order to allow the free type of Pisopproin to be contained in the adhesive layer, the free type of Bisoppro can be directly blended, and the pharmaceutically acceptable salt of Bisopoulol can be administered only after the blending or the preparation of the patch preparation. Desalting treatment to form free type of soxoplo. That is, it is sufficient to contain the free type of bidoploc in the adhesive layer at the time of using the patch preparation. The pharmaceutically acceptable salt of Pisopoulol can be, for example, fumarate, hydrochloride or the like. Further, the free type of soxoplozole used in the present invention is a liquid drug at a normal temperature (for example, 25 ° C), and therefore, not only as a pharmacological action of Bisoppro, but also in the adhesive layer, There is a tendency to soften the adhesive layer by the plasticizing action of Bisoplot, which has the effect of improving the comfort when attached to the skin and reducing the skin irritation caused by peeling of the stratum corneum of the skin when peeling.

The free form of Bisoppro is appropriately set as needed, usually in adhesion The agent layer contains 0.5 to 40% by weight, preferably 0.5 to 30% by weight. If the content is more than 0.5% by weight, a therapeutically effective amount of drug release can be expected. If it is 40% by weight or less, a sufficient therapeutic effect can be exhibited, and it is advantageous to the economic level, and when it is 30% by weight or less, it is more advantageous to the economic level.

The adhesive is not particularly limited and may, for example, be an acrylic adhesive such as an acrylic polymer; a styrene-diene-styrene block copolymer (for example, a styrene-isoprene-styrene block copolymer, Rubber-based adhesives such as styrene-butadiene-styrene block copolymer, polyisoprene, polyisobutylene, polybutadiene; polyoxyxylene rubber, dimethyloxyalkylene, diphenyl a polyoxynoxy adhesive such as a phthalocyanine; a vinyl ether adhesive such as polyvinyl methyl ether, polyethylene diethyl ether or polyethylene isobutyl ether; a vinyl ester adhesive such as a vinyl acetate-ethylene copolymer; A carboxylic acid component such as dimethyl diformate, dimethyl isophthalate or dimethyl phthalate, or a polyester-based adhesive such as polyester composed of a polyol component such as ethylene glycol. Among them, a rubber-based adhesive is preferred.

Preferred rubber-based adhesives can be, for example, from polyisobutylene, polyisoprene, butyl rubber, styrene-isoprene-styrene block copolymer, and styrene-butadiene-styrene. Among the segment copolymers, at least one rubber-based adhesive containing a main component is selected. Among these, a polyisobutylene and/or a styrene-isoprene-styrene block copolymer is preferably used from the viewpoint of high drug stability and the ability to combine the necessary adhesion and cohesive force. Further, the "styrene-isoprene-styrene block copolymer" in the present invention encompasses a single triblock (polymerization of a polystyrene block at the two ends of the polyisoprene block) a block copolymer of a chain, or a mixture of a triblock and a diblock (a polymer chain of a single-end end of a polyisoprene block bonded to a single-end end of a polyisoprene block) The concept of the block copolymer is preferably a block copolymer composed of a mixture of a triblock and a diblock.

When the rubber-based adhesive is made of polyisobutylene, it may be contained alone. One type of polyisobutylene may contain two or more types of polyisobutylene having different molecular weights.

When a single polyisobutylene is contained alone, the polyisobutylene content in the adhesive layer is preferably 15 to 60% by weight, more preferably 15 to 55% by weight. If the polyisobutylene content is less than 15% by weight, it is difficult to impart the necessary internal cohesive force to the adhesive layer. On the other hand, if it exceeds 60% by weight, the adhesiveness and adhesion of the adhesive layer may be lowered. After that.

Further, in the case where one type of polyisobutylene is contained alone, the molecular weight of the polyisobutylene is not particularly limited, and the viscosity average molecular weight is preferably from 40,000 to 5,500,000, more preferably from 45,000 to 5,000,000. If the viscosity average molecular weight is less than 40,000, it is difficult to impart the necessary internal cohesive force to the adhesive layer. On the other hand, if it exceeds 5,500,000, the skin adhesion and viscosity of the adhesive layer may be lowered.

