JP2007022939A - Plaster for external use - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a plaster for external use free from the adsorption of a drug on a printed face even in a plaster having a substrate with a printed layer and capable of suppressing the decomposition or discoloration of the drug caused by light exposure, etc. <P>SOLUTION: The plaster for external use is composed of a substrate layer, a plaster layer and a releasing liner. The substrate layer is a polyester film having a polyester-coated printed layer on one surface and the plaster layer contains nicotine as an active component. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to an external patch containing a drug. More specifically, in a patch having a support having a printed layer, the drug is prevented from adsorbing on the printed surface of the support, and the drug is decomposed or colored by light exposure or the like. The present invention relates to a patch for external use capable of suppressing the above.

  An external patch is an excellent dosage form in that it does not cause side effects of drugs that cause problems when taking oral preparations, does not decrease bioavailability, etc., and can be administered continuously. one of. Currently used as an external patch, for example, as an anti-inflammatory analgesic such as indomethacin, an angina / heart failure treatment such as nitroglycerin, a climacteric / osteoporosis treatment such as estradiol, and a bronchodilator such as tulobuterol An external patch has been developed and is commercially available.

  This external patch is generally composed of a support layer impermeable to the drug or other components, a paste layer containing the drug, and a separable release liner. Since the target for application of the external patch containing the drug is mainly human skin, the formulation is designed in consideration of the least possible adverse effects on the skin. Among them, the support for external patches is required to have properties such as flexibility, moisture permeability, self-supporting (rigidity), and excellent adhesion to the plaster layer in addition to drug impermeability. .

  On the other hand, the drug contained in the paste layer of the external patch includes various components, but components having problematic properties are also known. For example, nicotine, which is a volatile drug, has properties such as oxidation by strong alkali, decomposition or coloration by exposure to light. Further, depending on the support used for the external patch, nicotine has problems such as a decrease in nicotine content due to adsorption or permeation of nicotine to the support. Therefore, in a patch containing nicotine, it is necessary to select and use a support that does not cause adsorption or permeation of nicotine.

  Then, in order to solve the above problems, for example, a nicotine transdermal administration device using a nicotine-impermeable support is disclosed (Patent Document 1). However, since the support of the patch of the invention of Patent Document 1 uses a transparent laminate film or the like as the nicotine-impermeable support, the decomposition or coloring of nicotine in the plaster layer due to light is suppressed. There is a problem that you can not.

  In order to solve the problem of decomposition or coloring of nicotine in the plaster layer due to light, a nicotine-containing transdermal absorption patch using an opaque film coated with a metal such as aluminum as a support is commercially available. As a nicotine patch containing a metal coating layer, for example, a patch using a support in which aluminum is vapor-deposited on both sides of a plastic film and a release liner is disclosed (Patent Document 2).

  On the other hand, by forming a printing layer on the surface of the support described in Patent Document 1, that is, the nicotine impermeable laminate film support, nicotine in the plaster layer is decomposed or colored by light. It is possible to suppress. By applying a print layer such as skin color on the surface of the support, it is possible to suppress the decomposition or coloring of nicotine in the plaster layer due to light, and to make the application of the patch inconspicuous. It is possible to improve. Furthermore, compared with the case where a metal coating layer such as aluminum is included, the number of manufacturing steps is reduced, the material cost is reduced, and the patch can be manufactured at a low cost.

  However, when a printing layer is provided on the surface of the patch support, the nicotine volatilized from the cut surface (side surface) of the patch is absorbed or adsorbed on the printed layer part, and the nicotine absorbed or adsorbed on the printed layer part is absorbed. New problems such as decomposition or coloring by light have occurred. From the above, there has been a demand for a patch that can suppress the adsorption of nicotine to the printed layer portion, improve the feeling of use when the patch is applied, and can be manufactured at a lower cost.

Special Table 2002-532540 Special table 2003-509363 gazette

  The present invention solves the above-described problems, and even in a patch having a support having a printed layer, there is no adsorption of the drug to the printed surface, and the decomposition or coloring of the drug due to light exposure or the like can be suppressed. The problem is to provide an external patch.

