Blonanserin-containing patch

Abstract

To provide a patch containing blonanserin and a rubber-based adhesive base, ensuring superior skin penetrability of blonanserin.SOLUTION: A patch includes an adhesive layer on a support. The adhesive layer includes blonanserin or a pharmaceutically acceptable salt thereof, a rubber-based adhesive base, acetic acid, acetate, and liquid paraffin. In the adhesive layer, the value calculated by the formula: {acetic acid content (mass%)×acetate content (mass%)} / blonanserin content (mass%) is 0.02-30.SELECTED DRAWING: None

Description

[Technical Field]

[0001] This invention relates to a blonanserin-containing patch. [Background technology]

[0002] 2-(4-ethyl-1-piperazinyl)-4-(4-fluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine (hereinafter referred to as blonanserin) is used clinically as a treatment for schizophrenia, and recently it has also been sold as a transdermal patch (product name: Lonasen® Tape).

[0003] The properties of transdermal patches containing blonanserin have been studied. Patent Document 1 describes that transdermal patches containing blonanserin and an acrylic adhesive suppress the formation of metabolites and can maintain a sustained blood drug concentration. Patent Document 2 describes that transdermal patches containing blonanserin, an acrylic polymer, lactic acid, and a specified stabilizer maintain a blood concentration sufficient for the blonanserin to exert its therapeutic effect and also exhibit excellent storage stability. Patent Document 3 describes that transdermal patches containing blonanserin, lactic acid, and a specific additive exhibit excellent skin permeability of blonanserin.

[0004] Most of the blonanserin-containing patches studied to date have contained acrylic adhesive bases, and research on patches containing rubber adhesive bases has been insufficient. [Prior art documents] [Patent Documents]

[0005] [Patent Document 1] International Publication No. 2007 / 142295 [Patent Document 2] Japanese Patent Publication No. 2016-130269 [Patent Document 3] International Publication No. 2012 / 105624 [Overview of the Initiative] [Problems that the invention aims to solve]

[0006] The present inventors investigated the skin permeability of blonanserin in a patch containing blonanserin and a rubber-based adhesive base, and found that skin permeability may be insufficient in some cases. Therefore, the object of the present invention is to provide a patch containing blonanserin and a rubber-based adhesive base that exhibits excellent skin permeability of blonanserin. [Means for solving the problem]

[0007] Through diligent research, the inventors discovered that a patch containing acetic acid, acetate, and liquid paraffin, in which the content of acetic acid, acetate, and blonanserin in the adhesive layer satisfies a predetermined relationship, exhibits excellent skin permeability of blonanserin, thus completing the present invention.

[0008] In other words, the present invention includes the following [1] to [4]. [1] A patch comprising an adhesive layer on a support, The above adhesive layer contains blonanserin or a pharmaceutically acceptable salt thereof, a rubber-based adhesive base, acetic acid, an acetate, and liquid paraffin. In the above adhesive layer, the following formula: {Acetic acid content (mass%) × Acetate salt content (mass%)} / Blonanserin content (mass%) A transdermal patch whose calculated value is between 0.02 and 30. [2] The adhesive patch according to [1], wherein the adhesive layer does not contain lactic acid. [3] The patch according to [1] or [2], wherein the acetate salt is sodium acetate. [4] The adhesive patch according to any one of [1] to [3], wherein the rubber-based adhesive base is a styrene-isoprene-styrene block copolymer, polyisobutylene, or a combination thereof. [Effects of the Invention]

[0009] According to the present invention, it is possible to provide a patch containing blonanserin and a rubber-based adhesive base that exhibits excellent skin permeability of blonanserin. [Modes for carrying out the invention]

[0010] The present invention will be described in detail below with reference to embodiments of the present invention.

[0011] A patch according to one embodiment of the present invention comprises an adhesive layer on a support, wherein the adhesive layer contains blonanserin or a pharmaceutically acceptable salt thereof, a rubber-based adhesive base, acetic acid, an acetate salt, and liquid paraffin, and the value calculated in the adhesive layer using the following formula: {acetic acid content (mass%) × acetate salt content (mass%)} / blonanserin content (mass%) is 0.02 to 30. Here, the content (mass%) of each component is based on the total mass of the adhesive layer. In the case of a patch containing a pharmaceutically acceptable salt of blonanserin in the adhesive layer, "blonanserin content (mass%)" means the mass% of blonanserin on a free form basis.

