Adhesive patch

Abstract

To provide an adhesive patch containing an oil that is liquid at room temperature in an amount above a certain level, the patch having a good balance among three properties, i.e., tack, cohesion, and adhesion.SOLUTION: An adhesive patch comprises a support and a plaster disposed on one surface of the support, wherein the plaster comprises (i) an oil which is liquid at room temperature in an amount of 20 wt.% or more with respect to the total weight of the plaster, (ii) a rubber-based polymer in an amount of 5 wt.% to 20 wt.% with respect to the total weight of the plaster, and (iii) a terpene resin, wherein the content of the terpene resin is up to 2.3 times the content of the rubber-based polymer.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a patch, and more particularly to a matrix-type patch containing an oil that is liquid at room temperature as an active ingredient. [Background technology]

[0002] Matrix-type adhesive patches, which comprise a support and a plaster containing a drug and an adhesive composition, require a balance of three fundamental properties: tack, cohesive strength, and peel adhesion. Tack, also known as instantaneous adhesion, is the property of immediately adhering to the skin upon application and exhibiting the minimum necessary adhesive strength. Insufficient tack results in poor adhesion to the skin and insufficient penetration of medicinal ingredients. Cohesive strength is the property required for the adhesive to maintain its shape without flowing. Insufficient cohesive strength results in the plaster breaking down upon removal and remaining on the skin. Adhesion strength is the resistance to peeling from the skin and is a measure of adhesive strength. Appropriate adhesive strength allows the patch to remain attached to the skin for a long time and be easily removed. However, excessive adhesive strength increases the resistance upon removal, causing pain and a poor user experience. Generally, tack / adhesive strength and cohesive strength are in a trade-off relationship, making it difficult to achieve a good balance between these three properties. For example, improving the tack and adhesive strength of a patch reduces the cohesive strength, causing the paste to remain on the skin when removed, while improving the cohesive strength of the patch reduces the tack and adhesive strength, making it difficult for the patch to adhere to the skin. Therefore, there is a demand for a patch that has excellent tack, cohesive strength and adhesive strength properties, and that maintains a good balance of these properties.

[0003] In recent years, the physiological activities of various oils extracted from plants have attracted attention, and they are also incorporated into pharmaceuticals and cosmetics used as external preparations. If a patch containing such oils could be prepared, the active ingredient could be administered in a sustained release manner, providing a stable blood concentration and sustained efficacy, while also reducing side effects, making it extremely useful.

[0004] Patent Document 1 discloses a patch preparation composition containing a drug, an organic solvent, a lipophilic plaster base, and powder. Patent Document 1 describes that, while using a lipophilic plaster base alone can cause the active ingredient solution to form independent vacuoles, making it difficult to release from the plaster, adding powder allows the active ingredient solution stored in the gaps between the powder and between the powder and the plaster to gradually reach the plaster surface via the gaps between the powder and the plaster, improving drug release and, as a result, improving the adhesive strength of the patch and enabling improved transdermal absorbability and sustained release. Furthermore, Patent Document 2 discloses a patch that exhibits excellent tackiness to the skin when applied and is less likely to peel off from the skin during application. Patent Document 2 describes that the patch is characterized by comprising a support and an adhesive layer that is laminated and integrated onto one surface of the support and contains an acrylic adhesive, a solid resin that is incompatible with the acrylic adhesive and is solid at 40°C, a plasticizer, and a drug, and that the use of a combination of the solid resin and the plasticizer makes it possible to achieve both tackiness and cohesive strength in the adhesive layer. However, no patch has been reported that contains a certain amount of oil that is liquid at room temperature and has a good balance of the three properties of tack, cohesive strength, and adhesive strength. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] International Publication No. 2013 / 191187 [Patent Document 2] International Publication No. 2016 / 121805 Summary of the Invention [Problem to be solved by the invention]

[0006] An object of the present invention is to provide a patch that contains a certain amount or more of oil that is liquid at room temperature and has a good balance of the three properties of tack, cohesive strength, and adhesive strength. [Means for solving the problem]

