WO2004058232A1

WO2004058232A1 - Adhesive patch

Info

Publication number: WO2004058232A1
Application number: PCT/JP2003/016785
Authority: WO
Inventors: Makoto Kanebako; Masayuki Kanishi; Toshio Inagi; Hisanori Takahashi; Masayuki Konno
Original assignee: Kowa Co., Ltd.; Nitto Denko Corporation
Priority date: 2002-12-26
Filing date: 2003-12-25
Publication date: 2004-07-15
Also published as: AU2003292830A8; JPWO2004058232A1; AU2003292830A1

Abstract

An adhesive patch which comprises a releasable protective film having a moisture permeability of 0 to 50 (g/m2/24 h), a moisture-permeable film superposed on the protective film, a nonwoven or woven fabric superposed on the moisture-permeable film through a pressure-sensitive adhesive, a layer of a hydrous drug-containing plaster which contains water in an amount of 20 to 70 wt.% based on the plaster and has been applied to the nonwoven or woven fabric, and a liner disposed on the plaster layer, wherein the plaster substrate constituted of the moisture-permeable film, the pressure-sensitive adhesive layer, and the nonwoven or woven fabric has a moisture permeability of 500 to 1,000 (g/m2/24 h). The adhesive patch is reduced in skin irritation and is excellent in long-term drug absorption and appearance stability.

Description

Patch

Technical field

The present invention provides a patch having low skin irritation, excellent drug absorption over time, and excellent appearance stability.

It relates to a patch.

Background art

Generally, a non-woven fabric or a woven fabric is used as a support for a water-containing plaster containing a drug such as an anti-inflammatory analgesic. These supports have advantages such as excellent drapability, adhesiveness to plasters and stretchability, and high skin permeability due to high air permeability. However, the drug in the plaster penetrates the surface of the support over time, and the drug content decreases, and the moisture in the plaster evaporates at the time of application, reducing the transferability of the drug to the skin and the adhesiveness. There was a problem.

In order to solve these problems, it is already known to use a support in which a polymer film is laminated on a nonwoven fabric or a woven fabric. Japanese Patent Application Laid-Open No. H08-216668, Japanese Patent Application Laid-Open No. H08-217668, and Japanese Patent Application Laid-Open No. H08-216678 disclose a support comprising a polymer film laminated on a nonwoven fabric or a woven fabric. The technology described in Japanese Patent Application Publication No. 0-143530 and Japanese Patent Application Publication No. 2565534 is known. In Patent No. 30440432, a moisture permeability of 100 to 400 (g / m ² / 24h), which is composed of a laminate of a polymer film and a porous sheet such as a nonwoven fabric or a woven fabric, is used. The use of a plaster having a pole-tack adhesive strength of No. 10 or more for the support of ()) reduces the skin irritation of the patch and improves the absorbability and adhesiveness. In JP-A-8 2 1 7 6 6 8 discloses, using moisture permeation degree of 4 8 0~9 6 0 0 (g / m 2 / 24h) moisture-permeable film and the nonwoven fabric and a portion adhered supporting lifting body This suppresses a decrease in moisture permeability due to the adhesive. In Japanese Patent Application Laid-Open No. 2000-2004-5033, a nonwoven fabric is laminated with a porous synthetic resin film having fine pores and a moisture permeability of 500 to 700 (g / m ² / 24h). The use of such a support improves the therapeutic effect of the patch and reduces skin irritation. In Japanese Patent No. 256553334, a film and / or sheet having different moisture permeability has a laminated structure of two or more layers, and by using a film and / or sheet having a low moisture permeability toward the outer layer, It controls the amount of drug permeated through the skin.

However, any of the patches described in the above-mentioned prior art documents has a problem that wrinkles are generated on the surface of the moisture-permeable film with time and the commercial value is reduced, and the drug absorbability is reduced with time. there were. A patch using a water-containing drug-containing plaster, which has low skin irritation, excellent drug absorption over time and appearance stability, has not yet been obtained.

Therefore, there has been a need for a patch having good elasticity after application, excellent drug absorption over time, and excellent appearance stability. Disclosure of the invention

The present inventors have conducted intensive studies in consideration of the above points, and as a result, a peelable protective film having a specific moisture permeability is composed of a moisture-permeable film, an adhesive layer, and a nonwoven fabric or a woven fabric. A time-dependent drug absorption is provided by providing a plaster support on the surface of the moisture-permeable film, setting the moisture permeability of the support within a specific range, and using a plaster containing a specific moisture. The present inventors have found that a patch that maintains the properties and appearance stability can be obtained, and have completed the present invention.

