JP2005126341A - Antiinflammatory analgesic plaster for external application - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a water-containing antiinflammatory analgesic plaster for external applications, which has an excellent antiinflammatory effect and an excellent analgesic effect against inflammations such as muscle ache, sprain, bruise, lumbago, and shoulder stiffness, and has a low skin irritating property. <P>SOLUTION: This water-containing antiinflammatory analgesic plaster for the external applications is characterized by comprising a glycol salicylate and/or methyl salicylate selected from anti-inflammatory agents and lidocaine selected from local anesthetics. The water-containing antiinflammatory analgesic plaster exhibits an especially excellent synergistic effect on the antiinflammatory effect and the analgesic effect. Preferably, a highly water-containing substrate comprising a polyacrylic acid-based paste as a base material is used. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to a hydrous external anti-inflammatory analgesic patch having excellent anti-inflammatory and analgesic effects against inflammation such as muscle pain, sprains, bruises, low back pain, and stiff shoulders, and has low skin irritation.

Conventionally, external anti-inflammatory analgesic patches are known to contain anti-inflammatory agents such as salicylic acid compounds, indomethacin, ketoprofen as active ingredients, and l-menthol, camphor, tocopherol acetate, red pepper extract, etc. It may be used together. (For example, JP-A-5-105628: Patent Document 1, JP-A-59-110617: Patent Document 2)
However, salicylic acid anti-inflammatory drugs do not have sufficient analgesic effects, and indomethacin and ketoprofen have problems with solubility and transdermal absorption, and the composition is greatly restricted from the viewpoint of chemical stability in the preparation. There was a problem.

  On the other hand, as patches containing a local anesthetic, JP-A-9-268123 (Patent Document 3), JP-A-7-157424 (Patent Document 4), JP-A-4-305523 (Patent Document 5). Describes a patch for local anesthesia containing lidocaine as an active ingredient. However, although it can be expected to reduce pain due to the local anesthetic effect, the anti-inflammatory effect cannot be sufficiently obtained. JP-A-9-315964 and JP-A-2001-302501 disclose a patch for treatment of stiff shoulders and the like containing lidocaine as an active ingredient, but the effect is not sufficient.

JP-A-2002-128699 (Patent Document 6) and WO01 / 47559 (Patent Document 7) disclose an external anti-inflammatory analgesic composition and patch containing a non-steroidal anti-inflammatory analgesic and a local anesthetic. However, a composition using a specific combination of drugs disclosed therein does not necessarily provide a sufficient therapeutic effect, and is particularly basic when a plaster base having an anionic group is used. The effect of a local anesthetic (for example, lidocaine) is not sufficiently exhibited, and a high effect due to the drug combination cannot be obtained.
JP-A-5-105628 JP 59-110617 JP-A-9-268123 JP-A-7-157424 JP-A-4-305523 JP 2002-128699 A WO01 / 47559

  The present invention has been made in view of the above circumstances, and an object thereof is to provide an external anti-inflammatory analgesic patch that improves the analgesic effect and anti-inflammatory effect by the combined use of a local anesthetic and an anti-inflammatory agent, and has little skin irritation. .

  As a result of intensive studies to achieve the above object, the present inventors selected lidocaine as a local anesthetic and glycolic salicylate and / or methyl salicylate as an anti-inflammatory agent, and has a high water content plaster using these in combination. It was found that by using a patch, an external anti-inflammatory analgesic having both an analgesic effect and an anti-inflammatory effect and having low skin irritation was obtained, and the present invention was completed. Further, when a highly hydrous gel having a crosslinked polymer obtained by crosslinking a polyacrylic acid-based water-soluble polymer compound with a crosslinking agent such as synthetic hydrotalcite is used as the paste base of such a patch, It has also been found that the effectiveness is increased without impairing the medicinal effect.

That is, the present invention
(1)
A topical anti-inflammatory analgesic patch comprising glycol salicylate and / or methyl salicylate and lidocaine.
(2)
The external anti-inflammatory analgesic patch according to (1), further comprising menthol and / or a blood flow promoter.
(3)
The external anti-inflammatory analgesic patch according to (1) or (2), further comprising 0.1 to 5% by mass of an oily compound having a melting point of 40 ° C. or lower and / or glycol.
(4)
The external anti-inflammatory analgesic patch according to any one of (1) to (3), which contains crosslinked polyacrylic acid and / or a salt thereof as a plaster base.
I will provide a.