  As a result of intensive studies to solve the above problems, the present inventors have solved the above problems by using a laminate film in which a polyester coating layer is further laminated on the printed layer provided on the support layer. As a result, the present invention was completed.

  That is, the present invention is an external patch composed of a support layer, a paste layer and a release liner, and the support layer is a polyester film having a printed layer coated with polyester on one side, and the paste layer is effective. An external patch characterized by containing nicotine as a component.

  The support layer used in the present invention is a laminate film in which a printing layer is applied on one side of a polyester film and the surface of the printing layer is coated with polyester. Examples of the polyester film forming the support include polyethylene terephthalate, polyethylene isophthalate, polypropylene terephthalate, and polypropylene isophthalate. Among them, polyethylene terephthalate is preferable.

  Although there is no restriction | limiting in particular as this polyester film, From the surface of a softness | flexibility etc., the thing of the thickness of about 1-20 micrometers is preferable, and the thing of about 10-16 micrometers is especially preferable.

  The printed layer formed on the polyester film is colored to a skin color or the like so that light transmission is suppressed and the patch is not noticeable. The ink used for this printing is not particularly limited, and is particularly excellent when using an ink that has excellent light-shielding properties, improves the feeling of use when applying a patch, and has nicotine absorbability or adsorptivity. Is highly effective. Examples of preferable ink include urethane-based ink.

  Further, as a printing method for forming the printing layer, a known printing method can be used, and for example, a gravure printing method, a flexographic printing method, an offset printing method, or the like can be used. Among these, a preferred printing method for the support of the present invention is a gravure printing method, which can transfer a sufficient amount of ink and enables printing with a dense and heavy feeling.

  Further, the printed layer may be a single layer, or may be a printed layer of two layers, three layers or more. However, considering the light shielding property, texture, cost, etc., 2 It is preferred to use a printing layer consisting of layers.

  In addition, you may display information, such as a handling method, notes, and a brand name, on this printed layer as needed.

  In the support of the present invention, it is necessary to further coat the polyester on the printed layer. This polyester coating is performed by a conventionally used coating method such as a dry laminating method.

  Examples of the polyester used in the polyester coating include polyethylene terephthalate, polyethylene isophthalate, polypropylene terephthalate, and polypropylene isophthalate.

  The support used in the present invention may be the above-mentioned polyester film / printing layer / polyester coating layer, but in order to improve the feeling of use and feel of the support, a polyolefin resin such as polyethylene is further laminated. be able to.

  The lamination of the polyolefin resin can be performed, for example, by an extrusion coating / laminating method. The polyolefin resin used is preferably a polyethylene film, and the thickness of the film is preferably about 5 to 30 μm.

  The external patch of the present invention contains nicotine as an active ingredient in the plaster layer. Since this nicotine is a drug that has volatility and has properties such as decomposition and coloring upon exposure to light, the effect of the support layer of the present invention is remarkable.

  The plaster layer containing nicotine of the present invention as an active ingredient contains an adhesive in the base. Examples of the pressure sensitive adhesive include rubber pressure sensitive adhesive, acrylic pressure sensitive adhesive, and silicon pressure sensitive adhesive. Among them, a rubber-based pressure-sensitive adhesive is preferable, and natural rubber, polyisoprene, styrene-isoprene-styrene block copolymer, styrene-butadiene-styrene block copolymer, butyl rubber, styrene-butadiene rubber, and the like as an elastomer of the rubber-based pressure-sensitive adhesive It is preferable to use one kind selected from polyisobutylene alone, or to use two or more kinds in combination.

  The external patch includes, as its configuration, a drug-containing means for storing a necessary drug and a fixing means for fixing the drug-containing layer on the skin. There are a patch and a reservoir-type patch, and any of them may be used in the present invention. That is, a reservoir-type patch, which is a patch comprising two layers of a drug storage layer containing a drug and an adhesive layer for fixing to the skin, and a drug containing the drug and the adhesive, the two layers being integrated Any of the matrix type patches comprising the containing pressure-sensitive adhesive layer may be used. However, the reservoir type patch has a complicated formulation design due to the use of a drug storage layer and an adhesive layer, and the cost increases when expensive materials are used. It is preferable from the viewpoint of formulation and economy.