That is, the present invention provides a peelable protective film having a moisture permeability of 0 to 50 (g / m ² / 24h); a moisture-permeable film laminated on the protective film; Nonwoven fabric or woven fabric laminated with a water-containing drug-containing plaster layer containing 20 to 70% by weight of water based on the amount of the plaster spread on the nonwoven fabric or woven fabric; and the plaster body The moisture-permeable film, the pressure-sensitive adhesive layer, and the nonwoven fabric. Alternatively, the patch is characterized in that the moisture permeability of the plaster support composed of a woven fabric and a woven fabric has a moisture permeability of 500 to: L0000 (g / mV24h). BEST MODE FOR CARRYING OUT THE INVENTION

Hereinafter, the present invention will be described in detail.

Examples of the material of the peelable protective film of the present invention include polyethylene, polypropylene, polyester, polyvinyl chloride, polyvinylidene chloride, polystyrene, polybutadiene, and ethylene monoacetate copolymer, and the like. , Polypropylene and ethylene-vinyl acetate copolymer are preferred. The thickness is preferably about 10 to 10 mm, particularly preferably about 20 to 80 m. The protective films may be used alone or in combination of two or more.

The moisture permeability of peelable protective films ^{0~ 5 0 (g / m 2} / 24h), preferably ^{0~ 3 0 (g / m 2} / 24h), particularly preferably 0~ ² 0 (g / m 2 / 24h). When the moisture permeability of the protective film exceeds 50 (g / m ² / 24h), the effect of the present invention is not exerted because wrinkles are generated in the moisture-permeable film and water vaporization in the plaster cannot be suppressed. There is a fear. It is preferable that the protective film be peeled off after the patch is applied, since it is easy to stick to the skin and furthermore, the elasticity of the patch is improved.

Examples of a method of laminating the protective film and the moisture-permeable film include a method of indirectly laminating with an adhesive, and a method of directly laminating without using an adhesive. Examples of the adhesive include polyvinyl acetate-based, polyvinyl alcohol-based, polyvinyl acetal-based, polyvinyl chloride-based, acrylic-based, polyamide-based, and cellulose-based thermoplastic resins and urea-based, melamine-based, phenol-based, and epoxy-based adhesives. Thermosetting resins such as polyester, polyurethane, and polymatic resins are preferable, and pinyl acetate, polyvinyl chloride, and acrylic thermoplastic resins are particularly preferable.

Examples of the moisture-permeable film of the present invention include polyethylene, ethylene-biacetic acid, and the like. Nyl copolymer, polypropylene, polyamide, polyester, polyvinyl chloride, polyvinyl chloride, polyurethane, polystyrene, polyvinyl alcohol, polybutadiene, polyether urethane, polyester urethane, polyether polyamide block polymer, polyacrylic acid Esters, etc., of which ethylene-vinyl acetate copolymers, polyamides, polyurethanes, polyether urethanes, polyester urethanes, polyester polyamide block polymers, and polyacrylates are preferred. The thickness is preferably about l to 100 m, especially about 5 to 50 m. The moisture-permeable films may be used alone or in combination of two or more. In the present invention, when the film material itself does not have moisture permeability or is insufficient, the moisture-permeable film can be provided with a moisture-permeable property by performing a perforation treatment.

Examples of the adhesive for laminating the moisture permeable film and the nonwoven fabric or the woven fabric include, for example, polyvinyl acetate-based, polyvinyl alcohol-based, polyvinyl acetal-based, polyvinyl chloride-based, acrylic, polyamide-based, and cellulose-based heat-sensitive adhesives. Examples of the thermoplastic resin include thermosetting resins of urea type, melamine type, phenol type, epoxy type, polyester type, polyurethane type, or polyamatic type. Among these, a polyvinyl acetate-based, polyvinyl alcohol-based, acrylic-based, polyamide-based, or cellulose-based thermoplastic resin, and a polyurethane-based thermosetting resin are preferable. Further, it is preferable that the moisture-permeable film and the nonwoven fabric or the woven fabric are entirely adhered with an adhesive from the viewpoint of good adhesion between the moisture-permeable film and the nonwoven fabric and suppression of drug leakage from the plaster. The thickness of the pressure-sensitive adhesive layer is not particularly limited, but is usually about 10 to 100 x m.