  By setting it as said structure, the external anti-inflammatory analgesic which has a high analgesic effect and an anti-inflammatory effect and low skin irritation is obtained.

  Here, the blending amount of glycol salicylate and / or methyl salicylate in the patch of the present invention is 0.01 to 10% (mass%, hereinafter the same unless otherwise specified) in the plaster composition, particularly 0.1 to 5% is preferable. If the amount is too small, the efficacy of the anti-inflammatory drug combination may not be obtained sufficiently, and even if it is at most, the effect of further compounding can not be expected, and it may cause skin irritation or damage the physical properties of the plaster. is there.

  The amount of lidocaine in the patch of the present invention is preferably 0.01 to 10%, particularly 0.1 to 5% in the plaster composition. If the blending amount is too small, the medicinal effect of lidocaine blending may not be sufficiently obtained, and even if the blending amount is too large, the effect of blending beyond that cannot be expected.

  A high analgesic effect and anti-inflammatory effect can be obtained by using the above lidocaine in combination with glycol salicylate or methyl salicylate, but preferably lidocaine / glycol salicylate or methyl salicylate = 4/1 to 1/10, more preferably 3/1 to 1. / 5 is preferable because the effect is particularly high.

  In addition to the above active ingredients, the paste composition for external anti-inflammatory analgesic patches of the present invention includes monoterpenoid compounds (menthol, camphor, limonene, terpinolene, menthane, terpinene, etc., preferably menthol, camphor), blood flow promotion. Agents (capsaicin, capsaicin, capsaicinoids, divitrocapsaicin, capsaicin analogs such as capsanthin, hot pepper-derived warming substances such as pepper extract, red pepper tincture, red pepper powder, benzyl nicotinate, β-butoxyethyl nicotinate, N-acyl Vanillamide, Nonyl acid vanillamide, Vanillyl butyl ether, Tocopherol acetate, Tocopherol, Tocotrienol, Acetyl eugenol, Caihi oil, Life-extending herbal extract, Buttonpi extract, Arnica tincture, Ginger extract, etc. Preferably it is blended. An essential oil containing the above components (for example, mint oil containing menthol) can also be blended.

  Among them, menthol, camphor, tocopherol acetate, capsaicin, pepper extract, nonyl acid vanillylamide, vanillyl butyl ether, and benzyl nicotinate can be further enhanced. More preferably, menthol and / or camphor and a blood flow promoter are used in combination.

  The blending amount of the monoterpenoid and / or blood flow promoter is preferably 0.001 to 10%, particularly preferably 0.01 to 5% in the plaster.

  The plaster of the present invention preferably further contains glycol and / or liquid oil (40 ° C.) in order to enhance the transdermal absorbability and skin irritation mitigation property of the drug. Examples of the glycol include ethylene glycol, diethylene glycol, polyethylene glycol, propylene glycol, polypropylene glycol, butylene glycol, hexylene glycol and the like. The blending amount of glycol is preferably 0.01 to 10%, more preferably 0.05 to 5%, and most preferably 0.1 to 3%.

Liquid oil (40 ° C) includes castor oil, olive oil, macadamia nut oil, cinnamon oil,
Examples include jojoba oil, squalane, sunflower oil and camellia oil. The blending amount of the liquid oil is preferably 0.01 to 10%, more preferably 0.05 to 5%, and most preferably 0.1 to 3%. Within this range, the effectiveness and low irritation of the external anti-inflammatory analgesic patch of the present invention is particularly excellent, and the skin adhesiveness can be maintained well.

  The above glycol and liquid oil can be used alone, but a higher effect can be obtained by using glycol and liquid oil in combination.

  The plaster of the external anti-inflammatory analgesic patch of the present invention is a pressure-sensitive adhesive composition that is a water-containing gel having a water content of 40 to 95%, preferably 55 to 90%, more preferably 60 to 90%, and even more preferably 70 to 90%. It is a thing. Specifically, various components and water are held in a crosslinked polymer matrix formed by blending a water-soluble polymer compound as a main base and a crosslinking agent for crosslinking the water-soluble polymer compound.

