Ultraviolet curable hydrogel resin for transdermal administration, hydrogel, and poultice containing the same

Abstract

The present invention relates to an ultraviolet-curable hydrogel resin for transdermal administration, its hydrogel and a poultice using the same, and more specifically to the following hydrogel resin, ultraviolet-cured hydrogel and a poultice containing the same, wherein the hydrogel increases the water content of the hydrogel of a drug layer suitable for a poultice, can adjust the adhesion by relieving skin irritation and adjusting the cross-linking degree, and has an optimal composition and composition ratio that can adjust drug release and transdermal absorbability.

Description

[0001] The present application is a divisional application of a patent application with application number 201780011252.6, application date February 1, 2017, and invention name “UV-curable hydrogel resin for transdermal administration, hydrogel, and poultice containing the same”. Technical Field

[0002] The present invention relates to a hydrogel resin for transdermal administration prepared by ultraviolet rays, a hydrogel cured by ultraviolet rays, and a poultice introduced with the hydrogel, and specifically to the following hydrogel and poultice containing the hydrogel. The hydrogel contains a large amount of water and can relieve skin irritation, and the cross-linking degree of the hydrogel is easy to adjust, and has the best drug release and transdermal absorbability, and has an effect equivalent to oral administration. It not only maintains excellent adhesion and elasticity, but also is easy to modulate. After cross-linking, no separate aging process or cooling process is required, and it can be directly cut and packaged before shipment, so it is easy to prepare. Background Art

[0003] Polyacrylic acid prepared by metal ion bonding is a material with outstanding biocompatibility and adhesion to the human body. U.S. Patent No. 4320040 (1982) discloses an example of using acrylic acid or methacrylic acid together with polyvinyl alcohol to prepare hydrogel. U.S. Patent No. 5223569 (1993) also discloses an example of using acrylic acid and starch to prepare hydrogel. In particular, as a method for improving the water resistance of hydrogel using polyacrylic acid to sweat and the like generated in the human body, regarding hydrogel cross-linked with polyacrylic acid, U.S. Patent No. 4200561 (1980) discloses a method of preparing hydrogel using a gelling agent and a copolymer mixture of acrylic acid, ethyl acrylic acid, esterified acrylic acid, vinyl acetate, vinyl formate, and vinyl propionate. In addition, U.S. Patent No. 3937680 (1976) discloses a method of using ethylene glycol and methacrylate, methacrylic acid, and 2-hydroxyethyl methacrylate as a cross-linking agent to maintain a high level of water content.

[0004] The crosslinking time of the polyacrylic acid paste for crosslinking by metal complex ion bonding is too long to be shipped directly as a product. The aqueous solution of polyvinyl alcohol as a synthetic polymer can be crosslinked by formaldehyde, glutaraldehyde, etc., and can be repeatedly frozen and thawed to form a gel. However, the crosslinking based on aldehydes has the problem of toxicity of the aldehydes remaining due to incomplete removal, the gel formed by repeated freezing and thawing has the problem of low strength, and the long process required for repeated freezing and thawing has the problem of increased product cost.

[0005] In order to prepare a hydrogel using polyvinyl pyrrolidone by a chemical crosslinking method, polyvinyl pyrrolidone is dissolved in distilled water, and then a multifunctional monomer such as ethylene glycol dimethacrylate, propylene glycol dimethacrylate, tetraethylene glycol dimethacrylate or trimethoxypropane triacrylate is added together with a chemical initiator and heated. However, the chemical thermal crosslinking method has the problem that unreacted initiator or crosslinking agent remains after the reaction is completed.

[0006] Therefore, there is a need for a preparation technology that can shorten the cross-linking time based on the cross-linking agent, does not use toxic solvents, and does not contain unreacted initiators or cross-linking agents.

[0007] In the case of conventional hydrogels that are commercially available and sold, metal ion crosslinking is mainly used, but in this case, it takes a long time of about one to three weeks to complete crosslinking, so it is difficult to adjust the adhesion and gel strength. In addition, there is a problem that crosslinking cannot be smoothly performed under conditions of pH 7 or above. Due to the various problems mentioned above, it is difficult to add a variety of drugs to the hydrogel. Summary of the invention

[0008] Technical issues

[0009] The present invention provides the following hydrogel and a paste compress using the hydrogel. In order to solve the problem of long preparation time of the hydrogel, the above-mentioned hydrogel is cured by ultraviolet light to greatly shorten the curing time of the hydrogel and greatly improve productivity. The hydrogel has an optimal composition and composition ratio to achieve excellent skin absorption and delivery of the drug contained in the hydrogel and improve adhesion to the skin.

[0010] Means of solving the problem

[0011] In order to solve the above problems, the present invention provides an ultraviolet curable hydrogel resin for transdermal administration, comprising a hydrophilic polymer, an active ingredient, a wetting agent, a solvent, a transdermal penetration enhancer, an ultraviolet initiator and an ultraviolet crosslinking agent.

[0012] As a preferred embodiment of the present invention, the hydrogel resin of the present invention may include 5 weight percent to 60 weight percent of a hydrophilic polymer, 0.1 weight percent to 15 weight percent of an active ingredient, 0.6 weight percent to 80 weight percent of a wetting agent, 13.5 weight percent to 90 weight percent of a solvent, 0.5 weight percent to 25 weight percent of a transdermal penetration enhancer, 0.01 weight percent to 2.0 weight percent of an ultraviolet initiator, and 0.01 weight percent to 2.0 weight percent of an ultraviolet crosslinking agent.

[0013] As a preferred embodiment of the present invention, the hydrogel resin of the present invention may further include a pH adjuster.

[0014] As a preferred embodiment of the present invention, the hydrophilic polymer in the composition of the hydrogel resin of the present invention may include one or more selected from polyvinyl alcohol, polyvinyl pyrrolidone, polyvinyl pyrrolidone / vinyl acetate copolymer, vinyl ether / maleic anhydride copolymer, isobutylene / maleic anhydride copolymer, vinyl methyl ether / maleic anhydride copolymer, methacrylic acid / butyl acrylate copolymer, alginate, hydroxyethyl methacrylate, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, ethyl cellulose, methyl cellulose, sodium carboxymethyl cellulose, carboxyethylene copolymer, polyethylene oxide, polyethylene glycol, polyacrylamide, polyhydroxyethyl methacrylate, polydioxolane, polyacrylic acid, sodium polyacrylate, polyethylene acrylate, polyacrylate and polyvinyl chloride.

[0015] As a preferred embodiment of the present invention, the above-mentioned active ingredients in the composition of the hydrogel resin of the present invention may include one or more selected from lidocaine, lidocaine hydrochloride, loxoprofen, loxoprofen salt, ketoprofen, flurbiprofen, diclofenac, diclofenac salt, indomethacin, piroxicam, meloxicam, naproxen, ibuprofen, felbinac, menthol, ethylene glycol salicylate, methyl salicylate, capsicum extract, nonanoic acid vanillamide, vinyl butyl ether, Centella asiatica, fusidic acid, fusidic acid salt, rivanol, Pueraria lobata, heparin, heparin salt and allantoin.

[0016] As a preferred embodiment of the present invention, the wetting agent in the composition of the hydrogel resin of the present invention may include one or more selected from glycerol, 1,3-butylene glycol, propylene glycol, polypropylene glycol, sorbitol, mannitol, ethylene glycol, diethylene glycol, polyethylene glycol and hyaluronic acid.

[0017] As a preferred embodiment of the present invention, the above-mentioned transdermal permeation enhancer in the composition of the hydrogel resin of the present invention may include propylene glycol, dipropylene glycol, polyethylene glycol, polyoxyethylene oleate, polyglyceryl diisostearate, glyceryl oleate, polyoxyethylene sorbitan, N-methyl-2-pyrrolidone, N-octanoyl-2-pyrrolidone, N-dodecyl-2-pyrrolidone, dodecyl pyrrolidone, dodecanol, glyceryl dodecanol, oleyl alcohol, isopropyl myristate, sorbitan oleate, propylene monoisostearate, propylene glycol, polyoxyethylene sorbitan, N-methyl-2-pyrrolidone, N-octanoyl-2-pyrrolidone, N-dodecyl-2-pyrrolidone, dodecyl pyrrolidone, dodecanol, glyceryl dodecanol, oleyl alcohol, isopropyl myristate, sorbitan oleate ... One or more of laurate, propylene oleate, oleoyl macrogol glyceride, oleic acid, lauryl macrogol glyceride, linoleic macrogol glyceride, propylene glycol caprylate, propylene glycol caprate, sorbitan monostearate oleate, glyceryl monolaurate, glyceryl oleate, propylene glycol monolaurate, propylene glycol monocaprylate, sorbitan monolaurate, lauryl lactate, caprylic triglyceride, capric triglyceride, corn oil PEG-8 ester, corn oil PEG-6 ester and triacetin.