Examples of the material of the nonwoven fabric or woven fabric of the present invention include cotton, polyester, rayon, nylon, polyolefin, polyethylene, vinylon, acetate, polypropylene, polyurethane, and the like, and polyester, rayon, and nylon are preferred. Non-woven fabrics are manufactured by the needle punch method, spunlace method, Examples include the pan-pound method, the latch-pound method, and the melt blown method, with the spun-lace method and the spun-pound method being preferred. The thickness is preferably | l to 200 m, particularly preferably 100 to 100 m. The basis weight is preferably about 50 to 200 g / m ² , particularly preferably 70 to 15 O g / m ² .

Moisture permeability of moisture-permeable film and the adhesive layer and the nonwoven fabric or composed of a woven fabric plaster for support, 5 0 0~ 1 0 0 0 (g / m 2/24), preferably 5 5 0 ^{9 0 0 (g / m 2} /24), particularly preferably 6 0 0~8 5 0 (g / m 2 / 24h) are preferred. If the moisture permeability exceeds 100 (g / m ² / 24h), the moisture-permeable film swells over time, causing wrinkles, and the absorption of the drug in the plaster into the skin at the time of application. It is not preferable because it decreases. Also, 5 0

If it is less than 0 (g / m ² / 24h), it is not preferable because the skin has irritation due to low air permeability at the time of application.

The water-containing drug-containing plaster according to the present invention is composed of a drug, a base, a solvent, an additive, and water, and can be prepared by an ordinary production method.

The amount of water in the plaster is from 20 to 70% by weight, preferably from 25 to 65% by weight, particularly preferably from 30 to 60% by weight, based on the weight of the plaster. If the amount of water exceeds 70% by weight, the adhesiveness of the plaster drops significantly, which is not preferable. On the other hand, when the content is less than 20% by weight, a crosslinking reaction by the crosslinking agent in the plaster hardly occurs, and a plaster remains when the patch is peeled from the skin, which is not preferable.

The above-mentioned drugs include bone calcium regulators such as etidronate disodium, antihistamines such as ebastine, cetirizine hydrochloride, epinastine hydrochloride, hemedastine fumarate, diphenhydramine hydrochloride, antiemetic agents such as azesetron hydrochloride, ondansetron hydrochloride, daranisetron hydrochloride, etc. Gastrointestinal motility promoters such as itopride hydrochloride and cisapride; ACE inhibitors such as imidabril hydrochloride, temocapril hydrochloride, quinapril hydrochloride, benazepril hydrochloride, cilazapril, trandolapril, lisinopril, etc .; Manidipine hydrochloride, balunidipine hydrochloride, disordipine, nilvadipine, ferodipine, etc. Calcium antagonists, hydrochloric port hexa cytidine § diacetate, ranitidine hydrochloride, Famochiji emissions, H ₂ receptor antagonists such as nizatidine, anti-inflammatory agents such as mesalazine, Ranakonazo one Le, itraconazole, hydrochloric Amororufuin, hydrochloride Terupinafin, hydrochloride Butena fins , Antifungal agents such as ketoconazole and fluconazole, antidiabetic agents such as acarpose, epalles citrate, poglipoise, antirheumatic agents such as akuxylit, antiviral agents such as acyclovir, ophthalmology such as oxidadar thione Surgical aids, fungicides such as popidone iodine, ampiroxicam, zaltoprofen, mofezolac, methyl salicylate, glycol salicylate, indomethacin, ketoprofen, flurbiprofen, ibuprofen, diclofenac sodium, Non-steroidal anti-inflammatory agents such as fenamic acid, flufenamic acid, bufexamac, ibufenac, alclofenac, glycyrrhetinic acid, keratin softeners such as urea, sodium sodium benetate, benexate hydrochloride betadex, enprostil, sofacalcone Ulcer treatments such as polaprezinc, rebamipide, sucrose, etc., 0-blocking agents such as amosulalol hydrochloride, betaxolol hydrochloride, carvedilol hydrochloride, nipradilol, etc. 1, sodium flubas, simbas, pravas, pivas basin HMG-CoA reductase inhibitor, such as prostatic disease therapeutic agents such as mucus oscine hydrochloride, arrhythmia therapeutic agents such as pyridicanide hydrochloride, pyrmenol hydrochloride, vasodilators such as fasudil hydrochloride hydrate, propiverine hydrochloride, Therapeutic agents for urinary incontinence such as oxypeptinine hydrochloride, Cardiotonic agents such as midodrine acid, denopamine, and amedinium methylsulfate; antipsychotics such as mosaburamin hydrochloride, nemonapride and risperidone; hyperplatelet aggregating agents such as ozadarel sodium; proton pump inhibitors such as omebrazole and lansoprazole; rilmazahon hydrochloride Non-valpituric acid, antidepressants such as tandospirone quenate, etc., hormones such as nafarelin acetate, buserelin acetate, prednisolone valerate, immunosuppressants such as tacum limus hydrate, and acne treatments such as nadifloxacin. Dexamethasone palmitate, flutizone dipropionate, furanca, cortisteroids such as mometasone rubonate, positive inotropic substances such as pimobendan, Anti-leukotriene agents such as lanlukast hydrate; cardiac glycoside agents such as bezafibrate; conjunctivitis agents such as milorast potassium; local anesthetics such as lidocaine; antihypertensive agents such as doxazosin mesylate; vinegar; and tocopherol acid Examples include vitamin E and vitamin K such as menatetrenone. The content of the drug is preferably from 0.001 to 10% by weight, particularly preferably from 0.01 to 5% by weight, based on the weight of the plaster.