  Preferred examples of the water-soluble polymer include polyacrylic acid and / or polyacrylate. In particular, a crosslinked polyacrylic acid (salt) obtained by crosslinking a mixture of polyacrylic acid and polyacrylate with various crosslinking agents is preferable. The crosslinked polyacrylic acid-based water-containing gel provides a patch with high water content and excellent adhesion to the skin, so that a patch excellent in the percutaneous absorption of the active ingredient can be obtained. Examples of the crosslinked product of polyacrylic acid and polyacrylate include, for example, JP-A Nos. 59-110614, 59-110616, 59-110617, 60-99180, and 60-260512. No. 60-260513 and the like.

  Examples of the polyacrylate include monovalent metal salts of polyacrylic acid such as sodium polyacrylate and potassium polyacrylate, monoethanolamine polyacrylate, diethanolamine polyacrylate, and triethanolamine polyacrylate. One kind or two or more kinds such as an amine salt of polyacrylic acid and an ammonium salt of polyacrylic acid can be suitably used.

  When polyacrylic acid salt and polyacrylic acid are used in combination, the compounding ratio (weight ratio) is polyacrylic acid salt: polyacrylic acid = 1: 0.1 to 1:10, particularly preferably 1: 1 to 1: 9 is desirable. For blending, it is preferable to mix polyacrylic acid and polyacrylate, but polyacrylic acid or a salt partially neutralized so that the polyacrylate is in the above ratio may be used. . The total blending amount of polyacrylic acid and polyacrylate is preferably 0.5 to 20%, particularly 1 to 15% of the entire plaster composition, and if less than 0.5%, the adhesive strength is insufficient. In some cases, if it exceeds 20%, the viscosity increases, which may cause problems in workability during production.

  The polyacrylic acid (salt) preferably has a linear or branched molecular weight of 10,000 to 10,000,000. In particular, polyacrylic acid and / or a salt thereof having an average molecular weight of 10,000 to less than 500,000, less than 500,000 to less than 2,000,000, and 2,000,000 to 5,000,000, particularly preferably three or more. In combination, better adhesion and usability can be obtained. In addition, as the polyacrylic acid (salt) of the present invention, a partially crosslinked acrylic acid polymer such as Carbopol (trade name: manufactured by Goodrich, USA) can be water-soluble and can form a hydrous gel. Can be used.

  Furthermore, it is preferable to add a cellulose derivative in order to improve the feeling of use of the gel in terms of adhesiveness. Examples of the cellulose derivative include alkali metal salts of carboxymethyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, methyl cellulose and the like. In particular, alkali metal salts of carboxymethyl cellulose such as sodium carboxymethyl cellulose and potassium carboxymethyl cellulose can be preferably used. Preferred cellulose derivatives are those having a 1 mass% viscosity at 25 ° C. of 500 to 8000 mpa · s. The blending amount of the cellulose derivative is preferably 15% or less of the entire plaster composition. If it exceeds 15%, the viscosity becomes high, which may cause problems in workability during production.

  Furthermore, in order to improve the physical properties of the plaster, other water-soluble polymers such as polyvinyl alcohol, polyvinyl pyrrolidone, gelatin, pectin, vinyl pyrrolidone / vinyl acetate copolymer, hydroxypropyl cellulose, sodium alginate, xanthan gum, tragacanth, etc. Can be blended. When mix | blending these water-soluble polymers, it is preferable that the compounding quantity shall be 0 to 10% of the whole plaster composition. In addition, since the composition will become hard when this compounding quantity is more than 10%, it will become a problem when manufacturing a patch.

  The crosslinking agent used for the water-containing plaster is a compound that acts on the carboxyl group of polyacrylic acid (salt) to form a crosslinked structure and has at least two reactive sites in the molecule. Examples include compounds having an epoxy group such as bisepoxide, dialdehyde starch, glycidyl ether, dibenzylidene sorbitol, polyvalent metal compounds, polycationic polymers or salts thereof, and the like. A polymer or a salt thereof is particularly preferred.