[0012] The support material can be any material capable of maintaining the shape of the adhesive, particularly the adhesive layer. Examples of support material materials include polyethylene, polypropylene, polybutadiene, ethylene-vinyl chloride copolymer, polyvinyl chloride, polyamides such as nylon, polyester, cellulose derivatives, and synthetic resins such as polyurethane. The properties of the support material can be, for example, films, sheets, porous sheets, foamed sheets, woven fabrics, knitted fabrics, nonwoven fabrics, and laminates thereof. The thickness of the support material is not particularly limited, but is usually preferably about 2 μm to 3000 μm.

[0013] The adhesive layer is formed from an adhesive composition obtained by mixing blonanserin or a pharmaceutically acceptable salt thereof, a rubber-based adhesive base, acetic acid, an acetate, liquid paraffin, and optional components described later. The mass per unit area of ​​the adhesive layer is not particularly limited, but is 30 g / m². 2 ~400g / m 2 It can be done as 40g / m 2~300 g / m 2 、 40 g / m 2 ~200 g / m 2 、 or 60 g / m 2 ~180 g / m 2 may be used. When the mass per unit area of the adhesive layer exceeds 400 g / m 2 , the patch is likely to fall off when the clothing is put on or taken off. When the mass per unit area of the adhesive layer is less than 30 g / m 2 , the adhesiveness of the patch is likely to decrease.

[0014] The pharmaceutically acceptable salts of bronanthan serin refer to those of the acid addition salts of bronanthan serin that are available for pharmaceutical use. Examples of organic acids include formic acid, acetic acid, adipic acid, citric acid, tartaric acid, methanesulfonic acid, fumaric acid, maleic acid, etc. Examples of inorganic acids include hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, etc. Bronanthan serin or its pharmaceutically acceptable salts may be anhydrides or hydrates.

[0015] The content of bronanthan serin can be 1% to 20% by mass, based on the total mass of the adhesive layer, and may be 3% to 20% by mass, 3% to 15% by mass, 3% to 11% by mass, 3% to 7% by mass, or 6% to 10% by mass. Note that the above mass% means the mass% in terms of the free form of bronanthan serin when the patch contains a pharmaceutically acceptable salt of bronanthan serin in the adhesive layer.

[0016] Examples of rubber-based adhesive bases include natural rubber, polyisobutylene, alkyl vinyl ether (co) polymer, polyisoprene, polybutadiene, styrene-butadiene copolymer, styrene-isoprene copolymer, styrene-isoprene-styrene block copolymer, etc. The rubber-based adhesive base may be used alone or in combination of two or more. Among them, from the perspective that the rubber-based adhesive base according to this embodiment tends to exhibit more sufficient adhesive force of the adhesive layer, a styrene-isoprene-styrene block copolymer, polyisobutylene, or a combination thereof is preferable.

[0017] Specific examples of styrene-isoprene-styrene block copolymers include Quintac® 3570C (trade name, manufactured by Nippon Zeon Co., Ltd.), SIS5002, SIS5229, SIS5505, SIS5505P (trade names, manufactured by JSR Corporation), SIBSTAR® T102 (trade name, manufactured by Kaneka Corporation), and others. Polyisobutylene also includes so-called butyl rubber (isobutylene-isoprene rubber), with Oppanol® being a specific example. Examples include N50, N80, N100, N150, B11, B12, B50, B80, B100, B120, B150, B220 (product names, manufactured by BASF), JSR® Butyl065, 268, 365 (product names, manufactured by JSR Corporation), X_Butyl® RB100, 101-3, 301, 402 (product names, manufactured by ARLANXEO), Exxon® Butyl065, 065S, 068, 068S, 268, 268S, 365, 365S (product names, manufactured by Exxon Mobile), Butyl065, 268, 365 (product names, manufactured by Nippon Butyl Co., Ltd.), etc.

[0018] The content of the rubber-based adhesive base can be 10% to 90% by mass, based on the total mass of the adhesive layer, and may be 15% to 60% by mass, 15% to 40% by mass, or 15% to 30% by mass.

[0019] The adhesive layer contains acetic acid and an acetate along with liquid paraffin, resulting in excellent skin permeability of blonanserin. Examples of acetates include sodium acetate, calcium acetate, and potassium acetate, and one of these may be used alone or in combination of two or more. Sodium acetate is preferred.

