WO2022064607A1 - 医薬品用含水系貼付剤 - Google Patents
医薬品用含水系貼付剤 Download PDFInfo
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- WO2022064607A1 WO2022064607A1 PCT/JP2020/036080 JP2020036080W WO2022064607A1 WO 2022064607 A1 WO2022064607 A1 WO 2022064607A1 JP 2020036080 W JP2020036080 W JP 2020036080W WO 2022064607 A1 WO2022064607 A1 WO 2022064607A1
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- Prior art keywords
- water
- mass
- pressure
- sensitive adhesive
- adhesive layer
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- BARWIPMJPCRCTP-CLFAGFIQSA-N oleyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCCOC(=O)CCCCCCC\C=C/CCCCCCCC BARWIPMJPCRCTP-CLFAGFIQSA-N 0.000 description 1
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- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
- 229920001495 poly(sodium acrylate) polymer Polymers 0.000 description 1
- 229920002239 polyacrylonitrile Polymers 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 229920001748 polybutylene Polymers 0.000 description 1
- 229920000259 polyoxyethylene lauryl ether Polymers 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010483 polyoxyethylene sorbitan monopalmitate Nutrition 0.000 description 1
- 239000000249 polyoxyethylene sorbitan monopalmitate Substances 0.000 description 1
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 1
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 1
- 235000010988 polyoxyethylene sorbitan tristearate Nutrition 0.000 description 1
- 239000001816 polyoxyethylene sorbitan tristearate Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- GRLPQNLYRHEGIJ-UHFFFAOYSA-J potassium aluminium sulfate Chemical compound [Al+3].[K+].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O GRLPQNLYRHEGIJ-UHFFFAOYSA-J 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
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- NNMHYFLPFNGQFZ-UHFFFAOYSA-M sodium polyacrylate Chemical compound [Na+].[O-]C(=O)C=C NNMHYFLPFNGQFZ-UHFFFAOYSA-M 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 1
- JGMJQSFLQWGYMQ-UHFFFAOYSA-M sodium;2,6-dichloro-n-phenylaniline;acetate Chemical compound [Na+].CC([O-])=O.ClC1=CC=CC(Cl)=C1NC1=CC=CC=C1 JGMJQSFLQWGYMQ-UHFFFAOYSA-M 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 229940035044 sorbitan monolaurate Drugs 0.000 description 1
- 235000011071 sorbitan monopalmitate Nutrition 0.000 description 1
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- 229940031953 sorbitan monopalmitate Drugs 0.000 description 1
- 235000011076 sorbitan monostearate Nutrition 0.000 description 1
- 239000001587 sorbitan monostearate Substances 0.000 description 1
- 229940035048 sorbitan monostearate Drugs 0.000 description 1
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- 238000003892 spreading Methods 0.000 description 1
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- 229920003048 styrene butadiene rubber Polymers 0.000 description 1
- 229920000468 styrene butadiene styrene block copolymer Polymers 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
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- 229920002994 synthetic fiber Polymers 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- ISXSCDLOGDJUNJ-UHFFFAOYSA-N tert-butyl prop-2-enoate Chemical compound CC(C)(C)OC(=O)C=C ISXSCDLOGDJUNJ-UHFFFAOYSA-N 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 229940042585 tocopherol acetate Drugs 0.000 description 1
- 229940045136 urea Drugs 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 235000019168 vitamin K Nutrition 0.000 description 1
- 239000011712 vitamin K Substances 0.000 description 1
- 150000003721 vitamin K derivatives Chemical class 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 229940046010 vitamin k Drugs 0.000 description 1
- 239000002759 woven fabric Substances 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
Definitions
- the present invention relates to a water-containing patch for pharmaceuticals, and more specifically, a water-containing patch having high adhesive strength and low skin irritation even after the water in the pressure-sensitive adhesive layer is volatilized. Regarding.
- a patch using a water-containing adhesive base which is also generally referred to as a "pap agent” (referred to as a water-containing patch in the present specification) is a plaster layer (adhesive layer) containing an active ingredient such as a drug. It is a kind of patch provided on a support such as woven cloth, knitted cloth, and non-woven fabric. Since the poultice uses an adhesive base containing water in the plaster layer, the adhesive strength is weak although the skin irritation is low, and the adhesive strength decreases with time, especially with the volatilization of water in the plaster layer. The problem was that it was easy to peel off from the skin.
- an emulsion (also called emulsion) base in which an acrylic acid alkyl ester copolymer known as one component constituting a non-aqueous (hydrophobic or lipophilic) adhesive is dispersed is used.
- a technique of blending a water-containing patch into a plaster layer (adhesive layer) is known.
- Patent Document 1 aims to provide a water-containing patch having excellent adhesive force and re-sticking force even after long-term sticking, and suppressing hardening and suppleness due to loss of water. 5.0% by mass or more and 10% by mass or less of the methyl acrylate / 2-ethylhexyl acrylate copolymer and 0.01% by mass or more of the water-dispersible surfactant with respect to the entire composition for a water-containing external patch. A patch containing 10.0% by mass or less is disclosed. Further, in Patent Document 2, a polyacrylic acid neutralized product and the neutralized product 2.
- Patent Document 3 contains poly (methyl acrylate / 2-ethylhexyl acrylate) and a monofatty acid ester of polyethylene glycol as a surfactant for the purpose of providing a poultice that can peel off a peeling liner with a smaller force.
- Pap agents are disclosed.
- Patent No. 5650684 Patent No. 5921779 Patent No. 6469136
- an acrylic acid alkyl ester copolymer such as a methyl acrylate / 2-ethylhexyl acrylate copolymer is blended in the pressure-sensitive adhesive layer in order to enhance the adhesive durability of the water-containing patch. ing.
- the adhesive strength particularly after the moisture in the adhesive layer is volatilized is not sufficiently satisfactory as compared with the tape agent.