  Furthermore, as an external patch of the present invention, a plaster layer containing a drug in a base containing an adhesive, in addition to a single layer of a drug-containing adhesive layer containing a drug and an adhesive as a paste layer And a layer formed by laminating two layers of a paste layer containing or not containing a drug in a base containing an adhesive, or a layer formed by laminating three or more paste layers You can also.

  In the present invention, nicotine used as a drug is 0.1 to 50% by mass (hereinafter simply referred to as “%”), preferably 1 to 30%, based on the entire composition constituting the plaster layer. Used. If it is less than 0.1%, a sufficient amount of transdermal absorption of the drug cannot be obtained, which is not preferable. On the other hand, when the amount exceeds 50%, the pseudo-collectability of the paste layer is lowered due to the influence of the drug, and a good paste layer cannot be obtained.

  In the external patch of the present invention, the plaster layer can contain known optional components in addition to the components described above. Examples of the optional component include tackifiers such as alicyclic saturated hydrocarbon resins, terpene resins, and rosin resins, softeners such as liquid paraffin, castor oil, and lanolin, pentaerythrityl-tetrakis- [3- (3, 5-di-t-butyl-4-hydroxyphenyl) propionate], antioxidants such as dibutylhydroxytoluene and the like.

  The thickness of the paste layer in the external patch of the present invention is not particularly limited, but is 30 to 1000 μm, preferably 50 to 800 μm. If it is less than 30 μm, it is difficult to adjust the thickness of the paste layer with high accuracy, and a good paste layer cannot be obtained. On the other hand, if the thickness exceeds 1000 μm, the transdermal absorbability of the drug and its utilization rate decrease, which is not preferable.

  In the external patch of the present invention, a drug-impermeable release liner is used on the exposed surface of the plaster layer (the surface on the opposite side of the support attachment surface). Examples of the release liner include a film made of a polymer material such as polyethylene, polypropylene, and polyester, a film in which aluminum is vapor-deposited on a film, and a film in which silicone oil is coated on paper. However, a polyester film is preferable from the viewpoint of no nicotine permeation, processability and low cost, and a polyethylene terephthalate film is particularly preferable. Further, the release liner may be a laminate film obtained by bonding a plurality of materials.

  Production of the external patch of the present invention is not particularly limited and can be produced by a known production method. For example, it can be carried out by applying and spreading a drug and other components to be blended into the plaster layer on a release liner or the like by an appropriate coating method, providing a matrix layer, and attaching a support to the matrix layer. it can. As another method, a drug and other components to be blended in the plaster layer are coated and spread on a support by an appropriate coating method to provide a matrix layer, and a release liner or the like is bonded to the matrix layer. A method is also mentioned.

  In the external patch of the present invention obtained as described above, the support layer to be used is preferably formed from a polyester film that does not contain a metal coating such as aluminum. As the support of the present invention, a polyester film having a metal coating can be used. However, in the present invention, a metal coating layer is not originally required, and the drug can be sufficiently decomposed or eliminated without the metal coating layer. It is possible to suppress coloring. In addition, the addition of a metal coating layer is not preferable because it causes an increase in cost and a complicated manufacturing process.

  Hereinafter, the present invention will be described in more detail with reference to examples and test examples, but the present invention is not limited thereto.

Example 1
External patch (1):
An external patch was prepared by the following composition and production method.
(Composition) Weight part (1) Nicotine 10 parts (2) Raw rubber 20 parts (3) Styrene-isoprene-styrene block copolymer 20 parts
(Product name: Clayton KX-401, manufactured by Shell Japan)
(4) 20 parts liquid paraffin
(Product name: High Call M-352, manufactured by Kaneda Corporation)
(5) Hydrogenated terpene resin 30 parts
(Product name: Clearon P-105, manufactured by Yasuhara Chemical)

(Production method)
Dissolve nicotine, raw rubber, styrene-isoprene-styrene block copolymer, liquid paraffin and hydrogenated terpene resin in toluene, and on a polyethylene terephthalate film (average thickness 75 μm) so that the thickness after evaporation of the solvent is 50 μm. And the toluene layer was distilled off to obtain a plaster layer. Then, the paste layer was bonded to the lower surface side of the following laminate film (1). Thereafter, cutting and packaging were performed to obtain an external patch (Product 1 of the present invention).