[0018] As a preferred embodiment of the present invention, the above-mentioned ultraviolet initiator in the composition of the hydrogel resin of the present invention may include one or more selected from ketone ultraviolet initiators, thioxanthone ultraviolet initiators, benzophenone ultraviolet initiators, coumarin ultraviolet initiators, thiazoline ultraviolet initiators, rhodanine ultraviolet initiators and other ultraviolet initiators.

[0019] As a preferred embodiment of the present invention, the above-mentioned ketone ultraviolet initiator may include one or more of 1-hydroxy-cyclohexyl-phenyl-ketone, 2-hydroxy-2-methyl-1-phenyl-1-propanone, 2-hydroxy-1-[4-(2-hydroxyethoxy)phenyl]-2-methyl-1-propanone, 2-benzyl-2-(dimethylamino)-1-[4-(4-morpholinyl)phenyl]-1-butanone, and 2-methyl-1-[4-(methylthio)phenyl]-2-(4-morpholinyl)-1-propanone.

[0020] As a preferred embodiment of the present invention, the above-mentioned thioxanthone ultraviolet initiator includes thioxanthone, 2-isopropyl thioxanthone, 2-chlorothioxanthone, 1-chloro-4-propoxy thioxanthone, 2-dodecyl thioxanthone, 2,4-diethyl thioxanthone, 2,4-dimethylthioxanthone, 1-methoxy-carbonyl thioxanthone, 2-ethoxycarbonyl thioxanthone, 3-(2-methoxyethoxycarbonyl)-thioxanthone, 4-butoxycarbonyl thioxanthone, 3-butoxycarbonyl-7-methylthioxanthone, 1-cyano-3-chlorothioxanthone, 1-ethoxycarbonyl-3-chlorothioxanthone, 1-ethoxycarbonyl-3-ethoxythioxanthone, 1-ethoxycarbonyl-3-aminothioxanthone, 1-ethoxycarbonyl-3-phenylsulfonyl thioxanthone, 3,4-bis[2-(2-methoxyethoxy)ethoxycarbonyl]-thioxanthone, 1,3-dimethyl-3-hydroxy-9H-thioxanthone-9-one 2-ethylhexyl ester, 1-ethoxycarbonyl-3-(1-methyl-1-morpholinoethyl)-thioxanthone, 2-methyl-6-dimethoxymethyl-thioxanthone, 2-methyl-6-(1,1-dimethoxybenzyl)-thioxanthone, 2-morpholinomethylthioxanthone, 2-methyl-6-morpholinomethylthioxanthone, N-arylthioxanthone-3,4-dicarboxamide, 1-phenoxythioxanthone, 6-ethoxycarbonyl-2-methoxythioxanthone, 6-ethoxycarbonyl-2-methylthioxanthone, thioxanthone-2-carboxylic acid polyethylene glycol ester, 2-hydroxy-3-(3,4-dimethyl-9-oxo-9H-thioxanthone-2-2-monooxy)-N,N,N-trimethyl-1-propaneammonium chloride (Propanaminium chloride) or more.

[0021] As a preferred embodiment of the present invention, the above-mentioned benzophenone ultraviolet initiator may include benzophenone, 4-phenylbenzophenone, 4-methoxybenzophenone, 4,4'-dimethylbenzophenone, 4,4'-dichlorobenzophenone, 4,4'-bis(dimethylamino)-benzophenone, 4,4'-bis(diethylamino)benzophenone, 4,4'-bis(methylethylamino)benzophenone, 4,4'-bis(p-isopropylphenoxy)benzophenone, 3, 3'-dimethyl-4-methoxybenzophenone, methyl-2-benzoylbenzoate, 4-(2-hydroxyethylthio)-benzophenone, 4-(4-tolylthio)benzophenone, 1-[4-(4-benzoyl-phenylsulfonyl)-phenyl]-2-methyl-2(toluene-4-sulfonyl)-propane-1-one, 4-benzoyl-N,N,N-trimethylbenzylpropane ammonium chloride (trimethyldimethyl benzylammonium chloride), 2-hydroxy-3-(4-benzoyl-phenoxy)-N,N,N-trimethyl-1-propane ammonium chloride monohydrate, 4-(13-acryloyl-1,4,7,10,13-pentaoxytridecyl)-benzophenone, and 4-benzoyl-N,N-dimethyl-N-[2-(1-oxy-2-propionaldehyde)oxy]ethyl-benzylammonium chloride.

[0022] As a preferred embodiment of the present invention, the above-mentioned coumarin ultraviolet initiator may include coumarin 1, coumarin 2, coumarin 6, coumarin 7, coumarin 30, coumarin 102, coumarin 106, coumarin 138, coumarin 152, coumarin 153, coumarin 307, coumarin 314, coumarin 314T, coumarin 334, coumarin 337, coumarin 500, 3-benzoyl coumarin, 3-benzoyl-7-methoxy coumarin, 3-benzoyl-7-methoxy coumarin, 3-Benzoyl-5,7-dimethoxycoumarin, 3-Benzoyl-5,7-dipropoxycoumarin, 3-Benzoyl-6,8-dichlorocoumarin, 3-Benzoyl-6-chloro-coumarin, 3,3'-carbonyl-bis[5,7-di(propoxy)-coumarin], 3,3'-carbonyl-bis(7-methoxycoumarin), 3,3'-carbonyl-bis(7-diethylamino-coumarin), 3-isobutyroylcoumarin, 3-Benzoyl-5,7-dimethoxy-coumarin, 3- benzoyl-5,7-diethoxy-coumarin, 3-benzoyl-5,7-dibutoxy-coumarin, 3-benzoyl-5,7-di(methoxyethoxy)-coumarin, 3-benzoyl-5,7-di(aryloxy)-coumarin, 3-benzoyl-7-dimethylamino-coumarin, 3-benzoyl-7-diethylamino-coumarin, 3-isobutyryl-7-dimethylamino-coumarin, 3-benzoyl-7-diethylamino-coumarin, 3-isobutyryl-7-dimethylamino-coumarin, At least one of 5,7-dimethoxy-3-(1-naphthoyl)-coumarin, 5,7-diethoxy-3-(1-naphthoyl)-coumarin, 3-benzoylbenzo[f]coumarin, 7-diethylamino-3-thenoylcoumarin, 3-(4-cyanobenzoyl)-5,7-dimethoxycoumarin, 3-(4-cyanobenzoyl)-5,7-dipropoxycoumarin, 7-dimethylamino-3-phenylcoumarin and 7-diethylamino-3-phenylcoumarin.

[0023] As a preferred embodiment of the present invention, the above-mentioned thiazoline ultraviolet initiator may include one or more of 3-methyl-2-benzoylmethylene-β-naphthothiazolin, 3-methyl-2-benzoylmethylene-benzothiazoline, and 3-ethyl-2-propionylmethylene-β-naphtholthiazoline as 3-(aroylmethylene)-thiazolines.

[0024] As a preferred embodiment of the present invention, the rhodanine-based ultraviolet initiator may include at least one of 4-dimethylaminobenzylidene rhodanine, 4-diethylaminobenzylidene rhodanine, and 3-ethyl-5-(3-octyl-2-benzothiazoline)-rhodanine.