Examples of the base include gelatin, poly'acrylic acid, partially neutralized polyacrylic acid, sodium polyacrylate, polyvinyl alcohol, polyvinylpyrrolidone, polyethylene oxide, carboxymethylcellulose, sodium carboxymethylcellulose, hydroxypropylcellulose, Acrylics such as hydroxyethyl cellulose, methylcellulose, methylcellulose sodium, sodium alginate, xanthan gum, gum arabic, tragacanth gum, karaya gum, maleic anhydride copolymer, n-butyl acrylate, 2-ethylhexyl polyacrylate Adhesive, silicone adhesive of polydimethylsiloxane acid, rubber adhesive such as styrene-isoprene-styrene block copolymer, polyisoprene, alicyclic Group saturated hydrocarbon resins, ester gums, etc., and these can be used alone or in combination of two or more. The amount of the base is preferably 1 to 50% by weight, and more preferably 5 to 25% by weight, based on the weight of the base.

Examples of the solvent include (concentrated) glycerin, D-sorbitol solution, propylene glycol, dipropylene glycol, ethylene glycol, diethylene glycol, 1,3-butylene glycol, dipropylene glycol, polyethylene glycol, 2-ethyl-1, Polyhydric alcohols such as 3-hexanediol and polypropylene glycol 2000, monohydric alcohols such as ethanol, isopropanol, benzyl alcohol, stearyl alcohol and oleyl alcohol, diisopropyl adipate, isopropyl myristate, and triacetin Esters of medium chain fatty acids such as triglyceride with 6 to 12 carbon atoms in the middle chain such as diisopropyl sebacate, getyl sebacate, and triisooctanoic acid, and ketones such as black mitten And the like, and these can be used alone or in combination of two or more. The compounding amount of the solvent is preferably 1 to 70% by weight, particularly preferably 10 to 50% by weight, based on the weight of the paste.

Examples of the additives include a crosslinking agent, a curing regulator, an oil component, a mineral powder, an absorption accelerator, a stabilizer, a surfactant and the like. These additives can be used alone or in combination of two or more. The compounding amount of the additive is preferably from 0.1 to 30% by weight, particularly preferably from 1 to 20% by weight, based on the weight of the plaster.

Examples of the crosslinking agent include magnesium aluminate magnesium, aluminum hydroxide magnesium, magnesium aluminate metasilicate, synthetic hydrotalcite, dihydroxyaluminum aminoacetate, and dried aluminum hydroxide gel.

Examples of the curing regulator include cunic acid, malic acid, tartaric acid, sodium edetate, dalconic acid, and lactic acid.

Examples of the above oil components include olive oil, camellia oil, castor oil, safflower oil, castor oil, southern power oil, soybean oil, cottonseed oil, sesame oil, coconut oil, palm oil, cinnamon oil and the like.