  As polyvalent metal compounds, magnesium compounds, calcium compounds, zinc compounds, cadmium compounds, aluminum compounds, titanium compounds, tin compounds, iron compounds, chromium compounds, manganese compounds, cobalt compounds, nickel compounds, etc. can be used. The external patch of the invention is applied to the skin, and it is particularly preferable to use an aluminum compound, a magnesium compound, a calcium compound, etc. in view of safety to the skin.

  Any of aluminum compounds, magnesium compounds and calcium compounds can be suitably used, for example, alums such as potassium alum, ammonium alum, iron alum, aluminum hydroxide, aluminum sulfate, aluminum chloride, aluminum glycinate, aluminum acetate , Aluminum oxide, Aluminum silicate, Aluminum metasilicate, Calcium hydroxide, Calcium carbonate, Calcium sulfate, Calcium nitrate, Calcium chloride, Calcium acetate, Calcium oxide, Calcium phosphate, Magnesium hydroxide, Magnesium carbonate, Magnesium sulfate, Magnesium nitrate, Chloride Magnesium, magnesium acetate, magnesium silicate, magnesium oxide, magnesium hydroxide, magnesium aluminate metasilicate Arm, magnesium aluminosilicate, synthetic hydrotalcite, water soluble compounds such as double salts containing these metals, may be used one or more poorly water-soluble compounds.

  The blending amount of the polyvalent metal compound is suitably 0.001 to 10%, preferably 0.01 to 5%, more preferably 0.02 to 2% of the entire plaster composition. If it is less than 001%, the plaster may remain on the skin at the time of peeling due to a decrease in cohesive force. If it exceeds 10%, the adhesive strength is lowered, so that it peels off when it is applied, and the original support function cannot be exhibited.

  Examples of the polycationic polymer or a salt thereof include a polymer having at least two cationic groups such as N + and S + or a salt thereof. Preferably, it is water-soluble. Of these, those in which the cationic group is an N + group are preferred, and those in which the cationic group is a trimethylammonium group or a polydimethylallylammonium group are preferred. In addition, a polymer whose main chain is polysaccharide-based is preferable.

  Examples of such materials include vinyl-based cationic polymers and cationized polysaccharides, specifically, poly-4 (2) -vinylpyridine, ionene polymer (manufactured by Aldrich), N-trialkylaminomethyl polystyrene, Aminoacetalized polyvinyl alcohol, poly-4 (5) -vinylimidazole, linear polyethyleneimine, polyethyleneimine, polydialkyldiallylammonium salt, dialkyldiallylammonium salt-SO2 copolymer, cationized dextran, cationized starch, cationized PVP , Cationized cellulose such as trimethylammonium type cationized cellulose, polydimethyldiallylammonium type cationized cellulose, or dimethyllaurylammonium type cationized cellulose, cationized PVA, Examples thereof include dimethyldiallylammonium salt-acrylamide copolymer, cationic guar gum, chitosan, gelatin, or salts thereof such as fluoride, chloride, bromide, iodide and the like.

  In addition, as a polycationic polymer or its salt, a single thing may be used or 2 or more types may be used together. The polycationic polymer or a salt thereof preferably has a weight average molecular weight of 1,000 to 100,000,000. In particular, from the viewpoint of elasticity and shape retention of the plaster composition, the weight average molecular weight is preferably 10,000 to 10,000,000, more preferably 50,000 to 10,000,000. .

  The blending amount of the polycationic polymer or a salt thereof is preferably 0.1 to 40%, more preferably 0.5 to 20% based on the mass of the entire plaster composition. The blending ratio of the polycationic polymer or salt thereof to polyacrylic acid (salt) is (mass ratio) (polycationic polymer or salt thereof) / (polyacrylic acid and / or salt thereof) = 10. / 1 to 1/100 is preferable, and 5/1 to 1/40 is more preferable.

  Furthermore, it is preferable to adjust the crosslinking reaction by adding a speed adjusting agent for the crosslinking reaction of polyacrylic acid (salt). Examples of the rate adjusting agent for the crosslinking reaction include chelate or coordination ability with respect to metal ions such as edetic acid (EDTA) disodium, citric acid, malic acid, tartaric acid, sodium pyrophosphate, urea, ammonia and the like. Organic acids, organic acid salts, organic bases and the like can be used. The addition amount of the speed regulator is preferably 0.001 to 5%, particularly 0.01 to 1% in the composition.