[0020] The acetic acid content can be 0.1% to 10% by mass, based on the total mass of the adhesive layer, and may be 0.2% to 10%, 0.4% to 10%, 0.2% to 6%, 0.5% to 4.5%, or 1.5% to 4.5% by mass. The acetate content can be 0.1% to 10% by mass, based on the total mass of the adhesive layer, and may be 0.2% to 10%, 0.4% to 10%, 0.2% to 6%, 0.4% to 4.5%, or 1.4% to 4.5% by mass.

[0021] Due to the excellent skin permeability of blonanserin, the value calculated in the above adhesive layer using the following formula: {acetic acid content (mass%) × acetate content (mass%)} / blonanserin content (mass%) is 0.02 to 30, may be 0.3 to 30, preferably 0.02 to 13, more preferably 0.15 to 3, and particularly preferably 0.3 to 3.

[0022] The adhesive layer contains liquid paraffin along with acetic acid and acetate, resulting in excellent skin permeability of blonanserin. Specific examples of liquid paraffin include Hycol M-222, Hycol M-352 (trade names, manufactured by Kaneda Corporation), Hydrobrite HV, and Hydrobrite 1000 (trade names, manufactured by Sonneborn). When the adhesive layer contains liquid paraffin, the liquid paraffin content is, for example, 3% to 50% by mass, preferably 5% to 50% by mass, more preferably 6% to 45% by mass, and particularly preferably 13% to 41% by mass, based on the total mass of the adhesive layer.

[0023] Because patches containing lactic acid and a rubber-based adhesive base tend to reduce the skin permeability of blonanserin, it is preferable that the adhesive layer does not contain lactic acid.

[0024] The adhesive layer may optionally further contain other additives. Examples of other additives include tackifying resins, plasticizers (excluding liquid paraffin), absorption enhancers, solvents, stabilizers, fillers, and fragrances.

[0025] Tackifying resins are components that adjust the tackiness of the adhesive layer. Examples of tackifying resins include petroleum resins, terpene resins, rosin resins, phenolic resins, and xylene resins. Examples of petroleum resins include alicyclic petroleum resins (alicyclic saturated hydrocarbon resins, etc.), aliphatic petroleum resins (aliphatic hydrocarbon resins, etc.), and aromatic petroleum resins. More specifically, examples include Alcon P-70, Alcon P-85, Alcon P-90, Alcon P-100, Alcon P-115, Alcon P-125, Alcon M-70, Alcon M-85, Alcon M-90, Alcon M-100, Alcon M-115, Alcon M-125 (all trade names, manufactured by Arakawa Chemical Industries, Ltd.), and Escolets 8000 (trade name, manufactured by Esso Petrochemical Co., Ltd.). Examples of terpene resins include pinene polymers (α-pinene polymers, β-pinene polymers, etc.), terpene polymers, dipentene polymers, terpene-phenol polymers, aromatically modified terpene polymers, and pinene-phenol copolymers. More specifically, examples include YS resins (YS resin PXN (1150N, 300N), YS resin PX1000, YS resin TO125, YS resin TO105, etc.), Clearon P105, Clearon M115, Clearon K100 (all trade names, manufactured by Yasuhara Chemical Co., Ltd.), and Tamanol 901 (trade name, manufactured by Arakawa Chemical Industries, Ltd.). Examples of rosin resins include hydrogenated rosin glycerol ester, ultra-pale rosin, ultra-pale rosin ester, and acid-modified ultra-pale rosin. More specifically, examples include Pine Crystal (KE-311, PE-590, KE-359, KE-100, etc.) (trade name, manufactured by Arakawa Chemical Industries, Ltd.). One of these tackifying resins may be used alone, or two or more may be used in combination. Among these, alicyclic saturated hydrocarbon resins, terpene resins, hydrogenated rosin glycerol ester, or a combination thereof is preferred, and alicyclic saturated hydrocarbon resins, terpene resins, or a combination thereof is more preferred. When the adhesive layer contains a tackifying resin, the content of the tackifying resin can be 15% to 80% by mass, or 30% to 65% by mass, based on the total mass of the adhesive layer.