Examples of the above-mentioned mineral powder include kaolin, bentonite, montmorillonite, zinc oxide, titanium oxide, and silicic anhydride.

As the above-mentioned absorption promoter, aprotic polar solvents such as dimethyl sulfoxide,

L-Men] 一, dl-Camphor and other terpenes; keratin such as urea; softeners; fatty acids such as oleic acid and stearic acid; keratolytics such as azone. Examples of the stabilizing agent include phenolic substances such as methyl parahydroxybenzoate and propyl benzoate, neutral substances such as chlorobutanol and phenylethyl alcohol, and salts such as chlorobenzanikonium chloride and benzonitani chloride. Antioxidants such as invertite, vitamin E, butylhydroxyanisole, tocopherol acetate, propyl gallate, 2-mercaptobenzimidazole, ascorbic acid, bisulfite And reducing agents such as thorium and sodium thiosulfate.

Examples of the surfactant include anionic surfactants such as calcium stearate, magnesium stearate, and sodium lauryl sulfate; cationic surfactants such as cetylpyrizonium chloride; glyceryl monostearate; sucrose fatty acid ester; Non-ionic surfactants such as polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene fatty acid ester, and polyoxyethylene alkyl ester.

In addition, the water-containing drug-containing plaster having a pole tack adhesive strength of No. 3 or more and No. 9 or less ensures that the plaster does not peel off from the support at the time of application of the patch, and that the skin of the patch It is preferable from the viewpoint that irritation to the skin is low when peeled from the skin. The plaster is usually applied on the support in a thickness of l to 2 mm, preferably 0.15 to 1.5 mm, more preferably 0.2 to 1 mm.

Examples of the liner of the present invention include a plastic film such as a polyethylene film and a polypropylene film, a cellulose film, and the above-mentioned film or paper sheet coated on the surface with a silicone-based release agent. Or a polypropylene film is preferred. The thickness is about 1 to 200 rn, especially 5 to: L 00 m is preferred.

As a method for producing the patch of the present invention, a usual method of preparation can be used. For example, a protective film and a moisture-permeable film are laminated, and further, a surface of the moisture-permeable film on which the protective film is not laminated. Then, a non-woven fabric is laminated via an adhesive, and a water-containing drug-containing plaster is spread between the non-woven fabric or woven fabric surface of the laminate thus obtained and the liner to prepare a patch.

As a method for storing the patch of the present invention, it is preferable to use a paper Z-aluminum / polyethylene laminated sheet having excellent sealing properties and light-shielding properties, and pack it in a bag.

By laminating a protective film that can be peeled off, the moisture-permeable film is not directly exposed to the surface during the manufacture of the patch, so that the moisture-permeable film can be protected from mechanical damage. It is possible. In addition, since the protective film does not peel off until after application, the stiffness of the preparation at the time of application is increased, and the application property is improved. By peeling off the protective film after pasting, there is no discomfort such as a decrease in elasticity. Furthermore, in conventional patches in which the moisture-permeable film is exposed, water vaporization from the plaster causes "wrinkles" on the surface of the moisture-permeable film, which significantly reduces the commercial value. By laminating, generation of “wrinkles” and deterioration of the performance of the moisture-permeable film can be suppressed. Furthermore, the patch has no leakage of the drug, can suppress a decrease in the drug content, and has little skin irritation. Example

Examples 1 to 3 and Comparative Example 1

0.8 parts by weight of polyvinyl alcohol (PVA217S) was dissolved in 30 parts by weight of purified water by heating to 60 ° C, and then cooled to room temperature. After dissolving 1.3 parts by weight of tartaric acid and 0.1 part by weight of sodium edetate, 25 parts by weight of D-sorbitol solution (70%) and 3 parts by weight of phorolin A were uniformly suspended (water). phase).

Separately, 0.375 parts by weight of indomethacin and 0.5 parts by weight of L-menthol were heated and dissolved at 40 ° C. in 400 parts by weight of McGall and then cooled to room temperature. After dissolving 20 parts by weight of concentrated glycerin, 3.5 parts by weight of carmerol sodium, 6 parts by weight of partially neutralized polyacrylic acid, and 0.1 part by weight of dihydroxyaluminum aminoacetate are uniformly dispersed. (Oil phase).

