Adhesive patch

Abstract

To provide a patch with excellent initial adhesion and skin permeability of felbinac. [Solution] A patch comprising an ointment, wherein the ointment contains felbinac, styrene-isoprene-styrene block copolymer, and zinc oxide, and the zinc oxide content in the ointment is 0.08 to 5% by mass.

Description

Technical Field

[0001] The present invention relates to a patch containing felbinac.

Background Art

[0002] Felbinac is one of the non-steroidal anti-inflammatory drugs that exhibit excellent anti-inflammatory and analgesic effects and has been used as a topical agent for a long time. For example, felbinac-containing patches as shown in Patent Documents 1 to 5 are known.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

Patent Document 5

Summary of the Invention

Problems to be Solved by the Invention

[0004] As described above, patches containing felbinac as a drug are known. However, the inventors' study has found that it is difficult to achieve both improved adhesiveness and improved skin permeability of felbinac with conventional felbinac-containing patches. The present invention has been made in view of the above circumstances, and an object thereof is to provide a patch excellent in initial adhesiveness and skin permeability of felbinac.

Means for Solving the Problems

[0005] The patch according to the embodiment that has solved the above problems is as follows. [1] Having an ointment, The ointment is Felbinac, Styrene-isoprene-styrene block copolymer, and Contains zinc oxide, A patch containing 0.08 to 5% by mass of zinc oxide in the ointment.

[0006] The patch according to the embodiment can improve initial tackiness and skin permeability of felbinac by containing a styrene-isoprene-styrene block copolymer and a predetermined amount of zinc oxide in the ointment. The patch according to the embodiment is preferably one of the following [2] to [9]. [2] The patch according to [1], wherein the content of the styrene-isoprene-styrene block copolymer in the ointment is 1 to 350 parts by mass per 1 part by mass of zinc oxide. [3] The patch according to [1] or [2], further comprising l-menthol. [4] The patch according to [3], wherein the content of l-menthol in the ointment is 1 to 50 parts by mass per 1 part by mass of zinc oxide. [5] The adhesive patch according to any one of [1] to [4], further comprising an tackifier, wherein the tackifier comprises an alicyclic saturated hydrocarbon resin. [6] The patch according to any one of [1] to [5], further comprising liquid polybutene. [7] The patch according to any one of [1] to [6], wherein the content of felbinac in the ointment is 0.1 to 10% by mass. [8] The patch according to any one of [1] to [7], wherein the content of the styrene-isoprene-styrene block copolymer in the ointment is 1 to 30% by mass. [9] The patch according to any one of [1] to [8], further comprising a support, wherein the ointment is disposed on one side of the support. [Effects of the Invention]

[0007] The above configuration makes it possible to provide a patch with excellent initial adhesion and skin permeability of felbinac. [Modes for carrying out the invention]

[0008] The patch according to this embodiment has an ointment, which contains felbinac, styrene-isoprene-styrene block copolymer, and zinc oxide, with the zinc oxide content in the ointment being 0.08 to 5% by mass. Thus, the patch according to this embodiment can improve initial tackiness and skin permeability of felbinac by containing styrene-isoprene-styrene block copolymer and a predetermined amount of zinc oxide in the ointment. The components of the patch according to this embodiment will be described in detail below.

[0009] The patch according to this embodiment has an ointment. The ointment contains felbinac. Felbinac can be used, for example, as an anti-inflammatory and analgesic drug.

[0010] The felbinac content in the ointment is preferably 0.1 to 10% by mass, more preferably 0.3 to 8% by mass, and even more preferably 0.5 to 6% by mass. A felbinac content of preferably 0.1% by mass or more enhances the effectiveness of felbinac in the body. More preferably 0.3% by mass or more, and even more preferably 0.5% by mass or more. On the other hand, a felbinac content of preferably 10% by mass or less improves the physical properties of the patch and reduces costs. More preferably 8% by mass or less, and even more preferably 6% by mass or less. The felbinac may be completely dissolved in the ointment, or it may be partially dispersed without dissolving.