[0025] As a preferred embodiment of the present invention, the other ultraviolet initiator may include phenylacetophenone, hydroxydimethylacetophenone, 4,4'-bis(dimethylamino)benzyl, methylbenzoyl formate, diphenyl(2,4,6-trimethylbenzoyl)-phosphine oxide, phenylbis(2,4,6-trimethylbenzoyl), oxy-phenyl-acetic acid-2-[2-oxy-2-phenyl-acetoxy-ethoxy]-ethyl ester, oxy-phenyl-acetic acid-2-[2-hydroxy-ethoxy]-ethyl ester, 4-cyclopentadien-1-yl)bis[2,6-difluoro-3-(1-H-pyrrol-1-yl)phenyl]titanium, 2-acetylnaphthalene, 2-naphthaldehyde, iodine, dansyl acid derivatives, 9.10-anthraquinone, anthracene, pyrene, aminopyrene, perylene, phenanthrene, phenanthrenequinone, 9-fluorenone, dibenzosuberone, curcumin, xanthanone, thio-Michler's ketone, α-(4-dimethylaminobenzylidene) ketone, phenylthiolphthalimide, N-methyl-3,5-bis(ethylthio)phthalimide, N-methyl- 3,5-bis(ethylthio)-phthalimide, phenothiazine, methylphenothiazine, amine, ethyl-p-dimethylaminobenzoate, 2-(dimethylamino)ethylbenzoate, 2-ethylhexyl-p-dimethylaminobenzoate, octyl-p-N,N-dimethylaminobenzoate, N-(2-hydroxyethyl)-N-methyl-p-toluidine, butoxyethyl 4-dimethylaminobenzoate, 4-dimethylaminoacetophenone, triethanolamine, methyl dihydroxyethylamine, dimethylaminoethanol, 2-( The invention relates to a novel polyol comprising: a polyol comprising: a poly(4-dimethylamino)ethyl benzoate, a poly(propylene glycol)-4-(dimethylamino)benzoate and a Michler's ketone; the α-(4-dimethylaminobenzylidene)ketone comprises 2,5-bis(4-diethylaminobenzylidene)cyclopentanone, 2-(4-dimethylamino-benzylidene)-indan-1-one and 3-(4-dimethylamino-phenyl)-1-indan-5-yl-p-hydroxypropiophenone; and the amine comprises N-phenylglycine, triethanolamine and N-methyldihydroxyethylamine.

[0026] As a preferred embodiment of the present invention, the ultraviolet crosslinking agent in the composition of the hydrogel resin of the present invention may include benzyl methacrylate, dodecyl methacrylate, isodecyl methacrylate, phenoxy methacrylate, 2-hydroxyethyl methacrylate, tetrahydrofurfuryl methacrylate, hexadecyl (C16) methacrylate, octadecyl methacrylate, methoxy polyethylene glycol 500 methacrylate, methoxy polyethylene glycol 600 methacrylate, methoxy polyethylene glycol 1000 methacrylate, 1,6-hexanediol dimethacrylate, butadiene dimethacrylate, neopentyl glycol dimethacrylate, ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, triethylene glycol dimethacrylate, tetraethylene glycol dimethacrylate, bisphenol A (epoxy) (EO) 4 dimethacrylate, bisphenol A (epoxy) 3 dimethacrylate acrylate, bisphenol A (epoxy) 10 dimethacrylate, bisphenol A (epoxy) 30 dimethacrylate, 1,3-butylene glycol dimethacrylate, polyethylene glycol 400 dimethacrylate, polyethylene glycol 200 dimethacrylate, polypropylene glycol 1000 (epoxy) 15 dimethacrylate, polypropylene glycol 1000 (epoxy) 3 dimethacrylate hydrogen furfuryl, trimethylolpropane trimethacrylate, benzyl acrylate, dodecyl acrylate, isodecyl acrylate, phenol (epoxy) acrylate, phenol (epoxy) 2 acrylate, phenol (epoxy) 4 acrylate, phenol (epoxy) 6 acrylate, tetrahydrofurfuryl acrylate, nonylphenol (epoxy) 4 acrylate, nonylphenol (epoxy) 8 acrylate, nonylphenol (epoxy) 2 acrylate, ethoxyethoxyethyl acrylate, octadecyl acrylate, 1,6-hexanediol diacrylate, 1,6-Hexanediol (epoxy) diacrylate, butanediol diacrylate, hydroxytrimethylol neopentyl glycol diacrylate, tripropylene glycol diacrylate, dipropylene glycol diacrylate, bisphenol A (epoxy) 4 diacrylate, bisphenol A (epoxy) 3 diacrylate, tricyclodecane dimethanol diacrylate, tetraethylene glycol diacrylate, polyethylene glycol 400 diacrylate, polyethylene glycol 200 diacrylate, polyethylene glycol 300 diacrylate, polyethylene glycol 600 diacrylate, polypropylene glycol 400 diacrylate, polypropylene glycol 750 diacrylate, bisphenol A (epoxy) 10 diacrylate, bisphenol A (epoxy) 30 diacrylate, tris (2-hydroxyethyl) isocyanurate At least one of diacrylate, trimethylolpropane triacrylate, trimethylolpropane (epoxy) 3 triacrylate, trimethylolpropane (epoxy) 6 triacrylate, trimethylolpropane (epoxy) 9 triacrylate, trimethylolpropane (epoxy) 15 triacrylate, glycerol propoxylated triacrylate, pentaerythritol triacrylate, trimethylolpropane (propylene oxide) (PO) 3 triacrylate, tris (2-hydroxyethyl) isocyanurate triacrylate, pentaerythritol N-epoxy tetraacrylate, pentaerythritol tetraacrylate, dipentaerythritol pentaacrylate, dipentaerythritol hexaacrylate, caprolactone acrylate, O-phenylphenol epoxy acrylate, and methylenebisacrylamide.

[0027] As a preferred embodiment of the present invention, the pH adjuster in the composition of the hydrogel resin of the present invention may include one or more selected from citric acid, acetic acid, malic acid, succinic acid, tartaric acid, lactic acid, triethanolamine, diisopropanolamine and dihydroxyethylamine.

[0028] As a preferred embodiment of the present invention, the pH of the hydrogel resin of the present invention may be 3-9.

[0029] Another object of the present invention is to provide a cured product obtained by ultraviolet curing of the above hydrogel resin, namely, a hydrogel.

[0030] As a preferred embodiment of the present invention, when the peel strength of the hydrogel of the present invention is measured, the adhesive force may be 50 gf to 120 gf.

[0031] Another object of the present invention is to provide a poultice comprising: a drug layer comprising the above-mentioned various forms of ultraviolet curable hydrogel for transdermal administration; and a drug support layer.

[0032] As a preferred embodiment of the present invention, in the poultice of the present invention, the drug supporting layer may include at least one selected from polyurethane film, porous film, perforated film, fabric, non-woven fabric and foam.

[0033] As a preferred embodiment of the present invention, the average thickness of the drug layer may be 20 to 2000 μm, and the average thickness of the drug support layer may be 7 to 500 μm.

[0034] As a preferred embodiment of the present invention, the poultice of the present invention may further include a peeling layer, and the peeling layer, the drug layer and the drug support layer may be stacked in sequence.

[0035] As a preferred embodiment of the present invention, the peeling layer may include a polymer film coated with silicone resin or fluororesin, and the polymer film may include one or more polymer compounds selected from polyester, polyvinyl chloride, polyvinylidene chloride, polyethylene terephthalate and copolymers thereof.

[0036] As a preferred embodiment of the present invention, the average thickness of the peeling layer may be 15 μm to 500 μm.

[0037] As a preferred embodiment of the present invention, the poultice of the present invention can be an anti-inflammatory and analgesic poultice.

[0038] Another object of the present invention is to provide a method for preparing a poultice, comprising the following steps:

[0039] In the first step, a hydrophilic polymer, an active ingredient, a wetting agent, a solvent, a transdermal penetration enhancer, an ultraviolet initiator and an ultraviolet crosslinking agent are mixed and stirred to prepare a hydrogel resin;

[0040] The second step is to apply the hydrogel resin to the release film;

[0041] The third step is to laminate a support body on the coated hydrogel resin;

[0042] Step 4: along the support direction, at 2000 mW / cm 2 ~8000mW / cm 2 The hydrogel resin is cured by irradiating ultraviolet rays at an intensity of 3 minutes to 10 minutes.