The aqueous phase is added to the oil phase, and the total weight is adjusted to 100 parts by weight with purified water. The mixture is kneaded with a kneading machine (revolution: 40 rpm, rotation: 80 rpm) for 15 minutes to obtain a water-containing drug. A containing plaster was obtained. Example 4

0.8 parts by weight of polyvinyl alcohol (PVA217S) was dissolved in 17 parts by weight of purified water by heating to 60 ° C, and then cooled to room temperature. After dissolving 1.3 parts by weight of tartaric acid and 0.1 part by weight of sodium edetate, 25 parts by weight of D-sorbitol solution (70%) and kaolin A 3 parts by weight were uniformly suspended. (Aqueous phase)

Separately, 0.375 parts by weight of indomethacin and 0.5 parts by weight of L-menthol were dissolved in 22.125 parts by weight of Macrogol 400 by heating to 40 ° C., and then cooled to room temperature. After dissolving 20 parts by weight of concentrated glycerin, 3.5 parts by weight of carmerol sodium, 6 parts by weight of partially neutralized polyacrylic acid, and 0.1 part by weight of dihydroxyaluminum acetate were uniformly dispersed. (Oil phase)

The aqueous phase is added to the oil phase, the total weight is adjusted to 100 parts by weight with purified water, and then kneaded with a kneading machine (revolution: 40 rpm, rotation: 80 rpm) for 15 minutes to obtain a water-containing drug-containing plaster. Was.

Example 5

0.8 parts by weight of polyvinyl alcohol (PVA217S) was dissolved in 62 parts by weight of purified water by heating to 60 ° C, and then cooled to room temperature. After dissolving 1.3 parts by weight of tartaric acid and 0.1 part by weight of sodium edetate, 3 parts by weight of kaolin A were uniformly suspended. (Aqueous phase) Separately, 0.375 parts by weight of indomethacin and 0.5 parts by weight of L-methyl were dissolved in 2.125 parts by weight of Macrogol 400 by heating to 40, and then cooled to room temperature. After dissolving 20 parts by weight of concentrated dariserin, 3.5 parts by weight of carmerol sodium, 6 parts by weight of partially neutralized polyacrylic acid, and 0.1 part by weight of dihydroxyaluminum acetate were uniformly dispersed. (Oil phase)

Comparative Example 2

0.8 parts by weight of polyvinyl alcohol (PVA217S) was dissolved in 7 parts by weight of purified water by heating to 60 ° C, and then cooled to room temperature. After dissolving 1.3 parts by weight of tartaric acid and 0.1 part by weight of sodium edetate, 25 parts by weight of D-sorbitol solution (70%) and 3 parts by weight of kaolin A were uniformly suspended. (Aqueous phase)

Separately, 0.375 parts by weight of indomethacin and 0.5 part by weight of L-menthol were dissolved in 32.125 parts by weight of Macrogol 400 by heating to 40 ° C., and then cooled to room temperature. Here, thick Dali After dissolving 20 parts by weight of serine, 3.5 parts by weight of carmellol sodium, 6 parts by weight of partially neutralized polyacrylic acid and 0.1 part by weight of dihydroxyaluminum acetate were uniformly dispersed. (Oil phase)

Comparative Example 3

0.8 parts by weight of polyvinyl alcohol (PVA217S) was dissolved in 72 parts by weight of purified water by heating to 60 ° C, and then cooled to room temperature. After dissolving 1.3 parts by weight of tartaric acid and 0.1 part by weight of sodium edetate, 3 parts by weight of kaolin A were uniformly suspended. (Aqueous phase) Separately, 0.375 parts by weight of indomethacin and 0.5 part by weight of L-menthol were dissolved in Macrogol 400 2.125 parts by weight at 40 ° C, and then cooled to room temperature. After dissolving 10 parts by weight of concentrated dariserin, 3.5 parts by weight of carmerol sodium, 6 parts by weight of partially neutralized polyacrylic acid and 0.1 part by weight of dihydroxyaluminum acetate were uniformly dispersed. (Oil phase)

A polyurethane permeable film is laminated on a polypropylene protective film (16 g / mV24h), and a nonwoven polyester fabric is applied via an acrylic adhesive on the surface where the protective film is not laminated. Were laminated. The wet-containing drug-containing plaster was spread using a spreader between the nonwoven fabric surface of the plaster support thus obtained and the polypropylene liner so that the thickness of the plaster became 1 mm. The patch was spread and cut into a size of 10 × 14 cm to prepare a patch.