In order to easily balance the moderate cohesive force of the adhesive layer with moderate softness and skin adhesion, it is preferred to contain two or more types of polyisobutylene having different molecular weights. In the present specification, "two or more types of polyisobutylene having different molecular weights" means polyisobutylene which is a peak of a molecular weight distribution measured by a gel permeation chromatography (GPC) and which is present in two or more independent regions. Further, the molecular weight distribution peak of each polyisobutylene is approximately one. The "two or more polyisobutylenes having different molecular weights" may be, for example, two or more types of polyisobutylene having different viscosity average molecular weights.

Two or more types of polyisobutylene having different molecular weights are preferably, for example, a mixture of a first polyisobutylene and a second polyisobutylene having a molecular weight relatively smaller than that of the first polyisobutylene. The first polyisobutylene can impart moderate cohesive force to the adhesive layer, and the second polyisobutylene can impart moderate flexibility and skin adhesion to the adhesive layer. The molecular weight of the first polyisobutylene and the second polyisobutylene is not particularly limited, and the viscosity of the first polyisobutylene is preferably 1,800,000 to 5,500,000, in order to obtain good adhesion and sufficient release property with the besoprofen. Good quality 2,000,000~5,000,000, and the viscosity average molecular weight of the second polyisobutylene is better It is 40,000~85,000, and more preferably 45,000~65,000. If the viscosity average molecular weight of the first polyisobutylene is less than 1,800,000, there is a possibility that it is difficult to impart the necessary internal cohesive force to the adhesive layer. On the other hand, if it exceeds 5,500,000, the skin adhesion and adhesion of the adhesive layer may occur. Reduce the possibility. Further, if the viscosity average molecular weight of the second polyisobutylene is less than 40,000, there is a possibility that the adhesive layer may be sticky or contaminate the skin surface. On the other hand, if it exceeds 85,000, the skin of the adhesive layer may be present. Then the possibility of lowering the viscosity and viscosity. Further, the first and second polyisobutylene systems may be used in combination of two or more kinds in the respective molecular weight distribution ranges.

In addition, the term "viscosity average molecular weight" in the present specification means a flow time of 20 ° C from a capillary of an Ubbel-type viscometer, and a Schulz-Blaschke type (the following formula (1)) is used to calculate a viscosity index (J _{0 ).} (Staudinger index), the value obtained by the following formula (2) using the J ₀ value.

J ₀ =η _SP /c(1+0.31 η _SP )(cm ³ /g)(Schulz-Blaschke)...(1)

η _SP =t/t ₀ -1

t: flow time of the solution (determined by Hagenbach-Couette correction formula)

t ₀ : solvent flow time (determined by Hagenbach-Couette correction formula)

c: concentration of the solution (g/cm ³ )

J ₀ =3.06×10 ^-2 Mv ^0.65 (2)

Mv: viscosity average molecular weight

When the rubber-based adhesive is two or more types of polyisobutylene having different molecular weights, the total content of polyisobutylene in the adhesive layer is preferably 15 to 70% by weight, more preferably 30 to 65% by weight, and particularly preferably 50%. 65% by weight. If the total content of the polyisobutylene is less than 15% by weight, it is difficult to impart the necessary internal cohesive force to the adhesive layer. On the other hand, if it exceeds 70% by weight, the skin adhesion and adhesion of the adhesive layer may occur. The reduction in sexuality.

When the rubber-based adhesive is a type of two kinds of polyisobutylene having different molecular weights, the first polyisobutylene (a) and the second polyisobutylene (b) are used, and the first polyisobutylene (a) and the second polyisobutylene are used. The blending ratio (a:b) of (b) is preferably 1:0.1 to 1:3, more preferably 1:0.5 to 1:2, and more preferably 1:0.65 to 1:0.97 by weight ratio. The best system 1:0.77~1:0.97. In the two types of polyisobutylene, when the blending ratio of the second polyisobutylene (b) exceeds the above upper limit, the internal cohesive force of the adhesive layer may decrease, and if the lower limit is not exceeded, The skin with the adhesive layer is then reduced in strength.

When the rubber-based adhesive is a styrene-isoprene-styrene block copolymer, the styrene-isoprene-styrene block copolymer preferably has a styrene ratio of less than 30% by weight. . Further, those having a diblock ratio of from 0 to 80% by weight and more preferably from 10 to 50% by weight are preferred. The content of the styrene-isoprene-styrene block copolymer in the adhesive layer is preferably from 5 to 50% by weight, more preferably from 10 to 30% by weight. If the content of the styrene-isoprene-styrene block copolymer is less than 5% by weight, it is difficult to impart the necessary internal cohesive force to the adhesive layer. On the other hand, if it exceeds 50% by weight, The adhesion and adhesion of the skin with the adhesive layer is reduced.

