JP2002363069A - Patch preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a patch preparation that includes an ointment having not so high cohesion while the amount of adhesive residue remaining on a releasing film is reduced. SOLUTION: This patch preparation is produced by laminating an adhesive layer including medicines and the surface release film on a substrate in order wherein the average roughness (Rz) at 10 points on the surface on the side of the release film contacting with the adhesive is in the range of 0.15-0.35 μm.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a patch preparation capable of continuously administering a drug from the skin into a living body.

[0002]

2. Description of the Related Art In recent years, various patch preparations for administering a drug into a living body through the skin surface have been developed, in which a pressure-sensitive adhesive layer containing the drug and a release film are sequentially laminated on a support. Have been. In order to effectively release the drug from the patch preparation to the skin surface and to absorb it into the skin, it is necessary to increase the drug concentration. Further, there has been proposed a method of improving absorption by adding a transdermal absorption enhancer having various functions.

[0003] However, by increasing the drug concentration, the drug becomes a supersaturated state or a crystalline state in the pressure-sensitive adhesive, and the bonding force, that is, the cohesive force of the plaster (pressure-sensitive adhesive containing the drug) is reduced. Even when a transdermal absorption enhancer is added, a substance that mixes well with the adhesive is selected from the viewpoint of compatibility, and the cohesive force of the plaster decreases due to its plasticizing action. When the cohesive force of the plaster decreases, when the release film is removed from the patch preparation, the pressure-sensitive adhesive remains on the adherend such as on the release film (adhesive residue), and the amount of drug in the preparation decreases. There is a problem that the therapeutic effect is reduced.

[0004] As a means for solving such problems, there is generally a method of adding a crosslinking agent to crosslink the polymer component in the pressure-sensitive adhesive, or adding a filler to improve the cohesive force of the plaster. is there. However, in the method of cross-linking the polymer component, cross-linking is inhibited depending on the drug or the transdermal absorption enhancer to be added, so that cross-linking may not be performed, and the method of adding a filler may be insufficient in effect. In particular, fabrics such as woven fabrics and nonwoven fabrics, and composite films obtained by laminating a nonwoven fabric on a single-layer film are frequently used as a support for a patch preparation in terms of good texture and flexibility. When a suitable support is used, adhesive residue is particularly likely to occur.

[0005]

SUMMARY OF THE INVENTION An object of the present invention is to provide a patch preparation in which the adhesive residue on the release film is suppressed even if the patch preparation does not have a high cohesive strength. .

[0006]

Means for Solving the Problems The present inventors have conducted intensive studies on a patch preparation which can be peeled off without leaving a plaster on the release film. As a result, the adhesive layer containing the drug on the support and the release layer were prepared. In a patch preparation in which mold films are sequentially laminated, a 10-point average roughness Rz (Rz defined in JIS B 0601) of the surface of the release film that is in contact with the adhesive is used.
Refers to _JIS . Hereinafter, it may be simply referred to as “Rz”. ) Is set to 0.15 to 0.35 μm, so that even if the pressure-sensitive adhesive has a very weak cohesive force, for example, 10 N / cm or less, the pressure-sensitive adhesive on the release film when the release film is peeled off. The present inventors have found that glue residue is effectively suppressed, and completed the present invention.

Generally, it is considered that the larger the surface roughness, the larger the adhesive residue of the pressure-sensitive adhesive. However, by increasing the surface roughness to some extent as in the above range, the adhesive residue on the release film is suppressed. That is surprising.

That is, the present invention is as follows. (1) In a patch preparation in which a pressure-sensitive adhesive layer containing a drug and a release film are sequentially laminated on a support, the 10-point average roughness Rz of the surface of the release film that is in contact with the pressure-sensitive adhesive
Is 0.15 to 0.35 μm. (2) The release force of the release film from the pressure-sensitive adhesive layer is 10 to 4
The patch preparation according to the above (1), wherein the patch preparation is 00 mN / cm. (3) The patch preparation according to the above (1) or (2), wherein the cohesive force of the adhesive containing the drug is 10 N / cm or less. (4) The release film is a polyester film, JIS
The patch preparation according to any one of the above (1) to (3), wherein the cloudiness value specified in K 7105 is 50 to 80%. (5) The above (1), wherein the support is a fabric.
The patch preparation according to any one of (1) to (4). (6) The patch preparation according to any one of the above (1) to (5), wherein the drug is a local anesthetic. (7) The adhesive preparation according to any one of the above (1) to (6), wherein the adhesive is an acrylic adhesive. (8) The patch preparation according to any one of (1) to (7) above, which is used for sticking a mucous membrane.