- hydrophilic acrylic pressure-sensitive adhesives polyacrylic acid partially neutralized products (manufactured by Showa Denko Corporation, Viscomate (registered trademark) NP-800, etc.), etc.
- stickiness constituting the pressure-sensitive adhesive layer of water-containing patches have been used.
- the thickening agent sodium carmellose, etc.
- the thickening agent sodium carmellose, etc.
- a cross-linking agent dihydroxyaluminum aminoacetate (manufactured by Kyowa Chemical Industry Co., Ltd., glycinal, etc.) so as not to dissolve in water and lose its function).
- a method of dispersing these components in a wetting agent containing almost no water and adding the components to a composition forming a pressure-sensitive adhesive layer is generally practiced in the production of a poultice.
- the present invention has been completed by finding that it does not decrease but rather significantly improves, and that the skin irritation is also low.
- the present invention is: [1] A water-containing patch for pharmaceutical products comprising a support, an adhesive layer provided on the support, and a release liner.
- the pressure-sensitive adhesive layer 1) Active ingredient, 2) Acrylic hydrophilic adhesive, 3) Acrylic acid alkyl ester-based copolymer emulsion, 4) Crosslinking agent, 5) Condensing agent, 6) Wetting agents containing little water, and 7) water, Contains,
- the acrylic acid alkyl ester copolymer is a copolymer of a monomer mixture composed of monomer A and monomer B.
- the monomer A is a polymer having a glass transition temperature (Tg) of 270 K or higher when the monomer A is homopolymerized.
- the monomer B is a polymer having a glass transition temperature (Tg) of 220 K or less when the monomer B is homopolymerized.
- Tg glass transition temperature
- the acrylic acid alkyl ester-based copolymer emulsion is contained in a proportion of 20% by mass or more and less than 70% by mass with respect to the total mass of the pressure-sensitive adhesive layer. Water-containing patch for pharmaceutical products.
- the acrylic acid alkyl ester-based copolymer is an acrylic acid alkyl ester-based copolymer in which the proportion of the monomer A is 30% by mass or more and 50% by mass or less with respect to the total mass of the monomer mixture. .. b)
- the pressure-sensitive adhesive layer has a pH of 2 to 4.
- the pressure-sensitive adhesive layer is It has a peel adhesive strength of 1N / 15 mm or more after storage at 50 ° C. for 16 hours from the date of manufacture of the patch. Immediately after the patch is manufactured, it has a probe tack of 0.7 N / mm ⁇ or more and has a probe tack.
- the probe tack value of the pressure-sensitive adhesive layer after storage at 50 ° C. for 16 hours from the date of manufacture of the patch is 1.8 times or more the probe tack value of the pressure-sensitive adhesive layer immediately after the production of the patch.
- the pressure-sensitive adhesive layer further comprises 8) a cooling agent 9) an organic solvent, 10) pH regulator, 11) Chelating agent, The water-containing patch for pharmaceutical products according to any one of [1] to [4].
- a monomer mixture consisting of a monomer A having a glass transition temperature (Tg) of 270 K or more at the time of homopolymerization and a monomer B having a Tg of 220 K or less at the time of homopolymerization.
- Tg glass transition temperature
- a monomer B having a Tg of 220 K or less at the time of homopolymerization.
- an acrylic acid alkyl ester-based copolymer in which the proportion of the monomer A is 30% by mass or more and 50% by mass or less with respect to the total mass of the monomer mixture, or b) the pressure-sensitive adhesive layer has a pH of 2 to 4. Or c) Total amount of hydrophilic polymer (hydrophilic acrylic pressure-sensitive adhesive and thickening agent) and cross-linking agent / mass ratio of amount of wetting agent containing almost no water (concentrated glycerin, etc.) By setting It is possible to provide a water-containing patch for pharmaceuticals having low skin irritation.
- acrylics such as methyl acrylate / 2-ethylhexyl acrylate copolymer resin emulsion (trade name: Nicazole TS-620, Nippon Carbide Industry Co., Ltd.), etc.
- Proposals have been made to blend an acid alkyl ester copolymer emulsion into the pressure-sensitive adhesive layer and to increase the blending amount.
- the adhesive strength after the water in the pressure-sensitive adhesive layer is volatilized is sufficiently sufficient as compared with the tape agent. I could't say that.
- the present inventors have encountered the above-mentioned problems in an amount of 20% by mass or more and less than 70% by mass, which exceeds the amount previously proposed, and is an emulsion of a copolymerized resin emulsion of methyl acrylate and 2-ethylhexyl acrylate (hereinafter, co-weight).
- co-weight an emulsion of a copolymerized resin emulsion of methyl acrylate and 2-ethylhexyl acrylate
- co-weight emulsion of a copolymerized resin emulsion of methyl acrylate and 2-ethylhexyl acrylate
- the water-containing patch for pharmaceutical products of the present invention (hereinafter, also simply referred to as “patch”) comprises a support, a pressure-sensitive adhesive layer provided on the support, and a release liner.
- the shape of the patch, particularly the support, and the preparation portion consisting of the pressure-sensitive adhesive layer provided on the support is not particularly limited, and is rectangular (square, rectangle, etc.), quadrangular (trapezoid, rhombus, etc.), polygonal. , Circular, oval, semi-circular, triangular, crescent-shaped, and a combination of these, etc., various shapes can be selected according to the attachment location.
- the area of the patch (particularly the above-mentioned pharmaceutical product portion) can be appropriately determined, and may be, for example, in the range of 2 to 300 cm 2 in consideration of the amount of the active ingredient to be blended in the pressure-sensitive adhesive layer.
- the water-containing patch for pharmaceuticals of the present invention is an acrylic acid alkyl ester that generally constitutes a non-aqueous acrylic pressure-sensitive adhesive in addition to the hydrophilic acrylic pressure-sensitive adhesive described later for the water-containing pressure-sensitive adhesive layer. It is characterized by blending an emulsion of a system copolymer.