  In addition to the above components, other components such as an inorganic powder and a trihydric or higher polyhydric alcohol can be appropriately added to the aqueous plaster of the present invention as long as the effects of the present invention are not impaired. Examples of the inorganic powder include kaolin, smectite, titanium oxide, zinc oxide, anhydrous silicic acid and layered silicate, and these can be used alone or in combination of two or more.

  Specific examples of clay minerals composed of layered silicates include smectite clay minerals such as montmorillonite, beidellite, nontronite, saponite, hectorite, soconite, and stevensite. These may be used alone or in combination of two. The above is used in appropriate combination.

  Smectite clay minerals are produced from nature, for example, products containing montmorillonite, from Toyshun Mining Co., Ltd. to Bentonite W, Bengel, Kuniminee Co., Ltd. from Kunipia G and Kunipia F, American Colloid Co., Ltd. From Western Bond, Yellowstone from Dresser Minerals, Inc., as a product containing saponite, from Vanderbuild Inc., as a product containing hectorite, such as Veegum T, Peagam HV, Veegum F, and Veegum K, from American Colloid Hectablite AW, Hectablite 200, Penton EW, Macaroid, etc. are commercially available from National Reed. In addition, various synthetic smectite clay minerals are also on the market. Ionite H is available from Mizusawa Chemical Industry Co., Ltd., SWN, SAN from Lab Chemical Co., Ltd., and Labonite from Laporte Industry Company. In addition, Coma Chemical Co., Ltd. Somasif, Topy Industries, Ltd. DP-DM or DM Clean may be mentioned.

  Further, as the smectite clay mineral, an alkaline treated product of acidic clay can also be used. That is, normally, the acid clay is one having a 1% aqueous dispersion having a pH of 5 to 6 or less, a degree of swelling of 10 ml / 2 g or less, and a content of SiO2 and A12 O3 in a molar ratio of SiO2 / A12 O3 = 6-10. These acid clays are the acid clays from Nakajo, Kodo, Kamiakadani, Itoigawa, Niigata Prefecture, Mizusawa, Yamagata, Kawasaki, Matsune, Kamiakadani, Mikawa, Ome, Kamisami. In addition, UK's Fuller's earth, US-made Fluoride earth, German-made Warkel erde, etc. exhibiting similar properties to these acidic clays. Examples of the exchangeable cation present in the acid clay include sodium ion, potassium ion, magnesium ion, and iron ion. These acidic clays can be blended in the same manner as the above smectite clay mineral by alkali treatment.

  Here, in the case of the present invention, the smegtite-based clay mineral has an average particle size measured by a dynamic light scattering method of 10 to 5000 nm, an absolute value of ζ potential measured by an electrophoretic light scattering method of 30 mV or more, It is preferable to use one having a purity of 90% or more determined by powder X-ray diffraction. If the average particle size of the clay mineral is too smaller than 10 nm, a large amount of clay mineral may be required to thicken the paste, whereas if the average particle size is larger than 5000 nm, a stable dispersion state is required. May not be obtained. In addition, when the absolute value of the ζ potential is less than 30 mV, clay mineral particles are likely to condense, and there is a risk that the dispersion stability may be lowered due to sedimentation of aggregates during the production of the plaster composition. Furthermore, if the purity is too low, a sufficient thickening effect may not be obtained.

  The said inorganic powder mix | blended in the paste of this invention can use these individually by 1 type or in combination of 2 or more types. Although the compounding quantity of inorganic powder can be selected suitably, about 0.01 to 30% of the whole plaster composition is normally suitable, More preferably, 0.1 to 15% is suitable. If the amount is too large, the plaster hardness may become so hard that it cannot be spread.

  Moreover, as trihydric or more polyhydric alcohol, 1 type (s) or 2 or more types, such as glycerol, sorbitol, maltitol, xylitol, betaine ethylene glycol, diglycerol, can be used, for example. The blending amount of these polyhydric alcohols is preferably 5 to 40% in the plaster composition.

  In the plaster composition used in the present invention, in addition to the above, various components, for example, medicinal components other than those described above, superabsorbent polymer compounds, surfactants, preservatives, as long as the effects of the present invention are not impaired. , Dyes, pigments, fragrances, humectants, antioxidants, ultraviolet absorbers, pH adjusters, and the like can be blended in appropriate amounts.