[0009]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below in detail.

[0010] The support used in the present invention is not particularly limited, but preferably has flexibility.
A fabric is most preferable in terms of flexibility, followability to an application site, and adhesion. The fibers constituting the fabric are not particularly limited as long as the object of the present invention can be achieved, and specifically, for example, viscose rayon, copper ammonia rayon, diacetate,
Triacetate, nylon, polyvinylidene chloride, polyvinyl alcohol, polyvinyl chloride, polyester, polyacrylonitrile, polyethylene, polypropylene,
Synthetic fibers obtained from at least one of polyurethane, polyalkylene paraoxybenzoate, polychlor (a 1: 1 mixture of vinyl chloride and polyvinyl alcohol), and natural fibers such as cotton, wool, silk, and hemp. Among the above fibers, polyolefin fibers such as polyethylene and polypropylene are preferable because they are hydrophobic. These fibers may be used alone or in combination of two or more.

Further, a split fiber composed of two different components may be used. A split fiber is a split of a composite fiber spun by combining two components, for example, polypropylene and polyester with a die, and this composite fiber extracts one component or gives a strong impact. Thus, when the tangerine is cut into slices, it is possible to divide the tufts so that the tufts are divided into divided fibers, which are finer fibers.

Examples of the form of the fabric include a knitted fabric, a woven fabric, and a nonwoven fabric. A nonwoven fabric is preferable in terms of economy. Nonwoven fabrics composed of conjugate fibers are preferred. These fabrics can be used by laminating a film for the purpose of improving handleability or preventing strike-through of the pressure-sensitive adhesive layer. As a film to be laminated, polyethylene, polyolefin such as polypropylene, polyester, polyamide, polybutadiene, polybutene, polyisoprene, polyvinyl chloride,
Polyvinylidene chloride, ethylene-vinyl acetate copolymer,
A single-layer film or a laminated film made of a synthetic resin such as cellulose acetate, ethyl cellulose, polyvinyl alcohol, an ethylene-ethyl acrylate copolymer, polytetrafluoroethylene, polyurethane, and an ionomer resin is exemplified. A polyethylene film, a polypropylene film, and a polyethylene terephthalate film having a thickness of 1 to 15 μm are preferred in terms of economy and workability.

Further, for the purpose of water-repellent treatment, a known water-repellent, for example, a silicone-based water-repellent, a fluorine-based water-repellent, or the like may be applied to a support (for example, a cloth).

The method for producing the non-woven fabric is not particularly limited, but may be a dry binder method, a thermal bond method, a spun bond method, a spun lace method, an air lay process, a needle punch method, a TFC method, a Bemliese method, a wet method used in medical products. There is a melt blown method and the like, and those manufactured by a spunlace method are preferably used from the viewpoint of the degree of entanglement and safety.

The fabric preferably has a mass defined by JIS L 1085 of 20 to 150 g / m ² , more preferably 50 to 120 g / m ² . When the mass is smaller than the above range, there is a danger that the handle becomes too soft and the handleability of the patch preparation is reduced, and that the pressure-sensitive adhesive containing the drug passes through between the fibers of the fabric and leaks to the back side. If it is larger than the above range, the whole will be hard, and the flexibility will be impaired, or it will be difficult to obtain the adhesion to the application site.

For the same reason as described above, the thickness of the cloth is 0.1 to 0.1% as defined in JIS L 1085.
It is preferably 1 mm, more preferably 0.2 to 0.8 mm. In addition, the fabric is JIS L 10
The rigidity (based on the 45 ° cantilever method) specified in 85 is preferably from 10 to 80 mm, more preferably from 30 to 70 mm. When the bending resistance is within this numerical range, the handleability at the time of application and the adhesion to the application site are improved.

The drug in the present invention is not particularly limited as long as it can be percutaneously absorbed by itself or in combination with a percutaneous absorption enhancer, and may be any of a topical drug and a systemic drug. Good. For example, systemic drugs include corticosteroids, analgesics and anti-inflammatory agents, hypnotic sedatives, tranquilizers, antihypertensives, antihypertensive diuretics, antibiotics,
General anesthetics, antibacterials, antifungals, vitamins, coronary vasodilators, antihistamines, antitussives, sex hormones, antidepressants,
Examples include cerebral circulation improving agents, antiemetic agents, antitumor agents, enzyme agents, biopharmaceuticals and the like. As the topical drug, for example, a local anesthetic such as lidocaine, a dental antibiotic such as tetracycline hydrochloride, a disinfectant such as cetylpyridinium chloride, an anti-infective agent such as chlorhexidine hydrochloride, an anti-inflammatory agent such as dimethylisopropylazulene, And corticosteroids such as hydrocortisone acetate.