[0011] The ointment may contain active ingredients other than felbinac. Hereinafter, active ingredients that exhibit pharmacological effects other than felbinac will simply be referred to as active ingredients. Examples of active ingredients include glycyrrhetinic acid, tocopherol acetate, camphor, methyl salicylate, glycol salicylate, and lidocaine. The ointment may contain only one of these, or two or more. The ointment preferably contains at least one active ingredient selected from the group consisting of glycyrrhetinic acid and tocopherol acetate, and more preferably contains glycyrrhetinic acid and tocopherol acetate. The content of active ingredients in the ointment is preferably 0.05 to 15% by mass, more preferably 0.05 to 10% by mass, even more preferably 0.1 to 5% by mass, and even more preferably 1 to 4% by mass. As will be described later, l-menthol has analgesic and anti-inflammatory effects, but it also has functions as a cooling agent and a transdermal absorption enhancer. Therefore, when calculating the content of active ingredients other than felbinac, l-menthol will not be included in the calculation.

[0012] The ointment contains a styrene-isoprene-styrene block copolymer. Hereinafter, the styrene-isoprene-styrene block copolymer may be simply referred to as SIS. SIS is an adhesive and is not particularly limited as long as it is commonly used in adhesive patches. Examples of SIS include DX401, D1111K, D1119P, D1161P (manufactured by Kraton Polymer Japan Co., Ltd.), SIS5002, SIS5229 (manufactured by ENEOS Material Corporation), Quintac3421, Quintac3620, Quintac3450 (manufactured by Nippon Zeon Co., Ltd.). The ointment may contain only one of these, or two or more. The ratio of the mass of styrene in SIS to the mass of isoprene is preferably 10-30%, more preferably 12-28%, and even more preferably 15-25%.

[0013] The content of styrene-isoprene-styrene block copolymer in the paste is preferably 1 to 30% by mass. More preferably, it is 13 to 25% by mass, and still more preferably, it is 15 to 20% by mass. When the content of SIS is preferably 1% by mass or more, the cohesive force of the paste is improved, and the physical properties of the adhesive are improved. More preferably, it is 13% by mass or more, and still more preferably, it is 15% by mass or more. On the other hand, when the content of SIS is preferably 30% by mass or less, the workability during the production of the adhesive is improved. More preferably, it is 25% by mass or less, and still more preferably, it is 20% by mass or less.

[0014] The paste contains zinc oxide. Zinc oxide is considered to have a function of suppressing the generation of the decomposition product of felbinac and also has an effect of enhancing the transdermal absorption of felbinac. In addition, zinc oxide shows an effect of improving the initial adhesiveness of the paste.

[0015] The content of zinc oxide in the paste is 0.08 to 5% by mass, preferably 0.10 to 3% by mass, more preferably 0.12 to 1.0% by mass, still more preferably 0.15 to 0.7% by mass, and even more preferably 0.17 to 0.5% by mass. When the content of zinc oxide is 0.08% by mass or more, it becomes easier for zinc oxide to improve the initial adhesiveness and transdermal absorption. Preferably, it is 0.10% by mass or more, more preferably 0.12% by mass or more, still more preferably 0.15% by mass or more, and even more preferably 0.17% by mass or more. On the other hand, when the content of zinc oxide is too large, it becomes difficult to improve the transdermal absorption, but when the content of zinc oxide is 5% by mass or less, the transdermal absorption can be maintained at a high level. Preferably, it is 3% by mass or less, more preferably 1.0% by mass or less, still more preferably 0.7% by mass or less, and even more preferably 0.5% by mass or less. In the paste, zinc oxide preferably exists in a dispersed state. Considering the dispersibility and transdermal absorption during production, zinc oxide with an average particle diameter of 0.01 to 50 μm is preferred.