- the pressure-sensitive adhesive used for the pressure-sensitive adhesive layer (plaster layer) of a water-containing patch includes polyacrylic acid, partially neutralized polyacrylic acid, sodium polyacrylate, and N-vinylacetamide / sodium acrylate copolymer. Hydrophilic acrylic pressure-sensitive adhesives such as resins are widely used.
- the non-water-based pressure-sensitive adhesive to be blended in the water-containing pressure-sensitive adhesive layer of the water-containing patch includes acrylic and methacrylic adhesives.
- An emulsion-type pressure-sensitive adhesive is preferably blended.
- the "acrylic acid alkyl ester-based copolymer” is intended to contain both acrylic acid and methacrylic acid alkyl esters, and the "acrylic adhesive” is also an acrylic pressure-sensitive adhesive and methacrylic acid. It is intended to contain both of the adhesives.
- the acrylic acid alkyl ester-based copolymer (non-aqueous pressure-sensitive adhesive base) constituting the non-aqueous acrylic pressure-sensitive adhesive has an alkyl ester having 2 to 9 carbon atoms as a component that exhibits adhesive strength, and is homopolymerized.
- the acrylic acid alkyl ester-based copolymer used in the present invention has a monomer A that becomes a polymer having a glass transition temperature (Tg) of 270 K or more when homopolymerized, and a glass transition temperature (Tg) of 220 K or less when homopolymerized. It is a copolymer of a monomer mixture composed of a monomer B as a polymer.
- the upper limit of the glass transition temperature Tg of the homopolymer of the monomer A is about 500 K
- the lower limit of the glass transition temperature Tg of the homopolymer of the monomer B is about 200 K.
- homopolymers obtained by polymerizing only a monomer that exhibits adhesive strength are said to have high adhesive strength but weak mechanical strength, and generally, copolymerization with a monomer that improves cohesive strength improves mechanical strength.
- the coalescence is used as an adhesive.
- the monomer exhibiting the adhesive strength shown in Table 1 above in the present invention, as a monomer having a higher adhesive strength, acrylic acid having a Tg of 220 K or less when the monomer is homopolymerized (homopolymer). Butyl acrylate, 2-ethylhexyl acrylate, octyl acrylate, isononyl acrylate and the like are used.
- butyl acrylate and 2-ethylhexyl acrylate are preferable, and 2-ethylhexyl acrylate, which has a proven track record as a pharmaceutical additive and has high adhesive strength (low homopolymer Tg), can be preferably used. ..
- the monomers that improve the aggregating power include the monomers listed in Table 1.
- methyl acrylate, methyl methacrylate, ethyl methacrylate and n-butyl methacrylate are preferable.
- methyl acrylate which has high mechanical strength and does not significantly reduce the adhesiveness (the Tg of the homopolymer is relatively low), is particularly preferable.
- the amount of evaporation residue is 57 to 61%.
- the proportion of the monomer A in which the Tg of the homopolymer is 270 K or more to 30% by mass or more and 50% by mass or less, improvement in the adhesive strength of the pressure-sensitive adhesive layer at the time of water dispersal can be expected. ..
- the blending amount of the acrylic acid alkyl ester-based copolymer emulsion is 20% by mass or more based on the total mass of the pressure-sensitive adhesive layer of the water-containing patch for pharmaceuticals. It can be less than mass%, and can be 20% by mass or more and 60% by mass or less.
- the blending amount (solid content equivalent amount) of the acrylic acid alkyl ester-based copolymer is, for example, 0.1% by mass or more and 40% by mass or less, or 10 by mass, based on the total mass of the pressure-sensitive adhesive layer of the water-containing patch for pharmaceuticals. It can be mass% or more and 37 mass% or less.
- the pressure-sensitive adhesive layer in the water-containing patch for pharmaceuticals of the present invention contains an active ingredient.
- the active ingredient include physiologically active substances, which are not particularly limited as long as they have transdermal absorbability and exhibit pharmacological activity when administered into the body, and even water-soluble substances are fats. It may be a soluble substance.
- Physiologically active substances include, for example, non-steroidal anti-inflammatory agents such as fervinac, flurbiprofen, diclofenac, diclofenac sodium, methyl salicylate, glycol salicylate (ethylene glycol salicylate), indomethacin, ketoprofen, ibuprofen, or esters thereof; diphenhydramine.
- Anti-histamines such as chlorpheniramine; analgesics such as aspirin, acetaminophen, ibuprofen, sodium loxoprofen; local anesthetics such as lidocaine and diclofenac; muscle relaxants such as schisametonium chloride; antifungal agents such as clotrimazole; Anti-inflammatory agents such as; vasodilators such as nitroglycerin and isosorbide nitrate; vitamins such as vitamin A, vitamin E (tocopherol), tocopherol acetate, vitamin K, octothiacin, riboflavine butyrate, prostaglandins; Examples thereof include extracts, nonyl acid vanillylamide, capsaicin, l-menthol, dl-camfur and the like.
- the bioactive substance may be used alone or in combination of two or more.
- the blending amount of the above active ingredient can be appropriately determined depending on the type thereof, and for example, 0.1% by mass or more and 30% by mass or less, or 0.5% by mass, based on the total mass of the pressure-sensitive adhesive layer of the water-containing patch for pharmaceuticals. It can be 15% by mass or less.
- the pressure-sensitive adhesive layer of the water-containing patch for pharmaceuticals of the present invention contains an acrylic hydrophilic pressure-sensitive adhesive.
- the acrylic hydrophilic pressure-sensitive adhesive include water-soluble (meth) acrylic polymers.
- the water-soluble (meth) acrylic polymer is a polymer obtained by polymerizing a (meth) acryloyl group-containing monomer having a functional group (hydrophilic group) having water solubility, and can be blended with water in the pressure-sensitive adhesive layer. , Demonstrates adhesiveness.
- water-soluble (meth) acrylic polymer examples include homopolymers such as polyacrylic acid and a neutralized product of polyacrylic acid; and copolymers such as N-vinylacetamide / sodium acrylate copolymer resin.
