JP2505674B2 - Patch - Google Patents

Description

TECHNICAL FIELD The present invention relates to a patch that can be used for treating various diseases.

BACKGROUND ART Conventionally, oral, injection, and rectal administrations as well as ointments and the like have been widely used as local administration routes for administration of pharmaceuticals. Furthermore, in recent years, the development of a technique for transdermally administering a drug that acts on the whole body has advanced, and several drugs have actually been clinically used.

By transdermal administration of a drug, for example, the first-pass effect in the liver that the drug receives when it is orally administered can be avoided, and thus a much more stable blood concentration of the drug can be obtained as compared with oral administration and injection. It has been found that there are many advantages such as that it can be maintained and that its duration is long and that a transdermal preparation can be easily removed when a serious side effect of the drug occurs.

Focusing on these advantages, many pharmaceutical products are being studied for conversion from conventional formulations to transdermal formulations.

However, as clinical applications of pharmaceuticals for transdermal administration have progressed, difficulties and problems of the transdermal administration route have become clear.

 Some of them are:

(1) The biggest problems with transdermal preparations are local irritation and skin irritation. According to some statistics, the incidence of skin irritation due to a sealed transdermal preparation is as high as 20 to 50%.

However, because patients have the advantages of transdermal formulations,
Even if skin irritation occurs, it is often the case that such a preparation has to be used.

In addition, many of the drugs currently in clinical use are difficult to be percutaneously absorbed, and even those that are percutaneously absorbed may require a large patch area to absorb a clinically effective amount, such as absorption. It is necessary to use an auxiliary agent such as an accelerator for promoting absorption.

However, increasing the application area or using an absorption enhancer often leads to an increase in the area of skin rash and a deterioration in the extent of skin rash.

Therefore, a transdermal preparation capable of absorbing a clinically effective amount of a drug while suppressing the occurrence of skin rash is desired.

(2) In addition, when the transdermal preparation is applied for a long time, it naturally becomes not only dirty, but also peels off more naturally, especially when entering a bath in the meantime, it is easy to peel off.

However, it is not only complicated to replace each time, but it is difficult to control the dose, a sufficient medicinal effect is not obtained, and there are problems in appearance and hygiene.

Therefore, there is a demand for a transdermal preparation that is unlikely to be contaminated and is not easily peeled off even if it is applied for a long time.

(3) By the way, the transdermal preparation is a long-lasting preparation and is particularly effective for chronic diseases or diseases requiring long-term treatment. And there is a high proportion of elderly people in these patients.

However, in general, elderly people are not good at handling complicated movements.

Therefore, as described above, there is a demand for a transdermal preparation that is not only a formulation that is pharmaceutically satisfactory in terms of absorbability but also that is easy to handle for patients.

Conventionally, as a patch for reducing skin rash and absorbing a clinically effective amount of a drug, for example, a patch having a knitted microporous hollow fiber by the present inventors as its constituent element is known. (WO87 / 00046, WO87 / 043
43, WO90 / 09784).

Such a patch was sufficiently effective in reducing skin rash and absorbing a clinically effective amount of the drug. However, even when applied for an extremely long time, there is no skin rash, the amount of drug contained in the patch is sufficiently small, and it is difficult to peel off with sufficient medicinal effect, there is no problem in appearance, etc. A patch having an effect has been desired.

That is, an object of the present invention is to provide a patch that can absorb a clinically effective amount of a drug, has extremely little skin rash, and does not tear or peel off sufficiently following the stretching movement of the skin. Especially.

Further, the object of the present invention is to absorb a clinically effective amount of the drug, and the occurrence of skin rash is extremely small, does not tear or peel off sufficiently following the stretching movement of the skin, and further, it is easy to handle. It is to provide an excellent patch.

Further, the object of the present invention is to use a small amount of the contained drug, such as buprenorphine or buprenorphine hydrochloride, for which the bulk powder is expensive, or the drug which is desired to have a small residual drug amount after use according to the psychotropic drug handling regulations. It is to provide a patch that can be expected to have a sufficient clinical effect.

DISCLOSURE OF THE INVENTION The present inventors can reduce the skin rash and absorb a clinically effective amount of a drug that is difficult to be transdermally absorbed while utilizing the advantages of conventional transdermal preparations. The present invention has been achieved as a result of earnestly examining measures for a patch having excellent handleability.

That is, the present invention provides (1) a thickness of 0.5 to 4.9 μm, a strength in two substantially orthogonal directions of 8 to 85 g / mm, and an elongation in two substantially orthogonal directions of 30 to 150%. And the ratio of the elongations in the two directions is
1.0 to 5.0 (however, if the elongations in the two directions are not the same, the smaller elongation is used as the denominator) (wherein the polyester film has the average particle diameter of (a)) 0.01 to 3.0 μm, and (b) the average particle diameter is substantially not more than 1.5 times the thickness of the polyester film.
The film contains 01 to 1.0% by weight. ) And (2) the thickness of the film layer laminated on one surface is 2
An adhesive patch comprising an adhesive layer a composed of an adhesive containing a drug having a transdermal absorbability of -60 μm.

The present invention also provides (1) a thickness of 0.5 to 4.9 μm, a strength in two substantially orthogonal directions of 8 to 85 g / mm, and an elongation in two substantially orthogonal directions of 30 to 150%. The ratio of elongation in the two directions
1.0 to 5.0 (however, if the elongations in the two directions are not the same, the smaller elongation is used as the denominator) (wherein the polyester film has the average particle diameter of (a)) 0.01 to 3.0 μm, and (b) the average particle diameter is substantially not more than 1.5 times the thickness of the polyester film.
The film contains 01 to 1.0% by weight. ) And (2) the thickness of the film layer laminated on one surface is 2
A pressure-sensitive adhesive layer a made of a pressure-sensitive adhesive containing a percutaneously absorbable drug of -60 μm, and (3) a surface of the film layer opposite to the surface where the pressure-sensitive adhesive layer a is laminated. Part or all,
A patch comprising a planar support laminated on the film layer with an adhesive force of 3 g / 12 mm or more via an adhesive layer b.

Furthermore, the present invention provides (1) a thickness of 0.5 to 4.9 μm, a strength in two substantially orthogonal directions of 8 to 85 g / mm, and an elongation in two substantially orthogonal directions of 30 to 150%. And the ratio of the elongations in the two directions is
1.0 to 5.0 (however, if the elongations in the two directions are not the same, the smaller elongation is used as the denominator) a film layer a (wherein the polyester film is (a) average particle diameter) Is 0.01 to 3.0 μm, and (b) the average particle diameter does not substantially exceed 1.5 times the thickness of the polyester film.
The film contains 01 to 1.0% by weight. And (2) a pressure-sensitive adhesive layer a formed of a pressure-sensitive adhesive containing a transdermal drug having a thickness of 2 to 60 μm laminated on one surface of the film layer a, and (3) the film layer a. On the surface opposite to the surface on which the adhesive layer a is laminated, partly or entirely of the surface is laminated on the film layer a through the adhesive layer b ₁ with an adhesive force a ₁ of 20 g / 12 mm or more. And (4) on a surface of the planar body opposite to the surface on which the adhesive layer b ₁ is laminated, a pressure-sensitive adhesive layer b ₂ is provided on a part or all of the surface. Laminated on the sheet with an adhesive force b ₁ of 3 g / 12 mm or more, the thickness is 0.5 to 4.9 μm, the strength in two directions that are substantially orthogonal to each other is 8 to 85 g / mm, and substantially orthogonal to each other. The elongation in the two directions is 30 to 150% and the ratio of the elongations in the two directions is 1.0 to 5.0 (however, if the elongations in the two directions are not the same, the smaller elongation is A film layer b comprising a polyester film (wherein the polyester film has (a) an average particle size of 0.01 to 3.0 μm, and (b) the average particle size is substantially 1.5 times the thickness of the polyester film. Solid particles not exceeding twice the total amount of the polyester film 0.
The film contains 01 to 1.0% by weight. ) Is a patch.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a cross-sectional view of the patch of the present invention, which is the patch obtained in Example 1. In the figure, 1 is a planar support (hollow fiber sample), 2 is an adhesive layer b, 3 is a film layer (PET film), 4 is an adhesive layer a (progesterone content), and 5 is a release film (sticking). Peel off and discard when using the agent)
Indicates.

FIG. 2 is a cross-sectional view of the patch of the present invention, which was obtained in Example 4. In the figure, 1 is a film layer (PET
Film), 2 is an adhesive layer a (progesterone-containing layer),
And 3 indicate a release film.

FIG. 3 is a cross-sectional view of the patch of the present invention, which was obtained in Example 22. In the figure, 1 is a film layer b (PE
T film), 2 is an adhesive layer b ₂ , 3 is a sheet (hollow fiber sample), 4 is an adhesive layer b ₁ , 5 is a film layer a, 6 is an adhesive layer a
(Estradiol content) and 7 represent release films.

BEST MODE FOR CARRYING OUT THE INVENTION The patch of the present invention has a thickness of 0.5 to 4.9 μm, a strength in two substantially orthogonal directions of 8 to 85 g / mm, and an elongation in two substantially orthogonal directions. Polyesters each having a degree of 30 to 150% and an elongation ratio in the two directions of 1.0 to 5.0 (however, if the elongations in the two directions are not the same, the smaller elongation is the denominator). A film layer made of a film (however, the polyester film (a) has an average particle size of 0.01 to 3.0 μm).
And (b) 0.01 to 1.0% by weight of solid fine particles whose average particle diameter does not substantially exceed 1.5 times the thickness of the polyester film, relative to the total amount of the polyester film. ). In order to reduce skin irritation, it is first of all important to reduce the physical irritation of the formulation. For this purpose, the smaller the thickness of the film used, the less the irritation. Therefore, the thickness is 4.9 μm or less, preferably 4.0 μm or less, and more preferably 3.5 μm or less, since this tendency becomes remarkable. On the other hand, since the patch is used by being applied to human skin, it is necessary to be able to follow the expansion and contraction movement of human skin due to human activity to some extent. If it is too thin, the film may break, or if it hardly follows the stretching movement of the skin, the skin irritation may increase. Even if the thickness is reduced to less than 0.5 μm, the physical irritation does not change so much, and the inconvenience that it tends to be inconvenient for manufacturing increases.