Preferably, cocaine, procaine, chloroprocaine, tetracaine, benzocaine, lidocaine, mepivacaine, prilocaine, bupivacaine, dibucaine, propoxycaine, etidocaine, dyclonine, oxybuprocaine, thecaine, amethocaine,
Propitocaine, Piperokine, Catacaine, Butanicain, Hexothiokine, Meprilcaine, Epilocaine, Amylokine, Isobucaine, Tricaine, Palethoxycaine, Pyrocaine, Hexylcaine, Metabutoxycaine, Xylocaine, Metabutetamine, Oxisezaxin, Pidomixin, Amin At least one local anesthetic selected from the group consisting of ethyl peridinoacetylaminobenzoate, benzyl alcohol, chlorobutanol and pharmacologically acceptable salts thereof is used, more preferably lidocaine, lidocaine hydrochloride , Procaine hydrochloride, mepivacaine hydrochloride, dibucaine hydrochloride, bupivacaine hydrochloride, propitocaine hydrochloride, tetracaine hydrochloride, tricaine hydrochloride, oxesa Inn is used.

The content of these drugs in the pressure-sensitive adhesive can be appropriately increased or decreased depending on the kind of the drug, the purpose of administration, etc., but is usually 1 to 80% by weight, preferably 2 to 70% by weight.
It is about. If the content is less than 1% by weight, release of a therapeutically effective amount of the drug cannot be expected. If the content is more than 80% by weight, the adhesiveness is reduced and the adhesive is not sufficiently adhered. In addition, there are limits to the preventive effect and economic disadvantages.

The drug can be contained in the pressure-sensitive adhesive in a dissolved state, a supersaturated crystal precipitated state or a dispersed state, depending on its medicinal effect. Thereby, a transdermal absorption preparation for the purpose of treating and / or preventing various diseases can be obtained.

Examples of the pressure-sensitive adhesive for a drug-containing pressure-sensitive adhesive used in the present invention include a pressure-sensitive adhesive comprising an acrylic polymer, a styrene-isoprene-styrene block copolymer, a styrene-butadiene-styrene block copolymer, Rubber-based adhesives such as polyisoprene, polyisobutylene, and polybutadiene; silicone adhesives such as silicone rubber, dimethylsiloxane-based and diphenylsiloxane-based; vinyl ether-based adhesives such as polyvinyl methyl ether, polyvinyl ethyl ether, and polyvinyl isobutyl ether; vinyl acetate -A vinyl ester-based pressure-sensitive adhesive such as ethylene copolymer, a carboxylic acid component such as dimethyl terephthalate, dimethyl isophthalate, and dimethyl phthalate, and a polyester-based material including a polyhydric alcohol component such as ethylene glycol. There is an incoming agents, and the like. Above all, an adhesive made of an acrylic polymer is preferred from the viewpoints of anchoring property to fabric, sticking property, drug solubility, drug stability and the like.

The above-mentioned acrylic polymer is obtained by copolymerizing a functional monomer with (meth) acrylic acid alkyl ester, which is generally used for an acrylic pressure-sensitive adhesive, as a main component. . As the alkyl (meth) acrylate, specifically, when the alkyl group is butyl, pentyl, hexyl, heptyl, octyl,
(Meth) acrylic acid alkyl esters having a straight-chain alkyl group or a branched alkyl group having 4 to 13 carbon atoms such as -ethylhexyl, nonyl, decyl, undecyl, dodecyl, tridecyl and the like can be used. The above can be used. The (meth) acrylic acid ester is not limited to those exemplified above, but may be an alkyl group having 1 to 3 carbon atoms or 14 or more carbon atoms within a range that does not change the characteristics of the present invention. (Meth) acrylic acid alkyl ester may be used in combination.