- the polyacrylic acid neutralized product may be a completely neutralized product of polyacrylic acid, a partially neutralized product of polyacrylic acid, or a mixture thereof.
- the neutralized polyacrylic acid means a polyacrylic acid salt, and for example, sodium salt, potassium salt, calcium salt, ammonium salt and the like can be used.
- the blending amount of the acrylic hydrophilic pressure-sensitive adhesive is, for example, 0.1% by mass or more and 10% by mass or less, and 1% by mass or more and 8% by mass or less, based on the total mass of the pressure-sensitive adhesive layer of the water-containing patch for pharmaceuticals. be able to.
- the pressure-sensitive adhesive layer of the water-containing patch for pharmaceuticals of the present invention further contains a cross-linking agent.
- the cross-linking agent include polyvalent metal salts, and examples thereof include polyvalent metal compounds containing aluminum.
- hydroxides such as aluminum hydroxide and alumina magnesium hydroxide; aluminum chloride, aluminum sulfate, potassium aluminum sulfate, aluminum glycinate (dihydroxyaluminum aminoacetal), dihydroxyaluminum aminoacetate, synthetic aluminum silicate, dry hydroxide.
- Positive salts of inorganic or organic acids such as aluminum gel, kaolin and aluminum stearate or basic salts thereof; re-salts such as aluminum myoban; aluminate such as aluminate; inorganic aluminum complex salts and organic aluminum chelate compounds.
- examples thereof include polyvalent metal compounds such as synthetic hydrotalcite, magnesium aluminate silicate, and magnesium aluminate metasilicate, and these can be used alone or in combination of two or more.
- the amount of the cross-linking agent to be blended may be appropriately selected in consideration of the degree of cross-linking that may contribute to the residual adhesive on the skin and the adhesiveness.
- the blending amount thereof is, for example, 0.01% by mass or more and 6.0% by mass or less, 0.01% by mass or more and 4.0% by mass or less, based on the total mass of the pressure-sensitive adhesive layer of the water-containing patch for pharmaceuticals.
- the range of 0.01% by mass or more and 2.0% by mass or less can be mentioned.
- the pressure-sensitive adhesive layer of the water-containing patch for pharmaceuticals of the present invention contains a thickening agent, which is expected to function as improving the shape retention and the tackiness of the pressure-sensitive adhesive.
- the thickening agent include celluloses such as ethyl cellulose, sodium carmerol, hydroxyethyl cellulose, hydroxypropyl cellulose, hypromellose and methyl cellulose, polysaccharides such as sodium alginate, carrageenan, xanthan gum and sodium hyaluronate, gelatin and urea. Can be mentioned. Of these, carmellose sodium, which has thixotopy properties and improves ductility, is preferable.
- the blending amount of the thickening agent is usually, for example, 0.1% by mass or more and 10% by mass or less, 0.5% by mass or more and 20% by mass or less, based on the total mass of the pressure-sensitive adhesive layer of the water-containing patch for pharmaceuticals. Or, it can be in the range of 1.0% by mass or more and 10% by mass or less.
- the pressure-sensitive adhesive layer of the water-containing patch for pharmaceuticals of the present invention contains a wetting agent (also referred to as a moisturizing agent).
- the wetting agent has a function of suppressing evaporation of water over time, and can be directly mixed with water such as a water-soluble polymer such as a hydrophilic acrylic pressure-sensitive adhesive, a thickening agent such as carmellose sodium, and a cross-linking agent. It is expected to have a function of suppressing thickening due to lump generation and cross-linking. For the reason of avoiding the latter direct addition to water, it is desirable to use a wetting agent that contains almost no water.
- the hydrophilic acrylic pressure-sensitive adhesive the thickening agent, etc.
- a cross-linking agent or the like By blending a cross-linking agent or the like to prepare a pre-formation and then mixing it with other components constituting the pressure-sensitive adhesive layer, lump generation and thickening can be suppressed.
- wetting agents include concentrated glycerin, glycerin, D-sorbitol, ethylene glycol, propylene glycol, polyethylene glycol, polypropylene glycol, liquid paraffin, 1,3-propanediol, 1,4-butanediol, and martitol.
- Polyhydric alcohols such as xylitol.
- a wetting agent containing water can be preferably blended.
- the D-sorbitol solution which is usually used as a 70% aqueous solution, contains water, so that it is difficult to use it for suppressing the generation of lumps and thickening (preparation of the above-mentioned preform), but it is mixed with other components thereafter. It is possible to mix them together.
- the blending amount of the wetting agent (the total amount of the wetting agent containing almost no water and the wetting agent containing water) is usually 1.0, for example, based on the total mass of the pressure-sensitive adhesive layer of the water-containing patch for pharmaceuticals. It can be in the range of mass% or more and 70% by mass or less, 5.0% by mass or more and 60% by mass or less, or 10% by mass or more and 60% by mass or less.
- the total amount ⁇ A> of the above-mentioned hydrophilic acrylic pressure-sensitive adhesive, the thickening agent, and the cross-linking agent and the amount ⁇ B> mass ratio of the wetting agent containing almost no water for example, concentrated glycerin
- ⁇ A> / ⁇ B> 7.25 / 25 to 7.25 / 10
- the water-containing patch for pharmaceutical products of the present invention contains water (moisture) in the pressure-sensitive adhesive layer.
- the "water” contained in the pressure-sensitive adhesive layer includes not only water separately added as water at the time of forming the pressure-sensitive adhesive layer, but also water contained in the form of an emulsion or an aqueous solution.
- the blending amount of water is not particularly limited, but based on the total mass of the pressure-sensitive adhesive layer of the water-containing patch for pharmaceuticals, for example, 10% by mass or more and 90% by mass or less, 15% by mass or more and 70% by mass or less, 20% by mass or more. It can be in the range of 50% by mass or less. It should be noted that this water content is a value at the time of preparing the patch or before the patch is applied, and is not limited to the case where water volatilizes from the adhesive layer with the progress of the application.