The purpose of providing a film layer as a support on the patch is to enhance the sealing property of the patch to promote percutaneous absorption, and to cover the adhesive surface to prevent the adhesive from adhering to clothing or other places on the skin. This is for things to do. The smaller the thickness of the film is, the smaller the sealing property becomes. When the film thickness is less than 5 μm, the sealing property tends to decrease. However, when the film thickness is less than 1 μm and less than 0.5 μm, it is difficult to obtain sufficient sealing property as a patch.

Regarding the strength of the film, if the strength in the two directions that are substantially orthogonal to each other exceeds 85 g / mm, the physical irritation is not sufficiently small, no matter how thin the thickness is. The formulation is likely to be damaged during use by applying or, and it tends to be difficult to use with confidence.

Regarding the elongation of the film, when the elongations in the two directions which are substantially orthogonal to each other exceed 150%, the handleability is poor, while
If the elongation is less than 30%, physical irritation becomes large, and breakage during sticking tends to occur.

Further, according to the results of examination by the present inventor, the ratio of the elongations in the two directions is 1.0 to 5.0 (however, when the respective elongations are not the same, the smaller elongation is used as the denominator), and particularly 1.0 to It is preferable to use a film having a thickness of 3.0, since it gives a good feeling when applied. When this ratio exceeds 5.0, that is, when a film having an extremely small elongation in a certain direction is used, the film cannot sufficiently follow the expansion and contraction of the skin in that direction, resulting in a tight feeling. It is not appropriate because it tends to cause problems such as uncomfortable attachment, easy peeling, and easy breakage.

Therefore, the film of the present invention has a thickness of 0.5 to 4.9 μm.
m, the strength in two directions that are substantially orthogonal to each other is 8 to 85 g / mm,
And elongation in two directions that are substantially orthogonal to each other is 30 to 150%
And the ratio of the elongations in the two directions is 1.0 to 5.0 (however, if the respective elongations are not the same, the smaller elongation is the denominator).
Is. Above all, the thickness is 3.5μm or less, especially 0.5-2.0μ
A film having m, a strength of 8 to 85 g / mm, an elongation of 45 to 150% and an elongation ratio of 1.0 to 3.0 is preferable.

The strength referred to in the present invention, according to the tensile strength measuring method of the Japanese Pharmacopoeia "Band plaster", the maximum load until cutting is obtained by converting it to a load per unit mm (g / mm), and the elongation is The elongation before pulling and the elongation at the time of cutting (%) are shown. Further, the two directions orthogonal to each other mean so-called vertical direction and horizontal direction.

In the present invention, it is more preferable that such a film has good stability over time, and that it is highly safe such that it does not easily cause an allergic reaction when applied to human skin. As such a film, a film made of polyolefin such as polyethylene or polypropylene; polyester such as polyethylene terephthalate or polyethylene naphthalate; polyamide such as nylon 6 or nylon 66; ethylene-vinyl acetate copolymer or the like can be used. These films may be used alone, or may be compounded or laminated.

Of these films, polyester film is preferred. Polyester films are generally stable to heat and light, have low drug adsorption and interaction with drugs, and are highly safe for humans. Furthermore, since the film having the above-mentioned specific thickness has an appropriate sealing property, the water permeability is appropriate and the water content of the stratum corneum of the site where the patch is applied is sufficient to assist the transdermal absorbability of the drug. It is preferable because it becomes the amount. Among the polyester films, a film made of polyethylene terephthalate is preferable.

In the present invention, in particular, the thickness of the film is 3.5 μm or less, the strength is 8 to 85 g / mm, and the elongation is 45 to 150%.
When using the ultrathin film which is, the thickness of the adhesive layer a is
Even if it is 30 μm or less, it can be stuck stably for a long time.

Furthermore, the thickness is 0.5 to 2.0 μm, and the strength is 8 to 85 g / mm,
In addition, when a thinner film having an elongation of 45 to 150% is used, the thickness of the adhesive layer a is 2 to 15 μm, especially 10 μm.
It is surprising that even if it is less than m, it can be applied to human skin with sufficient stability.

A normal film with a thickness of 5 to 20 μm, for example, a thickness of 10 μm
It is possible to make a patch with the m adhesive attached.

However, in this case and when the 10 μm pressure-sensitive adhesive layer is attached to the ultrathin film of the present invention having a thickness of 0.5 to 4.9 μm, and particularly 0.5 to 2.0 μm, the adhesive strength to human skin and its stability are surprising. In contrast, ultra-thin films are significantly better. This is because human skin has irregularities when viewed microscopically. Therefore, a film of ordinary thickness does not follow the irregularities of the skin, whereas the film of the present invention follows the irregularities of the skin. It is presumed that even a very small amount of adhesive layer can exhibit sufficient adhesive force in order to proceed.

That is, in the present invention, specific strength, by laminating a thin adhesive layer containing a drug on an ultrathin film layer of elongation,
It is possible to obtain a patch that is stable, has a small dosage, and has less skin irritation unlike conventional patches.

In the present invention, it is particularly preferable to use a polyester film as the above-mentioned film layer, but a small proportion of solid fine particles may be present in this polyester film for the purpose of improving its slipperiness. However, hitherto, there has not been sufficient knowledge as to what kind of effects such solid fine particles have on the patch of the present invention.

As a result of diligent study on this point, the present inventor found that the amount of solid fine particles present in the polyester film layer was 0.01 to 1
% By weight, having an average particle size of 0.01 to 3.0 μm and having an average particle size not substantially exceeding 1.5 times the thickness of the polyester film, while absorbing a clinically effective amount of the drug, especially on the skin. It was found to be important in reducing rash.

Examples of such solid fine particles include silicon dioxide, alumina, silicates containing 30% by weight or more of silicon dioxide, aluminosilicate compounds, and oxidation of one or more metals selected from magnesium, zinc, zirconium, and titanium. Compounds, nitrates of one or more metals selected from calcium, barium, phosphates of one or more metals selected from lithium, sodium, calcium, terephthalates of one or more metals selected from calcium, barium, zinc, manganese, Titanate of one or more metals selected from magnesium, calcium, barium, iron, cobalt, manganese, nickel, etc., one selected from calcium, magnesium, carbon, glass, inorganic or organic solid fine particles such as crosslinked polystyrene It can be illustrated. Of course, these may be used alone or as a mixture of two or more.

When the amount of the solid fine particles is less than 0.01% by weight, the effect of reducing skin irritation tends to be insufficient, which is not preferable, and when it exceeds 1% by weight, transdermal absorption of the drug There is a case where the adhesiveness is not sufficiently satisfied, which is not preferable as a patch. In addition, if the average particle size is less than 0.01 μm, the effect of reducing skin rash may be insufficient and handling may not be satisfactory, and if it exceeds 3.0 μm or 1.5 times the film thickness. If it exceeds the range, the transdermal absorbability of the drug may not be sufficiently satisfied as described above. It is considered that this is because in such a case, the water vapor permeability and the air permeability are excessively increased due to the voids between the solid fine particles and the film layer.

When the patch of the present invention is a patch consisting of the film layer and the pressure-sensitive adhesive layer a, this film layer plays a role as a support layer for the pressure-sensitive adhesive layer while preventing skin rash.
Further, when the patch of the present invention comprises the film layer, the pressure-sensitive adhesive layer a, the pressure-sensitive adhesive layer b and a planar support, it can be used also as a planar support. The film layer used as a support for the layer plays a role of improving the handling property. The patch of the present invention comprises a film layer a
And the film layer b, the former plays a role as a support layer of the adhesive layer a while preventing skin fogging, and the latter plays a role of improving handleability.

The patch of the present invention has an adhesive layer a, which is laminated on one surface of the former film layer and has a thickness of 2 to 60 μm and is made of an adhesive containing a transdermally absorbable drug.

Generally, the adhesive layer has a role of holding a necessary amount of a transdermally absorbable drug, which is a main ingredient, and stably attaching the patch to human skin, but various solvents used when forming the adhesive layer are used. The residual solvent is a major cause of skin irritation. Therefore, if it is possible to play these roles, it is easy to remove the residual solvent and it is economical.
The smaller the thickness of the adhesive layer, the more preferable.

In the present invention, since the above-mentioned specific film is used as the film layer, if the thickness of the adhesive layer is 2 μm or more, the thickness is 60 μm or less, preferably 30 μm or less, even if the patch is peeled off during application. Therefore, the residual solvent should be 100ppm or less, preferably 50pp as necessary.
It is possible to make the thickness m or less, and it is possible to hold the required amount of the drug and to apply the drug stably while reducing skin irritation due to the residual solvent.