The functional monomer capable of being copolymerized with the alkyl (meth) acrylate ester has at least one unsaturated double bond involved in the copolymerization reaction in the molecule and has a functional group at one side. Those having a chain can be used. Examples of such functional monomers include carboxyl group-containing monomers such as (meth) acrylic acid, itaconic acid, maleic acid, and maleic anhydride, hydroxyethyl (meth) acrylate, and hydroxypropyl (meth) acrylate. Such as hydroxyl group-containing monomers such as styrene sulfonic acid, allyl sulfonic acid, sulfopropyl (meth) acrylate, (meth) acryloyloxynaphthalene sulfonic acid, and acrylamidomethyl propanoic acid; and (meth) acrylic Amino group-containing monomers such as acid aminoethyl ester, (meth) acrylic acid dimethylaminoethyl ester, and (meth) acrylic acid tert-butylaminoethyl ester;
Acrylamide, dimethyl (meth) acrylamide, N
-Amide group-containing simple substance such as methylol (meth) acrylamide, N-methylolpropane (meth) acrylamide, N-vinylacetamide, (meth) acrylic acid methoxyethyl ester, (meth) acrylic acid ethoxyethyl ester, (meth) acrylic acid Alkoxy group-containing monomers such as methoxyethylene glycol ester, methoxydiethylene glycol (meth) acrylate, methoxypolyethylene glycol (meth) acrylate, methoxypolypropylene glycol (meth) acrylate, and tetrahydrofuryl (meth) acrylate Is mentioned.

Other monomers that can be copolymerized include, for example, (meth) acrylonitrile, vinyl acetate, vinyl propionate, N-vinyl-2-pyrrolidone, methylvinylpyrrolidone, vinylpyridine, vinylpiperidone, vinylpyrimidine, Examples include vinylpiperazine, vinylpyrrole, vinylimidazole, vinylcaprolactam, vinyloxazole, vinylmorpholine and the like.

Among the acrylic polymers obtained by copolymerizing one or more of these main monomers and functional monomers, pressure-sensitive adhesive and cohesive properties as adhesive properties, adhesives Those having excellent release properties of the drug contained in the layer are preferably used. That is, a copolymer of (meth) acrylic acid alkyl ester and (meth) acrylic acid,
More preferably, 65 to 99% by weight of an alkyl (meth) acrylate and 1 to 35% by weight of (meth) acrylic acid
Are obtained by polymerizing

Various additives may be used for the pressure-sensitive adhesive, if necessary. As the additives, other various additives such as a plasticizer and a transdermal absorption enhancer, for example, an antioxidant and the like can be used. The plasticizer can adjust the sticking force to the sticking site by plasticizing the adhesive. Examples of the plasticizer include, for example, diisopropyl adipate and diacetyl sebacate, and one or more of these plasticizers can be used.

As the transdermal absorption enhancer, a compound having a function of improving the solubility and diffusibility of the drug in the pressure-sensitive adhesive layer and improving the transdermal absorption of the drug is used. Specific examples of such transdermal absorption enhancers include the following compounds. For example, as compounds mainly improving drug solubility, ethylene glycol, diethylene glycol, propylene glycol, triethylene glycol,
Glycols such as polyethylene glycol and polypropylene glycol, and compounds mainly improving drug diffusibility include oils and fats such as olive oil, castor oil, squalane, and lanolin.

Other hydrocarbons such as liquid paraffin, various surfactants, glycerin monoesters such as ethoxylated stearyl alcohol, oleic monoglyceride, caprylic monoglyceride, lauric monoglyceride, or glycerin diester, glycerin triester or Higher fatty acid esters such as mixtures thereof, ethyl laurate, isopropyl myristate, isotridecyl myristate, octyl palmitate, isopropyl palmitate, ethyl oleate, diisopropyl adipate, higher fatty acids such as oleic acid, caprylic acid, etc. N-methylpyrrolidone,
1,3-butanediol and the like can be mentioned.

The thickness of the pressure-sensitive adhesive layer of the patch preparation of the present invention is usually 10 to 200 μm, preferably 15 to 150 μm.

In the release film used in the present invention, it is necessary that the pressure-sensitive adhesive remain on the release film during use. For that purpose, the ten-point average roughness Rz of the surface of the release film on the side in contact with the pressure-sensitive adhesive is 0.15 to 0.5.
It needs to be 35 μm, preferably 0.2 to 0.3 μm.

The release film used in the present invention is usually one in which the interface side with the pressure-sensitive adhesive is easily peeled off so as to facilitate the peeling from the pressure-sensitive adhesive layer. That is, the release film is obtained by forming a release treatment layer on a film of the material shown below, and the 10-point average roughness according to the present invention is determined on the release-treated surface on the side in contact with the adhesive. This is a 10-point average roughness of the release film.

Examples of the material of the release film include those known per se in the art, and specifically, polyesters such as polyethylene terephthalate, polyvinyl chloride, polyvinylidene chloride, various acrylic and methacrylic polymers, Examples thereof include plastic films such as polystyrene, polycarbonate, polyimide, cellulose acetate (acetate), regenerated cellulose (cellophane), and celluloid, and laminated films of high-quality paper or glassine paper and polyolefin. Thus, it is preferable to use a polyester film in terms of safety, economy, and drug transferability. Polyester constituting the polyester film is a crystalline linear saturated polyester composed of an aromatic dibasic acid component and a diol component, for example, polyethylene terephthalate, polybutylene terephthalate, polypropylene terephthalate,
Polyethylene-2,6-naphthalate and the like can be exemplified. In particular, a polyethylene terephthalate (PET) film is preferable in terms of economy.