[0026] Examples of plasticizers other than liquid paraffin include light liquid paraffin, squalane, squalene, vegetable oils (olive oil, camellia oil, castor oil, tall oil, peanut oil, spearmint oil, eucalyptus oil, jojoba oil, camphor oil, sunflower oil, orange oil, etc.), fats and oils (dibutyl phthalate, dioctyl phthalate, etc.), and liquid rubber (liquid polybutene, liquid isoprene rubber, etc.). When the adhesive layer contains a plasticizer other than liquid paraffin, its content is, for example, 3% to 50% by mass, 5% to 30% by mass, or 7% to 20% by mass, based on the total mass of the adhesive layer.

[0027] The absorption enhancer can be any compound conventionally known to have transdermal absorption-enhancing properties. Examples of absorption enhancers include organic acid esters (e.g., fatty acid esters, cinnamic acid esters), organic acid amides (e.g., fatty acid amides), aliphatic alcohols, polyhydric alcohols, and ethers (e.g., aliphatic ethers, polyoxyethylene alkyl ethers). These absorption enhancers may have unsaturated bonds and may have cyclic, linear, or branched chemical structures. The absorption enhancer may also be a monoterpene compound, a sesquiterpene compound, or a vegetable oil (e.g., olive oil). These absorption enhancers may be used individually or in combination of two or more.

[0028] Examples of organic acid esters include ethyl acetate, propyl acetate, cetyl lactate, lauryl lactate, methyl salicylate, ethylene glycol salicylate, methyl cinnamate, and fatty acid esters. Examples of fatty acid esters include methyl laurate, hexyl laurate, isopropyl myristate, myristyl myristate, octyldodecyl myristate, isopropyl palmitate, and cetyl palmitate. Fatty acid esters may also be glycerin fatty acid esters, propylene glycol fatty acid esters, sorbitan fatty acid esters, polyethylene glycol sorbitan fatty acid esters, polyethylene glycol fatty acid esters, sucrose fatty acid esters, or polyoxyethylene hydrogenated castor oil. Specific examples of fatty acid esters include glycerin monocaprylate, glycerin monocaprate, glycerin monolaurate, glycerin monooleate, sorbitan monolaurate, sucrose monolaurate, polysorbate 20, propylene glycol monolaurate, polyethylene glycol monolaurate, polyethylene glycol monostearate, Span 40, Span 60, Span 80, Span 120 (product names, manufactured by Croda Japan Co., Ltd.), Tween® 20, Tween® 21, Tween® 40, Tween® 60, Tween® 80, and NIKKOL® HCO-60 (product name, manufactured by Nikko Chemicals Co., Ltd.).

[0029] Examples of organic acid amides include fatty acid amides (e.g., lauric acid diethanolamide), hexahydro-1-dodecyl-2H-azepine-2-one (also known as Azone) and its derivatives, and pyrothiodecane.

[0030] Aliphatic alcohols refer to alcohols with 6 to 20 carbon atoms. Examples of aliphatic alcohols include lauryl alcohol, myristyl alcohol, oleyl alcohol, isostearyl alcohol, and cetyl alcohol. An example of a polyhydric alcohol is propylene glycol.

[0031] Aliphatic ethers refer to ethers that have an aliphatic group (e.g., alkyl or alkenyl group) with 6 to 20 carbon atoms. An example of a polyoxyethylene alkyl ether is polyoxyethylene lauryl ether.

[0032] Examples of monoterpene compounds include geraniol, thymol, terpineol, l-menthol, borneol, d-limonene, isoborneol, nerol, and dl-camphor. Peppermint oil may also be used as a monoterpene compound.

[0033] If the adhesive layer contains an absorption accelerator, the amount of the absorption accelerator can be 2% to 40% by mass, based on the total mass of the adhesive layer.

[0034] The solvent is a component that facilitates the dissolution of blonanserin or a pharmaceutically acceptable salt thereof in the adhesive composition. Examples of solvents include fatty acid alkyl esters (e.g., isopropyl myristate, isopropyl palmitate), fatty acid polyhydric alcohol esters (e.g., propylene glycol monolaurate, glyceryl monolaurate, glyceryl monooleate, sorbitan monolaurate), fatty acid amides (e.g., diethanolamide laurate), aliphatic alcohols (e.g., octyldodecanol, isostearyl alcohol, oleyl alcohol), polyhydric alcohols (e.g., propylene glycol, dipropylene glycol, polyethylene glycol), and pyrrolidone derivatives (e.g., N-methyl-2-pyrrolidone). When the adhesive layer contains a solvent, the solvent content can be 2% to 40% by mass based on the total mass of the adhesive layer.