- a refreshing agent in the water-containing patch for pharmaceuticals of the present invention, when a non-steroidal anti-inflammatory analgesic such as loxoprofen sodium is used as an active ingredient to be blended in the pressure-sensitive adhesive layer, a refreshing agent can be preferably blended.
- the refreshing agent include l-menthol, dl-camphor, kehi oil, geraniol, peppermint oil, bergamot oil, d-borneol, eucalyptus oil and the like, and these may be used alone or in combination of two or more. can.
- l-menthol and dl-camphor fall under the above-mentioned ⁇ active ingredient>, they can be blended as a ⁇ cooling agent> in an amount that does not contribute to the manifestation of the effect as an active ingredient.
- the blending amount may be appropriately selected within the range of the amount used as a pharmaceutical additive in consideration of not exhibiting a medicinal effect and exhibiting a refreshing sensation at the time of application.
- the blending amount of l-menthol as a refreshing agent is, for example, 0.01% by mass or more and 4.0% by mass or less, 0.01% by mass, based on the total mass of the pressure-sensitive adhesive layer of the water-containing patch for pharmaceuticals. The range of 3.0% by mass or less can be mentioned.
- the pressure-sensitive adhesive layer of the water-containing patch for pharmaceuticals of the present invention may further contain an organic solvent.
- the organic solvent blended in the pressure-sensitive adhesive layer may have a role of assisting the dissolution of the active ingredient such as a drug and preventing the active ingredient from precipitating from the pressure-sensitive adhesive layer.
- organic solvent such as crotamitone; N-methyl-2-pyrrolidone; polyalkylene glycol such as macrogol 400 (polyethylene glycol) and polybutylene glycol; diethyl adipate, diisopropyl adipate, diethyl sebacate , Fatty esters such as diisopropyl sebacate, isopropyl myristate, isopropyl palmitate, oleyl oleate; sorbitan esters such as polyoxyalkylene fatty acid esters; polyhydric alcohols such as 1,3-butanediol; dimethylformamide; dimethylsulfoxide, etc. Can be mentioned. These can be used alone or in combination of two or more.
- the blending amount of the organic solvent is, for example, 0.1% by mass or more and 20% by mass or less, 0.5% by mass or more and 10% by mass or less, or 1. It can be in the range of 0% by mass or more and 5% by mass or less.
- the pressure-sensitive adhesive layer of the water-containing patch for pharmaceuticals of the present invention may further contain a pH adjuster.
- a pH adjuster either an organic acid or an inorganic acid can be used, and these may be used in combination.
- the organic acid include citric acid, lactic acid, tartrate acid, gluconic acid, glycolic acid, malic acid, fumaric acid, metasulfonic acid, maleic acid, acetic acid and the like, and these may be used alone or in combination of two or more. Can be done.
- hydroxy acids such as lactic acid also have the effect of improving the solubility of the sparingly soluble aluminum compound (crosslinking agent).
- the inorganic acid examples include hydrochloric acid, boric acid, phosphoric acid, sulfuric acid and the like, and these can be used alone or in combination of two or more.
- the blending amount of the organic acid can be, for example, in the range of 0.01% by mass or more and 5% by mass or less based on the total mass of the pressure-sensitive adhesive layer of the water-containing patch for pharmaceuticals.
- the blending amount of the inorganic acid can be, for example, in the range of 0.1% by mass or more and 1.2% by mass or less based on the total mass of the pressure-sensitive adhesive layer of the water-containing patch for pharmaceuticals.
- a chelating agent can be added to the pressure-sensitive adhesive layer of the water-containing patch for pharmaceuticals of the present invention in order to control the dissolution rate of the poorly soluble aluminum compound (crosslinking agent).
- the chelating agent include sodium edetate (ethylenediaminetetraacetic acid disodium salt).
- the blending amount of the chelating agent is usually in the range of 0.01% by mass or more and 1% by mass or less, based on the total mass of the pressure-sensitive adhesive layer of the water-containing patch for pharmaceuticals.
- a water-soluble polymer compound a surfactant, a stabilizer (antioxidant, an ultraviolet absorber, etc.), an inorganic powder, etc.
- These optional components can be used alone or in combination of two or more.
- water-soluble polymer compound examples include polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer, sucrose fatty acid ester and the like. These can be used alone or in combination of two or more.
- the blending amount of the water-soluble polymer compound is usually, for example, 1.0% by mass or more and 30% by mass or less, 3.0% by mass or more and 20% by mass, based on the total mass of the pressure-sensitive adhesive layer of the water-containing patch for pharmaceuticals. Below, or in the range of 5.0% by mass or more and 20% by mass or less.
- surfactant examples include polyoxyethylene fatty acid esters such as polyoxyethylene monolaurate, polyoxyethylene monostearate, polyoxyethylene monooleate, polyethylene glycol distearate, polyethylene glycol dilate, and polypropylene glycol dioleate.
- the blending amount of these surfactants is, for example, in the range of 0.001% by mass or more and 10% by mass or less, 0.01% by mass or more and 5% by mass or less, based on the total mass of the pressure-sensitive adhesive layer of the water-containing patch for pharmaceuticals. Can be.
- a stabilizer may be added to the pressure-sensitive adhesive layer of the water-containing patch for pharmaceuticals of the present invention in order to improve the storage stability of the active ingredient and the like against light (particularly ultraviolet rays), heat or oxygen.
- the stabilizer include an antioxidant such as dibutylhydroxytoluene (BHT); an ultraviolet absorber such as a benzoylmethane derivative; and the like.
- BHT dibutylhydroxytoluene
- the blending amount of the stabilizer is usually in the range of 0.01% by mass or more and 1% by mass or less, based on the total mass of the pressure-sensitive adhesive layer of the water-containing patch for pharmaceuticals.