  In the present invention, the medicinal component contained in the plaster layer is not particularly limited, and examples thereof include cooling agents, warming agents, blood flow promoters, herbal medicines, and the like. Two or more kinds may be used in combination.

  Examples of herbal medicines / essential oils include herbal powders such as pistol, and herbal extracts such as buckwheat, salamander, sea bream, licorice, oxon, sanshishi, toki, sekotsuboku, yobaihi, yokuinin, and the like.

  When blending these medicinal ingredients in the plaster, if the substance is listed in the Japanese Pharmacopoeia or if the appropriate amount of use is determined by other literature, etc., blend with the appropriate amount of use. Is preferred. The blending amount of other substances for which the appropriate amount is not determined is preferably 0.0001 to 10%, preferably about 0.001 to 5%, based on the total amount of the plaster. When the compounding amount of the medicinal component is lower than 0.0001%, the effect as a drug is not recognized, and even if it exceeds 10%, the effect is not changed.

The type of the superabsorbent polymer compound is not particularly limited. Modified polyalkylene oxide, N-vinylacetamide crosslinked product, acrylamide crosslinked product, and vinyl acetate-alkyl (meth) acrylate copolymer hydrolyzate Metal salt, vinyl alcohol-maleic anhydride copolymer crosslinked product, vinyl alcohol-acrylic acid-maleic anhydride copolymer crosslinked product, isobutylene-maleic acid copolymer crosslinked product, polyacrylonitrile graft polymer saponified product, starch -Acrylic acid graft polymer etc. can be mentioned, More specifically, Sunwet, Sunfresh AT-35 (manufactured by Sanyo Chemical Co., Ltd.), Aqua Coke (manufactured by Sumitomo Seika Co., Ltd.), Noniolex NA-010, Noniolex NA -150, Noniolex NA-500 (Showa Denko) It can be suitably used.
(Preferred blending amount 0.1 to 5%)
Examples of the surfactant include polyglycerin fatty acid ester, polyoxyethylene glycerin fatty acid ester, polyoxyethylene fatty acid ester, polyoxyethylene alkyl ether, polyoxyalkylene alkyl ether, polyoxyethylene alkyl ether sulfate (ester) salt, sorbitan Fatty acid ester, glycerin fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene hydrogenated castor oil, fatty acid soap, alkyl sulfate, N-acylmethyl taurate, alkyl ammonium salt, betaine acetate, propylene glycol fatty acid ester, vitamin derivative, Examples thereof include glycyrrhizic acid, glycyrrhetinic acid, and derivatives thereof.

  More specifically, sorbitan monooleate, glyceryl monooleate, diglycerin monostearate, decaglyceryl monooleate, diglyceryldiolate, hexaglyceryl monolaurate, propylene glycol monostearate, POE (20) sorbitan monooleate, POE (60) sorbite tetraoleate, POE (40) monostearate, polyoxyethylene (POE) (10) glyceryl monooleate, POE (25) lauryl ether, POE (10) oleyl ether, POE (10) nonylphenyl Ether, polyoxyethylene polyoxypropylene alkyl ether, POE (50) hydrogenated castor oil, POE (5) oleic acid amide, sodium lauryl sulfate, sodium POE alkyl ether sulfate POE alkyl ether sodium acetate, tri POE (10) alkyl ether phosphoric acid, stearyl trimethyl ammonium chloride, benzalkonium chloride, lauryl betaine, egg yolk, lecithin, betaine, diethyl sebacate.

  The blending amount of the surfactant is preferably 0.1 to 5% in the plaster composition.