As the adhesive containing the drug used in the present invention,
Conventional pressure sensitive adhesives are used, such as silicone rubber, polyisoprene rubber, styrene-butadiene copolymer rubber,
A rubber-based viscous composition containing acrylic rubber, natural rubber or the like as a main component; for example, a vinyl-based viscous composition such as polyvinyl alcohol (PVA) or ethylene-vinyl acetate copolymer; for example, a silicon-based adhesive, a polyurethane elastic body, A viscous composition containing a polyester elastic body, a polybutadiene elastic body or the like as a main component; an acrylic resin or the like can be selected. Among them, acrylic resins are preferable, and particularly from the viewpoint of less skin irritation, moderate tackiness, adhesiveness and high internal cohesive force, and excellent solvent resistance (1)
An acrylic resin obtained by copolymerizing at least 80 to 98 mol% of a (meth) acrylic acid alkyl ester having an alkyl group having 4 or more carbon atoms and (2) acrylic acid and / or methacrylic acid of 2 to 20 mol% is particularly preferable. Examples of the (meth) acrylic acid ester of an alkyl group having 4 or more carbon atoms include:
For example, butyl (meth) acrylate, amyl (meth) acrylate, hexyl (meth) acrylate, heptyl (meth) acrylate, octyl (meth) acrylate, nonyl (meth) acrylate, decyl (meth) acrylate, 2-ethylhexyl (meth) acrylate Etc. These pressure-sensitive adhesives may be used alone or in combination of two or more. The copolymer composition may be a terpolymer or a multicomponent copolymer obtained by further copolymerizing an ester of acrylic acid and / or methacrylic acid.

As described above, the patch comprising the specific film layer of the present invention and the adhesive layer a having a specific thickness containing the transdermal drug is an extremely thin layered product as a whole, and is not likely to cause damage or adhesion of the film. In some cases, care must be taken in handling such as adhesion of layers a.

In the patch of the present invention, on the surface opposite to the surface on which the pressure-sensitive adhesive layer a of the film layer is laminated, a part or the whole of that surface, 3 g of the film layer via the pressure-sensitive adhesive layer b.
-A surface support can be attached with an adhesive force of 12 mm or more.

Such a planar support may be directly on the patch, but the patch is first applied to human skin and then removed to leave only the film layer and the adhesive layer a. You can also

By attaching such a planar support, the patch is less likely to curl or break, and the patient can easily apply the patch.

Examples of the planar support that can be used in the present invention include a film, a non-woven fabric, a paper-like material, and / or a woven or knitted fabric, or a combination thereof. There are no particular restrictions on these materials when the planar support of the present invention is removed after application of the patch, but when the sheet is still laminated after application, it prevents skin fogging and stretches the skin. It is preferable that the film layer be flexible and moderately stretchable so as not to interfere with the moisture permeability of the film layer so that it can follow the movement.

When the planar support of the present invention is a film, the base material of such a film is, for example, a polyolefin such as polyethylene or polypropylene; a polyester such as polyethylene terephthalate or polyethylene naphthalate; a nylon 6 or the like. Examples thereof include polyamides such as nylon 66; ethylene-vinyl acetate copolymers, vinyl copolymers such as PVA, and the like. Among the planar supports made of these films, the average diameter of the micropores is 0.01 to 5 μm, the porosity is 20 to 80%, and some of the micropores communicate with the front and back surfaces of the film. Film is preferable because it hardly interferes with the moisture permeability of the film layer of the present invention.

Among them, the specific thickness used for the film layer of the present invention,
A film having strength and elongation is preferable, and among them, a polyester film containing solid fine particles having the above amount and particle diameter can be mentioned as a preferable example.

When the planar support is a non-woven fabric, a paper-like product, a woven fabric or a knitted fabric, the base material for these is
Fibers made of synthetic fiber such as nylon, polyester, acrylic, urethane, etc., and natural or regenerated fibers such as cotton, rayon, acetate, etc. may be used alone or in combination.

Among these non-woven fabrics, paper-like materials, woven fabrics and knitted fabrics,
A knitted fabric is preferable as a planar support because it causes relatively little skin irritation.

Among them, a knitted fabric having a basis weight of 10 to 300 g / m ² can be mentioned. Not only does such a knit produce little skin irritation, but it has little effect on the moisture permeability of the film layer. Also, when the knitted fabric and the film layer are laminated, the flexibility is hardly lost. It is considered that this is because the delicate margin in the fiber structure of the knit absorbs external stress. In addition, a film layer that adheres to human skin with a relatively small adhesive force via an adhesive layer a having a small thickness,
Despite the fact that each layer has a sheet-like support made of a large weight and volume of knitting, the adhesiveness of the patch to human skin and the adhesion between the knitting and the film layer are stable. Is amazing. Therefore, the use of the adhesive layer a or the film layer can be decided independently of the planar support. When the basis weight is less than 10 g / m ² , the handling property is not improved so much, and when it exceeds 300 g / m ² , the appearance is deteriorated and the appearance is deteriorated, which is not preferable. On the other hand, if it is too sublime, it is not preferable because when the hand is placed around the patch, the patch is liable to be touched, and the patch is apt to be unintentionally peeled off.

When such a knitted fabric is a knitted fabric made of hollow fibers having holes penetrating in the outer peripheral direction, preferable results are given.

As the hollow fiber having a hole penetrating in the outer peripheral direction, a hollow fiber having fine pores scattered over the entire cross section of the hollow fiber, arranged in the fiber axial direction, and at least a part of which communicates with the hollow portion is preferable. .

The hollow fiber of the present invention may have any shape in the cross section and the shape of the hollow portion. For example, when both the outer shape and the hollow part are substantially circular, even when one of the outer shape and the hollow part is substantially circular and the other is irregular, even when the outer shape and the hollow part are both similar or dissimilar Good. Further, there is no particular limitation on the size of the outer shape.

The thickness of the hollow fiber is preferably 4 to 45 μm.
If the thickness is 45 μm or more, skin irritation may be excessive. In addition, if it is 4 μm or less, the handling property may be deteriorated.

The hollow ratio of the hollow fiber of the present invention may be arbitrary, but especially 5%
It is preferable that the ratio is 0.01% to 70% of the fiber cross-sectional area excluding the hollow portion, particularly 0.01 to 50%, and further 1 to 50%. Is preferred.

The knitted fabric may be mainly composed of the hollow fibers described above, and may have some fibers other than the hollow fibers mixed therein as long as the effect of the present invention is not impaired.

As a material for the hollow fiber, there is no interaction with the drug, it has excellent stability and safety, and polyester.
Of these, polyethylene terephthalate is particularly desirable.

Hollow fibers of polyethylene terephthalate used in the present invention include, for example, JP-A-56-20612 and JP-A-56-206.
It can be produced by the methods described in JP-A No. 13 and JP-A-56-43420.

The planar support and the film layer are laminated via the adhesive layer b. As an example of the pressure-sensitive adhesive that can be used for the pressure-sensitive adhesive layer b, various ordinary pressure-sensitive adhesives exemplified as the pressure-sensitive adhesive of the pressure-sensitive adhesive layer a can be used.
Acrylic resins are preferable, and among them, from the viewpoints of less skin irritation, moderate tackiness, adhesiveness and high internal cohesive force, and excellent solvent resistance, (1) alkyl groups having 4 or more carbon atoms An acrylic resin obtained by copolymerizing at least 80 to 98 mol% of (meth) acrylic acid alkyl ester and (2) 2 to 20 mol% of acrylic acid and / or methacrylic acid is particularly preferable. Examples of the (meth) acrylic acid ester of an alkyl group having 4 or more carbon atoms include, for example, butyl (meth) acrylate, amyl (meth) acrylate, hexyl (meth) acrylate, heptyl (meth).
Acrylate, octyl (meth) acrylate, nonyl (meth) acrylate, decyl (meth) acrylate, 2
-Ethylhexyl (meth) acrylate etc. are mentioned. These pressure-sensitive adhesives may be used alone or in combination of two or more.

Alternatively, in the case of removing the planar support after sticking, the adhesive of the adhesive layer b may be PVA, ethylene-
Mention may be made of vinyl acetate copolymer, polyvinylpyrrolidone, sorbitol, starch, or adhesive substances such as the above-mentioned vinyl acetate.

When PVA or polyvinyl acetate is used as the adhesive for the adhesive layer b, the average degree of polymerization is 100 to 2000, and the concentration is 3 to 20%.
Examples of PVA include polyvinyl acetate having an average degree of polymerization of 100 to 1000 and a concentration of 3 to 20%. When the planar support is removed after application, good results are easily obtained, especially when a woven or knitted material is used as the base material of the planar support and an adhesive substance such as PVA is used.

That is, the planar support adheres to the film layer during handling of the patch, and can be used after being removed as necessary after the patch has been applied to human skin. However, since the patch is sealed in an aluminum bag etc. during storage, the solvent used for the adhesive substance used to attach the planar support to the film layer, such as methanol, ethyl acetate and water, remain. Then, these residual solvents are likely to move and diffuse into the adhesive layer a containing the drug during storage of the patch. Therefore, it may cause skin rash and decrease the stability of the drug over time.

In order to eliminate such inconvenience, it is necessary to prevent the solvent used for attaching the planar support and the film layer from remaining, but when the planar support is made of a film, it is necessary to remove the solvent completely. It is difficult to remove it easily, and the production method may require special measures. In this case, since the patch of the present invention uses a specific film as a support layer, if a complicated step is taken, the film is likely to be broken or wrinkled, and the production efficiency tends to be lowered. However, when the planar support is a porous film or a non-woven fabric, a paper-like material, a woven / knitted product, etc., especially when the planar support is a woven / knitted product, the vapor of the solvent or the like easily escapes from the woven / knitted product. The solvent and the like can be removed very easily, which is a preferred embodiment.