[0043] Effects of the Invention

[0044] The ultraviolet curable hydrogel for transdermal administration of the present invention is prepared by a non-toxic solvent, can contain a large amount of water to relieve skin irritation, is easy to adjust the degree of crosslinking, and is easy to adjust the adhesion and elasticity. The crosslinking degree of the hydrogel can be adjusted to adjust the drug release and transdermal absorbability, and the skin permeation amount and skin permeation rate are excellent. In addition, the poultice using the hydrogel of the present invention is easy to prepare, and compared with the poultice based on the metal ion combined with the hydrogel component, it is easy to ensure safety during long-term storage. After the hydrogel is cross-linked, there is no need for a separate aging process or cooling process, and it can be directly cut and packaged before shipment, and it is economical and commercially excellent. DETAILED DESCRIPTION

[0045] Hereinafter, the present invention will be described in detail.

[0046] The preparation method of the poultice of the present invention comprises: a first step of preparing a hydrogel resin; a second step of applying the hydrogel resin to a release film; a third step of laminating a support body on the applied hydrogel resin; and a fourth step of curing the hydrogel resin by irradiating ultraviolet rays along the direction of the support body.

[0047] In the first step, a mixture of a hydrophilic polymer, an active ingredient, a wetting agent, a solvent, a transdermal permeation enhancer, a UV initiator and a UV crosslinking agent can be stirred and crosslinked for 5 to 12 hours at a speed of 150 rpm to 1650 rpm at room temperature (15° C. to 35° C.) to allow the composition to be fully dissolved in the solvent to prepare the above-mentioned hydrogel resin.

[0048] The hydrophilic polymer in the components of the hydrogel resin in the first step plays a role in imparting viscoelasticity to the hydrogel and maintaining the water content. Relative to the total weight of the hydrogel resin, the hydrophilic polymer may comprise 5 to 60 weight percent, preferably 5 to 40 weight percent, and more preferably 8 to 35 weight percent. At this time, if the content of the hydrophilic polymer is less than 5 weight percent, there may be a problem that the hydrogel cannot maintain the water content and viscoelasticity and the components are difficult to penetrate the skin. If it exceeds 60 weight percent, there may be a problem that the viscosity is too high and it is difficult to apply in the second step and the cross-linking property is greatly reduced.

[0049] In addition, the hydrophilic polymer can be selected from polyvinyl alcohol, polyvinyl pyrrolidone, polyvinyl pyrrolidone / vinyl acetate copolymer, vinyl ether / maleic anhydride copolymer, isobutylene / maleic anhydride copolymer, vinyl methyl ether / maleic anhydride copolymer, methacrylic acid / butyl acrylate copolymer, alginate, hydroxyethyl methacrylate, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, ethyl cellulose, methyl cellulose, sodium carboxymethyl cellulose, carboxyethylene copolymer, polyethylene oxide, polyethylene glycol, polyacrylamide, polyhydroxyethyl methacrylate, polydioxolane, polyacrylic acid, sodium polyacrylate, polyethylene acrylate, poly One or more of acrylate and polyvinyl chloride, preferably one or more selected from polyvinyl pyrrolidone, polyvinyl pyrrolidone / vinyl acetate copolymer, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl methacrylate, sodium polyacrylate, polyacrylic acid, sodium carboxymethyl cellulose and polyacrylamide, more preferably, the above-mentioned hydrophilic polymer can be mixed with 5 to 100 parts by weight relative to 100 parts by weight of polyvinyl pyrrolidone, preferably 10 to 50 parts by weight of one or more selected from hydroxypropyl cellulose, sodium polyacrylate, polyacrylic acid, sodium carboxymethyl cellulose and polyacrylamide. As a specific example, the above-mentioned hydrophilic polyvinyl pyrrolidone and sodium polyacrylate, polyvinyl pyrrolidone and polyacrylic acid, polyvinyl pyrrolidone and polyacrylamide, polyvinyl pyrrolidone and polyvinyl alcohol, polyvinyl pyrrolidone and sodium carboxymethyl cellulose, polyvinyl pyrrolidone and hydroxyethyl cellulose, polyvinyl pyrrolidone and hydroxypropyl cellulose, polyvinyl pyrrolidone and hydroxyethyl methacrylate can be mixed.

[0050] Furthermore, the hydrophilic polymer may be treated with a known crosslinking agent or polymer.

[0051] The above-mentioned effective ingredients in the components of the hydrogel resin in the first step can be effective ingredients commonly used in the art according to the purpose of the hydrogel, and preferably, the effective ingredients can be mixed and used in one or more selected from lidocaine, lidocaine hydrochloride, loxoprofen, loxoprofen salt, ketoprofen, flurbiprofen, diclofenac, diclofenac salt, indomethacin, piroxicam, meloxicam, naproxen, ibuprofen, felbinac, menthol, salicylic acid glycol, methyl salicylate, pepper extract, nonanoic acid vanillamide, vinyl butyl ether, Centella asiatica, fusidic acid, fusidic acid salt, rivanol, Pueraria lobata root, heparin, heparin salt and allantoin. As a specific example, one or more of lidocaine, lidocaine hydrochloride, loxoprofen, loxoprofen salt, etc. with anti-inflammatory and analgesic effects can be mixed and used.

[0052] Furthermore, the hydrogel resin may contain 0.1 to 15 weight percent of the above-mentioned active ingredient relative to the total weight, preferably 1 to 10 weight percent of the above-mentioned active ingredient. If the content of the active ingredient is less than 0.1 weight percent, the amount used is too small to obtain the effect brought about by the use of the active ingredient. If it exceeds 15 weight percent, too much active ingredient affects crosslinking and affects the preparation of the hydrogel.

[0053] The wetting agent in the hydrogel resin of the first step plays the role of maintaining the moist state of the hydrogel, reducing skin irritation, maintaining continuous cooling and improving the volatility of water. Conventional wetting agents commonly used in the art can be used, preferably including one or more selected from glycerol, 1,3-butylene glycol, propylene glycol, polypropylene glycol, sorbitol, mannitol, ethylene glycol, diethylene glycol, polyethylene glycol and hyaluronic acid, preferably including one or more selected from glycerol, sorbitol and hyaluronic acid, more preferably glycerol and sorbitol can be mixed in a weight ratio of 1:0.2 to 0.5.

[0054] Furthermore, the hydrogel resin may contain 0.6 to 80 weight percent, preferably 5 to 50 weight percent, and more preferably 12 to 40 weight percent of the wetting agent relative to the total weight of the hydrogel resin. At this time, if the content of the wetting agent is less than 0.6 weight percent, the hydrogel cannot maintain a sufficient wet state. If it exceeds 80 weight percent, there may be a problem that the hydrogel cannot be cured.

[0055] The above-mentioned solvent in the composition of the hydrogel resin in the first step can use purified water, distilled water or other water. The content of the solvent is 13.5 weight percent to 90 weight percent, preferably 18 weight percent to 70 weight percent, and more preferably 30 weight percent to 60 weight percent relative to the total weight of the hydrogel resin.

[0056] The above-mentioned transdermal penetration enhancer in the components of the hydrogel resin in the first step is used to promote the transdermal absorption of the active ingredient and the sustained effect of the drug effect. Its content is 0.5 weight percent to 25 weight percent, preferably 0.5 weight percent to 23 weight percent, and more preferably 1 to 20 weight percent relative to the total weight of the hydrogel resin. At this time, if the content of the transdermal penetration enhancer is less than 0.5 weight percent, there may be a problem that the transdermal absorption of the active ingredient in the hydrogel is greatly reduced. If it exceeds 25 weight percent, the adhesion of the hydrogel may have problems.

[0057] The above-mentioned transdermal penetration enhancers can be mixed and used and are selected from propylene glycol, dipropylene glycol, polyethylene glycol, polyoxyethylene oleate, polyglyceryl diisostearate, glyceryl oleate, polyoxyethylene sorbitan, N-methyl-2-pyrrolidone, N-octanoyl-2-pyrrolidone, N-dodecyl-2-pyrrolidone, dodecyl pyrrolidone, dodecanol, glyceryl dodecanol, oleyl alcohol, isopropyl myristate, sorbitan oleate, propylene monolaurate, propylene oleate, oleoyl macrogol glyceride, oleic acid, dodecanoyl macrogol glyceride, linoleic acid macrogol glyceride, propylene glycol caprylate, propylene glycol caprate, sorbitan monostearate oleate, glyceryl monolaurate, glyceryl oleate, propylene glycol monolaurate, propylene glycol monocaprylate, One or more of sorbitan monolaurate, lauryl lactate, caprylic triglyceride, capric triglyceride, corn oil PEG-8 ester, corn oil PEG-6 ester and triacetin can be preferably mixed with one or more of propylene glycol, dipropylene glycol, glyceryl oleate, polyoxyethylene sorbitan, N-methyl-2-pyrrolidone, sorbitan oleate, isopropyl myristate, polyoxyethylene oleate, glyceryl oleate, propylene glycol monocaprylate and polyglyceryl diisostearate, more preferably propylene glycol and one selected from sorbitan oleate, isopropyl myristate, polyoxyethylene oleate, glyceryl oleate, propylene glycol monocaprylate and polyglyceryl diisostearate are mixed in a weight ratio of 1:0.03 to 0.5. Furthermore, more preferably, when the active ingredient is loxoprofen sodium and its salt, three or more selected from propylene glycol, glyceryl oleate, glyceryl oleate, polyoxyethylene sorbitan, N-methyl-2-pyrrolidone and lauryl pyrrolidone may be used in combination.