[0016] The ointment preferably contains l-menthol. L-menthol is a cooling agent, but also has analgesic and anti-inflammatory effects, and further has a function of promoting transdermal absorption. The l-menthol content in the ointment is preferably 0.5 to 10% by mass, more preferably 1 to 8% by mass, even more preferably 2 to 6% by mass, and even more preferably 3.5 to 5% by mass. A l-menthol content of preferably 0.5% by mass or more makes it easier for the cooling agent function and the function of promoting transdermal absorption to be exhibited. More preferably 1% by mass or more, even more preferably 2% by mass or more, and even more preferably 3.5% by mass or more. On the other hand, a l-menthol content of preferably 10% by mass or less can improve the physical properties of the ointment. More preferably 8% by mass or less, even more preferably 6% by mass or less, and even more preferably 5% by mass or less.

[0017] The ointment preferably contains a styrene-isoprene-styrene block copolymer in addition to other adhesives (hereinafter sometimes referred to as "other adhesives"). Examples of other adhesives include liquid rubbers such as liquid polybutene, liquid polyisoprene, and liquid polyisobutylene; styrene-butadiene-styrene block copolymer; styrene-butadiene rubber; natural rubber; and rubber-based elastomers such as isoprene rubber. The ointment may contain only one of these, or two or more. The ointment preferably contains liquid rubber, and more preferably liquid polybutene. The inclusion of liquid polybutene improves the plasticity of the ointment. In particular, liquid polybutene is thought to enhance the initial tackiness improvement effect of zinc oxide. The content of other adhesives in the ointment is preferably 0.5 to 20% by mass, more preferably 1.0 to 15% by mass, even more preferably 1.5 to 10% by mass, and even more preferably 1.8 to 8% by mass. The content of other adhesives in the ointment is preferably less than the content of SIS. This makes it easier to adjust the balance of physical properties such as adhesiveness and plasticity.

[0018] The paste preferably contains an adhesion-imparting agent. The adhesion-imparting agent preferably contains at least one selected from the group consisting of an alicyclic saturated hydrocarbon resin, a terpene resin, and an ester gum, more preferably contains at least one selected from the group consisting of an alicyclic saturated hydrocarbon resin and a terpene resin, and still more preferably contains an alicyclic saturated hydrocarbon resin. In particular, the alicyclic saturated hydrocarbon resin can prevent the paste from bleeding through during high-temperature storage. The bleeding through of the paste means that the paste leaks out to the other side of the support on which the paste is placed, which is the side opposite to one side of the support. The softening point of the alicyclic saturated hydrocarbon resin measured by the ring and ball method is preferably 90 to 120°C, and more preferably 95 to 105°C. Thereby, it becomes easier to achieve both the adhesion-imparting property of the alicyclic saturated hydrocarbon resin and the property of preventing the paste from bleeding through during high-temperature storage. Examples of the alicyclic saturated hydrocarbon resin include the Alcon series manufactured by Arakawa Chemical Industries, Ltd., and Alcon P100 is preferred. The content of the adhesion-imparting agent in the paste is preferably 10 to 50% by mass, more preferably 20 to 45% by mass, and still more preferably 30 to 40% by mass. When the content of the adhesion-imparting agent is preferably 10% by mass or more, the adhesive force tends to improve. More preferably, it is 20% by mass or more, and still more preferably 30% by mass or more. On the other hand, when the content of the adhesion-imparting agent is preferably 50% by mass or less, an excessive improvement in the adhesive force can be avoided. More preferably, it is 45% by mass or less, and still more preferably 40% by mass or less.

[0019] The ointment preferably contains a softening agent. The softening agent is not particularly limited as long as it has good compatibility with other base components and gives flexibility to the ointment. Examples of softening agents include paraffin oil such as liquid paraffin; fatty acid esters such as isopropyl myristate, diisopropyl adipate, diethyl sebacate, diisopropyl sebacate, and isopropyl palmitate; higher alcohols such as octyldodecanol; silicone oil; lanolin; squalane; squalene; castor oil, etc. The ointment may contain only one of these, or it may contain two or more. The ointment preferably contains at least one softening agent selected from the group consisting of diethyl sebacate and liquid paraffin, and more preferably contains diethyl sebacate and liquid paraffin. The content of the softening agent in the ointment is preferably 10 to 70% by mass, more preferably 15 to 60% by mass, and even more preferably 20 to 50% by mass, taking into account the content of other components.