- Inorganic powder As the inorganic powder, calcium carbonate, magnesium carbonate, silicate, zinc oxide, titanium oxide, magnesium sulfate, calcium sulfate and the like can be blended.
- Examples of the support used for the water-containing patch for pharmaceuticals of the present invention include flexible supports such as films, non-woven fabrics, Japanese paper, cotton cloths, knitted fabrics, woven fabrics, and laminated composites of non-woven fabrics and films. These supports are preferably made of a flexible material that can adhere to the skin and can follow the movement of the skin, and a material that can suppress the occurrence of skin irritation after long-term application.
- Examples of the material of these supports include polyethylene, polypropylene, polyethylene terephthalate, polybutylene terephthalate, polyethylene naphthalate, polystyrene, nylon, cotton, acetate rayon, rayon, rayon / polyethylene terephthalate composite, polyacrylonitrile, polyvinyl alcohol, and the like.
- the support such as cloth can be colored with a colorant to a color tone such as skin color to reduce the difference from the skin color at the time of application. Further, in that the color tone of the skin under the application can be easily seen through, the form of a plastic film having excellent transparency can be adopted.
- the thickness of the support is usually about 5 ⁇ m to 1 mm.
- its thickness is preferably 50 ⁇ m to 1 mm, more preferably 100 to 800 ⁇ m, and further preferably 200 to 700 ⁇ m.
- the support is a plastic film, its thickness is preferably 10 to 300 ⁇ m, more preferably 12 to 200 ⁇ m, and even more preferably 15 to 150 ⁇ m.
- the thickness of the support is as thin as about 5 ⁇ m to 30 ⁇ m, if a peelable carrier film layer is provided on the surface opposite to the pressure-sensitive adhesive layer formed on the support, the handleability as a patch can be improved. It is preferable because it improves.
- the thickness of the support is smaller than 5 ⁇ m, the strength and handleability of the patch will decrease, making it difficult to stick to the skin, tearing due to contact with other members, or with water for bathing, etc. It may peel off from the skin in a short time due to contact.
- the thickness of the support is too large (more than 1 mm), it becomes difficult for the patch to follow the movement of the skin, and it becomes easy to form a trigger for peeling off at the edge of the patch, so that the patch can be peeled off from the skin in a short time. There is a risk of peeling or an increase in discomfort during application.
- one or both sides of the support may be sandblasted, corona-treated, or the like for the purpose of improving the anchoring property of the adhesive and the support. Further, in order to facilitate removal from the packaging material, unevenness may be provided on one side or both sides of the support by a method other than sandblasting.
- the release liner (also referred to as release layer / release paper) used in the water-containing patch for pharmaceuticals of the present invention is preferably made of a material that does not easily absorb or adsorb drugs or the like in the pressure-sensitive adhesive layer. Conventional ones can be used in.
- plastic films such as polyester (polyethylene terephthalate, polybutylene terephthalate, polyethylene naphthalate, etc.), polypropylene (non-stretched, stretched, etc.), polyethylene, polyurethane, polyvinyl chloride, polystyrene, etc .; high-quality paper, glassin paper, parchment paper, craft Paper such as paper and synthetic paper; peeling processed paper in which the plastic film, paper or synthetic paper, synthetic fiber and the like are coated with a release agent having peeling performance such as silicone resin and fluororesin; aluminum foil; various films and sheets are used. Examples thereof include colorless or colored sheets such as laminated laminated paper and laminated peeled paper obtained by coating the laminated paper with a release agent.
- the release liner can also be provided with irregularities so that it can be easily taken out from the packaging material.
- the thickness of these release liners is not particularly limited, but is usually in the range of 10 ⁇ m to 1 mm, for example, 20 ⁇ m to 500 ⁇ m, preferably 40 ⁇ m to 200 ⁇ m.
- the shape of the release liner can be a square, a rectangle, a circle, or the like, and if desired, a shape with rounded corners can be used.
- the size may be the same as or slightly larger than the size of the support in the patch.
- the peeling liner may be composed of one or a plurality of strips, and the cut may be formed of a straight line, a wavy line, or a sewing machine line, or a part of the peeling liners may overlap each other.
- the water-containing patch for pharmaceuticals of the present invention can be produced by a conventionally known method. For example, it can be manufactured through the following steps i) or ii). i) A step of applying the pressure-sensitive adhesive layer forming composition on the support to form the pressure-sensitive adhesive layer, and a step of bonding the pressure-sensitive adhesive layer formed on the support and the release liner. ii) A step of applying the pressure-sensitive adhesive layer forming composition on the release liner to form the pressure-sensitive adhesive layer, and a step of bonding the pressure-sensitive adhesive layer formed on the release liner and the support.
- the thickness of the pressure-sensitive adhesive layer is not particularly limited, but is usually 10 ⁇ m to 1000 ⁇ m, for example, about 20 ⁇ m to 800 ⁇ m.
- the pressure-sensitive adhesive layer-forming composition includes various components contained in the above-mentioned pressure-sensitive adhesive layer: active ingredient, acrylic hydrophilic pressure-sensitive adhesive, acrylic acid alkyl ester-based copolymer, cross-linking agent, thickening agent, and wetting agent. And water, a semi-solid composition which may contain a cooling agent, an organic solvent, a pH adjuster and a chelating agent, and may further contain any other component. It is preferable to set the pH of the pressure-sensitive adhesive layer forming composition to 2 to 4 because good crosslinkability and shape retention can be expected.
- the water-containing patch for pharmaceuticals of the present invention is characterized in that the adhesive strength is maintained when it contains water (immediately after application) and when it does not contain water (after the water volatilizes after application), and it has low skin irritation. It is a patch.
- the pressure-sensitive adhesive layer of the water-containing patch for pharmaceuticals of the present invention has i) a peel adhesive strength of 1 N / 15 mm or more after storage at 50 ° C. for 16 hours from the date of manufacture of the patch, and ii) the patch.
- the probe tack value of the subsequent adhesive layer is 1.8 times or more.