In particular, by combining a planar support made of a woven and knitted material with a film layer, adding a solution of an adhesive substance from the top of the woven and knitted material, and then heating the planar support and the film layer, there is no fear of residual solvent. Can adhere well. In addition, a method in which an adhesive substance is attached to a planar support made of a woven or knitted material in advance and dried or as it is attached to a film layer, and heating or air drying is performed to remove residual solvent as necessary is adopted. it can. The adhesive layer a containing the drug may be attached to the film layer before or after attaching the planar support, but since the drug is generally unstable to heat, the film layer and the planar support are previously attached. A method of keeping the body attached is preferable.

In the present invention, the attachment surface of the planar support and the film layer may be the whole surface or a part of the film layer. However, even if the adhesive force between the planar support and the film layer is small,
When the patch is applied to human skin and then only the planar support is to be removed, the film layer may also be peeled off. In order to prevent this, the entire surface of the planar support and the surface of the film layer are not adhered, but it is also possible to form a part where both surfaces are not adhered, that is, simply overlap each other. This is a desirable mode. The patient can more easily remove the planar support from this unattached area. It is also useful to put a film, paper, cloth or the like having a thickness of 5 to 100 μm between these two surfaces to form a surface on which the planar support surface and a part of the film layer surface are not attached. is there.

It has been found that the patient can very easily remove the planar support, especially when the non-adhesive portions of the planar support surface and the film layer surface are on the edges of the patch. Moreover, the patient should only attach a planar support from this edge, for example 90 ° or 180 °.
Since it is pulled and peeled in the direction of °, the risk of peeling the patch from the human skin and the risk of breaking the film layer are reduced. It is particularly preferable in the case of the patch of the present invention, which uses an extremely thin film having a small skin irritation to the patient and weak strength and a thin adhesive layer.

As a method for laminating the film layer and the planar support, for example, such an adhesive is dissolved in a solvent to form an adhesive layer b having a thickness of 2 to 100 μ on the film layer, and then a planar support is prepared. There is a method of crimping. Or 2 in advance
Adhesive layer b having a thickness of 100 μm is prepared in advance, and the adhesive layer b is pressure-bonded to one surface of the planar support and / or one surface of the film layer, and then the planar support and the film layer are applied. You may crimp through b. Further, the film layer and the planar support can be pressure-bonded on a part of these surfaces via the pressure-sensitive adhesive layer b, but can also be pressure-bonded on the entire surfaces of these surfaces via the pressure-sensitive adhesive layer b. . Among them, if the planar support is not removed after being attached, it is possible to press-bond the planar support to a part of these surfaces within a range in which the planar support can be stably attached for a long time. It is preferable because the moisture permeability is not reduced. As a mode of crimping with such a part, for example, there are scattered islands, the size of each island is 0.5 to 100 mm ² , and the adhesive layer b having a thickness of ² to 100 μ is used, or the width is 1 One having a plurality of adhesive layers b having a linear shape of ˜20 mm and a thickness of 2 to 100 μ can be mentioned. Such partial pressure bonding is preferable because the patch is easy to handle and the irritation to the skin by the planar support can be further reduced.

The thickness of the adhesive layer b is 2 to 100 μm, preferably 5 to 2
0 μm can be mentioned.

In the present invention, the adhesive force between the planar support and the film layer is 3 g / 12 mm or more, but the planar support is adhered to the film layer by the adhesive force, so It is preferable because even if an elderly patient does not curl or break, the agent can be easily applied to the local area.

The term "adhesiveness" as used in the present invention means, for example, that a laminate composed of a planar support attached to a film layer via an adhesive layer b is cut into a slit having a width of 12 mm, and the planar support or film is Measure the load (gr) when peeling at a speed of 30 cm / min in the direction of °, and convert that value to a width of 12 mm (g / mm). When the film and the planar support are partially adhered in the form of slits or dots, measure the load (gr) when peeling off the adhered part and measure the value with a width of 12 mm.
The value is equivalently converted (g / mm).

The adhesive force can be appropriately changed depending on whether or not the planar support is attached to the local area and then removed, or the relationship between the adhesive force between the skin and the film layer via the adhesive layer a.

For example, the adhesive force between the planar support and the film layer is 20g / 12
If it exceeds mm, the film layer may be broken when the planar support is removed from the film layer. From a theoretical point of view, when the strength of the film is 8 to 85 g / mm each, it is considered that the film does not break even if the adhesive force exceeds 20 g / 12 mm, for example, 24 g / 12 mm (2 g / mm). . However, in the case of an actual patch, if the adhesive force exceeds 20 g / 12 mm, the film may be broken or the patch may be peeled off from human skin. If it is less than 3 g / 12 mm, the layer between the support and the film layer may be peeled off during production, storage, or handling. Therefore, when the patch is removed after being applied locally, the preferable adhesive force is 3 g / 12 mm or more and 20 g / 12 mm or less, and when it is not removed, it may exceed 20 g / 12 mm.

When removing this planar support after applying it locally,
The characteristics of the film layer are fully exerted during application, and various purposes such as reduction of skin rash are achieved.

As a measure for the same purpose, for example, Japanese Patent Publication 1-51
As shown in Japanese Patent No. 260, one of such measures has been proposed. However, the detailed structure of the patch body has not been studied as in the present invention, and neither the skin irritation nor the amount of drug used is attempted as in the present invention.

In the present invention, a more preferable patch can be obtained by adjusting the waist strength of the planar support. The waist strength of the planar support is, for example, JIS P-8143.
It can be expressed as a stiffness test method by stiffness of the (cm ^3/100), and preferably 0.08 or higher stiffness, more preferably 0.27 or more.

Furthermore, in the patch comprising the film layer and the pressure-sensitive adhesive layer a of the present invention, in the surface opposite to the surface of the film layer a comprising the specific film on which the pressure-sensitive adhesive layer a is laminated, Partly or entirely, a planar body laminated with an adhesive force a1 of 20 g / 12 mm or more on the film layer a via an adhesive layer b1 and the adhesive layer b1 of the planar body are laminated. On the surface opposite to the surface, part or all of the surface was laminated on the planar body with an adhesive force b1 of 3 g / 12 mm or more via an adhesive layer b2, a thickness of 0.5 to 4.9 μm, and a strength. Is from 8 to 85 g / mm, and the elongations in two directions substantially orthogonal to each other are from 30 to 150%, and the ratio of the elongations in the two directions is from 1.0 to 5.0.
(However, when the ratio of the elongations in the two directions is not the same, the smaller elongation is used as the denominator), and the patch can be a film layer b made of the film.

Examples of the planar body of the patch include a breathable one of the films, non-woven fabrics, paper-like materials, and woven or knitted fabrics exemplified as the planar support. The moisture permeability as referred to in the present invention means that the vapor permeability is 10 mg / day · cm ² or more when measured by the method for measuring the moisture vaporization property shown in (vi) of the examples of the present invention.

Among these moisture-permeable sheet materials, a knitted fabric is preferable, and the basis weight is
A knitted fabric having 10 to 300 g / m ² and having a hole penetrating in the circumferential direction, which is exemplified as a preferred embodiment of the above-mentioned planar support, and a knitted fabric made of polyethylene terephthalate hollow fibers is more preferred. You can

That is, in the patch, it is further desirable that the transdermal absorbability of the drug is sufficiently high while satisfying that it is soft, has less skin rash, and has good handleability. Is important to give. At this time, rather than simply sticking the patch coated with the film layer a on the adhesive layer a, a sheet-like body made of a knitted fabric is laminated between the adhesive layers b ₁ and b ₂ , and the adhesive layer b ₂ Film layer b on the outer surface
Is preferably arranged. The role of the knitted fabric at this time is not only an intervening substance when laminating the film layer b to compensate for the lack of the sealing effect of the film layer a, but also contributes greatly to improving the handleability of the patch, and further It is presumed that it is also related to the moisturizing effect of the application site. Moreover, the basis weight is 10 to 30
It is a knit of 0 g / m ² , which itself has a room inside the tissue and can delicately follow the expansion and contraction of the applied skin, which causes physical irritation to the affected part of the applied skin. The skin irritation is reduced, probably because it helps to reduce it.

Further, as the film of the film layer b, the same base material as the film of the film layer a can be preferably mentioned.

The sheet-like body and the film layer b are bonded to the film layer a via the pressure-sensitive adhesive layer b ₁ and the pressure-sensitive adhesive layer b ₂ , and the above-mentioned sheet-like support is a film layer. As in the case of laminating a part or the whole of the surface, the film layer a and the part of the planar body and the part of the planar body and the film layer b are laminated by pressure bonding. . As in the case of laminating the planar support by pressure bonding to the film layer a, the pressure-sensitive adhesive layer b ₁ and the pressure-sensitive adhesive layer b ₂ are separately prepared under heating, if necessary. For example, a method of laminating by pressure bonding one by one, or, for example, an adhesive layer b ₁ on a sheet
The laminate 1 obtained by laminating the film 1 and the laminate 2 obtained by laminating the pressure-sensitive adhesive layer b ₂ on the film layer b It is possible to cite a method of crimping to. Among them, the sheet ₂ is laminated on the free surface of the adhesive layer b ₂ of the laminate 2 obtained by laminating the adhesive layer b ₂ on the film layer b, and the film layer b, the adhesive layer b _2. A laminate 4 which is a sheet is obtained, and then an adhesive layer b ₁ is laminated on one surface of the sheet 4 which is free of the laminate 4, and then a film layer a is laminated. To obtain a laminate 5 laminated with the film layer b, the adhesive layer b ₂ , the sheet, the adhesive layer b ₁ , and the film layer a from the above. A method of laminating the adhesive layer a on the free surface or forming the adhesive layer a on the laminate 5 is preferable. That is,
A film layer b, a pressure-sensitive adhesive layer b ₂ , a sheet, which composes the present adhesive agent,
Since both the adhesive layer b ₁ and the film layer a are thin and have elasticity, it is desirable to take special care in handling them individually, but by sequentially stacking them in this manner,
Manufacturing is easy. In particular, the step of laminating the adhesive layer a containing a drug is the most important step that controls the content and cost of the patch of the present invention to be obtained. A uniform patch can be obtained.