[0058] The ultraviolet initiator in the hydrogel resin of the first step is a crosslinking reaction initiating component used to form a hydrogel based on ultraviolet (UV), and can be mixed with one or more selected from ketone ultraviolet initiators, thioxanthone ultraviolet initiators, benzophenone ultraviolet initiators, coumarin ultraviolet initiators, thiazoline ultraviolet initiators, rhodanine ultraviolet initiators and other ultraviolet initiators. And, relative to the total weight of the hydrogel resin, its content is 0.01 weight percent to 2.0 weight percent, preferably 0.025 weight percent to 1.5 weight percent, and more preferably 0.1 weight percent to 1.0 weight percent. At this time, if the content of the ultraviolet initiator is less than 0.01 weight percent, there may be a problem that the curing time due to ultraviolet irradiation is too long and the commerciality is reduced, and the viscoelasticity of the cured hydrogel is insufficient. If the content of the ultraviolet initiator exceeds 2 weight percent, there may be a problem that the curing speed is too fast and it is difficult to control the curing speed and the adhesive force is reduced.

[0059] The specific types of ultraviolet initiators that can be used in the present invention are as follows:

[0060] The above-mentioned ketone ultraviolet initiator can be used in combination as α-hydroxyketones, and one or more selected from 1-hydroxy-cyclohexyl-phenyl-ketone, 2-hydroxy-2-methyl-1-phenyl-1-propanone, 2-hydroxy-1-[4-(2-hydroxyethoxy)phenyl]-2-methyl-1-propanone, 2-benzyl-2-(dimethylamino)-1-[4-(4-morpholinyl)phenyl]-1-butanone and 2-methyl-1-[4-(methylthio)phenyl]-2-(4-morpholinyl)-1-propanone as α-aminoketones can be used.

[0061] The above-mentioned thioxanthone ultraviolet initiator can be mixed and used and is selected from thioxanthone, 2-isopropyl thioxanthone, 2-chlorothioxanthone, 1-chloro-4-propoxy thioxanthone, 2-dodecyl thioxanthone, 2,4-diethyl thioxanthone, 2,4-dimethylthioxanthone, 1-methoxy-carbonyl thioxanthone, 2-ethoxycarbonyl thioxanthone, 3-(2-methoxyethoxycarbonyl)-thioxanthone, 4-butoxycarbonyl thioxanthone, 3-butoxycarbonyl-7-methylthioxanthone, 1-cyano-3-chlorothioxanthone, 1-ethoxycarbonyl-3-chlorothioxanthone, 1-ethoxycarbonyl-3-ethoxythioxanthone, 1-ethoxycarbonyl-3-aminothioxanthone, 1-ethoxycarbonyl-3-phenylsulfonyl thioxanthone, 3,4-bis[2-(2-methoxyethoxy)ethoxycarbonyl]-thioxanthone, 1 , 3-dimethyl-3-hydroxy-9H-thioxanthone-9-one 2-ethylhexyl ester, 1-ethoxycarbonyl-3-(1-methyl-1-morpholinoethyl)-thioxanthone, 2-methyl-6-dimethoxymethyl-thioxanthone, 2-methyl-6-(1,1-dimethoxybenzyl)-thioxanthone, 2-morpholinomethylthioxanthone, 2-methyl-6-morpholinomethylthioxanthone, N-arylthioxanthone-3,4-dicarboxamide, 1-phenoxythioxanthone, 6-ethoxycarbonyl-2-methoxythioxanthone, 6-ethoxycarbonyl-2-methylthioxanthone, thioxanthone-2-carboxylic acid polyethylene glycol ester, 2-hydroxy-3-(3,4-dimethyl-9-oxo-9H-thioxanthone-2-2-monooxy)-N,N,N-trimethyl-1-propane ammonium chloride.

[0062] The above-mentioned benzophenone ultraviolet initiator can be mixed and used and is selected from benzophenone, 4-phenylbenzophenone, 4-methoxybenzophenone, 4,4'-dimethylbenzophenone, 4,4'-dichlorobenzophenone, 4,4'-bis(dimethylamino)-benzophenone, 4,4'-bis(diethylamino)benzophenone, 4,4'-bis(methylethylamino)benzophenone, 4,4'-bis(p-isopropylphenoxy)benzophenone, 3,3'-dimethyl-4-methoxybenzophenone, methyl-2-benzoylbenzoate, 4-(2-hydroxyethylthio)-benzophenone, 4-(4-tolylthio)benzophenone, 1 -[4-(4-benzoyl-phenylsulfonyl)-phenyl]-2-methyl-2(toluene-4-sulfonyl)-propane-1-one, 4-benzoyl-N,N,N-trimethylbenzylpropane ammonium chloride, 2-hydroxy-3-(4-benzoyl-phenoxy)-N,N,N-trimethyl-1-propane ammonium chloride monohydrate, 4-(13-acryloyl-1,4,7,10,13-pentaoxotridecanyl)-benzophenone, 4-benzoyl-N,N-dimethyl-N-[2-(1-oxo-2-propionaldehyde)oxy]ethyl-benzylpropane ammonium chloride.

[0063] The above-mentioned coumarin ultraviolet initiator can be mixed and used and is selected from coumarin 1, coumarin 2, coumarin 6, coumarin 7, coumarin 30, coumarin 102, coumarin 106, coumarin 138, coumarin 152, coumarin 153, coumarin 307, coumarin 314, coumarin 314T, coumarin 334, coumarin 337, coumarin 500, 3-benzoyl coumarin, 3-benzoyl-7-methoxy coumarin, 3-benzoyl-5,7-dimethoxy coumarin, Methoxycoumarin, 3-benzoyl-5,7-dipropoxycoumarin, 3-benzoyl-6,8-dichlorocoumarin, 3-benzoyl-6-chloro-coumarin, 3,3'-carbonyl-bis[5,7-di(propoxy)-coumarin], 3,3'-carbonyl-bis(7-methoxycoumarin), 3,3'-carbonyl-bis(7-diethylamino-coumarin), 3-isobutyroylcoumarin, 3-benzoyl-5,7-dimethoxy-coumarin, 3-benzoyl-5 , 7-diethoxy-coumarin, 3-benzoyl-5,7-dibutoxycoumarin, 3-benzoyl-5,7-di(methoxyethoxy)-coumarin, 3-benzoyl-5,7-di(aryloxy)coumarin, 3-benzoyl-7-dimethylaminocoumarin, 3-benzoyl-7-diethylaminocoumarin, 3-isobutyryl-7-dimethylaminocoumarin, 3-benzoyl-7-diethylaminocoumarin, 3-isobutyryl-7-dimethylaminocoumarin, 5, At least one of 7-dimethoxy-3-(1-naphthoyl)-coumarin, 5,7-diethoxy-3-(1-naphthoyl)-coumarin, 3-benzoylbenzo[f]coumarin, 7-diethylamino-3-thenoylcoumarin, 3-(4-cyanobenzoyl)-5,7-dimethoxycoumarin, 3-(4-cyanobenzoyl)-5,7-dipropoxycoumarin, 7-dimethylamino-3-phenylcoumarin and 7-diethylamino-3-phenylcoumarin.