[0020] The ointment preferably contains an antioxidant. Examples of antioxidants include dibutylhydroxytoluene, ascorbic acid, 2-mercaptobenzimidazole, and pentaerythrityl-tetrakis-[3-(3,5-di-t-butyl-4-hydroxyphenyl)propionate]. The ointment may contain only one of these, or two or more. The ointment preferably contains dibutylhydroxytoluene. The antioxidant content in the ointment is preferably 0.1 to 5% by mass, more preferably 0.15 to 3% by mass, even more preferably 0.2 to 2% by mass, and even more preferably 0.3 to 1% by mass.

[0021] The ointment may contain other components. Examples of other components include hydrophobic polymers such as polyacrylic acid polymers and silicone rubber; inorganic fillers such as aluminum hydroxide, hydrated aluminum silicate, titanium dioxide, zinc acetate, anhydrous silicic acid, and magnesium silicate; and liquid components. Liquid components do not necessarily have to be liquid at room temperature; they may also become liquid when heated during manufacturing. Examples of liquid components include polyhydric alcohols, pyrrolidone compounds, surfactants, and crotamiton. The ointment may contain only one of these other components, or it may contain two or more.

[0022] The content of styrene-isoprene-styrene block copolymer in the ointment is preferably 1 to 350 parts by mass, more preferably 35 to 320 parts by mass, and even more preferably 50 to 300 parts by mass, per 1 part by mass of zinc oxide. Skin permeability is improved when the SIS content relative to zinc oxide is preferably 1 part by mass or more. More preferably 35 parts by mass or more, and even more preferably 50 parts by mass or more. On the other hand, adhesive strength is improved when the SIS content relative to zinc oxide is preferably 350 parts by mass or less. More preferably 320 parts by mass or less, and even more preferably 300 parts by mass or less.

[0023] The l-menthol content in the ointment is preferably 1 to 50 parts by mass, more preferably 4 to 48 parts by mass, even more preferably 8 to 46 parts by mass, and even more preferably 10 to 44 parts by mass, per 1 part by mass of zinc oxide. A l-menthol content of 1 part by mass or more relative to zinc oxide improves skin permeability. More preferably 4 parts by mass or more, even more preferably 8 parts by mass or more, and even more preferably 10 parts by mass or more. On the other hand, an l-menthol content of 50 parts by mass or less relative to zinc oxide improves adhesiveness. More preferably 48 parts by mass or less, even more preferably 46 parts by mass or less, and even more preferably 44 parts by mass or less.

[0024] The thickness of the ointment is preferably 10 to 500 μm, more preferably 50 to 200 μm, and even more preferably 70 to 150 μm.

[0025] The patch preferably has a support. It is preferable that the ointment is disposed on one side of the support. The patch further preferably has a release liner. The release liner is preferably disposed on the side opposite the support, with the ointment in between. Specifically, the patch preferably has a support, ointment, and release liner in this order. For example, in the manufacturing process of the patch, the ointment can be attached to the support by spreading or coating.

[0026] The support preferably has a porous body, foam, knitted fabric, woven fabric, nonwoven fabric, film, or a laminate thereof, and more preferably a woven fabric. Examples of materials for the support include polyethylene, polypropylene, polyvinyl chloride, polyester, nylon, polyurethane, and rayon. The support may contain only one of these materials, or two or more.

[0027] The release liner preferably has a film, paper, or a laminate thereof. The film preferably includes a polyethylene terephthalate film, a polypropylene film, or a laminate thereof, and more preferably a polyethylene terephthalate film. The release liner may be silicone-treated as needed to optimize the release force.