[0007] The present inventors have investigated the formulation of a matrix-type patch containing 20% by weight or more of oil, and have found that by using a rubber-based polymer as an adhesive and blending a terpene resin in a specified ratio with the rubber-based polymer, a patch can be obtained that is excellent in tack, cohesive strength, and adhesive strength, and that maintains a good balance of these physical properties, thereby completing the present invention. That is, the present invention provides the following aspects. [Item 1] A patch having a paste layer on one surface of a support, the paste layer comprising: (i) 20% by weight or more of an oil component that is liquid at room temperature based on the total weight of the paste; (ii) 5% by weight to 20% by weight of a rubber polymer based on the total weight of the base; (iii) a terpene resin; and wherein the content of the terpene resin is 2.3 times or less the content of the rubber-based polymer. [Item 2] The patch according to Item 1, wherein the terpene resin is contained in an amount of 30% by weight to 40% by weight based on the total weight of the paste base. [Item 3] The patch according to Item 1 or 2, wherein the rubber polymer is a styrene-isoprene-styrene block copolymer. [Item 4] The patch according to Item 3, wherein the styrene-isoprene-styrene block copolymer is contained in an amount of 15 wt % or more based on the total weight of the paste. [Item 5] The patch according to any one of Items 1 to 4, wherein the oil is at least one selected from the group consisting of MCT oil, hemp oil, and CBD oil. [Item 6] The patch according to any one of Items 1 to 5, wherein the paste further contains a powder that is insoluble in the oil and the rubber-based polymer. [Item 7] The patch according to Item 6, wherein the powder is silicic anhydride. [Item 8] The patch according to any one of Items 1 to 7, wherein the paste further contains liquid paraffin. [Item 9] A patch having a paste layer on one surface of a support, the paste layer comprising: (i) 20% by weight or more of an oil component that is liquid at room temperature based on the total weight of the paste; (ii) 5% by weight to 20% by weight of a rubber polymer based on the total weight of the base; (iii) a terpene resin; and (iv) a powder that is insoluble in the oil and the rubber-based polymer; (v) liquid paraffin; wherein the content of the terpene resin is 2.3 times or less the content of the rubber-based polymer. [Effects of the Invention]

[0008] According to the present invention, it is possible to provide a patch containing a certain amount or more of oil that is liquid at room temperature and that maintains a good balance of tack, cohesion, and adhesive strength. The patch of the present invention exhibits excellent tack and adhesive strength to the skin when applied, and also exhibits cohesion that allows the patch to be easily peeled off without leaving any adhesive layer on the skin when removed. DETAILED DESCRIPTION OF THE INVENTION

[0009] The patch of the present invention has a paste layer on one surface of a backing.

[0010] (Support) The support may be any material that can hold the adhesive layer, and may be any material that is generally used for patches. Examples of the support include woven fabric, nonwoven fabric, and resin film. The support may also be a laminate of woven fabric and film, or a laminate of nonwoven fabric and film, such as a nonwoven fabric laminate film in which a polyester film or a PET film is laminated with a nonwoven fabric.

[0011] Examples of materials for the support include polyester (polyethylene terephthalate (PET), polyethylene isophthalate, polypropylene terephthalate, polypropylene isophthalate, polybutylene terephthalate, polyethylene naphthalate, etc.), polyolefin (polymer or copolymer of vinyl monomers such as ethylene, propylene, vinyl acetate, or acrylonitrile), polyamide (nylon or silk, etc.), polyurethane (PU), cellulose (cotton or linen, etc.), etc.

[0012] (plaster) The paste is a drug-containing layer (matrix) that is solid or semi-solid at room temperature. The paste of the present invention contains 20% by weight or more of an oil that is liquid at room temperature based on the total weight of the paste, 5% to 20% by weight of a rubber polymer based on the total weight of the paste, and a terpene resin (wherein the content of the terpene resin is 2.3 times or less the content of the rubber polymer).