[0035] The stabilizer should be capable of suppressing the generation of free radicals and the progression of their chain reactions, which are generated by the action of light such as ultraviolet rays, heat, or activated chemical species. Examples of stabilizers include tocopherol and its ester derivatives, ascorbic acid and its ester derivatives, 2,6-dibutylhydroxytoluene (BHT), butylhydroxyanisole (BHA), and 2-mercaptobenzimidazole. The stabilizer may be used alone or in combination of two or more. If the adhesive layer contains a stabilizer, the stabilizer content may be 0.05% to 3% by mass, 0.05% to 1% by mass, 0.05% to 0.25% by mass, or 0.1% to 0.25% by mass, based on the total mass of the adhesive layer.

[0036] Examples of fillers include powders or short fibers of resins containing metal compounds (aluminum oxide, aluminum hydroxide, zinc oxide, titanium dioxide, calcium carbonate, etc.), ceramics (talc, clay, kaolin, silica, hydroxyapatite, synthetic aluminum silicate, magnesium aluminometasilicate, etc.), or organic compounds (cellulose powder, stearate, etc.). When the adhesive layer contains a filler, the filler content can be 0.1% to 20% by mass, based on the total mass of the adhesive layer.

[0037] The adhesive may further include a release liner. The release liner is laminated on the side opposite to the support relative to the adhesive layer. The presence of a release liner tends to reduce the adhesion of dust and other debris to the adhesive layer during storage. Preferably, the surface of the release liner that contacts the adhesive layer is treated with a release agent such as silicone or fluorinated polyolefin.

[0038] The material of the release liner is not particularly limited, and liners generally known to those skilled in the art can be used. Examples of release liners include paper; polyester such as polyethylene terephthalate and polyethylene naphthalate; polyolefins such as polyethylene and polypropylene; and films such as polyvinyl chloride, polyvinylidene chloride, nylon, and aluminum. The release liner may also be a laminated film of fine paper and polyolefin. A film made of polypropylene or polyethylene terephthalate is preferred as the material of the release liner.

[0039] The adhesive patch can be manufactured, for example, by the following method, but is not limited to this, and known methods can be used. First, the components constituting the adhesive layer are mixed in predetermined proportions to obtain a uniform solution (adhesive composition). Next, the adhesive composition is spread on a peelable film (release liner) at a predetermined mass per unit area to form an adhesive layer. Furthermore, the support is pressed onto the adhesive layer so that the adhesive layer is sandwiched between the release liner and the support. Finally, the adhesive patch can be obtained by cutting to the desired shape and dimensions. In this case, the release liner is removed when the adhesive patch is applied. The area of ​​the adhesive patch is 1 to 200 cm². 2 It is fine to be 5-100cm 2 It is fine to be 30-80cm 2 The shape and dimensions of the patch may be, for example, a rectangle with a short side of 3 to 14 cm and a long side of 7 to 20 cm, or a circle with a diameter of 1 to 10 cm. [Examples]

[0040] Test Example 1: Evaluation of the presence or absence of lactic acid in adhesive patches containing a rubber-based adhesive base. 1. Manufacturing of adhesive patches The components were mixed according to Table 1 below to obtain an adhesive composition. The obtained adhesive composition was applied to a release liner (a polyethylene terephthalate film with a release treatment) at a mass of 80 g / m² per unit area. 2The material was spread out to form an adhesive layer by drying and removing the solvent. A support layer (polyethylene terephthalate film) was laminated onto the opposite side of the obtained adhesive layer, and an adhesive patch was obtained in the order of support layer / adhesive layer / release liner.