Further, by changing the styrene ratio of the styrene-isoprene-styrene block copolymer and the content of the styrene-isoprene-styrene block copolymer in the adhesive layer, The required stress relaxation rate and shear stress are easily obtained.

For example, when the rubber-based adhesive is a styrene-isoprene-styrene block copolymer alone, it is preferably a styrene ratio of 10 to 24% by weight, and a more preferable styrene ratio of 15 to 24 % by weight. Further, when the styrene ratio of the styrene-isoprene-styrene block copolymer is 10% by weight or more and less than 15% by weight, the styrene-isoprene-benzene in the adhesive layer The ethylene block copolymer content is preferably 10 to 30% by weight, and when the styrene-isoprene-styrene block copolymer has a styrene ratio of 15 to 24% by weight, The content of the styrene-isoprene-styrene block copolymer in the adhesive layer is preferably from 17.5 to 22.5 wt%.

When the rubber-based adhesive is a styrene-isoprene-styrene block copolymer and a polyisobutylene, the styrene-isoprene-styrene block copolymer preferably has a styrene ratio of more than 24 % by weight and less than 30% by weight. Further, the total content of the styrene-isoprene-styrene block copolymer and the polyisobutylene in the adhesive layer is preferably from 5 to 50% by weight. Further, the blending ratio (I/m) of the polyisobutylene (I) to the styrene-isoprene-styrene block copolymer (m) is preferably 0.20 to 0.80, more preferably 0.30 to 0.70, The special system is 0.40~0.60.

When an acrylic adhesive is used as the adhesive, the acrylic adhesive is preferably a polymer having an alkyl (meth)acrylate as an essential monomer (hereinafter referred to as "acrylic polymer"). An acrylate-based adhesive contained in the composition. The acrylic polymerization system may, for example, be a monomer or a copolymer of an alkyl (meth)acrylate. Among them, the alkyl (meth) acrylate preferably has an alkyl carbon number of 4 to 12. The alkyl group may be a straight chain or a branched chain. The alkyl group may be, for example, butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, isooctyl, 2-ethylhexyl, decyl, isodecyl, decyl, undecyl. , dodecyl group, etc., among these, 2-ethylhexyl group is preferred. The alkyl (meth)acrylate may be used alone or in combination of two or more. The content of the acrylic polymer in the acrylate-based adhesive is preferably 50% by weight or more, and more preferably 60% by weight or more.

Further, the acrylic polymer may further contain a copolymer of the above (meth)acrylic acid alkyl ester and another monomer copolymerizable therewith. Such other single systems may, for example, be a monomer having a carboxyl group such as (meth)acrylic acid, itaconic acid, maleic acid or maleic anhydride; styrenesulfonic acid, allylsulfonic acid, (A) a monomer having a sulfo group such as sulfopropyl acrylate, (meth) propylene decyl naphthalenesulfonic acid or acrylamide methyl sulfonic acid; hydroxyethyl (meth) acrylate or hydroxypropyl (meth) acrylate a monomer having a hydroxyl group such as an ester; (meth) acrylamide, dimethyl (meth) acrylamide, N-butyl (meth) acrylamide, N-methylol (meth) propylene oxime a (meth)acrylic acid derivative having a mercaptoamine group such as an amine or a hydroxyethyl (meth) acrylamide; an amine ethyl (meth)acrylate; dimethylaminoethyl (meth)acrylate; Aminoalkyl (meth)acrylate such as tributylaminoethyl acrylate; methoxyethyl (meth)acrylate, ethoxyethyl (meth)acrylate, tetrahydro(meth)acrylate Alkyl (meth)acrylate such as oxime ester; methoxyethylene glycol (meth)acrylate, methoxydiethylene glycol (meth)acrylate, methoxypolyethylene (meth)acrylate Glycol ester, methoxypoly(meth)acrylate Alcohol alkyl ester of (meth)acrylic acid alkyl (meth) acrylate; (meth) acrylonitrile; vinyl acetate, vinyl propionate, vinyl pyrrolidone, methyl vinyl pyrrolidone, vinyl pyridine, vinyl Pyridone, vinylpyrimidine, vinylpiper , vinylpyrrole, vinylimidazole, vinyl caprolactam, ethylene Azole, ethylene A vinyl compound such as a phenyl compound or the like. The (meth)acrylic acid alkyl ester and the other monomer of the above-mentioned copolymer monomer unit may be used alone or in combination of two or more.