The moisture permeability of the plaster support composed of the moisture-permeable film, the pressure-sensitive adhesive layer and the nonwoven fabric or woven fabric was 642 (g / m ² / 24h) in Examples 1, 4 and 5, and Example 2 There ^{7 3 4 (g / m 2} /24 h), example 3 9 2 5 (g / mV24h) , Comparative example 1 1 1 2 9 (g / m 2 / 24h), Comparative example 2及beauty 3 there was ^{6 4 2 (g / m 2} / 24h). The measurement of the moisture permeability was performed by the following method. <Moisture permeability test>

1 OmL of distilled water was placed in a glass container having an inner diameter of 40 cm and a height of 40 Onim, and a round-cut Sankare having a diameter of 50 thighs was attached to the mouth of the container and fixed. After measuring the weight (W 3) of the whole container on which the sample was attached, put it in a thermo-hygrostat at 40 ° C and a relative humidity of 30% RH, and left it for 24 hours (W 4) Was measured. From the measured weight, the moisture permeability was calculated by the following equation.

Moisture permeability (g / m ² / 24h) = (W 3 -W 4) / (0.02 X 0.02 X π) Comparative test 1 (wrinkle test on film surface)

The patches prepared in Examples 1 to 5 and Comparative Examples 1 to 3 were cut into 3 × 4 cm pieces, placed in an aluminum bag, sealed, and allowed to stand at room temperature. Similarly, the protective film was peeled off from the cut adhesive patch, placed in an aluminum bag, sealed, and left at room temperature. After one month, it was removed from the aluminum bag, and the wrinkled state of the film (protective film or moisture-permeable film) surface was visually checked. The results are shown in Tables 1 and 2, where the patch with wrinkles is indicated by X, and the patch without wrinkles is indicated by Δ. Comparative test 2 (drug absorption)

The patches prepared in Examples 1 to 5 and Comparative Examples 1 to 3 were cut into 3 × 4 cm pieces, placed in an aluminum bag, sealed, and allowed to stand at room temperature for one month (Patch A). Separately, the same water-containing drug-containing plaster as in Examples 1 to 5 and Comparative Examples 1 to 3 was applied between a polyester nonwoven fabric and a polypropylene liner by using a spreading machine to reduce the thickness of the plaster to one thigh. , And cut into a size of 3 × 4 cm to prepare a preparation. This preparation was preserved in the same manner as Patch A, and on the day of the experiment, it was laminated on a nonwoven fabric via an acrylic adhesive on a moisture-permeable polyurethane film (Patch B). The drug absorption experiment was performed by applying patch A or B after removing hair from the abdomen of Wistar rats (male, 8 weeks old, weight: 190 to 220 g). Blood is collected at 2, 4 and 6 hours after application, and plasma The concentration of tacin was measured by the HP LC method, and AUC (area under blood drug concentration, areau nd erthecurve) was determined. The results are shown in Tables 1 and 2. Comparative test 3 (Adhesive strength of plaster)

Adhesion was measured by the Pole-Tack adhesion test (Pharmaceutical Manufacturing Guideline 2001, Part II Application for Pharmaceutical Approval, Chapter 1 Notes on Application for Prescription of Prescription Drugs: Adhesion Test). The pole tack type adhesive strength was the number of steel poles that stopped for 10 seconds or more. The results are shown in Tables 1 and 2.

Table 1. Wrinkles on the film surface due to moisture permeability of the plaster support, drug absorption and Pole-tack adhesive force Example 1 Example 2 Example 3 Comparative Example 1 Water content 44.7 44.7 44.7 44.7 Moisture permeability

642 734 925 1129

(g / ra ² / 24h)

1 month old

〇〇〇〇 (with film)

Wrinkles

1 month old

X X X X

(Without protective film)

AUC patch A 0.93 0.85 0.60 0.45 (μgh / mL)

Patch B 0.98 0.82 0.86 0.82

1 month old

6 6 6 6 Ball set (with protective film)

Type adhesive for 1 month

6 6 6 6 (without protective film)

Table 2. Film surface wrinkles according to the water content in plaster, drug absorption and Pole-tack adhesive strength