Laminate film (1):
A laminate film composed of polyethylene (12 μm, extrusion coating / laminating method) / polyethylene terephthalate (13 μm, dry lamination method) / printing layer (skin color / gravure printing) / polyethylene terephthalate (13 μm) from the upper surface to the lower surface.

Example 2
External patch (2):
An external patch was prepared by the following composition and production method.
(Composition) Weight part (1) Nicotine 10 parts (2) Styrene-isoprene-styrene block copolymer 25 parts
(Product name: Clayton KX-401, manufactured by Shell Japan)
(3) Alicyclic saturated hydrocarbon resin 45 parts
(Product name: Alcon P-100, Arakawa Chemical Co., Ltd.)
(4) 20 parts liquid paraffin
(Product name: High Call M-352, manufactured by Kaneda Corporation)

(Production method)
Polyethylene terephthalate film (average thickness 75 μm) so that nicotine, styrene-isoprene-styrene block copolymer, alicyclic saturated hydrocarbon resin and liquid paraffin are dissolved in toluene, and the thickness after evaporation of the solvent is 50 μm The mixture was spread out and toluene was distilled off to obtain a plaster layer. Thereafter, the plaster layer was bonded to the lower surface side of the laminate film (1). Thereafter, cutting and packaging were performed to obtain an external patch (Product 2 of the present invention).

Example 3
External patch (3):
An external patch was prepared by the following composition and production method.
(Composition) Weight part (1) Nicotine 10 parts (2) Styrene-isoprene-styrene block copolymer 25 parts
(Product name: Clayton KX-401, manufactured by Shell Japan)
(3) 45 parts of rosin ester
(Product name: KE-311, manufactured by Arakawa Chemical Co., Ltd.)
(4) 20 parts liquid paraffin
(Product name: High Call M-352, manufactured by Kaneda Corporation)

(Production method)
Nicotine, styrene-isoprene-styrene block copolymer, rosin ester and liquid paraffin are dissolved in toluene and spread on a polyethylene terephthalate film (average thickness 75 μm) so that the thickness after evaporation of the solvent is 100 μm. Toluene was distilled off to obtain a paste layer. Thereafter, the plaster layer was bonded to the lower surface side of the laminate film (1). Thereafter, cutting and packaging were performed to obtain an external patch (Product 3 of the present invention).

Example 4
External patch (4):
An external patch was prepared by the following composition and production method.
(Composition) Weight part (1) Nicotine 15 parts (2) Styrene-isoprene-styrene block copolymer 25 parts
(Product name: Clayton D-1107, manufactured by Shell Japan)
(3) 20 parts liquid paraffin
(Product name: High Call M-352, manufactured by Kaneda Corporation)
(4) 40 parts of rosin ester
(Product name: Esther Gum H, Arakawa Chemical Co., Ltd.)

(Production method)
Nicotine, styrene-isoprene-styrene block copolymer, liquid paraffin and rosin ester are dissolved in toluene and spread on a polyethylene terephthalate film (average thickness 75 μm) so that the thickness after evaporation of the solvent is 80 μm. Toluene was distilled off to obtain a paste layer. Thereafter, the plaster layer was bonded to the lower surface side of the laminate film (1). Thereafter, cutting and packaging were performed to obtain an external patch (present product 4).

Example 5
External patch (5):
An external patch was prepared by the following composition and production method.
(Composition) Weight part (1) Nicotine 5 parts (2) Acrylic pressure sensitive adhesive 95 parts
(Product name: DURO-TAK 87-2516,
(National Starch and Chemical)

(Production method)
Nicotine is dissolved in an acrylic pressure-sensitive adhesive, spread on a polyethylene terephthalate film (average thickness 75 μm) so that the thickness after evaporation of the solvent is 100 μm, and the organic solvent is distilled off to obtain a paste layer Got. Thereafter, the plaster layer was bonded to the lower surface side of the laminate film (1). Thereafter, cutting and packaging were carried out to obtain an external patch (Product 5 of the present invention).