When an acrylic adhesive is used, the acrylic adhesive content in the adhesive layer is preferably 30 to 75% by weight, more preferably 35 to 70% by weight, in order to impart sufficient skin adhesion to the adhesive layer. Tejia is 40~65% by weight.

When the adhesive layer contains a rubber-based adhesive, in order to impart a moderate adhesiveness to the adhesive layer, for example, a rosin-based resin, a polyterpene resin, a coumarone-indene resin, or a petroleum resin is preferably used. A tackifier such as a terpene-phenol resin or a xylene resin. The adhesive may be used alone or in combination of two or more. The tackifier is preferably a petroleum resin. The petroleum resin can be, for example, an aliphatic (C5-based) petroleum resin, an aromatic (C9-based) petroleum resin, a copolymer-based (C5-C9-based) petroleum resin, and an aromatic (C9-based) petroleum. A resin, an alicyclic saturated hydrocarbon resin obtained by partial hydrogenation or complete hydrogenation, or the like.

The softening point of the adhesive is preferably from 90 to 150 ° C, more preferably from 95 to 145 ° C. If the softening point is 90 ° C ~ 150 ° C, it is easy to be compatible with the various components of the adhesive layer, it will be easy The tendency to mix evenly. Further, the softening point of the present invention is a value measured by a ring and ball method.

The content of the binder in the adhesive layer is preferably 10 to 55% by weight, more preferably 10 to 50% by weight, and particularly preferably 10 to 45% by weight. When the content of the adhesive is less than 10% by weight, the viscosity and the cohesive force may be insufficient. On the other hand, when the content exceeds 55% by weight, the adhesive layer may be hard and the skin adhesion tends to be lowered.

Further, in the pressure-sensitive adhesive layer, various liquid or paste-like organic components may be further added from the viewpoint of imparting comfort when attached to the skin. Here, the term "liquid or paste-like organic component" means that the viscosity at 25 ° C is 0.01 mPa. s~10000Pa. s range. The viscosity measurement system described above can be carried out using, for example, an E-type viscometer (manufactured by Tokyo Keiki Co., Ltd.: EMD-type cone-plate type rotary type). The liquid or paste-like organic component is not particularly limited, and is preferably one having a transdermal absorption promoting effect. The liquid or paste-like organic component can be, for example, glycols such as ethylene glycol, diethylene glycol, propylene glycol, triethylene glycol, polyethylene glycol, polypropylene glycol, etc.; glycerin; olive oil, castor oil, and horn shark Oils such as squalane and lanolin; hydrocarbons such as mobile paraffin; surfactants such as polyoxyethylene hardened castor oil; ethoxylated stearyl alcohol; oleic acid monoglyceride, octanoic acid monoglyceride, lauric acid single Monoglycerides such as glycerides; triglycerides such as diglycerides and caprylic triglycerides or mixtures thereof; ethyl laurate, isopropyl myristate, isotridecyl myristate Fatty acid alkyl esters such as octyl palmitate, isopropyl palmitate, ethyl oleate, diisopropyl adipate, diethyl sebacate; fatty acids such as oleic acid and caprylic acid; 1-dodecanol Long-chain alcohols such as 1-tetradecanol, 1-hexadecanol, 2-hexyl-1-nonanol, 2-octyl-1-dodecanol, 2-hexyl-1-tetradecanol; N-A Pyrrolidone; 1,3-butanediol and the like. The liquid or paste-like organic component is preferably a fatty acid alkyl ester or a long-chain alcohol from the viewpoint of promoting the absorption of the Pisopoul and the greater contribution of the Bisopoulol to the improvement of the solubility of the adhesive layer. The liquid component or the paste-like organic component may be used singly or in combination of two or more.

When a liquid or paste-like organic component is used in combination with a fatty acid alkyl ester and a long-chain alcohol, it is preferred from the viewpoint of further enhancing the penetration and solubility of Bisopoulone and the skin adhesion property of the adhesive layer. The blending ratio (c:d) of the fatty acid alkyl ester (c) to the long-chain alcohol (d) is preferably 1:0.01 to 1:2, more preferably 1:0.01 to 1:1.5. Among the two organic components, if the weight ratio (d/c) of the long-chain alcohol (d) to the fatty acid alkyl ester (c) is 0.01 to 2, it is found that the solubility of the besoprox can be sufficiently improved. And the skin adhesion of the adhesive layer.