[0013] (liquid oil at room temperature) "Oils that are liquid at room temperature" refers to oils that are fluid at about 25°C. Oils that are liquid at room temperature include lipids in which glycerin and unsaturated fatty acids are ester-bonded. As long as the oil is suitable for administration as a patch, it may be extracted from natural ingredients or may contain synthetic lipids. Examples of oils that are liquid at room temperature include oils extracted from plants. Specific examples of oils that are liquid at room temperature include argan oil, avocado oil, canola oil, peanut oil, camellia oil, safflower oil, rapeseed oil, coconut oil, cottonseed oil, jojoba oil, linseed oil, corn oil, hazelnut oil, olive oil, orange oil, palm oil, rose oil, banana oil, vanilla oil, castor oil, sesame oil, sunflower oil, hemp oil, CBD oil, MCT oil, safflower oil, linseed oil, mint oil, peppermint oil, lavender oil, and lemon oil. One or more oils that are liquid at room temperature may be used in combination. In the present invention, the oil that is liquid at room temperature is preferably MCT oil, hemp oil, CBD oil, or a combination thereof. The content of oil components that are liquid at room temperature is, for example, 20% by weight or more, based on the total weight of the paste. This content may be 25% by weight or more, 30% by weight or more, or 35% by weight or more, and may be 50% by weight or less, 45% by weight or less, or 40% by weight or less, based on the total weight of the paste. The content of oil components that are liquid at room temperature may be, for example, 20% by weight to 50% by weight, 20% by weight to 45% by weight, 20% by weight to 40% by weight, 25% by weight to 50% by weight, 25% by weight to 45% by weight, 25% by weight to 40% by weight, 30% by weight to 50% by weight, 30% by weight to 45% by weight, 30% by weight to 40% by weight, 35% by weight to 50% by weight, 35% by weight to 45% by weight, or 35% by weight to 40% by weight, based on the total weight of the paste. In the present invention, the oil component that is liquid at room temperature may or may not exhibit physiological activity. The patch of the present invention may contain an oil component that is liquid at room temperature as an active ingredient, or may contain a component other than the oil component that is liquid at room temperature as an active ingredient, or may contain an oil component that is liquid at room temperature and another component as an active ingredient.

[0014] (rubber-based polymer) The rubber-based polymer is an adhesive that forms a plaster base. Examples of the rubber-based polymer include synthetic rubbers such as styrene-isoprene-styrene block copolymer (hereinafter sometimes referred to as "SIS"), styrene-butadiene-styrene block copolymer, styrene-ethylene-butadiene rubber-styrene block copolymer, styrene-butadiene rubber, polyisoprene, polyisobutylene, polybutene, butyl rubber, and silicone rubber; and natural rubber. The rubber-based polymer is preferably SIS. The content of the rubber polymer is, for example, 5 to 20% by weight relative to the total weight of the base, and may be, for example, 10 to 19% by weight or 13 to 18% by weight.

[0015] As long as the paste contains the rubber-based polymer in the above range, it may contain other adhesives such as acrylic polymers and silicone-based polymers within the range that does not impair the effects of the present invention. Examples of acrylic polymers include polymethyl acrylate, polymethyl methacrylate, etc. Specific examples thereof include DURO-TAK87-2097, 87-2194, 87-2196, 87-2287, 87-2516, 87-2852, and 87-235A (trade names, manufactured by Henkel Japan), and Nissetsu KP-77 and AS-370 (trade names, manufactured by Nippon Carbide Industries Co., Ltd.). Examples of silicone polymers include dimethylpolysiloxane and diphenylpolysiloxane.

[0016] (terpene resin) The terpene resin is a tackifier that imparts adhesiveness to the paste. The content of the terpene resin is, for example, 2.3 times or less the content of the rubber-based polymer. Alternatively, the content may be 2.25 times or less, or 2.2 times or less. By keeping the content of the terpene resin within this range, a patch with a good balance of tack, cohesive strength, and adhesive strength can be obtained. The content of the terpene resin is, for example, 30% to 40% by weight relative to the total weight of the paste, and may be, for example, 32% to 39% by weight or 33% to 38% by weight.

[0017] (tackifier) As long as the paste contains the terpene resin in the above range, it may contain other tackifiers to the extent that the effects of the present invention are not impaired. Examples of tackifiers include alicyclic hydrocarbon resins, aliphatic hydrocarbon resins, polystyrene resins, rosin, and hydrogenated rosin.