The release film having the above surface roughness (especially, polyester film) usually has a 10-point average roughness of 0.15 on the surface of the release film (especially, polyester film) before the release treatment. It can be manufactured by subjecting the substrate to a peeling treatment of about 0.35 μm.

The release film (particularly a polyester film) having such a surface roughness before the release treatment is, for example, 0.5 to 30% by weight, preferably 3 to 20% by weight of a filler having an average particle diameter of 1 to 10 μm. It can be obtained by forming a release film (especially a polyester film) blended in the range of weight%. In the case of laminating paper and plastic, the surface roughness depends on the surface roughness of the plastic film.

Here, the average particle diameter is a value measured by a commercially available particle size distribution analyzer using a laser diffraction / light scattering method.

The compounding ratio of the filler varies depending on the type of the filler, but may be 0.5 to the total amount of the film including the filler.
When the amount is less than 30% by weight, the surface roughness of 0.15 to 0.35 μm cannot be obtained. When the amount is more than 30% by weight, the surface roughness becomes too large, and the adhesion of the pressure-sensitive adhesive to the release film increases.
Further, when the amount of the filler is too large, the concealing property of the film is increased, and it is difficult to confirm foreign substances on the surface of the pressure-sensitive adhesive, which is not preferable.

The 10-point average roughness of the surface of the release film is as follows:
0.15 to 0.35 μm, preferably 0.2 to
The range is 0.3 μm. 10 points average roughness is 0.15
When the particle size is smaller than μm, the adhesion of the pressure-sensitive adhesive increases and the transfer of the drug to the release film increases, so that the amount of the drug in the preparation decreases and the expected effect of the drug cannot be obtained. On the other hand, if the surface roughness is larger than 0.35 μm, the concealing property of the film becomes high, and it becomes difficult to confirm foreign substances on the surface of the pressure-sensitive adhesive. This increases the amount of adhesion to the film.

The concealing property of the release film described above can be represented by the haze of the film and is defined by JIS K71.
It is most effective that the haze value specified in 05 is in the range of 50 to 80%. If the haze value is lower than 50%, an appropriate surface roughness cannot be obtained. A more preferred range is 55 to 75%.

The film having the above haze can be produced by the same method as that for the release film having the above surface roughness. The haze depends on the refractive index of light between the filler and the polymer of the base film. In the case of inorganic filler and PET,
It is preferable to mix the inorganic filler having an average particle diameter of 1 to 10 μm in the range of 0.5 to 2% by weight based on the total amount of the film including the filler. In the case of an organic filler, it is preferable to add an organic filler having an average particle diameter of 1 to 10 μm in a range of 10 to 30% by weight. When the surface roughness and the haze cannot be performed with the same composition, the films can be manufactured by laminating separately prepared films.

As a method for producing a release film, especially a polyester film, a conventionally known method, for example, a biaxially stretched polyester film is melted by an extruder and then melted from a T-type die or an I-type die. It can be manufactured by extruding on a rotating drum, rapidly cooling to an unstretched film, and then stretching the unstretched film in the biaxial direction and heat-fixing as necessary.

In the present invention, examples of the filler used to achieve the above surface roughness include inorganic fillers such as silica, kaolin, talc, titanium oxide, calcium carbonate, and alumina. Is most preferably 0.5 to 2% by weight with an average particle diameter of 1 to 10 μm based on the total amount of the film including the filler. As the organic filler, silicone resin particles, crosslinked polystyrene particles, polyester particles, polyethylene particles,
Examples thereof include polypropylene particles, and the compounding ratio is most preferably 10 to 30% by weight with an average particle diameter of 1 to 10 μm.

The release treatment in the present invention is usually carried out by forming a release treatment layer. The release treatment layer is formed, for example, by forming a thin film made of a material mainly containing a curable silicone resin. In addition to the main component, for example, a crosslinking agent, a reaction catalyst, an inorganic filler, silicone oil, other resin components, and the like may be blended.