[0028] The patch of this embodiment is useful for the prevention or treatment of diseases or symptoms in which improvement of the condition is expected by administering felbinac contained in the ointment. Such diseases or symptoms include inflammation or pain. Examples of inflammation or pain include muscle pain, osteoarthritis, and post-traumatic swelling and pain.

[0029] "Prevention" refers to administering a transdermal patch to an individual who has not yet developed the disease or symptoms. "Treatment," on the other hand, refers to administering a transdermal patch to an individual who has already developed the disease or symptoms. Therefore, administering a transdermal patch to an individual who has already developed the disease or symptoms to prevent worsening of symptoms, prevent seizures, or prevent recurrence is a form of "treatment."

[0030] The transdermal patch of this embodiment is preferably applied to patients, such as humans or animals, who are suffering from or at risk of suffering from a disease or symptoms, and more preferably to humans. The number of applications may be appropriately varied depending on the severity of the disease or symptoms, the patient's age, weight, sex, the amount of felbinac in the patch, etc. However, when administered to humans, the patch is preferably replaced once or multiple times a day, for example, 1 to 3 times, 1 to 2 times, or once, or once every few days (for example, every 2 to 3 days).

[0031] The following is an example of a method for manufacturing the patch according to the embodiment. First, an adhesive such as SIS, a softening agent such as liquid paraffin, an antioxidant, and a tackifier are mixed and heated to dissolve and prepare an adhesive base. Next, an active ingredient solution containing felbinac and other active ingredients, a fatty acid ester, l-menthol, and zinc oxide are added to the adhesive base and stirred and mixed to prepare an adhesive body. Next, the adhesive body is coated onto a silicone-treated polyethylene terephthalate film to form an adhesive layer with a thickness of 10 to 500 μm. A polyester woven fabric, which is a support, is laminated onto the adhesive body on the film formed in this way. After that, the patch can be obtained by cutting it to an appropriate size and shape as needed. [Examples]

[0032] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to the following examples, and can be implemented with modifications within the scope that is consistent with the spirit of the preceding and following descriptions, and all such modifications are included within the technical scope of the present invention. In addition, the numerical values ​​of content in the examples and comparative examples are in "mass%" unless otherwise specified.

[0033] (Example 1) Styrene-isoprene-styrene block copolymer (SIS), liquid polybutene, liquid paraffin, and dibutylhydroxytoluene were kneaded and melted at 170°C in the quantities shown in Table 1. An alicyclic saturated hydrocarbon resin was then added and kneaded and mixed at 130°C to prepare an adhesive base. Separately, diethyl sebacate, l-menthol, glycyrrhetinic acid, tocopherol acetate, felbinac, and zinc oxide were mixed and uniformly dispersed while stirring to prepare an active ingredient solution. This active ingredient solution was added to the above-mentioned adhesive base and kneaded until uniformly dispersed to prepare an ointment. The obtained ointment was coated to a thickness of 100 μm onto a silicone-treated polyethylene terephthalate film, and then layered with a polyester woven fabric to obtain a test formulation. Details of each component used are shown below. Zinc oxide (manufactured by Sakai Chemical Industry Co., Ltd., Type 1) SIS (Kraton DX401, manufactured by Kraton Polymers Japan Co., Ltd.) Liquid polybutene (manufactured by ENEOS Material Co., Ltd., HV-300) Alicyclic saturated hydrocarbon resin (Arakawa Chemical Industries, Ltd., Alcon P100) Liquid paraffin (manufactured by Kaneda Co., Ltd., Highcol M-352)

[0034] (Examples 2 and 3) The test formulations for Example 2 and Example 3 were obtained in the same manner as in Example 1, except that the liquid paraffin and zinc oxide content was as shown in Table 1.

[0035] (Comparative Example 1) The test formulation of Comparative Example 1 was obtained in the same manner as in Example 1, except that zinc oxide was not added and the liquid paraffin content was as shown in Table 1.

[0036] Table 1 shows the content of each component in the ointment of each test formulation.