[0018] (powder) The paste may further contain a powder that is insoluble in the oil and rubber polymer that are liquid at room temperature. In the present invention, the powder can contribute to the formation of voids in the paste. The powder is not particularly limited as long as it is a solid powdered agent (filler) used in the adhesive base of a patch, and examples thereof include silicic anhydride, crystalline cellulose, zinc oxide, titanium oxide, kaolin, calcium carbonate, etc., and may further include starch powder such as wheat flour or cornstarch, carmellose, carmellose metal salt, agar, carrageenan, pectin, powdered sugar, polyethylene powder, polystyrene sulfonate, etc. In the present invention, the powder is preferably crystalline cellulose, silicic anhydride, starch, carmellose, or carmellose metal salt. Increasing the amount of powder added improves the adhesive strength of the patch, but if the amount is too high, the patch will harden and the adhesive strength will decrease. Therefore, a preferred amount of powder added is, for example, 1 to 10% by weight, and preferably 2 to 6% by weight. Furthermore, taking into account the voids in the paste formed by the powder, if the amount of main liquid is high, the amount of powder added may be high, and if the amount is low, the amount of powder added may be low. For example, if the amount of main liquid is 1, the amount of powder is preferably in the range of 0.05 to 0.4. The powder can be combined with multiple powders of different bulk densities to appropriately adjust the voids formed. Therefore, it is possible to prepare an appropriate combination of powders corresponding to the amount of plaster and organic solvent used. For example, powders such as light anhydrous silicic acid, cornstarch, and crystalline cellulose can be used in combination. The powder does not dissolve in liquid oils or rubber-based polymers at room temperature. Here, "not soluble" means insoluble, and according to the US Pharmacopeia National Formulary's definition of solubility, this means that even 1 mg of powder does not dissolve in 10 g of oil or rubber-based polymer.

[0019] (additives) The paste may further contain other additives to the extent that the effects of the present invention are not impaired. Examples of additives include an agent for preventing accidental ingestion, a softener, an antioxidant, a pH adjuster, a thickener, an ultraviolet absorber, a surfactant, etc. These additives may be used alone or in combination of two or more in appropriate amounts. The agent for preventing accidental ingestion includes, but is not limited to, substances with a strong bitter taste such as denatonium, and denatonium benzoate is preferred. The content of the agent for preventing accidental ingestion is, for example, 0.01 to 0.1% based on the total weight of the plaster. When denatonium benzoate is included as the agent for preventing accidental ingestion, its content is preferably about 0.01 to 0.1% based on the total weight of the plaster. This amount produces a strong bitter taste when the patch is placed in the mouth, and is effective in preventing accidental ingestion by children, etc. A softener is an agent mixed with rubber-based polymers such as SIS to impart flexibility. Examples of softeners include petroleum-based softeners such as polybutene, polyisobutylene, and process oil; fatty oil-based softeners such as coconut oil and castor oil; refined lanolin; and liquid paraffin. The softener is preferably polybutene or liquid paraffin. The content of the softener in the adhesive patch of the present invention can be adjusted appropriately depending on the type of softener, but is, for example, 0.01 to 10% by weight based on the total weight of the plaster. One or more types of softeners may be used together. Examples of antioxidants include organic antioxidants such as dibutylhydroxytoluene (BHT), propyl gallate, and sodium ascorbate, and inorganic antioxidants such as sodium thiosulfate, sodium bisulfite, sodium sulfite, and sodium pyrosulfite. The content of the antioxidant in the patch of the present invention can be adjusted appropriately depending on the type of antioxidant, and is, for example, 0.01 to 10% by weight based on the total weight of the plaster. Furthermore, antioxidants may be used alone or in combination of two or more types. The pH adjuster may be any acid, base, or salt thereof commonly used in the pharmaceutical field for pH adjustment, including, for example, hydrochloric acid, sulfuric acid, phosphoric acid, citric acid, gluconic acid, succinic acid, acetic acid, methanesulfonic acid, edetic acid, aqueous ammonia, monoethanolamine, diethanolamine, triethanolamine, diisopropanolamine, triisopropanolamine, meglumine, trometamol, glycine, potassium hydroxide, calcium hydroxide, sodium hydroxide, magnesium hydroxide, sodium citrate, sodium acetate, sodium bicarbonate, potassium bicarbonate, and sodium carbonate. The content of the pH adjuster in the adhesive patch of the present invention can be adjusted appropriately depending on the type of pH adjuster, and is, for example, 0.01 to 10% by weight based on the total weight of the plaster. One or more pH adjusters may be used together. Examples of thickeners include, but are not limited to, carbopol. The content of the thickener in the patch of the present invention can be adjusted appropriately depending on the type of thickener, and is, for example, 0.01 to 10% by weight based on the total weight of the paste. Furthermore, one type of thickener may be used, or two or more types may be used together. Examples of ultraviolet absorbers include, but are not limited to, 2-hydroxy-4-methoxybenzophenone, t-butylmethoxydibenzoylmethane, para-aminobenzoic acid, etc. The content of the ultraviolet absorber in the patch of the present invention can be adjusted appropriately depending on the type of ultraviolet absorber, and is, for example, 0.01 to 10 wt% based on the total weight of the paste. Furthermore, one type of ultraviolet absorber may be used, or two or more types may be used together. Examples of surfactants include, but are not limited to, nonionic surfactants such as sorbitan monolaurate, anionic surfactants such as sodium lauryl sulfate, cationic surfactants such as benzalkonium chloride, and amphoteric surfactants such as uryldimethylaminoacetate betaine. The content of the surfactant in the adhesive patch of the present invention can be adjusted appropriately depending on the type of surfactant, and is, for example, 0.01 to 10 wt% based on the total weight of the plaster. Furthermore, one type of surfactant may be used, or two or more types may be used together.