The types of curable silicone resins include solvent addition type, solvent condensation type, solvent ultraviolet curing type, solventless addition type, solventless condensation type, solventless ultraviolet curing type, and solventless electron beam curing type. is there. Specific examples of the silicone resin used in the present invention include KS manufactured by Shin-Etsu Chemical Co., Ltd.
-774, KS-775, KS-778, KS-779
H, KS-856, X-62-2422, X-62-2
461, KNS-305, KNS-3000, X-62
-1256, DKQ manufactured by Dow Corning Asia Ltd.
3-202, DKQ3-203, DKQ3-204, D
KQ3-205, DKQ3-210, YSR-3022, TPR-6700, TP manufactured by Toshiba Silicone Co., Ltd.
R-6720, TPR-6721 and the like.

As a method of providing the release treatment layer, conventionally known coating methods such as bar coating, reverse roll coating, gravure coating, rod coating, air doctor coating, and doctor blade coating are used.

The thickness of the release treatment layer is from 0.01 to 5
μm is preferred. When the thickness of the release treatment layer is less than 0.01 μm, coating unevenness occurs and uniformity of the coating film cannot be obtained,
If it is 5 μm or more, the transfer amount of the drug increases, and the releasability deteriorates. The more preferable thickness of the release treatment layer is in the range of 0.1 to 3 μm.

The thickness of the release film is generally from 10 to 200 μm, preferably from 50 to 100, in view of handleability.
It is in the range of μm.

In the present invention, the release force of the release film from the pressure-sensitive adhesive layer is preferably from 10 to 400 mN / cm. If the release force is less than 10 mN / cm, when the preparation is taken out of the packaging bag, the preparation is likely to be peeled off from the release film and rolled up, or the preparation is rolled up during production. Remains on the release film, reducing the drug content and reducing the therapeutic effect. A more preferable range of the peeling force is 50 to 30.
The range is 0 mN / cm.

The release force can be adjusted by the type and composition of the silicone resin in the release treatment layer, the thickness of the release treatment layer, the thickness of the release film, and the like.

As a suitable release film, for example, 50E-0010 No. 33H, 75E
-0010 No. 33H or MRN U-100 series manufactured by Mitsubishi Polyester Film & Chemical Co., Ltd.

Further, the mere increase of the surface roughness of the release film increases the hiding power of the film due to the added filler, so that the foreign matter cannot be confirmed when inspecting the foreign matter of the adhesive during the production. There is. Therefore, by setting the haze value (JIS K 7105) of the release film to 50 to 80%, it is possible to have the same foreign substance inspection performance as that of a transparent film and maintain the above-mentioned peeling performance. is there.

The method for producing the patch preparation of the present invention is not particularly limited. For example, a drug and an adhesive are dissolved or dispersed in a solvent, and the resulting solution or dispersion is applied to one surface of a support and dried. A method in which an adhesive layer is formed on the surface of a support, and a release film is further provided. Also,
The above solution or dispersion is applied on a release film for protection, dried to form an adhesive layer on the release film,
Thereafter, the support can be manufactured by adhering the support to the pressure-sensitive adhesive layer.

The thickness of the pressure-sensitive adhesive layer of the present invention is usually 1
It is 0 to 200 μm, preferably 15 to 150 μm.

The patch preparation of the present invention can be applied not only to ordinary skin but also to mucous membranes such as oral mucosa.

The patch preparation of the present invention is used to prevent the adhesive layer from being unnecessarily adhered to instruments, containers and the like during production, transportation or storage, and to prevent deterioration of the preparation. Until immediately, it is desirable to cover and protect the exposed surface of the pressure-sensitive adhesive layer with a release film. Then, it is peeled off at the time of use to expose the surface of the pressure-sensitive adhesive layer, and is applied to an application site such as skin, mucous membrane or oral mucosa to be administered.

[0055]

EXAMPLES Hereinafter, the present invention will be described specifically with reference to examples, but the present invention is not limited to these examples. In addition,
In the following description, parts mean parts by weight.

Example 1 An adhesive A solution was prepared by copolymerizing 95 parts of 2-ethylhexyl acrylate and 5 parts of acrylic acid in ethyl acetate under an inert gas atmosphere. 60 parts of lidocaine was added to 40 parts (solid content) of the pressure-sensitive adhesive A solution and mixed and dissolved, and the resulting solution was subjected to a polyester release film (75E-00 manufactured by Fujimori Industries Co., Ltd.).
10 No. 33H), and the resultant was coated so as to have a thickness of about 20 μm after drying, and dried to form an adhesive layer. Then
This pressure-sensitive adhesive layer is split into nonwoven fabrics (thickness: 0.42 mm, mass: 90 g / m ² ) prepared by splitting and entangled composite fibers having a polypropylene content of 55% by weight and a polyester content of 45% by weight by a spunlace method. The patch preparation of the present invention was prepared by lamination.