As the pressure-sensitive adhesive for the pressure-sensitive adhesive layer b ₁ and the pressure-sensitive adhesive layer b ₂ used here, the same base material as the pressure-sensitive adhesive for the pressure-sensitive adhesive b can be used. Above all, the above-mentioned acrylic resins and adhesive substances can be preferably used as the pressure-sensitive adhesive. Further, the thickness of these adhesive layers b ₁ and b ₂ is 2 to
100 μm is preferable.

When the thickness of the pressure-sensitive adhesive layer is 2 μm or less, the adhesive force to the sheet-like body becomes weak, which may cause the sheet-like body to peel off during sticking. When the thickness is 100 μm or more, the adhesive may easily stick out from the side surface during cutting or during application of the adhesive, which may cause process troubles and stains.

Especially, the preferable range of the adhesive layer b ₂ is 5 to 20 μm, and the preferable range of the adhesive layer b ₁ is 10 to 50 μm. The thickness of the adhesive layer b ₁ is related to the adhesive strength of the patch, and it is not preferable that the thickness is extremely thin.

In the patch of the present invention, when the planar body and the film layer b are further laminated as described above, the planar body has an adhesive force of 20 g / 12 mm or more on the film layer a, and the film layer b is planar. It can be laminated on the body with an adhesive force of 3g / 12mm or more.

The patch of the present invention preferably has a water transpiration property of 10 mg / day · cm ² or more. If this value is less than 10 mg / day · cm ² , stuffiness when attached to the skin tends to be large, and skin irritation may occur.

On the other hand, when the water transpiration rate is higher than 80 mg / day · cm ² , the transdermal absorbability of the drug tends to be poor, and the preferable water transpiration rate is 10 to 80 mg / day · cm ² .

In some cases, the patch of the present invention comprises an adhesive layer b, an adhesive layer
It is connected partially or wholly by b ₁ , the adhesive layer b ₂ or the adhesive layer c. When the thickness of the adhesive layer is as thin as possible without impairing the adhesive force for stably laminating the film layer a and the planar support, the thickness of the adhesive patch as a whole is reduced and peeling due to catching is prevented. It is preferable above.
Generally, the pressure-sensitive adhesive layer b and the pressure-sensitive adhesive layer b ₂ are 20 μm or less, especially 10 μm.
m or less is often sufficient.

In the adhesive layer b ₁ , if the thickness is too small, the adhesive strength of the patch to human skin tends to be small,
The preferred range is 10 to 50 μm.

On the other hand, the adhesive layer a is also preferably as thin as possible in terms of the adhesiveness of the patch to the skin, but it should also be considered from the viewpoint of the compatibility between the adhesive and the drug and the dose.

It is generally known that the adhesive strength of a patch increases up to a thickness of about 50 μm as the thickness increases, and a stable adhesive strength of 30 to 100 μm is usually used in order to obtain stable adhesive strength. . In the present invention, since the adhesion to human skin can be improved by using the ultrathin film layer a, the preferable range of the adhesion layer a is 5 to 30 μm.

Regarding the size of the patch, that is, the patch area, the solubility and transdermal absorbability of the drug vary depending on the type of drug and the type of adhesive, so the patch area should be set to ensure sufficient transdermal absorbability. The result may be larger. However, of course, there is a limit to the area of sticking that can be tolerated by the human body, and a large area cannot be taken unnecessarily, and increasing the area increases the amount of drug,
It should be kept to a minimum, and there is no need to wait. It can be said that a range of about 5 to ²⁰⁰ cm ^{2 is} usually preferable because it is easy to handle.

As the drug of the present invention, for example, isosorbide nitrate, nitroglycerin, buprenorphine hydrochloride, morphine, estradiol, progesterone, ketotifen, vinfosetin, nicotine and their derivatives, and one or more known transdermally absorbable drugs are blended. The content can be used, for example, in a ratio of 0.1 to 20% with respect to the adhesive.

In particular, the present invention is extremely thin in the case of drugs that may cause abnormal skin absorption or cause serious problems in the case of any skin defect due to expensive drugs or excessive amounts of use. Since the adhesive layer is used, the amount of drug used can be extremely reduced, which is preferable. Examples of such drugs include anesthetic analgesics such as buprenorphine hydrochloride and morphine, and hormonal agents such as estradiol and progesterone derivatives.

The patch of the present invention may contain a dissolution aid, a diffusion aid, a filler, etc., if necessary.

Examples of the diffusion aid used in the present invention include alcohols such as glycerin, diethylene glycol, polyethylene glycol, and higher fatty acid alcohols; dimethyl sulfoxide and its alkylmethyl derivatives; salicylic acid, urea, dimethylacetamide, dimethylformamide, lanolin, allantoin, squalene. , Carbopol, diisopropyl adipate, pyroglutamic acid lauryl ester, ethyl laurate, methyl nicotinate, sorbitol, dodecylpyrrolidone, pyrrolidone derivatives such as methylpyrrolidone; olive oil, castor oil, liquid paraffin, petrolatum, gelatin, amino acids,
Benzyl nicotinate, camphor, etc. can be used.

As the filler, water, titanium oxide, calcium carbonate, gypsum, calcium silicate, aluminum silicate, diatomaceous earth, carbon black, red iron oxide, various face wash, lactose, fragrance, deodorant, polyethylene, polypropylene, polyester, Examples thereof include powders of synthetic resins such as polystyrene and molded products.

[Examples] The present invention will be described in more detail with reference to Examples and Reference Examples below. Parts in the examples and the like indicate parts by weight, and the characteristics appearing in the examples and the like were measured by the following methods.

(I) Water absorption rate test method (according to JIS-L 1018) A fiber is formed into a knitted fabric, and this knitted fabric is washed with a 0.3% aqueous solution of anionic detergent Zabb (manufactured by Kao Soap Co., Ltd.) at 40 ° C. for 30 minutes by a household electric washing machine. Wash the sample for a predetermined number of times, then dry it and stretch the sample horizontally. Drop a drop of water (0.04 cc) from the height of 1 cm above the sample. The water is completely absorbed by the sample and the reflected light is observed. The time was measured until it disappeared.

(Ii) Method for measuring water absorption rate A sample obtained by drying a knitted fabric is immersed in water for 30 minutes or more, and then dehydrated for 5 minutes with a dehydrator of a domestic electric washing machine. It was calculated from the weight of the dried sample and the weight of the sample after dehydration by the following formula.

(Iii) Method for measuring blood concentration of isosorbite nitrate After separating plasma from 3 ml of collected blood, extraction with 4 ml of N-hexane and concentration, addition of ethyl acetate to 100 μl
And quantified by GC-ECD.

(Iv) BN blood concentration measurement method After separating plasma from 1 ml of collected blood, the literature (Journ
Al-Chromatography, 338 (1985) 89-98) was used to quantify by the GC-MS method.

(V) Progesterone Blood Concentration Measurement Method After separating serum from 1 ml of collected blood, it was analyzed by a radioimmunoassay method.

(Vi) Method for measuring water vapor transpiration A dent (circle with a diameter of 4 cm, depth of 0.6 cm) is made in the center of a circular thick glass plate with a diameter of 12 cm, and 3 ml of water is placed therein.
I put it in. A patch with a sufficient patch (size 5 cm x 5
cm) on the patch so that the above-mentioned dent comes to the center of the patch, and leave it under ventilation at 37 ° C for 1 day to reduce the weight per day by the area of the patch above the dent (above In this example, it was divided by 12.56 cm ² ) and the water transpiration property was measured.

Reference Example A hollow fiber sample (knitted fabric) and an adhesive solution used in Examples were prepared by the following method.

(1) Hollow fiber sample (knit) 297 parts of dimethyl terephthalate, 265 ethylene glycol
Parts, sodium 3,5-di (carbomethoxy) benzenesulfonate 53 parts (11.7 mol% with respect to dimethyl terephthalate), manganese acetate tetrahydrate 0.084 parts and sodium acetate trihydrate 1.22 parts with a rectifying column glass Put in a flask, carry out transesterification reaction according to a conventional method, after the theoretical amount of methanol was distilled out, the reaction product was put into a flask for polycondensation with a rectification column, and 0.090 parts of a 56% aqueous solution of orthophosphoric acid as a stabilizer and 0.135 parts of antimony trioxide was added as a polycondensation catalyst at a temperature of 2
After reacting at 75 ° C. under normal pressure for 20 minutes and under reduced pressure of 30 mmHg for 15 minutes, the mixture was reacted under high vacuum for 100 minutes. Final internal pressure is 0.39mmH
g, the intrinsic viscosity of the obtained copolymer is 0.402,
The softening point was about 200 ° C. After completion of the reaction, the copolymerized polymer was made into chips by a conventional method.

15 parts of this copolymerized polymer chip and 85 parts of polyethylene terephthalate chip with an intrinsic viscosity of 0.640
After mixing for 5 minutes in a mixer (manufactured by Hosokawa Iron Works), after drying in a nitrogen stream at 110 ° C for 2 hours and further at 150 ° C for 7 hours, melt kneading at 285 ° C using a twin-screw extruder. And made into chips. This chip had an intrinsic viscosity of 0.535 and a softening point of 261 ° C.