Example 6
External patch (6):
An external patch was prepared by the following composition and production method.
(Composition)
A. First plaster layer Weight part (1) Nicotine 15 parts (2) Styrene-isoprene-styrene block copolymer 25 parts
(Product name: Clayton KX-401, manufactured by Shell Japan)
(3) Hydrogenated terpene resin 40 parts
(Product name: Clearon P-105, manufactured by Yasuhara Chemical)
(4) 20 parts liquid paraffin
(Product name: High Call M-352, manufactured by Kaneda Corporation)
B. Second plaster layer parts by weight (1) 30 parts of styrene-isoprene-styrene block copolymer
(Product name: Clayton KX-401, manufactured by Shell Japan)
(2) Hydrogenated terpene resin 30 parts
(Product name: Clearon P-105, manufactured by Yasuhara Chemical)
(3) 40 parts liquid paraffin
(Product name: High Call M-352, manufactured by Kaneda Corporation)

(Production method)
Nicotine, styrene-isoprene-styrene block copolymer, hydrogenated terpene resin, and liquid paraffin are dissolved in toluene, and on a polyethylene terephthalate film (average thickness 25 μm) so that the thickness after evaporation of the solvent is 100 μm. The first plaster layer was obtained by spreading and distilling off toluene. Then, the 1st plaster body layer was bonded together to the lower surface side of said laminate film (1). Next, a styrene-isoprene-styrene block copolymer, a hydrogenated terpene resin and liquid paraffin are heated and mixed, and spread on a polyethylene terephthalate film (average thickness 75 μm) so as to have a thickness of 400 μm. A plaster layer was obtained. Then, after removing the polyethylene terephthalate film of the first plaster layer and laminating the second plaster layer, it was cut and packaged to obtain an external preparation patch (Product 6 of the present invention).

Example 7
External patch (7):
An external patch was prepared by the following composition and production method.
(Composition)
A. First plaster layer parts by weight (1) 30 parts of nicotine (2) 40 parts of styrene-isoprene-styrene block copolymer
(Product name: Clayton D-1107, manufactured by Shell Japan)
(3) 30 parts of rosin ester
(Product name: KE-311, manufactured by Arakawa Chemical Co., Ltd.)
B. Second plaster layer parts by weight (1) 30 parts of styrene-isoprene-styrene block copolymer
(Product name: Clayton D-1107, manufactured by Shell Japan)
(2) 30 parts of rosin ester
(Product name: KE-311, manufactured by Arakawa Chemical Co., Ltd.)
(3) 40 parts liquid paraffin
(Product name: High Call M-352, manufactured by Kaneda Corporation)

(Production method)
Nicotine, styrene-isoprene-styrene block copolymer and rosin ester are dissolved in toluene and spread on a polyethylene terephthalate film (average thickness 25 μm) so that the thickness after evaporation of the solvent is 100 μm. Distilled off to obtain a first plaster layer. Thereafter, the first plaster layer was bonded to the lower surface side of the laminate film (1). Next, styrene-isoprene-styrene block copolymer, rosin ester and liquid paraffin are heated and mixed, and spread on a polyethylene terephthalate film (average thickness 75 μm) so as to have a thickness of 800 μm. A body layer was obtained. Then, after removing the polyethylene terephthalate film of the first plaster layer and laminating the second plaster layer, it was cut and packaged to obtain an external preparation patch (Product 7 of the present invention).

Example 8
External patch (8):
An external patch was prepared by the following composition and production method.
(Composition)
A. First plaster layer Weight part (1) Nicotine 15 parts (2) Styrene-isoprene-styrene block copolymer 25 parts
(Product name: Clayton KX-401, manufactured by Shell Japan)
(3) Hydrogenated terpene resin 40 parts
(Product name: Clearon P-105, manufactured by Yasuhara Chemical)
(4) 20 parts liquid paraffin
(Product name: High Call M-352, manufactured by Kaneda Corporation)
B. Second plaster layer parts by weight (1) 30 parts of styrene-isoprene-styrene block copolymer
(Product name: Clayton KX-401, manufactured by Shell Japan)
(2) Hydrogenated terpene resin 30 parts
(Product name: Clearon P-105, manufactured by Yasuhara Chemical)
(3) 40 parts liquid paraffin
(Product name: High Call M-352, manufactured by Kaneda Corporation)