Example 2 As a polyester release film, 75E-0010 No. manufactured by Fujimori Industries Co., Ltd. was used. 2
A patch preparation of the present invention was prepared in the same manner as in Example 1 except that 3 white was used.

Example 3 As a polyester release film, MRN manufactured by Mitsubishi Chemical Polyester Film Co., Ltd.
A patch preparation of the present invention was prepared in the same manner as in Example 1 except that 75U100 was used.

Example 4 As a polyester release film, MRD manufactured by Mitsubishi Chemical Polyester Film Co., Ltd.
A patch preparation of the present invention was prepared in the same manner as in Example 1 except that 75W100 was used.

Comparative Example 1 As a polyester release film, 75E-0010 No. 3
Except for using Sample No. 3, a patch preparation of Comparative Example 1 was prepared in the same manner as in Example 1.

[Comparative Example 2] Polyester release film 75E-0010 No. manufactured by Fujimori Kogyo KK 2
Except for using Sample No. 3, a patch preparation of Comparative Example 2 was prepared in the same manner as in Example 1.

Comparative Example 3 As a polyester release film, MRD manufactured by Mitsubishi Chemical Polyester Film Co., Ltd.
Comparative Example 3 in the same manner as in Example 1 except that No. 75 was used.
Was prepared.

The patch preparations obtained in the above Examples and Comparative Examples were subjected to the following performance evaluations (1) to (5), and the results are shown in Table 1.

(1) Measurement of Cohesion Force After cutting two preparations into a shape of 10 mm × 20 mm, the release film of each preparation was removed, and the adhesive surfaces of the two preparations were adhered to each other. 300 per minute
Pass twice over the formulation at a speed of mm and leave at room temperature for 30 minutes. The adjusted sample is 10 mm x 70 mm so that it can be easily peeled off by holding it with the chuck of the tensile tester.
Attach auxiliary paper of mm size. Next, using a tensile tester, the load when the two preparations were peeled off at a speed of 120 mm per minute was measured and defined as the cohesive force. At this time, it is confirmed that the pressure-sensitive adhesives of the two preparations are sufficiently integrated with each other, and that the state at the time of peeling is a stringing state. If the two preparations do not string, and peel off cleanly at the interface where they are stuck, they do not have cohesive strength.

(2) Measurement of Peeling Force A single preparation was cut into a size of 10 mm × 30 mm, and the load when the preparation was peeled from the release film at a speed of 120 mm per minute was measured with a tensile tester (manufactured by Shimadzu Corporation). EZ Te
Measured in st) and used as the peeling force. An auxiliary paper of 10 mm × 70 mm is attached to one end of the adhesive surface of the preparation so that the sample can be easily gripped by the chuck of the tensile tester.

(3) Measurement of 10-point average roughness Rz The surface roughness of the release surface of the release film was measured in accordance with JIS B060.
The 10-point average roughness Rz defined in 1 was measured three-dimensionally using an atomic force microscope (AFM) shown below. AFM
The equipment is Seiko Instruments SPI3800, Si
The measurement was performed in a non-contact mode using a deep needle (spring constant: 20 N / m) manufactured by Toshiba Corporation.

(4) Measurement of Transfer Rate of Drug to Release Film Sealed preparations prepared in Examples and Comparative Examples were sealed in a packaging bag, and stored at 50 ° C. for 3 months. The amount of drug attached to the mold film is
All were extracted and the amount of lidocaine was measured by high performance liquid chromatography. The transfer rate of the drug to the release film was calculated by the following equation. (Transfer rate to release film%) = A ÷ (A + B) × 10
0 A: Lidocaine amount attached to release film B: Lidocaine amount in formulation

(5) Visual Confirmation of Adhesive Residue The patch preparations prepared in Examples and Comparative Examples were sealed in a packaging bag, stored at 50 ° C. for 3 months, and then the release film was peeled off from the preparation to release. The amount of the adhesive adhered to the mold film was evaluated according to the following criteria. 0: No adhesive was visually observed. 1; Slight deposits can be confirmed. 2: Deposits can be clearly seen. 3: Deposits can be confirmed together with drug crystals.

(6) Measurement of Haze Value The haze values of the release films used in Examples and Comparative Examples were measured in accordance with JIS K 7105, Method A for measuring light transmittance.

(7) Visual Confirmation of Foreign Material on Adhesive Surface Visually, human hair (about 3 mm in length) was put between the adhesive and the release film of the preparations prepared in Examples and Comparative Examples. It was visually observed from the film side and evaluated according to the following criteria. 0: Hair is not visible at all. 1: A shadow can be seen through the light of a fluorescent lamp. 2: It can be confirmed visually.