[0064] The above-mentioned thiazoline ultraviolet initiator can be mixed and used to form one or more selected from 3-(aroylmethylene)-thiazolines, 3-methyl-2-benzoylmethylene-β-naphthothiazoline, 3-methyl-2-benzoylmethylene-benzothiazoline, and 3-ethyl-2-propionylmethylene-β-naphthothiazoline.

[0065] The above-mentioned rhodanine ultraviolet initiator can be used in combination with one or more selected from 4-dimethylaminobenzylidene rhodanine, 4-diethylaminobenzylidene rhodanine, and 3-ethyl-5-(3-octyl-2-benzothiazoline)-rhodanine.

[0066] In addition, the above other ultraviolet initiators can be mixed and used, and are selected from acetophenone, 3-methoxyacetophenone, 4-phenylacetophenone, α-dimethoxy-α-phenylacetophenone, hydroxydimethylacetophenone, benzyl, 4,4'-bis(dimethylamino)benzyl, methylbenzoyl formate, diphenyl(2,4,6-trimethylbenzoyl)-phosphine oxide, phenylbis(2,4,6-trimethylbenzoyl), oxy-phenyl-acetic acid-2-[2-oxy-2-phenyl-acetoxy-ethoxy]-ethyl ester, oxy-phenyl 2-[2-hydroxy-ethoxy]-ethyl acetate, 4-cyclopentadien-1-yl)bis[2,6-difluoro-3-(1-H-pyrrol-1-yl)phenyl]titanium, 2-acetylnaphthalene, 2-naphthaldehyde, iodine salts, dansyl acid derivatives, 9.10-anthraquinone, anthracene, pyrene, aminopyrene, perylene, phenanthrene, phenanthrenequinone, 9-fluorenone, dibenzosuberone, curcumin, xanthanone, thio-Michler's ketone, for example 2,5-bis(4-diethylaminobenzylidene)cyclopentanone, 2-(4- α-(4-dimethylaminobenzylidene)ketone such as 3-(4-dimethylaminophenyl)-1-dihydroindan-5-yl-p-hydroxypropiophenone, 3-phenylthiolphthalimide, N-methyl-3,5-di(ethylthio)phthalimide, N-methyl-3,5-di(ethylthio)phthalimide, phenothiazine, methylphenothiazine, amines such as N-phenylglycine, triethanolamine, N-methyldihydroxyethylamine, ethyl-p-dimethylaminobenzoate, 2- One or more of (dimethylamino)ethyl benzoate, 2-ethylhexyl-p-dimethylamino benzoate, octyl-p-N,N-dimethylamino benzoate, N-(2-hydroxyethyl)-N-methyl-p-toluidine, butoxyethyl 4-dimethylamino benzoate, 4-dimethylaminoacetophenone, triethanolamine, methyl dihydroxyethylamine, dimethylaminoethanol, 2-(dimethylamino)ethyl benzoate, poly(propylene glycol)-4-(dimethylamino)benzoate and Michler's ketone.

[0067] The above-mentioned ultraviolet crosslinking agent in the composition of the hydrogel resin in the first step plays a role in adjusting the crosslinking degree of the hydrogel to adjust the adhesion and elasticity of the hydrogel. Relative to the total weight of the hydrogel resin, its content is 0.01 to 2 weight percent, preferably 0.025 to 2 weight percent, and more preferably 0.025 to 1.5 weight percent. At this time, if the content of the ultraviolet crosslinking agent is less than 0.01 weight percent, there may be a problem that the viscoelasticity of the ultraviolet-cured hydrogel is too low. If it exceeds 2 weight percent, there may be a problem that the adhesion is reduced.

[0068] In addition, the ultraviolet crosslinking agent can be mixed and used and is selected from benzyl methacrylate, dodecyl methacrylate, isodecyl methacrylate, phenoxy methacrylate, 2-hydroxyethyl methacrylate, tetrahydrofurfuryl methacrylate, hexadecyl (C16) methacrylate, octadecyl methacrylate, methoxy polyethylene glycol 500 methacrylate, methoxy polyethylene glycol 600 methacrylate, methoxy polyethylene glycol 1000 methacrylate, 1,6-hexanediol dimethacrylate, butadiene dimethacrylate, neopentyl glycol dimethacrylate, ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, triethylene glycol dimethacrylate, tetraethylene glycol dimethacrylate, bisphenol A (epoxy) 4 dimethacrylate, bisphenol A (epoxy) 3 dimethacrylate, bisphenol A (epoxy) 10 dimethacrylate, bisphenol A (epoxy) 30 dimethacrylate, 1,3-butylene glycol dimethacrylate, polyethylene glycol 400 dimethacrylate, polyethylene glycol 200 dimethacrylate, polypropylene glycol 1000 (epoxy) 15 dimethacrylate, polypropylene glycol 1000 (epoxy) 3 dimethacrylate hydrogen furfuryl, trimethylolpropane trimethacrylate, benzyl acrylate, dodecyl acrylate, isodecyl acrylate, phenol (epoxy) acrylate, phenol (epoxy) 2 acrylate, phenol (epoxy) 4 acrylate, phenol (epoxy) 6 acrylate, tetrahydrofurfuryl acrylate, nonylphenol (epoxy) 4 acrylate, nonylphenol (epoxy) 8 acrylate, nonylphenol (epoxy) 2 acrylate, ethoxyethoxyethyl acrylate, octadecyl acrylate, 1,6-hexanediol diacrylate, 1,6-Hexanediol (epoxy) diacrylate, butanediol diacrylate, hydroxytrimethylol neopentyl glycol diacrylate, tripropylene glycol diacrylate, dipropylene glycol diacrylate, bisphenol A (epoxy) 4 diacrylate, bisphenol A (epoxy) 3 diacrylate, tricyclodecane dimethanol diacrylate, tetraethylene glycol diacrylate, polyethylene glycol 400 diacrylate, polyethylene glycol 200 diacrylate, polyethylene glycol 300 diacrylate, polyethylene glycol 600 diacrylate, polypropylene glycol 400 diacrylate, polypropylene glycol 750 diacrylate, bisphenol A (epoxy) 10 diacrylate, bisphenol A (epoxy) 30 diacrylate, tris (2-hydroxyethyl) isocyanurate At least one of trimethylolpropane triacrylate, trimethylolpropane triacrylate, trimethylolpropane (epoxy) 3 triacrylate, trimethylolpropane (epoxy) 6 triacrylate, trimethylolpropane (epoxy) 9 triacrylate, trimethylolpropane (epoxy) 15 triacrylate, glycerol propoxylated triacrylate, pentaerythritol triacrylate, trimethylolpropane (propylene oxide) 3 triacrylate, tris (2-hydroxyethyl) isocyanurate triacrylate, pentaerythritol N-epoxy tetraacrylate, pentaerythritol tetraacrylate, dipentaerythritol pentaacrylate, dipentaerythritol hexaacrylate, caprolactone acrylate, O-phenylphenol epoxy acrylate, and methylenebisacrylamide. Preferably, one or more selected from methylene bisacrylamide, 2-hydroxyethyl methacrylate, ethylene glycol dimethacrylate, 1,3-butylene glycol dimethacrylate, polyethylene glycol 400 dimethacrylate, tripropylene glycol diacrylate and tetraethylene glycol diacrylate can be mixed and used.

[0069] In the method for preparing the poultice of the present invention, the second step is a process of coating (or applying) the hydrogel resin prepared in the first step with a release film, and the coating method can utilize a conventional coating method commonly used in the art.

[0070] Furthermore, the above-mentioned peeling film is used to separate and remove the drug layer of the paste compress before using it on the skin after preparing the paste compress so that the drug layer of the paste compress adheres to the skin. Considering the ease of peeling and the ease of preparation, the average thickness of the peeling film (peeling layer) is 15μm to 500μm, preferably 20μm to 300μm, considering the ease of peeling and the ease of preparation.

[0071] Furthermore, the release film is a polymer film coated with a silicone resin or a fluororesin, and the polymer film may include one or more polymer compounds selected from polyester, polyvinyl chloride, polyvinylidene chloride, polyethylene terephthalate, and copolymers thereof.