[0037] [In vitro skin permeability test] In vitro skin permeability tests were performed on each test formulation in hairless rats. Specifically, abdominal skin was excised from male hairless rats (HWY strain, 7 weeks old), placed in a Franz-type diffusion cell, with the dermal side facing the receptor side, and the inside filled with phosphate-buffered saline. 37°C warm water was circulated through the water jacket. Each test formulation was placed in a circular (1.77 cm) container. 2 The receptor fluid was punched out and applied to the excised skin. Then, 24 hours after the start of the test, the receptor fluid was sampled and the amount of felbinac permeated the skin was measured by high-performance liquid chromatography. The measurement conditions were as follows. Column: ACQUITY UPLC BEH 1.7μm (2.1×100mm) Mobile phase: 10% acetonitrile:90% acetonitrile:phosphate = 40:60:0.1 Flow rate: 0.2mL Wavelength: 249nm Injection volume: 7μL The test results are shown in Table 1.

[0038] [Adhesion Test] Each test formulation was subjected to a 180° peel adhesion test in accordance with the Japanese Pharmacopoeia. The test results are shown in Table 1.

[0039] [Table 1]

[0040] As shown in Table 1, it was found that adding a predetermined amount of zinc oxide to an ointment containing felbinac and styrene-isoprene-styrene block copolymer increased the skin penetration of felbinac and improved its initial tackiness.

[0041] (Example 4) The test formulation for Example 4 was obtained in the same manner as in Example 2, except that the content of each component was as shown in Table 2. The content of each component and the results of the adhesion test for Example 2 and Example 4 are shown in Table 2.

[0042] [Table 2]

[0043] Based on the results in Table 2, it is considered that the initial tackiness improvement effect of zinc oxide is enhanced by liquid polybutene.

[0044] (Example 5) The test formulation of Example 5 was obtained in the same manner as in Example 2, except that the alicyclic saturated hydrocarbon resin was replaced with a rosin ester. Furthermore, the following ointment bleed-through test was performed. The content of each component in Example 2 and Example 5 and the results of the ointment bleed-through test are shown in Table 3.

[0045] [Patent bleed-through test] For each patch (7cm x 10cm) from Example 2 and Example 5, we checked for the presence or absence of ointment seepage after storage at 25°C for 24 hours and after storage at 70°C for 24 hours.

[0046] [Table 3]

[0047] As shown in Table 3, it was revealed that alicyclic saturated hydrocarbon resins can prevent the ointment from seeping through to the back of the paper during high-temperature storage. It is believed that this prevents the ointment from seeping through to the back of the paper, thereby maintaining its adhesive strength.

[0048] Table 4 shows other examples of transdermal patch formulations 1 to 5. Examples 1 to 5 can be prepared in the same manner as in Example 1, except, for example, the amounts of each component are as shown in Table 4.

[0049] [Table 4]

Claims

1. Having an ointment, The ointment is Felbinac, Styrene-isoprene-styrene block copolymer, and Contains zinc oxide, A patch in which the zinc oxide content in the ointment is 0.08 to 5% by mass.

2. The patch according to claim 1, wherein the content of the styrene-isoprene-styrene block copolymer in the ointment is 1 to 350 parts by mass per 1 part by mass of zinc oxide.

3. The patch according to claim 1, further comprising l-menthol in the ointment.

4. The patch according to claim 3, wherein the content of l-menthol in the ointment is 1 to 50 parts by mass per 1 part by mass of zinc oxide.

5. The adhesive patch according to claim 1, further comprising a tackifier, wherein the tackifier comprises an alicyclic saturated hydrocarbon resin.

6. The patch according to claim 1, further comprising liquid polybutene in the ointment.

7. The patch according to claim 1, wherein the content of felbinac in the ointment is 0.1 to 10% by mass.

8. The patch according to claim 1, wherein the content of the styrene-isoprene-styrene block copolymer in the ointment is 1 to 30% by mass.

9. The patch according to any one of claims 1 to 8, further comprising a support, wherein the ointment is disposed on one surface of the support.

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