[0041] 2. Hairless mouse skin permeability test The manufactured adhesive patch is 2 cm 2 Hairless mouse skin was punched out, the fat was removed, and a patch with the release liner removed was applied to the epidermal side. This was then placed in a flow-through type Franz permeability test cell with the dermal side in contact with the receptor side, and the cell was filled with receptor solution (physiological saline). Next, the receptor solution was delivered while heated circulating water was circulated around the outer periphery to maintain the receptor solution at 32°C, and the receptor solution was collected every 2 hours until 24 hours had passed. The concentration of blonanserin in the collected receptor solution was measured by high-performance liquid chromatography, and the cumulative skin permeability of blonanserin (μg / cm³) from the start of application to 24 hours was determined. 2 ) and maximum skin permeation rate (μg / cm 2 The calculation ( / hr) was performed. <Analysis conditions> Column: TSK gel ODS-80TsQA 5μm (4.6mm I.D. × 150mm) Mobile phase: 0.5% phosphate:acetonitrile = 73:27 Measurement wavelength: 248nm Flow rate: 1ml / min Column temperature: 40℃

[0042] [Table 1]

[0043] It was confirmed that the patch of Comparative Example 2, which contained lactic acid, had significantly lower skin permeability of blonanserin compared to the patch of Comparative Example 1, which did not contain lactic acid.

[0044] Test Example 2: Evaluation of a patch containing acetic acid and sodium acetate (1) Similar to Test Example 1, a patch was prepared according to the composition shown in Table 2 below, and a hairless mouse skin permeability test was performed.

[0045] [Table 2]

[0046] The patches in Examples 1-5 (patches with a value of 0.022-2.842 calculated by {acetic acid content (mass%) × acetate content (mass%)} / blonanserin content (mass%)) were confirmed to have excellent skin permeability.

[0047] Test Example 3: Evaluation of a patch containing alicyclic saturated hydrocarbon resin, terpene resin, and hydrogenated rosin glycerin ester as tackifying resins. Similar to Test Example 1, a patch was prepared according to the composition shown in Table 3 below, and a hairless mouse skin permeability test was performed. However, in this test example, 2.5 cm 2 The punched-out patches were applied to the mice.

[0048] [Table 3]

[0049] The patches of Examples 6-8 were confirmed to have excellent skin permeability for blonanserin.

[0050] Test Example 4: Evaluation of a patch containing liquid paraffin Similar to Test Example 1, a patch was prepared according to the composition shown in Table 4 below, and a hairless mouse skin permeability test was performed. However, in this test example, 2.5 cm 2 The punched-out patches were applied to the mice.

[0051] [Table 4]

[0052] The patches in Examples 9-12 (patches containing liquid paraffin) were confirmed to have excellent skin permeability for blonanserin.

[0053] Test Example 5: Evaluation of a patch containing acetic acid and sodium acetate (2) Similar to Test Example 1, a patch was prepared according to the composition shown in Table 5 below, and a hairless mouse skin permeability test was performed.

[0054] [Table 5]

[0055] In Comparative Example 6 (a patch with a value of 0.003 calculated by {acetic acid content (mass%) × acetate content (mass%)} / blonanserin content (mass%)), despite containing acetic acid, sodium acetate, and liquid paraffin, the value calculated by {acetic acid content (mass%) × acetate content (mass%)} / blonanserin content (mass%) was outside the range of values ​​for the patch of the present invention. Therefore, it was confirmed that the skin permeability of blonanserin was lower compared to the patch of Comparative Example 7 (a patch without liquid paraffin). In Examples 13-14 (patches with values ​​of 12.968-29.118 calculated by {acetic acid content (mass%) × acetate content (mass%)} / blonanserin content (mass%)), it was confirmed that the skin permeability of blonanserin was superior compared to the patches of Comparative Examples 5-7.

Claims

1. A patch comprising an adhesive layer on a support, The adhesive layer contains blonanserin or a pharmaceutically acceptable salt thereof, a rubber-based adhesive base, acetic acid, an acetate, and liquid paraffin. The blonanserin content is 3% to 7% by mass based on the total mass of the adhesive layer, and the liquid paraffin content is 13% to 41% by mass based on the total mass of the adhesive layer. In the aforementioned adhesive layer, the following formula applies: {Acetic acid content (mass%) × Acetate salt content (mass%)} / Blonanserin content (mass%) A transdermal patch whose calculated value is between 0.02 and 30.

2. The adhesive patch according to claim 1, wherein the adhesive layer does not contain lactic acid.

3. The patch according to claim 1 or 2, wherein the acetate salt is sodium acetate.

4. The adhesive patch according to claim 1 or 2, wherein the rubber-based adhesive base is a styrene-isoprene-styrene block copolymer, polyisobutylene, or a combination thereof.

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