When the adhesive layer contains a liquid or paste-like organic component, in order to prevent the organic component from oozing out from the adhesive layer, the content of the organic component in the adhesive layer is preferably 5 to 70% by weight, more preferably 10 ~65% by weight, particularly preferably 20 to 50% by weight.

Further, in the patch preparation of the present invention, it is removed before the adhesion of the adhesive layer is lifted, and the adhesive layer may contain a suitable filler as needed. The filler is not particularly limited and may, for example, be inorganic fine particles such as cerium oxide, titanium oxide, zinc oxide, magnesium oxide, iron oxide, aluminum hydroxide, talc, kaolin, bentonite, barium sulfate or calcium carbonate; Organic fine particles such as carbon black, polyvinylpyrrolidone, polyester, polyolefin, polyurethane, polyamide, cellulose, acrylic resin; and polyester, polyolefin, polyurethane, poly Fibers such as amines, celluloses, acrylics, and glass.

Further, if necessary, the upper patch or the like may be attached to cover a part or the whole of the patch preparation of the present invention to reinforce the skin adhesion, and the adhesion to the skin may be enhanced.

Further, the adhesive may be subjected to physical crosslinking by radiation such as ultraviolet irradiation or electron beam irradiation, or an isocyanate compound such as a trifunctional isocyanate, an organic peroxide, an organic metal salt or a metal alcohol. Chemistry of various cross-linking agents such as salts, metal chelate compounds, and polyfunctional compounds (polyfunctional external cross-linking agents, difunctional internal cross-linking monomers such as dimethacrylate) Sexual cross-linking treatment.

The thickness of the adhesive layer is preferably 10 to 300 μm, more preferably 10 to 250 μm, and particularly preferably 15 to 250 μm. When the adhesive layer contains a liquid or paste-like organic component, there is a possibility that the organic component or the like is oozing out from the peripheral edge portion of the patch before use or the cut marks formed on the release liner. However, by setting the content of the liquid or paste-like organic component of the adhesive layer and the thickness of the adhesive layer within the above range, it is possible to suppress formation from the peripheral portion of the patch before use or the release liner. The cut marks exude the organic component and the like.

The support is not particularly limited, and a plastic film, a nonwoven fabric, a paper, a woven fabric, a woven fabric, a metal foil, or the like can be used. Further, a metal vapor deposition may be applied to the support.

The material of the plastic film is not particularly limited, and may be, for example, polyvinyl chloride; ethylene, propylene, vinyl acetate, acrylic acid, acrylate, methacrylic acid, methacrylic acid ester, acrylonitrile, styrene, dichloroethylene, etc. Monomer, copolymer with other monomers; olefin polymer such as polyethylene, polypropylene, ethylene-vinyl acetate copolymer; polyester system such as polyethylene terephthalate (PET) or polyether polyester Polymer; polyamine polymer such as polyether polyamine block copolymer.

The thickness of the support is, for example, 5 to 500 μm, preferably 10 to 200 μm.

In the patch preparation of the present invention, a release liner may be further provided on the back surface of the adhesive layer on the support side (the attachment surface to the skin). The release liner is covered with an adhesive layer for protection until a patch preparation is used.

The release liner is not particularly limited, and may be, for example, a plastic film (for example, a polyester film such as a PET film, a polyimide film, a polypropylene film, a polyethylene film, a polycarbonate film, etc.); Metal vapor-deposited plastic film on metallization; Japanese paper, machine paper, kraft paper, cellophane, high-grade paper, etc.; non-woven fabric, cloth and other fibers Material; metal foil. Further, a laminated film of a plastic film and a paper, a laminated film of a plastic film and a metal foil, or the like may be used as a release liner.

There are many types of industrial products, and most of them are commercially available for the appropriate thickness of the attached preparation. In order to easily select the required quality, the release liner is preferably a plastic film, a better polyester film, and a special system. PET film. The thickness of the release liner is not particularly limited, and is, for example, 10 to 200 μm, preferably 25 to 150 μm.

The release liner may be easily peeled off from the adhesive layer to form a cut mark, and a light release layer which has been subjected to release treatment may be formed on one side of the adhesive layer.