The chips are dried by a conventional method, and the width of the spinneret is 0.05 m.
A hollow fiber with a circular slit of m and a diameter of 0.6 mm, which has two circular arc openings that are closed at two points, is spun according to a conventional method, and the ratio of the outer diameter to the inner diameter is 2: 1. %)made. This yarn is 300 denier / 24 filament, and this yarn is drawn at a draw ratio of 4.2 times according to a conventional method.
A multifilament of denier / 24 filament was obtained. This multifilament is knitted into a knitted fabric, scoured and dried by a conventional method, then treated with a 1% caustic soda aqueous solution and at a boiling temperature for 2 hours to obtain an alkali weight loss rate of 15%, a water absorption rate of 3 seconds, and a water absorption rate of 80%. I got a knit. The obtained knitted fabric was stretched 1.5 times in the machine direction and heated at 100 ° C. for 1 minute to heat set to obtain a knitted fabric having a basis weight of 38 g / m ² .

The hollow fibers of the obtained knitted fabric were hollow fibers which were scattered over the entire cross section of the hollow fibers and were arranged in the fiber direction, and at least a part of the hollow fibers had fine pores communicating with the hollow portions.

(2) Adhesive solution 97.4 parts of 2-ethylhexyl acrylate, 2.5 parts of methacrylic acid, 0.1 part of polyethylene glycol (polymerization degree 14) dimethacrylate, 1.0 part of benzoyl peroxide and 100 parts of ethyl acetate are equipped with a reflux condenser and an agitator. Polymerization was continued for 9 hours while charging in a reaction vessel and slowly expanding sales at 60 to 70 ° C under a nitrogen atmosphere. The polymerization conversion was 99.5-99.9%.

500 parts of ethyl acetate was added to the obtained polymer solution to adjust the solid content concentration to about 20%.

Example 1 To 500 parts of the adhesive solution of Reference Example (2), 8.8 parts of progesterone was added. Then, this is coated on a silicone-coated release film so that the thickness of the dried adhesive layer a is 15 μm, and dried at 70 ° C. for 3 minutes and 110 ° C. for 3 minutes to form a progesterone-containing adhesive layer. Obtained. The residual amount of ethyl acetate in this adhesive layer a was 18 ppm, and the content of progesterone was 1.3 g / m ² .

One side of the obtained adhesive layer a has a thickness of 1.3 μ and is orthogonal to 2
Strength in each direction 22 and 25 g / mm, and elongation 75 and 38
% Polyethylene terephthalate (PET) film (film layer) was pressure bonded. The thickness obtained by applying the adhesive solution of Reference Example (2) on a release film on the free surface of the film layer and drying (70 ° C. for 3 minutes, 110 ° C. for 3 minutes) A 10 μm pressure-sensitive adhesive layer b was pressure-bonded, and the hollow fiber sample (knitted fabric) of Reference Example (1) 3 was pressure-bonded as a planar support to one side of the free pressure-sensitive adhesive layer b. The adhesive force between the film and the knit of the laminate was 164 g / 12 mm.

The original fabric of the obtained patch was cut into a size of 3 cm × 3 cm to obtain a patch. The cross-sectional view is shown in FIG. This patch was applied to the back of a hair-removed rat weighing about 180 g. Blood was collected at the predetermined time shown in Table 1 and the progesterone level in serum was measured by the radioimmunoassay (RIA) method. The results and the skin condition of the rat after application for 24 hours are shown in Table 1.

Examples 2-3 and Comparative Examples 1-2 In Example 1, the progesterone application was carried out in exactly the same manner except that the PET film of Example 1 was replaced by a PET film having the thickness, strength and elongation shown in Table 1. Table 1 shows the results of obtaining the agent and conducting a rat sticking test.

Test Example 1 The pressure-sensitive adhesive solution of Reference Example (2) was applied onto a silicone-coated release film to obtain pressure-sensitive adhesive layers a having different thicknesses as shown in Table 2. Drying condition after coating is 70
C. for 3 minutes and 110.degree. C. for 3 minutes, and the amount of residual ethyl acetate in the obtained adhesive layer a was measured by a gas chromatography (GC) method.

To press-bond a PET film (film layer) having the thickness, strength and elongation shown in Table 2 as a film layer on one surface of the obtained adhesive layer a, and then to attach a planar support to the film layer. Then, an adhesive layer b as shown in Table 2 was pressure-bonded to the free surface of the film. Further, the hollow fiber sample (knitted fabric) of Reference Example (1) was pressed onto the free surface of the adhesive layer b as a planar support. The film layer and the planar support are attached to the entire surface of these surfaces via the adhesive layer b.

The raw material of the obtained placebo patch containing no drug was cut into a size of 3 cm x 3 cm, and 5 healthy adult males (age 22-
45 years old, weight 55-82kg) 1 different patch for each person on the back
A total of 12 sheets were attached to each sheet, and the feeling of use and the state of skin rash after attachment for 48 hours were determined. Judgment was set to 0 for no reaction,
A slight erythema was scored as 1, an apparent erythema was scored as 2, and a case where a hill examination or the like occurred was scored as 3.

The test conditions and results of this test are summarized in Table 2.

From Table 2, the skin rash has a film thickness of about 5 μm.
If it is above, it becomes suddenly large (No.4, 8), and if the thickness of the film is less than about 5 μm, it decreases (eg
You can see No. 1-3. In terms of usability, the film elongation may be less than about 30% (No.5), or the strength may be less than about 8 g / cm (No.6) and the film may tear during handling of the patch. I understand.

Example 4 In the same manner as in Example 1 except that the planar support was not used in Example 1, an adhesive layer a containing progesterone was pressure-bonded to a film layer made of a PET film having a thickness of 1.3 μm and the size was 3 cm. It was cut into 3 cm to obtain a patch for animal testing. The sectional view is shown in FIG.

This patch was very soft and required a lot of time to be applied to the back of the test animal, but there was no skin rash like the patch of Example 1.

Example 5 Buprenorphine hydrochloride was added in the same manner as in Example 1 except that buprenorphine hydrochloride was used instead of progesterone in Example 1 and the thickness of the adhesive layer containing buprenorphine hydrochloride after drying was 7 μm. g /
A patch containing m ² was obtained, and it was applied to the back of a rat that had been hair-removed to a size of 3 cm x 3 cm with n = 3, before application, and after application 2,8,24
Blood was collected at a time and the concentration of buprenorphine in the serum was 0, 3.1, 5.7, 5.6 (ng / ml), indicating a good analgesic effect. There was no skin rash on the skin patch after removal.

In addition, despite using an extremely thin adhesive layer of 7 μm, which is not seen in conventional patches, it has sufficient adhesive force to the skin and the amount of expensive buprenorphine hydrochloride used has been drastically reduced. We were able to.

Example 6 A patch was prepared in exactly the same manner as in Example 5, except that nicotine was contained instead of buprenorphine hydrochloride. This patch was applied to the back of the rat, and it was confirmed that skin irritation did not occur.

Example 7 A patch was prepared in exactly the same manner as in Example 5, except that estradiol was contained instead of buprenorphine hydrochloride. This patch was applied to the back of the rat, and it was confirmed that skin irritation did not occur.

Test Example 2 In No. 3 of Test Example 1, a strip-shaped pressure-sensitive adhesive layer b shown below was used in place of the pressure-sensitive adhesive layer b having a thickness of 10 μm in which a PET film having a thickness of 3.5 μm and a planar support were adhered. The human patch test was carried out in exactly the same manner as in No. 3 of Test Example 1 except for the above.
At this time, the adhesive force between the film layer and the planar support is 47 g / 12
Although it was mm, there was no peeling during application, and skin rash (total score of 5) was 3, which was good.

Preparation method of band-shaped pressure-sensitive adhesive layer b: The pressure-sensitive adhesive solution of Reference Example (2) was continuously extruded in a thread shape at equal intervals, and was formed into a band shape on the continuously moving release film.

The strip-shaped pressure-sensitive adhesive layer b thus obtained had an average thickness after drying of 10 μm, and each pressure-sensitive adhesive layer having a width of 2 mm was arranged with a gap of 3 mm.

Example 8 As a planar support, a fabric having a basis weight of 32 g / m ^{2 made} of PET was used, and polyvinyl alcohol (PV was used as an adhesive for the adhesive layer b.
A: A 10% aqueous solution having a polymerization degree of 500) was impregnated, and PVA was made to be 25% by weight based on the woven fabric after drying. The obtained PVA
Stiffness of the fabric was contained (cm ^3/100) was 6.2.

Wet the PVA impregnated and dried fabric with water,
A PET film (film layer) having the same thickness, strength, and elongation as in Example 1 was pressure-bonded and dried at 60 ° C to obtain a laminate.

The adhesive force between the film of the laminate and the woven fabric was 5 g / 12 mm. The stiffness (cm ^3/100) was 4.8. Adhesive layer a having a thickness of 15 μm containing 1.3 g / m ² of progesterone obtained in Example 1 on the free surface of the film layer of the laminate.
Was crimped.

The original fabric of the obtained patch was cut into a size of 3 cm × 3 cm and applied to the back of a rat having a hair weight of about 180 g, which was then peeled off, and then the woven fabric as a planar support was peeled off. No PVA was left on the surface of the film.

Table 3 shows the results of measuring blood progesterone levels in serum by the RIA method and the skin condition of the rat after 24 hours of application, which was obtained by collecting blood at the predetermined time shown in Table 1.

Examples 9 to 10 and Comparative Examples 3 to 4 Except that the PET film (film layer) of Example 1 in Example 8 was replaced with a PET film having the thickness, strength and elongation shown in Table 3. The progesterone patch was obtained in the same manner and the rat patch test was performed.
Shown in the table.