[0020] (Release liner) The patch of the present invention may further comprise a release liner on the surface opposite the adhesive body provided with the support. The release liner can protect the adhesive body until the patch is applied to the skin. Examples of release liners include polyolefins such as polyethylene and polypropylene; ethylene-vinyl acetate copolymer, vinyl acetate-vinyl chloride copolymer, polyvinyl chloride, etc.; polyamides such as nylon; polyesters such as polyethylene terephthalate; cellulose derivatives; synthetic resins such as polyurethane; films or sheets made of materials such as aluminum and paper, and laminates thereof.

[0021] (Method of manufacturing patch) The method for producing the patch of the present invention includes the steps of mixing a paste material containing an oil, a rubber polymer, and a terpene resin that are liquid at room temperature with a solvent to obtain a coating liquid, applying the resulting coating liquid onto a release film or support, and drying the coating liquid. For example, a patch can be produced by mixing paste materials containing oil, rubber polymer, and terpene resin that are liquid at room temperature with a solvent to obtain a coating liquid, which is then coated on a release liner such as a silicone-treated PET film, and the solvent is removed by heat drying to obtain a paste, which can then be laminated on a support such as a woven fabric, nonwoven fabric, or nonwoven fabric-laminated PET film. Alternatively, a patch can be produced by coating a support with the coating liquid, removing the solvent by heat drying to obtain a paste, and then laminating a release liner on the resulting paste. The resulting patch may be packaged in an appropriate package, such as a film bag, preferably a multilayer film, more preferably an aluminum laminate film, the innermost layer of which is preferably polyethylene, polypropylene, or PET. [Example]

[0022] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples in any way.

[0023] Example: Evaluation test of tack, cohesion and adhesive strength of patch (1) Preparation of test formulations The components were weighed according to the compositions shown in Tables 1 and 2 below, and patches of Examples 1 and 2 and Comparative Examples 1 to 7 were prepared. Comparative Examples 1 and 2 used an acrylic polymer instead of a rubber-based polymer (SIS), and Comparative Examples 3 to 7 had an adjusted terpene resin / SIS ratio. In the tables, liquid paraffin is Hicol M-352 (Kaneda Co., Ltd.), oil A is MCT oil (GTCC-LQ-(SG), Croda Japan Co., Ltd.), oil B is coconut oil extract FR00027 (provided by Functional Remedies LLC), and oil C is a commercially available product (CANNAPRESSO CBD oil 10ml) containing 10% by volume of cannabidiol in MCT oil. Specifically, the weighed components were mixed, and ethyl acetate was added as a solvent to prepare a coating liquid. The coating liquid was then applied to a silicone-treated PET film (release liner), and the resulting paste was dried by heating. A woven fabric (support) was then attached to this paste, and the resulting mixture was laminated at approximately 85°C to prepare each patch. [Table 1] [Table 2]