- Example 1 1 part by mass of polyvinyl alcohol was dissolved in 10 parts by mass of purified water by heating at 70 ° C., and then cooled to room temperature (preliminary preparation 1). Next, to 1.13 parts by mass of loxoprofen sodium (hydrate equivalent) and 1 part by mass of l-menthol, 3 parts by mass of Macrogol (registered trademark) 400 and 1 part by mass of lactic acid were added and dissolved at 40 ° C. , Cooled to room temperature (preliminary product 2).
- preform 1 methyl acrylate / 2-ethylhexyl acrylate copolymer emulsion (solid content 60%, polyoxyethylene nonylphenyl ether (30EO) trace amount contained in the emulsion), 20 parts by mass, sodium edetate water.
- the obtained pressure-sensitive adhesive layer-forming composition is spread on the silicone surface of a liner (pete (75 ⁇ m) treated with silicone on one side) with a spreading machine adjusted to a slit width of 0.5 mm, and a knit support (made of polyester) is formed. After laminating, it was punched into an arbitrary shape, sealed in an aluminum bag, and aged at 40 ° C. for 1 week to obtain the formulation of Example 1.
- Example 2 Same as Example 1 except that the amount of the methyl acrylate / 2-ethylhexyl acrylate copolymer emulsion was changed to 30 parts by mass (solid content 60%) and the amount of the D-sorbitol 70% aqueous solution was changed to 20 parts by mass. The preparation of Example 2 was obtained.
- Example 3 Same as Example 1 except that the compounding amount of the methyl acrylate / 2-ethylhexyl acrylate copolymer emulsion was changed to 40 parts by mass (solid content 60%) and the compounding amount of the 70% aqueous solution of D-sorbitol was changed to 15 parts by mass. The preparation of Example 3 was obtained.
- Example 4 The amount of methyl acrylate / 2-ethylhexyl acrylate copolymer compounded emulsion is 50 parts by mass (solid content 60%), the amount of D-sorbitol 70% aqueous solution is 10 parts by mass, and the amount of concentrated glycerin is 20 parts by mass.
- the pharmaceutical product of Example 4 was obtained in the same manner as in Example 1 except that it was changed.
- Example 5 The amount of methyl acrylate / 2-ethylhexyl acrylate copolymer compounded emulsion is 60 parts by mass (solid content 60%), the amount of D-sorbitol 70% aqueous solution is 0 parts by mass, and the amount of concentrated glycerin is 20 parts by mass.
- the pharmaceutical product of Example 5 was obtained in the same manner as in Example 1 except that it was changed.
- Comparative Example 1 A pharmaceutical product of Comparative Example 1 was obtained in the same manner as in Example 1 except that the blending amount of the methyl acrylate / 2-ethylhexyl acrylate copolymer emulsion was changed to 7 parts by mass (solid content 60%).
- Comparative Example 2 A pharmaceutical product of Comparative Example 2 was obtained in the same manner as in Example 1 except that the blending amount of the methyl acrylate / 2-ethylhexyl acrylate copolymer emulsion was changed to 10 parts by mass (solid content 60%).
- Comparative Example 3 The amount of the methyl acrylate / 2-ethylhexyl acrylate copolymer emulsion was changed to 70 parts by mass (solid content 60%), the amount of the D-sorbitol solution was changed to 0 parts by mass, and the amount of concentrated glycerin was changed to 10 parts by mass. Except for the above, an attempt was made to obtain a pressure-sensitive adhesive layer-forming composition in the same manner as in Example 1, but a large amount of lumps were generated in the obtained pressure-sensitive adhesive layer-forming composition, and the subsequent spread to the liner was not achieved. The formulation could not be obtained.
- Test Example 1 Adhesive layer (adhesive layer forming composition (plaster)) With respect to the formulations of Examples 1 to 5 and Comparative Examples 1 and 2 when they contained water (after aging) and when they did not contain water (after aging, the liner was peeled off to expose the pressure-sensitive adhesive layer). After drying at 50 ° C. for 16 hours), the color of the pressure-sensitive adhesive layer (the pressure-sensitive adhesive layer forming composition) was visually evaluated. The results obtained are shown in Table 2.
- Test Example 2 Cross-linked state of adhesive layer (adhesive layer forming composition (plaster))
- the formulations (after aging) of Examples 1 to 5 and Comparative Examples 1 to 3 were cut into 1 cm ⁇ 5 cm and immersed in 50 mL of purified water at room temperature (23 ° C. ⁇ 5 ° C.). After 16 hours from the immersion, the swelling state of the pressure-sensitive adhesive layer (the pressure-sensitive adhesive layer forming composition) was visually evaluated, and the cross-linked state of the pressure-sensitive adhesive layer (the pressure-sensitive adhesive layer forming composition) was evaluated according to the following evaluation criteria. The results obtained are shown in Table 2.
- ⁇ Evaluation criteria> No cross-linking (adhesive layer (adhesive layer forming composition) dissolved) +: Cross-linked (adhesive layer (adhesive layer forming composition) does not dissolve and swells greatly) ++: Strong cross-linking (adhesive layer (adhesive layer forming composition) does not dissolve and swells moderately) +++: Very strong cross-linking (adhesive layer (adhesive layer forming composition) does not dissolve and swells small)
- the pressure-sensitive adhesive layer-forming composition evaluated as “-” may dissolve a polymer compound such as a hydrophilic acrylic pressure-sensitive adhesive, and as the dissolution progresses, it may be deposited on the bottom of the immersed container. On the other hand, as the evaluation changes from "+" to "+++", the swelling of the polymer compound decreases, and it can be confirmed that the pressure-sensitive adhesive layer-forming composition is in
- Test Example 3 Adhesive strength test
- ⁇ Test product> For the formulations of Examples 1 to 5, Comparative Example 1 and Comparative Example 2, water-containing (after aging) and water-free (after aging, the liner was removed to expose the pressure-sensitive adhesive layer, and the temperature was 50 ° C. 16 After drying by storage for hours), the two types were set as the initial stage.