Table 1 and FIG. 1 show the measurement results.

[0072]

[Table 1]

As shown in Table 1, the adhesive preparations obtained in Examples 1 to 4 hardly adhered the adhesive to the release film, and were excellent in stability because of extremely suppressed drug transfer. It was a formulation. On the other hand, although the release films of the comparative examples are all transparent release films, foreign substances can be easily confirmed, but the release film is smooth and has a large peeling force, so that the adhesion of the adhesive and the migration of the drug are large and the drug in the preparation The content decreased, and a stable preparation could not be obtained.

Further, since the release films of Examples 1 and 3 had a haze value in the range of 50 to 80%, excellent performance that foreign substances on the pressure-sensitive adhesive surface could be easily confirmed through the release film. Having.

Generally, it is considered that if the surface roughness is large, the surface area is large, so that the peeling force is large and the adhesive residue is likely to be generated. However, surprisingly, it was found that as shown in FIG. 1, when the surface roughness (10-point average surface roughness) of the release film was increased, the adhesive residue and the accompanying migration of the drug were reduced. Therefore, by setting the 10-point average surface roughness to 0.15 to 0.35 μm, it is possible to suppress the adhesion of the pressure-sensitive adhesive to the release film and the transfer of the accompanying drug, and to provide a highly stable patch preparation. You can get it.

[0076]

According to the present invention, even when the cohesive force of the entire adhesive is reduced by adding a drug or an additive (a transdermal absorption enhancer or a plasticizer) to the adhesive, a crosslinking treatment or a filler is required. The adhesive residue on the release film of the pressure-sensitive adhesive can be reduced without performing an extra process such as addition of the adhesive. In the patch preparation of the present invention, adhesive residue is less likely to occur even when a flexible support such as a cloth is used.

That is, the present invention provides a method for producing a pressure-sensitive adhesive containing a drug, which has a weak cohesion of 10 N / cm or less.
10-point average roughness Rz of the surface of the release film is 0.15 to 0.15.
By setting the thickness to 0.35 μm, good releasability can be imparted without performing a cross-linking treatment or the like, so that the adhesive is suppressed from remaining on the release film.
The drug content in the preparation does not decrease, and a good therapeutic effect as designed can be obtained. The present invention can of course be applied to those having a cohesion force of more than 10 N / cm, but the effects of the present invention are more remarkably exhibited by applying to the above-mentioned cohesion force of 10 N / cm or less. In the patch preparation of the present invention, adhesive residue is less likely to occur even when a flexible support such as a cloth is used.

[Brief description of the drawings]

FIG. 1 is a graph showing the relationship between 10-point average roughness and adhesive residue on a release film (transfer of a drug to a release film).

 ──────────────────────────────────────────────────続 き Continuation of front page (72) Inventor Masaaki Ito 1-2-1, Shimohozumi, Ibaraki-shi, Osaka Nitto Denko Corporation F-term (reference) 4C076 AA80 BB31 CC01 EE09A EE10A EE12A EE48A FF70 4J004 AA04 AA05 AA08 AA09 AA10 AA11 AB01 CA02 CA04 CA05 CA06 CB01 CC05 CE01 CE02 DA04 DB03 EA06 FA09 4J040 CA041 CA091 DA141 DD051 DE031 DF001 DM011 ED021 EK031 GA07 GA08 GA14 GA19 GA22 GA25 LA06 MA09 MA10 MA11 MA15 MB02 NA02 PA23

Claims (8)

[Claims] 1. An adhesive preparation comprising a drug-containing pressure-sensitive adhesive layer and a release film sequentially laminated on a support, wherein the surface of the release film in contact with the pressure-sensitive adhesive has a 10-point average roughness Rz of 0. An adhesive preparation having a size of from 15 to 0.35 μm. 2. The patch preparation according to claim 1, wherein the release force of the release film from the pressure-sensitive adhesive layer is 10 to 400 mN / cm. 3. The cohesive force of a drug-containing adhesive is 10N.
The patch preparation according to claim 1 or 2 which is not more than / cm. 4. The release film is a polyester film and has a haze value of 50 to 80 specified in JIS K 7105.
% Of the patch preparation according to claim 1. 5. The patch preparation according to claim 1, wherein the support is a cloth. 6. The patch preparation according to claim 1, wherein the drug is a local anesthetic. 7. The adhesive preparation according to claim 1, wherein the adhesive is an acrylic adhesive. 8. The patch preparation according to any one of claims 1 to 7, which is used for mucosal patch.