The stress relaxation rate and shear stress of the present invention are calculated in accordance with the following measurement methods. As shown in Fig. 2, two sheets of rubber sheets 21 (width 100 mm × length 30 mm) were fixed to the upper and lower jig portions 31 of a tensile tester (EZ-S, manufactured by SHIMADZU Co., Ltd.), and the interval between the two sheets of rubber sheets 21 was adjusted. A parallel state of 0.1 mm. The patch preparation (test piece) which was cut into a width of 30 mm × a length of 12 mm was placed in a longitudinal direction across two sheets of plastic wood, and was attached in parallel with a 2 kg roller, and placed at 23 ° C and a relative humidity of 65%. minute. Then, the shearing direction toward the adhesive layer was measured, and the starting point was deformed to a length of 0.5 mm (0.1 mm + 0.5 mm) at a speed of 1 mm/min, and the stress was set as the shear stress of the present invention (F1). ). Next, the state at the time of deformation from the starting point to the length of 0.5 mm (0.1 mm + 0.5 mm) was measured, and the stress (F2) after holding for 120 seconds was measured. The stress relaxation rate was calculated according to the following formula.

Stress relaxation rate (%) = [1 - (stress (F2) after holding for 120 seconds after 0.5 mm deformation) / (stress (F1) at 0.5 mm deformation)] × 100

The preferred shear stress of the present invention is 1.0 to 6.5 N/30 mm wide, more preferably 1.0 to 4.0 N/30 mm wide, and particularly preferably 1.5 to 3.0 N/30 mm wide. By setting the shear stress to 1.0 to 6.5 N/30 mm wide, the adhesive layer can be easily deformed and the adhesive layer is comfortable. Enhancement has the effect of suppressing the tightness in the attachment and reducing the skin irritation. Further, when the shear stress exceeds 6.5 N/30 mm width, since the adhesive layer is not easily deformed, good traceability to the skin surface cannot be obtained.

The preferred stress relaxation rate of the present invention is 20 to 90%, more preferably 40 to 90%, and particularly preferably 50 to 80%. By setting the stress relaxation ratio to 20 to 90%, even if the adhesive layer is deformed, stress relaxation can be quickly caused, and the stress tends to be quickly alleviated. Therefore, even if it is attached to the skin surface, it is effective in reducing the stress applied to the patch preparation by the skin surface movement. Therefore, during the attachment period, the peripheral end portion of the preparation does not rise, and excellent skin adhesion can be exhibited. Further, since the stress relaxation rate exceeds 90%, the adhesive layer is excessively soft, and there is a tendency that residual glue tends to occur at the time of peeling.

The stress relaxation rate and the shear stress are combined with the adhesive component contained in the adhesive layer, the optional adhesive agent, the liquid or the paste-like organic component, and the like, by increasing or decreasing the content of each component, or The thickness of the adhesive layer can be increased or decreased as needed, and can be set within the above range. For example, when the rubber-based adhesive is the first polyisobutylene (a) having a different viscosity average molecular weight and the second polyisobutylene (b), the first polyisobutylene (a) and the second polyisobutylene in the adhesive layer are used. The total content of (b) is preferably 15 to 70% by weight, more preferably 30 to 65% by weight, and particularly preferably 50 to 65% by weight. The blending weight ratio (a:b) of the first polyisobutylene (a) to the second polyisobutylene (b) is preferably 1:0.1 to 1:3, more preferably 1:0.5 to 1:2. 1:0.65~1:0.97, the best system 1:0.77~1:0.97. The thickness of the adhesive layer is preferably 10 to 300 μm, more preferably 10 to 250 μm, and particularly preferably 15 to 250 μm. Accordingly, when the rubber-based adhesive is the first polyisobutylene (a) and the second polyisobutylene (b), the total of the components (a) and (b) in the adhesive layer is mainly used. The content and the blending weight ratio of the component (a) to the component (b) are set within the above preferred range, and the stress relaxation rate and the shear stress can be set within the above preferred range, and the values can be increased or decreased. .

[Examples]

In the following, the embodiments are specifically described, but the examples are not intended to limit the invention. In addition, the abbreviations used in the examples and the like are as follows.