- Reference Examples 1 to 3 commercially available formulations, after opening the product packaging, moisture-containing (immediately after opening) and moisture-free (take the liner and dry at 50 ° C. for 16 hours). The two types of the product) were used as the initial stage.
- Reference example 1 Pap agent (Vantelin Kowa Pat EX, Kowa Co., Ltd., lot number: DA8R, Nikazol combination (concentration unknown))
- Reference example 2 Tape agent (Loxonin S tape, Daiichi Sankyo Healthcare Co., Ltd., lot number LO193)
- Reference example 3 Pap agent (Loxonin S Pap, Daiichi Sankyo Healthcare Co., Ltd., lot number JO297)
- the white turbidity of the pressure-sensitive adhesive layer-forming composition disappears due to the volatilization of water, and in all the formulations prepared in the range of 7% by mass to 60% by mass of the 2-ethylhexyl acrylate copolymer resin emulsion, after drying.
- the color of the pressure-sensitive adhesive layer-forming composition became transparent.
- the pressure-sensitive adhesive layer-forming composition of Comparative Example 3 in which the blending amount of the methyl acrylate / 2-ethylhexyl acrylate copolymer resin emulsion was increased to 70% by mass caused a large amount of lumps to be generated in the formulation. It was impossible to manufacture.
- the pressure-sensitive adhesive layer-forming composition in which the blending amount of the methyl acrylate / 2-ethylhexyl acrylate copolymer resin emulsion was 7% by mass to 60% by mass was crosslinked, and the blending amount of the emulsion was increased.
- the crosslinked state tended to become stronger, while the pressure-sensitive adhesive layer-forming compositions of Comparative Example 1 and Comparative Example 2 in which the blending amount of the emulsion was less than 20% by mass resulted in large swelling.
- Table 3 ⁇ Test results (Table 3)> As shown in Table 3, in the results of ball tack adhesive strength, the formulations of Examples 1 to 5 were No. 1 in terms of water content (initial stage). The number was 21 or more, and no decrease with time was observed. In addition, the ball tack adhesive strength after the water volatilized tended to increase from the time when the water volatilized. On the other hand, the formulations of Comparative Examples 1 and 2 decreased with time when they contained water, and at 60 ° C. and 1 W, No. It was 17 or less.
- the ball tack adhesive strength of the commercially available poultices of Reference Example 1 and Reference Example 3 is as low as 6.7 or less when the water content is contained, and tends to decrease slightly when the water content is not contained. there were.
- the ball tack adhesive strength in the initial state was 11.3, which was higher than that of the commercially available pap agent, but it was dried for water-free treatment and decreased over time.
- the formulations of Examples 1 to 5 showed 1 N / 15 mm or more after the water volatilization, and depended on the blending amount of the methyl acrylate / 2-ethylhexyl acrylate copolymer resin emulsion. Therefore, the value of peel adhesive strength increased.
- the formulations of Comparative Example 1 to Comparative Example 2 show a peel adhesive strength of less than 1 N / 15 mm even after the water volatilization, and the formulations of Reference Example 1 to Reference Example 3 which are indicators of the conventional product are tape agents after the water volatilization. Although the value of the peel adhesive strength was relatively high only in (Reference Example 2), all of them showed less than 1N / 15 mm.
- the formulations of Examples 1 to 5 showed 1 N / 5 mm ⁇ or more after the water volatilization, and depended on the blending amount of the methyl acrylate / 2-ethylhexyl acrylate copolymer resin emulsion. As a result, the value of probe tack adhesive strength increased. In the formulations of Comparative Example 1 to Comparative Example 2, the probe tack adhesive strength after water volatilization exceeded 1 N / 5 mm ⁇ , but the value was lower than that of the examples.
- Example 1 Based on the above results, the formulations of Examples 1 to 5 were compared with the commercially available poultices (Reference Examples 1 and 3), and the ball tack and probe tack were either water-containing or water-free (after water volatilization). The results were clearly high, and the peel adhesive strength was significantly higher after the water volatilization. Further, as compared with the commercially available tape agent (Reference Example 2), the peel and probe tack adhesive strengths were equal to or less than the initial moisture content, but all the adhesive strengths were clearly high after the moisture volatilization.
- the ball tack and probe tack in the formulations of Comparative Examples 1 and 2 had lower values in both water-containing and water-free (after water volatilization) than in the formulations of Examples, and the peel adhesive strength also volatilized. Later, the result was much lower. That is, the results of the examples can be evaluated as having a high overall adhesive strength after the volatilization of water.
- the amount of the acrylic acid alkyl ester-based copolymer emulsion blended is 20% by mass or more and less than 70% by mass with respect to the total mass of the pressure-sensitive adhesive layer. It was confirmed that it is possible to provide a medicinal water-containing adhesive with low skin irritation while maintaining a higher adhesive strength than a commercially available tape agent at the time of volatilization of water, which is clearly higher in adhesive strength than the Pap agent.
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WO2006090782A1 (ja) * | 2005-02-23 | 2006-08-31 | Saitama Daiichi Pharmaceutical Co., Ltd. | 含水系外用貼付剤用組成物及びこの組成物を用いた貼付剤 |
WO2015025935A1 (ja) * | 2013-08-23 | 2015-02-26 | 久光製薬株式会社 | パップ剤及びその製造方法 |
WO2020066188A1 (ja) * | 2018-09-26 | 2020-04-02 | ニチバン株式会社 | 含水系貼付剤 |
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WO2006090782A1 (ja) * | 2005-02-23 | 2006-08-31 | Saitama Daiichi Pharmaceutical Co., Ltd. | 含水系外用貼付剤用組成物及びこの組成物を用いた貼付剤 |
WO2015025935A1 (ja) * | 2013-08-23 | 2015-02-26 | 久光製薬株式会社 | パップ剤及びその製造方法 |
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