The moisture permeability of the plaster support made of a moisture-permeable film, an adhesive layer, and a nonwoven or woven fabric

It was confirmed that wrinkles would occur if the protective film was not laminated on the support having a thickness of 500 (g / m ² / 24h) or more. However, it was confirmed that wrinkles did not occur when the protective film was laminated. In addition, the patch using a support with the moisture permeability of the plaster support exceeding 100 (g / m ² / 24h) is more protected than the patch B, which is laminated on the day when the moisture-permeable film is attached. The AUC was significantly reduced in the daily product (Patch A) where the film and the moisture-permeable film were laminated. However, for a patch using a plaster support with a moisture permeability of 100 (g / mV24h) or less, for a patch with a water content of 70% or less in the plaster, the moisture-permeable film was used on the day of the experiment. product Compared with the patch B, the daily product (paste A) in which the protective film and the moisture-permeable film were laminated showed a lower decrease in AUC. In Comparative Example 2 in which the water content was less than 20%, a patch could not be produced. Further, the adhesive patch of the patch excluding Comparative Example 2 was less than No. 10 in which no skin irritation was observed.

Production Examples 1 and 2

Dissolve 1 part by weight of gelatin in 27 parts by weight of purified water at 60 ° C, add 1.25 parts by weight of lactic acid, 22 parts by weight of D-sorbitol solution (70%) and 3 parts by weight of kaolin A, and uniformly disperse. Was. Ice phase)

Separately, 2.5 parts by weight of light liquid paraffin was dissolved at 120 ° C. in 10 parts by weight of ester gum. (Adhesive phase)

Separately, 1 part by weight of indomestic acid and 1 part by weight of L-menthol are dissolved at 40 ° C., cooled to room temperature, 22 parts by weight of concentrated glycerin, 3 parts by weight of carmellose sodium, partially neutralized polyacrylic acid 3 .5 parts by weight and 0.2 parts by weight of a dried aluminum hydroxide gel were added and uniformly dispersed. (Oil phase)

After heating the aqueous phase to 120, the adhesive phase was added and dispersed uniformly. After cooling to room temperature, the oil phase was added, and the total weight was adjusted to 100 parts by weight with purified water to obtain a hydrous drug-containing plaster. The resulting water-containing drug-containing plaster is laminated on a polypropylene protective film (16 g / m ² / 24h) and a polyether polyamide block polymer moisture-permeable film. Using a spreading machine, apply a water-containing drug-containing plaster between the non-woven fabric surface of the support and the polypropylene liner, where a polyethylene non-woven fabric is laminated via an acrylic adhesive on the non-laminated surface. The product was spread so that the thickness of the body became 0.2 讓, and cut into a size of 10 × 14 cm to prepare a preparation. The moisture permeability of the plaster support composed of the moisture-permeable film, the adhesive layer, and the nonwoven fabric or woven fabric was 642 (g / m 2/24) in Production Example 1 and 1129 (g / m ² ) in Production Example 2. m ² / h). Industrial applicability According to the present invention, it is possible to provide a patch having low skin irritation, excellent drug absorption over time, and excellent appearance stability.

Claims

The scope of the claims

1. A peelable protective film having a moisture permeability of 0 to 50 (g / m ² / 24h); a moisture-permeable film laminated on the protective film; laminated on the moisture-permeable film via an adhesive. A non-woven fabric or woven fabric; a layer of a water-containing drug-containing plaster containing 20 to 70% by weight of τΚ based on the amount of plaster applied to the non-woven fabric or woven fabric; and on the layer of the plaster The support for a plaster composed of the moisture-permeable film, the adhesive layer, and the nonwoven fabric or woven fabric has a moisture permeability of 500 to 100 (g / m ² / 24h).

2. The patch according to claim 1, wherein the moisture permeability of the protective film is 0 to 30 (g / m ² / 24h).

3. The patch according to claim 1, wherein the protective film is at least one film selected from polyester, polyethylene, polypropylene, and ethylene-vinyl acetate copolymer.

4. The patch according to any one of claims 1 to 3, wherein the protective film is peeled off after the patch is attached.

5. The patch according to any one of claims 1 to 4, wherein the water-containing drug-containing plaster has a port tack adhesive strength of No. 3 or more and No. 9 or less.