BSP: Free Bisopoulo

PIB1: polyisobutylene viscosity average molecular weight 4,000,000

PIB2: polyisobutylene viscosity average molecular weight 400,000

PIB3: polyisobutylene viscosity average molecular weight 55,000

SIS1: styrene-isoprene-styrene block copolymer (styrene ratio 25% by weight, diblock ratio 17% by weight)

SIS2: styrene-isoprene-styrene block copolymer (styrene ratio 25% by weight, diblock ratio 42% by weight)

SIS3: styrene-isoprene-styrene block copolymer (styrene ratio 22% by weight, diblock ratio 15% by weight)

SIS4: styrene-isoprene-styrene block copolymer (styrene ratio 14% by weight, diblock ratio 26% by weight)

TF1: tackifier alicyclic saturated hydrocarbon resin softening point 100 ° C

TF2: tackifier alicyclic saturated hydrocarbon resin softening point 140 ° C

Mobile paraffin: mobile paraffin

IPM: Isopropyl myristate

ODO: 2-octyl-1-dodecanol

(Examples 1 to 8 and Comparative Examples 1 to 8)

A viscous toluene solution of the adhesive composition was prepared according to the blending ratios shown in Table 1, and the obtained solution was placed on a polyethylene terephthalate (PET) liner (thickness 75 μm) subjected to polysilicon stripping treatment. The coating was applied so as to have a dry thickness as shown in Table 2, and dried at 100 ° C for 5 minutes in a hot air circulation dryer to form an adhesive layer. The adhesive layer was bonded to a non-woven fabric side of a PET film having a thickness of 2 μm and a PET nonwoven fabric of 12 g/m ^{2 to} obtain a sheet-like patch preparation. The stress relaxation rate and shear stress of the obtained patch preparation were measured in accordance with the above methods, and the results are shown in Table 2. Further, the blending ratio of each component described in Table 1 is a ratio (% by weight) to the entire adhesive composition.

(1) Adhesion

The adhesion of the patch preparations obtained in Examples 1 to 8 and Comparative Examples 1 to 8 was measured in accordance with the following method. The surface of the stainless steel plate (SUS304 steel plate specified in JIS G4305) was first uniformly polished by using No. 360 water-resistant abrasive paper, and then washed with a cloth impregnated with ethyl acetate. The test preparation containing Pisoppro was cut, and a test piece having a width of 24 mm and a length of 50 mm was prepared. The adhesive surface of the test piece after the release liner was applied to a surface polished and washed with a stainless steel plate using a 2 kg rubber roller (rubber roller passing speed of 300 mm/min, and the number of passes twice). The stainless steel sheet to which the test piece was attached was allowed to stand in an environment of 23 ± 2 ° C and 65 ± 10% R. H. for 30 minutes. The test piece was peeled from the stainless steel plate by about 5 mm at one end, and folded back at an angle of 180°, and an auxiliary paper (width 30 mm) was attached. Using a tensile tester, clamp the end of the auxiliary paper to the upper hook and clamp the stainless steel plate to the lower hook at 23 ± 2 ° C. In a 65±10% R.H. environment, the test piece was continuously torn at a speed of 300 mm/min in the direction of 180°, and the adhesion was measured. The results are shown in Table 3.

(2) Attachment

From the above adhesion, the adhesion was determined according to the following criteria.

If the adhesive force is weaker than 0.1 N/24 mm width, the peeling is likely to occur at the time of attachment, and thus the judgment is "poor (x)."

If the adhesion is more than 0.1 N/24 mm wide and less than 2.0 N/24 mm wide, there is no possibility of skin irritation at the time of peeling because of the moderate adhesion, so it is judged that "adhesiveness is good (○)" .

If the adhesive force is 2.0 N/24 mm or more and less than 3.0 N/24 mm wide, it is excellent in adhesion because it has excellent skin adhesion and there is no possibility of skin irritation during peeling. ◎)".

When the adhesive force is 3.0 N/24 mm or more and less than 3.9 N/24 mm wide, there is a possibility that skin irritation may occur at the time of peeling, and thus it is judged that "adhesiveness is acceptable (?)".

If the adhesive force is 3.9 N/24 mm or more, the skin is irritated during peeling because of the strong adhesive force, and thus it is judged that "adhesiveness is poor (x)".

The results are shown in Table 3.

(3) The flexibility of the adhesive layer

The stretchability of the adhesive layer was determined from the stress relaxation rate in accordance with the following criteria.

When the stress relaxation rate is less than 20%, the tracking property to the skin surface is insufficient, and there is a possibility that a feeling of tightness or peeling may occur at the time of attachment, and thus it is judged that "the stretchability is poor (x)".