(Production method)
Nicotine, styrene-isoprene-styrene block copolymer, hydrogenated terpene resin and liquid paraffin are dissolved in toluene and spread on a polyethylene terephthalate film (average thickness 25 μm) so that the thickness after evaporation of the solvent is 100 μm. And toluene was distilled off to obtain a first plaster layer. Then, the 1st plaster body layer was bonded together to the lower surface side of the following laminate film (2). Next, a styrene-isoprene-styrene block copolymer, a hydrogenated terpene resin and liquid paraffin are heated and mixed, and spread on a polyethylene terephthalate film (average thickness 75 μm) so as to have a thickness of 400 μm. A plaster layer was obtained. Then, after removing the polyethylene terephthalate film of the first plaster layer and laminating the second plaster layer, it was cut and packaged to obtain an external preparation patch (Product 8 of the present invention).

Laminate film (2):
Laminating film composed of polyethylene (12 μm, extrusion coating / laminating method) / polyethylene terephthalate (13 μm, dry lamination method) / printing layer (skin color, gravure printing) / aluminum-deposited polyethylene terephthalate (13 μm) from top to bottom .

Comparative Example 1
External patch for comparison:
An external patch (Comparative product 1) was obtained by the same composition and production method as in Example 6 except that the following comparative laminate film was used instead of the laminate film obtained in Production Example 1.

Comparative laminate film:
Commercially available aluminum deposition support (laminated film composed of polyethylene (dyeing) / aluminum deposition polyethylene terephthalate, from top to bottom).

Test example 1
Light irradiation test:
The inventive product 6, the inventive product 8, the comparative product 1 and the commercially available nicotine patch (aluminum-deposited film support: comparative product 2) obtained in the above examples were respectively combined with composite films (outside: polyethylene terephthalate / polyacrylonitrile: Each was packaged one by one in a bag consisting of the inside. After packaging, it was stored in a constant temperature and humidity room (3000 Lux, 25 ° C., 60% RH) for 25 days. The properties of the preparation after storage (whether the support and plaster were colored) were observed, and the drug content in the plaster layer was further measured. Nicotine was quantified by HPLC. The results are shown in Table 1.

  As is clear from Table 1, the product 6 of the present invention had no change in properties and drug content before the start of storage. In the product 8 of the present invention, a slight coloration was observed, but the degree thereof was very small, there was no decrease in drug content, and there was no problem in use. On the other hand, the comparative product 1 and the comparative product 2 showed clear coloring on the support and the paste, and the comparative product 1 showed a decrease in the drug content.

  As described above, in an external patch composed of a support layer, a paste layer and a release liner, a laminate film in which a printing layer is applied to one side of a polyester film as a support layer, and the surface of the printing layer is coated with polyester By using this, it is possible to obtain a patch for external use in which the drug is not adsorbed on the printing surface and the decomposition or coloring of the drug due to light exposure or the like is suppressed.

In particular, the support of the external patch of the present invention does not include a metal coating layer, so that the number of manufacturing steps is reduced compared to the case of including a metal coating layer, and the material cost is reduced, so that it is manufactured at a low cost. Is possible. Therefore, it is possible to manufacture and provide an external patch having a storage stability equivalent to or better than that of a commercially available external patch at a low cost.

more than

Claims (6)

  An external patch comprising a support layer, a paste layer and a release liner, the support layer being a polyester film having a printed layer coated with polyester on one side, the paste layer containing nicotine as an active ingredient A patch for external use characterized by the above.   The external patch according to claim 1, wherein the polyester film of the support layer is a polyethylene terephthalate film.   The external patch according to claim 1 or 2, wherein the support layer is a laminate film obtained by further laminating a polyolefin resin on a polyester-coated printing layer.   The external patch according to claim 3, wherein the polyolefin resin is polyethylene.   The external patch according to any one of claims 1 to 4, wherein the printed layer in the support layer is formed from two printed layers. The external patch according to any one of claims 1 to 5, wherein the support layer does not contain a metal coating layer.