[0072] In the preparation method of the poultice of the present invention, the third step is a process of laminating a support body with a hydrogel resin coated on a release film, and the support body acts as a drug support layer of the poultice, and the support body can use one or more selected from polyurethane films, porous films, perforated films, fabrics, non-woven fabrics and foams. In addition, the average thickness of the support body is 7 μm to 500 μm, preferably 50 μm to 250 μm. If the average thickness is less than 7 μm, it is too thin to ensure sufficient physical properties and cannot act as a support body for the solidified hydrogel (drug layer). If it exceeds 500 μm, it is too thick and the feel of use on the skin body is reduced. Therefore, it is preferred to use a support body with a thickness within the above range.

[0073] In the method for preparing the poultice of the present invention, the fourth step is a step of irradiating ultraviolet light along the direction of the support after laminating the release film, the hydrogel resin coating layer and the support to cure the hydrogel resin between the release film and the support to form a hydrogel (drug layer). At this time, the ultraviolet light irradiation can be 2000mW / cm 2 ~8000mW / cm 2 The ultraviolet light is irradiated for 3 to 10 minutes at an intensity of 2500 mW / cm 2 ~5000mW / cm 2 Irradiate ultraviolet light at an intensity of 3 to 10 minutes.

[0074] The average thickness of the hydrogel formed by ultraviolet curing is not particularly limited, but is preferably 20 μm to 2000 μm, and more preferably 40 μm to 1000 μm.

[0075] Furthermore, the effective area of ​​the UV-cured hydrogel is 0.64 cm 2 When the skin permeation of the active ingredient is measured in a Franz diffusion cell with a water-soluble phase volume of 5.2 ml under sink conditions and at 30°C to 33°C, the cumulative skin permeation amount can be 40 to 160 μg / cm 2 , preferably 45 to 150 μg / cm 2 , more preferably 50 to 150 μg / cm 2 , can have excellent skin permeability.

[0076] Furthermore, the effective area of ​​the UV-cured hydrogel is 0.64 cm 2When the Franz diffusion cell with a water-soluble phase volume of 5.2 ml is used to measure the skin permeation of the active ingredient at a sink condition and 30°C to 33°C, the cumulative skin permeation rate can be 1.0 to 7.5 μg / cm 2 / hr, preferably 1.0 to 7.0 μg / cm 2 / hr, more preferably 1.0 to 6.8 μg / cm 2 / hr, with excellent skin penetration rate.

[0077] Furthermore, when the peel strength of the ultraviolet-cured hydrogel is measured according to the adhesive strength test of the Korean Pharmacopoeia Band-Aid item, the adhesive strength is 40 to 150 gf, preferably 50 to 150 gf, and more preferably 60 to 150 gf, and the adhesive strength to the skin is excellent.

[0078] The poultice of the present invention prepared by the above method comprises: a peeling layer; a drug layer comprising an ultraviolet curable hydrogel for transdermal administration and a drug supporting layer, wherein the peeling layer is the peeling film described above, and the peeling layer is removed when the poultice is applied to the skin. Furthermore, the drug supporting layer is equivalent to the supporting body described above.

[0079] The poultice of the present invention as described above has different specific uses depending on the active ingredients in the drug layer. As an example, lidocaine, lidocaine hydrochloride, loxoprofen, loxoprofen salt, etc. are used as anti-inflammatory and analgesic poultices.

[0080] Hereinafter, the present invention will be described in more detail with reference to Examples, but the scope of the present invention is not limited to the scope illustrated in the Examples.

[0081] Example

[0082] Example 1: Preparation of hydrogel resin

[0083] 15 weight percent of polyvinyl pyrrolidone, 0.25 weight percent of flurbiprofen, 28.75 weight percent of glycerin, 10 weight percent of sorbitol, 15 weight percent of propylene glycol, 0.01 weight percent of 1-hydroxy-cyclohexyl-phenyl-ketone, 0.2 weight percent of methylenebisacrylamide and 30.79 weight percent of purified water were mixed, stirred and completely dissolved to prepare a hydrogel resin.

[0084] Example 2 to Example 62

[0085] The hydrogel resin was prepared by the same method as in Example 1, except that the hydrogel resin was prepared so as to have the composition and composition ratio shown in Tables 1 to 7 below.

[0086] Table 1

[0087]

[0088] Table 2

[0089]

[0090] Table 3

[0091]

[0092]

[0093] Table 4

[0094]

[0095]

[0096] Table 5

[0097]

[0098]

[0099] Table 6

[0100]

[0101]

[0102] Table 7

[0103]

[0104] Embodiment 63 to Embodiment 70

[0105] The hydrogel resin was prepared by the same method as in Example 1, except that the hydrogel resin was prepared so as to have the composition and composition ratio shown in Table 8 below.

[0106] Table 8

[0107]

[0108]

[0109] Example 71 to Example 74

[0110] The hydrogel resin was prepared by the same method as in Example 1, except that the hydrogel resin was prepared so as to have the composition and composition ratio shown in Table 9 below.

[0111] Table 9

[0112]

[0113] Comparative Example 1

[0114] A hydrogel resin having the composition and composition ratio shown in Table 10 was prepared. The curing of the hydrogel resin having the composition shown in Table 10 was performed by metal complex ion cross-linking bonding, and the curing time was 14 days.

[0115] Table 10

[0116]

[0117]

[0118] Comparative Example 2 to Comparative Example 10

[0119] The hydrogel resin was prepared by the same method as in Example 1, except that the hydrogel resin was prepared so as to have the composition and composition ratio shown in Table 11 below.

[0120] Table 11

[0121]

[0122] Preparation Example 1: Preparation of poultice

[0123] The hydrogel prepared in Example 1 was applied to one side of a polyester film (75 μm thick) coated with silicone resin, and then covered with nonwoven fabric and irradiated with ultraviolet light for 4 minutes to cure the hydrogel resin coating layer, thereby preparing a poultice in which a peeling layer (peeling film), a drug layer (hydrogel), and a drug support layer (nonwoven fabric) were laminated and integrated. Thus, a hydrogel with an average thickness of 500 μm was prepared.

[0124] Preparation Examples 2 to 74 and Comparative Preparation Examples 2 to 10

[0125] The poultices were prepared in the same manner as in Preparation Example 1, except that the hydrogel resins of Examples 2 to 74 were used instead of the hydrogel resin of Example 1 to prepare poultices to implement Preparation Examples 2 to 74.

[0126] Comparative Preparation Example 1

[0127] The poultice was prepared in the same manner as in Preparation Example 1, but was left at room temperature (25°C to 27°C) for 14 days instead of UV irradiation for metal ion bonding, thereby curing. Whether the poultice was cured was determined by whether the hydrogel was adhered and whether the nonwoven fabric was penetrated.

[0128] Comparative Preparation Examples 2 to 8

[0129] Comparative Preparation Examples 2 to 8 were carried out by preparing poultices in the same manner as in Preparation Example 1 except that the hydrogel resins of Comparative Examples 2 to 8 were used instead of the hydrogel resin of Example 1.

[0130] Experimental Example 1: Adhesion Measurement

[0131] In order to confirm the adhesiveness of the plaster prepared in the preparation example and the comparative preparation example, a 180° glass test (180° peel test) was performed, and the results are shown in Tables 12 and 13. At this time, regarding the measurement of the adhesive force, after removing the peeling layer of the plaster, it was sheared with a standard width of 12 mm and a length of 250 mm, and attached to a test plate of a phenol resin material with a width of 12 mm and a length of 250 mm, and a rubber roller with a mass of 850 g was passed at a speed of 300 mm for 1 minute, and after being closely attached twice, it was pulled at a speed of 300 mm using a tensile strength tester (Instron 5544), and the load was measured 4 times at intervals of about 20 mm.

[0132] Table 12

[0133]

[0134]

[0135] Table 13

[0136] distinguish Adhesion force (gf) distinguish Adhesion force (gf) Comparative Preparation Example 1 38 Comparative Preparation Example 5 32 Comparative Preparation Example 2 × Comparative Preparation Example 6 64 Comparative Preparation Example 3 58 Comparative Preparation Example 7 × Comparative Preparation Example 4 37 Comparative Preparation Example 8 ×

[0137] In the case of Comparative Example 2 in which a hydrogel resin with a hydrophilic polymer content of less than 5 weight percent was introduced, and Comparative Preparation Examples 7 and 8 in which a hydrogel resin without a UV initiator and a UV crosslinker was introduced, the gel formation effect was poor or no crosslinking occurred, and the adhesive strength could not be measured.