Test Example 3 In the same manner as in Test Example 1, an adhesive layer a containing no drug as shown in Table 4 was obtained, and the amount of residual ethyl acetate in the adhesive layer a was measured by the GC method.

On the other hand, a fabric having a basis weight of 32 g / m ^{2 made} of PET was impregnated with a 10% aqueous solution of PVA (polymerization degree of 500) shown in Table 4, and a planar support having different amounts of PVA for the dried fabric was used. made.

The dried sheet-like support and the PET film having the thickness, strength and elongation shown in Table 4 were pressure-bonded in the same manner as in Example 8 to obtain a laminate. The adhesion between the film of this laminate and the fabric was measured.

The adhesive layer a obtained above was combined and pressure-bonded to the free surface of the film of this laminate as shown in Table 4.

The raw material of the obtained placebo patch containing no drug was cut into a size of 3 cm x 3 cm, and 5 healthy adult males (age 22-
45 years old, weight 55-82kg) 1 different patch for each person on the back
A total of 12 sheets were attached to each sheet, and the feeling of use and the state of skin rash after attachment for 48 hours were determined. Judgment was set to 0 for no reaction,
A slight erythema was scored as 1, an apparent erythema was scored as 2, and a case where a hill examination or the like occurred was scored as 3.

The test conditions and results of this test are summarized in Table 4.

From Table 4, the skin rash has a film thickness of about 5 μm.
It can be seen that when the thickness is above, it suddenly increases (No. 4, 10) and decreases when the film thickness is less than about 5 μm (for example, Nos. 1 to 3). In terms of usability, the elongation of the film is less than about 30% (No.5), and the strength is about 8g / cm.
When the patch is less than (No. 6), it can be seen that the film breaks during handling of the patch. If the thickness of the adhesive layer a is large (No.8,9)
It can be seen that skin irritation increases.

Example 11 Buprenorphine hydrochloride was prepared in exactly the same manner as in Example 8 except that buprenorphine hydrochloride was used instead of progesterone in Example 8, and the thickness of the adhesive layer a containing buprenorphine hydrochloride after drying was 7 μm. 0.56
A patch containing g / m ² was obtained, and the patch was applied to the back of a rat having hair removed to a size of 3 cm × 3 cm with n = 3, before application, and after application 2,8,
Blood was collected at 24 hours and the serum buprenorphine concentration was 0, 4.2, 6.1, 5.7 (ng / ml), indicating a good analgesic effect. There was no skin rash on the skin patch after removal.

In addition, despite using an extremely thin adhesive layer of 7 μm, which is not seen in conventional patches, it has sufficient adhesive force to the skin and the amount of expensive buprenorphine hydrochloride used has been drastically reduced. We were able to.

Example 12 A patch was prepared in exactly the same manner as in Example 11, except that nicotine was contained instead of buprenorphine hydrochloride. This patch was applied to the back of the rat, and it was confirmed that skin irritation did not occur.

Example 13 A patch was prepared in exactly the same manner as in Example 11, except that estradiol was contained instead of buprenorphine hydrochloride. This patch was applied to the back of the rat, and it was confirmed that skin irritation did not occur.

Example 14 In Example 8, as a PET film, thickness 1.3μ
m, strength and elongation in two orthogonal directions are 22 and 32 g / m, respectively
m, 75 and 35%, in the same manner as in Example 8 except that a PET film having an average particle size of 0.70 μm and 0.08% by weight of synthetic silica added to the film as solid fine particles in the film was used. To obtain a laminate.

The adhesive force between the film of the laminate and the woven fabric was 5 g / 12 mm. The stiffness (cm ^3/100) was 4.8. 1.3 g of progesterone on the free side of the laminate film
A 15 μm thick adhesive layer a containing / m ² was pressure-bonded.

The original fabric of the obtained patch was cut into a size of 3 cm × 3 cm and applied to the back of a rat having a hair weight of about 180 g, which was then peeled off, and then the woven fabric as a planar support was peeled off. Substantially no PVA remained on the surface of the film. Subsequently, blood was collected at the predetermined time shown in Table 5, and the results of measuring the progesterone level in serum by the RIA method and the rat skin condition after application for 24 hours are shown in Table 5.

Examples 15 to 17 and Comparative Examples 6 to 7 Progesterone patches were obtained in exactly the same manner as in Example 14 using the films shown in Table 5, and the rat patch test results were shown in Table 5.

Example 18 Buprenorphine hydrochloride was prepared in the same manner as in Example 14 except that buprenorphine hydrochloride was used instead of progesterone in Example 14, and the thickness of the adhesive layer a containing buprenorphine hydrochloride after drying was 7 μm. 0.56
A patch containing g / m ² was obtained, and the patch was applied to the back of a rat having hair removed to a size of 3 cm × 3 cm with n = 3, before application, and after application 2,8,
Blood was collected at 24 hours and the serum buprenorphine concentration was 0, 4.3, 6.0, 5.8 (ng / ml), indicating a good analgesic effect. There was no skin rash on the skin patch after removal.

In addition, despite using an extremely thin adhesive layer of 7 μm, which is not seen in conventional patches, it has sufficient adhesive force to the skin and the amount of expensive buprenorphine hydrochloride used has been drastically reduced. We were able to.

Test Example 4 The placebo preparations of Example 11 and Example 18 were made into a size of 7.1 cm ² , and 5 people each were stuck on the right chest for 48 hours, and the condition of 1 hour after the removal was observed to observe skin irritation. The condition was 0 for no reaction, 0.5 for slight erythema, 1.0 for obvious erythema, 2 for erythema and edema, and 3 for erythema and edema and papules. As a result of determining the skin irritation of both groups, 2.0 with the placebo preparation of Example 11, Example 1
The placebo formulation of 8 was 1.0, and Example 18 was judged to be less irritating.

Example 19 A patch was prepared in exactly the same manner as in Example 18, except that nicotine was contained instead of buprenorphine hydrochloride. This patch was applied to the back of the rat, and it was confirmed that skin irritation did not occur.

Example 20 A patch was prepared in exactly the same manner as in Example 18 except that estradiol was contained instead of buprenorphine hydrochloride. This patch was applied to the back of the rat, and it was confirmed that skin irritation did not occur.

Example 21 and Comparative Example 8 PET film having a thickness of 1.8 μm as a planar support and the same P as used in Example 14 having a thickness of 1.3 μm as a film layer.
In the same manner as in the ET film and Example 1 except that coating and drying were performed so that the thickness of the pressure-sensitive adhesive layer after drying was 10 μm, and 10 μm containing progesterone at a rate of 1.3 g / m ^2.
And a pressure-sensitive adhesive layer a having a thickness of 10 μm obtained by using the pressure-sensitive adhesive solution of Reference Example (2) over the entire surface of the planar support and the film layer. did.

The PET film used in this laminate contains 0.08% by weight of rigid silica having an average particle size of 0.7 μm as solid fine particles. With respect to the original fabric of the adhesive patch thus obtained, the water transpiration property was measured and the result was 12.7 mg / day · cm ² .

For comparison, a preparation was prepared by adhering a 10 μm-thick adhesive layer a containing progesterone to the 12 μm-thick polyester film to the same thickness as used in Example 21 (Comparative Example 8).

The water transpiration property of this preparation was only 7.3 mg / day · cm ² .

Example 22 A knitted fabric made of the same microporous hollow fiber of polyester as used in Example 1 was used as the sheet between the film (film layer b) and the film layer a in the sheet-like support in Example 20. The three layers were pressure-bonded with acrylic adhesive layers (b ₁ and b ₂ ) each having a thickness of 10 μm. The adhesive layer a containing the drug used in Example 21 was pressure-bonded onto the film layer a of the obtained laminate to obtain a patch. The sectional view is shown in FIG.

With respect to the original fabric of the patch obtained in this way, its water transpiration property was 19.4 mg / day · cm ² .

Comparative Example 9 Exactly the same procedure as in Example 5 except that a polyethylene film having a thickness of 7 μm, a unidirectional strength of 20 g / mm ² , and an elongation of 276% was used in place of the 1.3 μm-thick PET film in Example 5. A patch containing 0.56 g / m ² of buprenorphine hydrochloride was obtained. The size of the patch was 3 cm × 3 cm, and the blood concentration when it was carried out at the same time as Example 5 was 0, 2, 8 and 24 hours after the patch, respectively. , 0.5, 1.2, 3.8 (ng / ml). There was no skin rash on the skin patch after removal.

The water transpiration property of this preparation was 133 g / day · cm ² .

Test Example 5 The patches of the placebo preparations of Examples 21 and 22 and Comparative Examples 8 and 9 were made to have a size of 7.1 cm ² , and they were applied to the right chest of a human for 2 hours each for 2 hours, and 1 hour after the removal. Was observed. The results are shown in Table 6.

It was revealed that the patch of the present invention does not substantially change the skin condition before and after application and is an excellent patch.

Example 23 On the PET film b having a thickness of 1.3 μm used in Example 14, a pressure-sensitive adhesive layer b ₂ having a thickness of 15 μm obtained by previously coating the pressure-sensitive adhesive solution shown in Reference Example was attached, and then the surface A hollow fiber material knitted fabric of the reference example (weight per unit area: 38 g / m ² ) is pressure-bonded as a body, and then a pressure-sensitive adhesive layer b ₁ having a thickness of 40 μm obtained by applying the adhesive solution shown in the reference example in advance is pressure-bonded. And then this adhesive layer
The thickness of 1.3μ used in Example 14 on the free surface of b _1.
A PET film a of m was pressure-bonded to obtain a laminate.