[0024] (2) Evaluation method Each patch was applied to the forearm and removed, and the tack, cohesive strength, and adhesive strength were evaluated. The evaluation criteria for tack, cohesive strength, and adhesive strength are as follows: <Tack (the property of sticking immediately when applied and showing the minimum necessary adhesive strength (instant adhesive strength))> Good: Moderate adhesive strength makes it difficult to peel off. △: In the case of SIS, it peels off a little easily. In the case of DUROTAK, the adhesive strength is too strong and it is difficult to peel off. ×: Easy to peel off. <Cohesion (the property necessary for an adhesive (paste) to maintain its shape and prevent it from flowing)> Good: No plaster remains on the skin when peeled off. △: No plaster remains, but the peeled area feels sticky. ×: The plaster remains on the skin when peeled off. <Adhesion strength (the resistance to peeling from the skin, a characteristic that serves as a measure of adhesive strength (adhesion strength))> Good: Easy to remove, but stays on the skin for a long time. △: No pain is felt, but there is resistance when peeling off. ×: There is a lot of resistance when peeling it off the skin, which causes pain.

[0025] The test results are shown in Tables 3 and 4. [Table 3] [Table 4]

[0026] As shown in the table above, Comparative Examples 1 and 2, which used an acrylic polymer (DUROTAK), were inferior in all properties of tack, cohesion, and adhesive strength. All of the patches using a rubber-based polymer (SIS) were excellent in tack and cohesion, but those (Comparative Examples 3 to 7) in which the terpene resin content was 2.3 times or more the SIS content experienced resistance when peeled from the skin, resulting in an inferior feel when used. On the other hand, the patches of Examples 1 and 2, in which the terpene resin content was 2.3 times or less the SIS content, adhered to the skin immediately after application, remained attached for a long time, and were easily peeled off, resulting in an excellent feel when used. [Industrial Applicability]

[0027] The present invention can provide a patch containing a certain amount or more of oil that is liquid at room temperature and that maintains a good balance of tack, cohesion, and adhesive strength. The patch of the present invention exhibits excellent tack and adhesive strength to the skin when applied, and also exhibits cohesion that allows the patch to be easily peeled off without leaving any adhesive layer on the skin when removed.

Claims

1. A patch having a paste body provided on one surface of a support, the paste body comprising: (i) 20% by weight or more of an oil component that is liquid at room temperature based on the total weight of the paste; (ii) 5% by weight to 20% by weight of a rubber-based polymer based on the total weight of the paste; (iii) a terpene resin; and wherein the content of the terpene resin is 2.3 times or less the content of the rubber-based polymer.

2. 2. The patch according to claim 1, wherein the terpene resin is contained in an amount of 30% by weight to 40% by weight based on the total weight of the paste base.

3. The patch according to claim 1, wherein the rubber-based polymer is a styrene-isoprene-styrene block copolymer.

4. 4. The patch according to claim 3, wherein the styrene-isoprene-styrene block copolymer accounts for 15% by weight or more of the total weight of the paste.

5. The patch according to claim 3, wherein the oil is at least one selected from the group consisting of MCT oil, hemp oil, and CBD oil.

6. The patch according to claim 1, wherein the paste further contains a powder that is insoluble in the oil and the rubber-based polymer.

7. The patch according to claim 6, wherein the powder is silicic anhydride.

8. The patch according to claim 1 , wherein the paste further contains liquid paraffin.

9. A patch having a paste body provided on one surface of a support, the paste body comprising: (i) 20% by weight or more of an oil component that is liquid at room temperature based on the total weight of the paste; (ii) 5% by weight to 20% by weight of a rubber-based polymer based on the total weight of the paste; (iii) a terpene resin; and (iv) a powder that is insoluble in the oil and the rubber-based polymer; (v) liquid paraffin; wherein the content of the terpene resin is 2.3 times or less the content of the rubber-based polymer.

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