[0138] In the case of Comparative Preparation Example 4 in which the active ingredient was used in an amount exceeding 15 weight percent, the adhesive force was 37 gf, which was less than 50 gf. It was judged that the excessive use of the active ingredient affected cross-linking and reduced the adhesive force of the hydrogel.

[0139] In the case of Comparative Preparation Example 5 in which the content of the wetting agent was less than 0.6 weight percent, the adhesive force was very low, and it was judged that the adhesive portion of the ultraviolet-cured hydrogel was too dry and the adhesive force decreased.

[0140] Experimental Example 2: Determination of Cumulative Skin Permeation Amount and Skin Permeation Rate

[0141] The cumulative permeation amount and permeation rate of the active ingredient in the drug layer of the poultices prepared in Preparation Examples 1 to 74 and Comparative Preparation Examples 1 and 3 to 6 were analyzed.

[0142] A Franz diffusion cell (effective area: 0.64 cm 2 The skin permeation test was performed under the sink condition (area: 0.64 cm) to obtain the cumulative skin permeation amount. Specifically, phosphate buffered saline (PBS) with a pH of 7.4 as the aqueous phase was first filled into the Franz diffusion cell and maintained at 32±0.5°C. 2 ) The sample was cut and attached to the central part of the prepared skin (human cadaver skin epidermis), the skin with the sample attached was placed on the upper part of the receiving part of the Franz diffusion cell, the Doner part was covered and fixed with a clamp, and then a permeation test was performed.

[0143] The skin was purchased from human cadaver skin epidermis, which was stored at -70°C and thawed at 40°C before use. The effective ingredient permeation analysis was performed using HPLC, and the results of the 24-hour measurement are shown in Tables 14 and 15.

[0144] Table 14

[0145]

[0146]

[0147]

[0148] Table 15

[0149]

[0150] As can be seen from Table 14, in the case of the poultices of Preparation Examples 1 to 74, the poultices had a concentration of 40 μg / cm 2 The cumulative skin penetration is 2.0 μg / cm2 / hr or more skin penetration rate.

[0151] However, in the case of Comparative Preparation Example 1, which is a conventional poultice prepared by metal complex ion bonding, the cumulative skin permeation amount and the skin permeation rate were low.

[0152] In addition, in the case of Comparative Preparation Example 3 using more than 60 weight percent of hydrophilic polymer, as shown in Table 13, the adhesive force is excellent, but compared with the preparation example in Table 14, it has a low cumulative skin permeation amount and skin permeation rate. It is judged that the large amount of hydrophilic polymer forming a cross-linked structure in the hydrogel actually leads to a decrease in the skin delivery ability of the active ingredient.

[0153] In addition, in the case of Comparative Preparation Example 4 in which the content of the active ingredient exceeded 15 weight percent and in the case of Comparative Preparation Example 5 in which the content of the wetting agent was less than 0.6 weight percent, excellent cumulative skin permeation amount and skin permeation rate were obtained. However, in the case of Comparative Preparation Example 4 and Comparative Preparation Example 5, as shown in Table 13, there was a problem of poor adhesion.

[0154] In the case of Comparative Preparation Example 6 in which no transdermal permeation enhancer was used, although the adhesive force was excellent, the cumulative amount of permeation through the skin and the skin permeation rate were very low.

[0155] Through the above-mentioned embodiments and experimental examples, it can be confirmed that the drug layer (hydrogel) of the poultice prepared by using the hydrogel resin of the present invention has a fast curing speed and excellent economic and commercial properties, and the drug layer has excellent skin transmission force and transmission speed, and excellent adhesion to the skin. Various pharmaceutical patches can be provided by using the poultice of the present invention.

[0156] A person skilled in the art may easily make simple deformation or modification to the present invention, and such deformation or modification shall all fall within the scope of the present invention.

Claims

1. A UV-curable hydrogel resin for a poultice, characterized in that: The invention comprises 8 to 35 weight percent of a hydrophilic polymer, 0.1 to 10 weight percent of an active ingredient, 12 to 40 weight percent of a wetting agent, 0.5 to 25 weight percent of a transdermal penetration enhancer, 0.01 to 2.0 weight percent of an ultraviolet initiator, 0.01 to 2.0 weight percent of an ultraviolet crosslinking agent, and the remainder of a solvent. The hydrophilic polymer comprises 5 to 100 parts by weight of one or more selected from hydroxypropyl cellulose, sodium polyacrylate, polyacrylic acid, sodium carboxymethyl cellulose and polyacrylamide, relative to 100 parts by weight of polyvinyl pyrrolidone. The above-mentioned active ingredient comprises one or more selected from lidocaine, lidocaine hydrochloride, loxoprofen, loxoprofen salt, ketoprofen, flurbiprofen, diclofenac, diclofenac salt, indomethacin, piroxicam, meloxicam, naproxen, ibuprofen, menthol, glycol salicylate, methyl salicylate, capsicum extract, nonanoic acid vanillamide, fusidic acid, fusidic acid salt, rivanol, heparin, heparin salt and allantoin, The above-mentioned wetting agent comprises one or more selected from glycerin and sorbitol, The transdermal penetration enhancer comprises one or more selected from propylene glycol, polyoxyethylene oleate, polyglyceryl diisostearate, glyceryl oleate, polyoxyethylene sorbitan, N-methyl-2-pyrrolidone, dodecyl pyrrolidone, isopropyl myristate, sorbitan oleate, glyceryl oleate, propylene glycol monolaurate and glyceryl triacetate, The ultraviolet initiator comprises one or more selected from 1-hydroxy-cyclohexyl-phenyl-ketone, benzophenone, methyl benzoyl formate, phosphine oxide, phenyl bis (2,4,6-trimethylbenzoyl) and 2-hydroxy-2-methyl-1-phenyl-1-propanone, The ultraviolet crosslinking agent includes one or more selected from methylene bisacrylamide, 2-hydroxyethyl methacrylate, ethylene glycol dimethacrylate, 1,3-butylene glycol dimethacrylate, polyethylene glycol 400 dimethacrylate, tripropylene glycol diacrylate, tetraethylene glycol diacrylate and ethylene glycol HEMA methacrylate, The above solvent includes purified water.

2. The ultraviolet curable hydrogel resin for poultice according to claim 1, characterized in that: The pH is 3-9.

3. A UV-curable hydrogel for a poultice, characterized in that: The ultraviolet-cured material of the ultraviolet-curable hydrogel resin for poultice according to claim 1 or 2, According to the Korean Pharmacopoeia Band-Aid Adhesion Test, the peel strength is 50-120gf. The effective area is 0.64cm 2 When the Franz diffusion cell with a water phase volume of 5.2 ml was used to measure the skin permeation of the active ingredient in a sink state at 30°C to 33°C, the cumulative skin permeation was 40 to 160 μg / cm 2 , the skin penetration rate is 2.0~7.5μg / cm 2 / hr.

4. A method for preparing a poultice, characterized in that: include: The first step is to prepare the ultraviolet curable hydrogel resin for the poultice according to claim 1 or 2; The second step is to apply the hydrogel resin to the release film; The third step is to laminate a support body on the coated hydrogel resin; Step 4: along the support direction, at 2000 mW / cm 2 ~8000mW / cm 2 The hydrogel resin is cured by irradiating ultraviolet rays at an intensity of 3 minutes to 10 minutes.

5. A poultice, characterized in that: include: A drug layer comprising the ultraviolet curable hydrogel for poultice according to claim 3; The drug supporting layer comprises at least one selected from polyurethane film, porous film, perforated film, fabric, non-woven fabric and foam.

6. The poultice according to claim 5, characterized in that The average thickness of the drug layer is 20 to 2000 μm, and the average thickness of the drug support layer is 7 to 500 μm.

7. The poultice according to claim 5, characterized in that Also includes a peeling layer, The peeling layer, the drug layer and the drug supporting layer are stacked in sequence.

8. The poultice according to claim 7, characterized in that The average thickness of the peeling layer is 15 μm to 500 μm. The release layer comprises a polymer film coated with a silicone resin or a fluororesin. The polymer film includes at least one polymer compound selected from polyester, polyvinyl chloride, polyvinylidene chloride and copolymers thereof.

9. The poultice according to claim 5, characterized in that The above-mentioned poultice is an anti-inflammatory and analgesic poultice.

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