On the other hand, an adhesive layer a having a thickness of 10 μm and containing buprenorphine hydrochloride 1.13 g / m ² was obtained in the same manner as in Example 1.
Was pressed onto the PET film a surface of the above-mentioned laminate to obtain a patch containing 2.8 mg of buprenorphine hydrochloride per size 5 cm × 5 cm. Cut this patch to a size of 4.5 cm ² ,
When the amount of buprenorphine hydrochloride in plasma was quantified by applying it to the neck of a hair-removed rat (n = 5) having an average body weight of 150 g, and collecting blood before, 2 hours, 8 hours, and 24 hours after application, 0 , 1.9,2.7,3.4 (ng / ml), showing a good analgesic effect.

It was confirmed that the patch was easy to handle, had no change in the skin after removal, and had little skin irritation.

INDUSTRIAL APPLICABILITY The patch of the present invention can be used in the clinical field of medicine as a patch with less skin rash and less likely to peel off and absorbing a clinically effective amount of a drug.

In particular, the planar support or the patch of the present invention in combination with the planar support becomes a patch with further excellent handling properties, and can be easily used even in elderly patients.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (31) Priority claim number Japanese patent application No. 2-202409 (32) Priority date Hei 2 (1990) August 1 (33) Priority claim country Japan (JP)

Claims (34)

(57) [Claims] (1) The thickness is 0.5 to 4.9 μm, the strength in two substantially orthogonal directions is 8 to 85 g / mm, and the elongation in two substantially orthogonal directions is 30 to 150, respectively. %, And the ratio of the elongations in the two directions is 1.0 to 5.0 (however, if the elongations in the two directions are not the same, the smaller elongation is the denominator). However, the polyester film has (a) an average particle size of 0.01 to 3.0 μm, and (b) the average particle size does not substantially exceed 1.5 times the thickness of the polyester film. Against 0.
The film contains 01 to 1.0% by weight. ) And (2) the thickness of the film layer laminated on one surface is 2
A patch comprising a pressure-sensitive adhesive layer a made of a pressure-sensitive adhesive containing a drug having a transdermal absorbability of -60 μm. 2. The patch according to claim 1, wherein the adhesive is an acrylic resin adhesive. 3. The patch according to claim 1, wherein the ratio is 1.0 to 3.0. 4. The patch according to claim 1, wherein the drug is one or more drugs selected from isosorbide nitrate, nitroglycerin, buprenorphine, estradiol, progesterone, ketotifen, vinvocetin, nicotine and their derivatives. 5. (1) The thickness is 0.5 to 4.9 μm, the strength in two substantially orthogonal directions is 8 to 85 g / mm, and the elongation in two substantially orthogonal directions is 30 to 150, respectively. %, And the ratio of the elongations in the two directions is 1.0 to 5.0 (however, if the elongations in the two directions are not the same, the smaller elongation is used as the denominator). (However,
The polyester film has (a) an average particle size of 0.01 to 3.0 μm, and (b) the average particle size does not substantially exceed 1.5 times the thickness of the polyester film. 0.
The film contains 01 to 1.0% by weight. ) And (2) the thickness of the film layer laminated on one surface is 2
A pressure-sensitive adhesive layer a made of a pressure-sensitive adhesive containing a percutaneously absorbable drug of -60 μm, and (3) a surface of the film layer opposite to the surface where the pressure-sensitive adhesive layer a is laminated. Part or all,
3 to the film layer through the adhesive layer b having a thickness of 2 to 100 μm
A patch consisting of a planar support laminated with an adhesive force of g / 12 mm or more. 6. The patch according to claim 5, wherein the adhesive is an adhesive made of an acrylic resin. 7. The patch according to claim 5, wherein the adhesive force is 3 g / 12 mm or more and 20 g / 12 mm or less. 8. The patch according to claim 5, wherein the adhesive force is greater than 20 g / 12 mm. 9. The patch according to claim 7, wherein the adhesive force is smaller than the adhesive force between the film layer and the adhesive layer a. 10. The planar support is a film, a non-woven fabric,
The patch according to claim 5, which is one kind of a cloth made of a paper-like material and / or a woven or knitted material or a combination thereof. 11. The patch according to claim 5, wherein the planar support is a porous film or a woven or knitted fabric having a basis weight of 10 to 300 g / m ² . 12. The patch according to claim 10, wherein the knitted fabric is a knitted fabric mainly having hollow holes penetrating in the outer peripheral direction and made of hollow fibers having a single yarn thickness of 4 to 45 μm. 13. The patch according to claim 5, wherein the adhesive layer b is composed of an adhesive containing polyvinyl alcohol and / or vinyl acetate polymer as a main component. 14. The patch according to claim 5, wherein the adhesive layer b is made of an acrylic resin adhesive. 15. The adhesive layer b has a thickness of 2 to 100 μm.
The patch according to claim 13 or 14, which is 16. The patch according to claim 5, wherein the ratio is 1.0 to 3.0. 17. The planar support on the surface of the planar support opposite to the surface on which the film layers are laminated, with a pressure-sensitive adhesive layer c on a part or the entire surface thereof. To 3g / 12m
The patch according to claim 5, which has a support laminated with an adhesive force of m or more and less than 20 g / 12 mm. 18. The patch according to claim 5, wherein the patch has a water transpiration property of 10 mg / day · cm ² or more. 19. The patch according to claim 5, wherein the drug is one or more drugs selected from isosorbide nitrate, nitroglycerin, buprenorphine, estradiol, progesterone, ketotifen, vinvocetin, nicotine and their derivatives. 20. (1) The thickness is 0.5 to 4.9 μm, the strength in the two substantially orthogonal directions is 8 to 85 g / mm, and the elongation in the two substantially orthogonal directions is 30 to 150, respectively. %, And the ratio of the elongations in the two directions is 1.0 to 5.0 (however, if the elongations in the two directions are not the same, the smaller elongation is used as the denominator). (However, the polyester film has (a) an average particle size of 0.01 to 3.0 μm, and (b) the average particle size does not substantially exceed 1.5 times the thickness of the polyester film. 0 for the total amount.
The film contains 01 to 1.0% by weight. And (2) a pressure-sensitive adhesive layer a formed of a pressure-sensitive adhesive containing a transdermal drug having a thickness of 2 to 60 μm laminated on one surface of the film layer a, and (3) the film layer a. On the surface opposite to the surface on which the adhesive layer a is laminated, a part or the whole of the surface is laminated on the film layer via the adhesive layer b ₁ with an adhesive force a ₁ of 20 g / 12 mm or more. And (4) the surface of the sheet opposite to the surface on which the pressure-sensitive adhesive layer b ₁ is laminated, a part or the whole of the surface having the pressure-sensitive adhesive layer b ₂ interposed therebetween. Laminated on a sheet with an adhesive force b ₁ of 3 g / 12 mm or more, the thickness is 0.5 to 4.9 μm, the strength in two directions that are substantially orthogonal to each other is 8 to 85 g / mm, and 2 that is substantially orthogonal to each other. The elongation in each direction is 30 to 150%, and the ratio of the elongations in the two directions is 1.0 to 5.0 (however, if the elongations in the two directions are not the same, the smaller elongation is the denominator. A film layer b comprising a polyester film (wherein the polyester film has (a) an average particle size of 0.01 to 3.0 μm, and (b) the average particle size is substantially 1.5 times the thickness of the polyester film. Solid fine particles not exceeding 0 based on the total amount of the polyester film.
The film contains 01 to 1.0% by weight. ) A patch consisting of 21. The patch according to claim 20, wherein the adhesive is an adhesive made of an acrylic resin. 22. The adhesive force b ₁ is 3 g / 12 mm or more and 20 g / 12 mm
21. The patch according to claim 20, which is less than 20. 23. The patch according to claim 20, wherein the adhesive force b ₁ is 20 g / 12 mm or more. 24. said adhesion force b ₁ is plaster of claim 22 or 23, wherein a small adhesive force than said adhesion force a _1. 25. The patch according to claim 20, wherein the sheet is a film, a nonwoven fabric, a paper-like material, and / or a cloth made of a woven or knitted material. 26. The patch according to claim 20, wherein the sheet is a woven or knitted fabric having a basis weight of 10 to 300 g / m ² . 27. The patch according to claim 25 or 26, wherein the knitted fabric is a knitted fabric mainly having hollow holes penetrating in the outer peripheral direction and made of hollow fibers having a single yarn thickness of 4 to 45 μm. 28. The patch according to claim 20, wherein the adhesive layers b ₁ and b ₂ are composed of an adhesive containing polyvinyl alcohol and / or vinyl acetate polymer as a main component. 29. The patch according to claim 20, wherein the adhesive layers b ₁ and b ₂ are made of an acrylic resin adhesive. 30. The patch according to claim 28, wherein the adhesive layers b ₁ and b ₂ each have a thickness of ₂ to 100 μm. 31. The patch according to claim 20, wherein the ratio is 1.0 to 3.0. 32. On the surface of the film layer b opposite to the surface on which the planar bodies are laminated, a part of or the entire surface of the film layer b is adhered to the film layer b with an adhesive layer c of 3 g / g. 21. The patch according to claim 20, which has a support laminated with an adhesive force of 12 mm or more and 20 g / 12 mm or less. 33. The patch according to claim 20, wherein the drug is one or more drugs selected from isosorbide nitrate, nitroglycerin, buprenorphine, estradiol, progesterone, ketotifen, vinvocetin, nicotine and their derivatives. 34. The moisture transpiration property of the patch is 10 mg / day.cm ^2.
21. The patch according to claim 20, which is as described above.