If the stress relaxation rate is more than 20% and less than 90%, it is moderately traceable. When the attachment is not caused, the uncomfortable feeling and the peripheral end portion are lifted, and it is determined that "the stretchability is good (○)".

When the stress relaxation ratio exceeds 90%, the adhesive layer is excessively soft, and there is a possibility that residual glue may occur at the time of peeling, and thus it is judged that "the stretchability is poor (x)".

The results are shown in Table 3.

(4) Whether the transfer material is present

In the above (1) adhesion test, the surface of the stainless steel plate after the adhesion was measured was visually observed, and the presence or absence of the transfer material on the surface of the stainless steel plate was evaluated according to the following criteria. The results are shown in Table 3.

○: The transfer product did not exist.

△: A part of the transfer material was present.

×: There are all transfer materials in the attached place.

It is known from Table 3 that in Tables 2 to 8 in which the shear stress and the stress relaxation rate are within an appropriate range, the adhesion and the stretchability are good, and there is no presence on the adherend after peeling. The transfer material exhibited good peelability. Further, in Examples 1 to 4 and 7, since the stress relaxation rate is sufficiently high, when applied to the skin surface, the effect of stress applied to the patch preparation by the skin surface action is reduced, and it is presumed that the preparation can be more effectively prevented. The peripheral end is picked up.

On the other hand, in Table 2, Comparative Examples 1 to 3 in which the shear stress was less than the lower limit of the appropriate range were exhibited, and the adhesion was markedly low and the adhesion was poor. Further, since the adhesive layer component could not be held in the adhesive layer, it was found to leak out of the surface, so that the transfer material was present on the adherend after peeling.

In the stress relaxation test, in Comparative Examples 4 to 8 in which the preparation was peeled off from the adherend, it was estimated that the stress relaxation rate was 10% or less, and the skin surface which was stretched by the adhesive surface could not be sufficiently traced, and it was presumed that The middle school will peel off.

From the above, the stress relaxation rate is set to 20 to 90%, and the shear stress is set to 1.0 to 6.5 N / 30 mm width, which can be alleviated. The stress on the skin surface is adhered and peeled off, and excellent skin adhesion is exhibited, and the irritation can be reduced at the time of peeling.

The present invention has been described in detail with reference to the specific embodiments thereof, and various changes and modifications can be made without departing from the spirit and scope of the invention.

In addition, this application is a Japanese patent application filed on Sep. 6, 2013 (Japanese Patent Application No. 2013-185601), and a Japanese patent application filed on Sep. 2, 2014 (Japanese Patent Application No. 2014-177675 Based on the basis, the overall content is quoted in this case.

Claims (8)

An adhesive preparation containing Pisoppro, comprising: a support; and an adhesive layer laminated on one side of the support and containing free type of Bisoppro and an adhesive; wherein the adhesive layer The stress relaxation rate is 20 to 90%, and the shear stress of the adhesive layer is 1.0 to 6.5 N/30 mm wide. For example, the Bisopoulol-containing patch preparation according to the first aspect of the patent application, wherein the stress relaxation rate of the adhesive layer is 40 to 90%, and the shear stress of the adhesive layer is 1.0 to 4.0 N/30 mm width. A Bisopoulol-containing patch preparation according to claim 1 or 2, wherein the adhesive contains a rubber-based adhesive. A Bisopoulol-containing patch preparation according to claim 3, wherein the rubber-based adhesive is a polyisobutylene and/or a styrene-isoprene-styrene block copolymer. The Bisoppro-containing patch preparation according to the fourth aspect of the patent application, wherein the polyisobutylene has a polyisobutylene having a viscosity average molecular weight of 40,000 to 5,500,000. The Bisoppro-containing patch preparation according to the fourth aspect of the patent application, wherein the polyisobutylene system comprises a first polyisobutylene (a) having a viscosity average molecular weight of 1,800,000 to 5,500,000, and a second viscosity average molecular weight of 40,000 to 85,000. The polyisobutylene (b) and the blending ratio (a:b) of the first polyisobutylene (a) and the second polyisobutylene (b) are 1:0.1 to 1:3 by weight. The Pesopoulin-containing patch preparation according to claim 4, wherein the styrene-isoprene-styrene block copolymer has a styrene ratio of less than 30% by weight. The Pesopoulin-containing patch preparation according to claim 4 or 7, wherein the content of the styrene-isoprene-styrene block copolymer in the adhesive layer is 5 to 50% by weight. .