Examples of the humectant include NMF components such as amino acids and sodium pyrrolidonecarboxylate; water-soluble polymer substances such as hyaluronic acid, collagen, mucopolysaccharide, chondroitin sulfate, and the like (preferred blending amount of 0.1 to 10) %). Examples of antioxidants include dibutylhydroxytoluene, butylhydroxyanisole, ascorbic acid and its salts (preferably 0.01 to 5%); pH adjusting agents include sodium hydroxide, potassium hydroxide, and triethanolamine. Ammonia water, boric acid, borax, potassium hydrogen phosphate and the like can be exemplified. (Preferable pH 4-7)
Examples of the ultraviolet absorbing / scattering agent include 2-hydroxy-4-methoxybenzophenone, octyldimethylparaaminobenzoate, ethylhexylparamethoxycynamate, titanium oxide, kaolin, talc and the like. (Preferred blending amount 0.01 to 5%)
Examples of amino acids include glycine, alanine, valine, leucine, isoleucine, phenylalanine, tryptophan, cystine, cysteine, methionine, proline, hydroxyproline, aspartic acid, glutamic acid, arginine, histidine, lysine and derivatives thereof. . (Preferred blending amount 0.1 to 10%)
Preservatives include phenols such as paraben, resorcin, phenol, phenoxyethanol, thymol, cresol, hinokitiol, benzoic acid (salt), benzyl benzoate, salicylic acid (salt), sorbic acid (salt), boric acid, etc. And quaternary ammonium compounds such as benzalkonium chloride, benzethonium chloride and alkyltrimethylammonium chloride, isothiazoline compounds such as chlorhexidine gluconate, chlorhexidine hydrochloride, chlorobutanol and caisson CG, dibutylhydroxytoluene and thymol. Preferred preservatives are parabens, benzoic acid (salts), hinokitiol, isothiazoline compounds, dibutylhydroxytoluene and thymol. (Preferred blending amount 0.001 to 5%)
The fragrance is not particularly limited. , Sage, geranium, celery, thyme, tarragon, turpentine, spruce, frankincense, violet, pine, parsley, birch, patchouli, rose, hyssop, fennel, black pepper, bodaiju flower, pill, yarow, lemon, lemongrass, rosemary , Laurel, Shimotsukigi, Peach, Cornflower, Eucalyptus, Yuzu, Lavender, and other herbal essential oils and extracts, and other lower alcohols and aldehydes. Available by mixing the seed above the normal plaster composition hull respectively, are blended in the range of 0.0001 to 1%.

As the pigment, acid dyes and pigments are preferably used, and pigments are particularly preferable from the viewpoint of preventing color transfer to the skin. As the acid dye, brown 201, black 401, shiba 401, blue 2, blue 202, blue 203, blue 205, green 201, green 205, green 401, green 402, Yellow 201, yellow 202-1, yellow 202-2, yellow 203, yellow 402, yellow 403-1, yellow 406, yellow 407, orange 205, orange 207, orange 402, Red No. 102, Red No. 104-1, Red No. 105-1, Red No. 106, Red No. 2, Red No. 227, Red No. 230-1, Red No. 230-2, Red No. 231, Red No. 232, Red No. 3 No., Red 401, Red 503, Red 506 and the like. As the pigment, blue 404, yellow 205, yellow 401, orange 204, orange 401, red 201, red 202, red 203, red 204, red 205, red 206, red 207 No., Red No. 208, Red No. 219, Red No. 220, Red No. 221, Red No. 228, Red No. 404, Red No. 405, Yellow iron oxide, Bengala, Gunjo, chromium oxide, chromium hydroxide, calamine, talc, etc. Can be mentioned.
(Preferred blending amount 0.00001 to 0.1%)
As the support, a fiber sheet such as a woven fabric, a nonwoven fabric, or a knitted fabric, a film, or a laminate thereof can be used. Preferred fibers for use in the fiber sheet include polyester, polyethylene, polypropylene, polyamide, polyvinyl chloride, polyurethane, polyvinyl alcohol, rayon, cupra, hemp, silk, cotton, etc., preferably polyester, polyethylene, and polypropylene. . These fibers may be used alone or as a blended fiber of two or more.

  As a method for forming the plaster layer, it can be prepared as follows. First, the preliminarily dispersed carboxyl group-containing polymer and / or salt thereof is added while rotating a commonly used mixer such as a Henschel mixer, a planetary mixer, a ribbon mixer, or a kneader. Next, reduce the rotation speed of the mixer or stop the rotation, and add clay mineral, inorganic powder, oil absorbent, water-soluble polymer compound, pigment, medicinal component, preservative, oil, etc., dispersed or dissolved in advance. . Finally, the pre-dispersed cross-linking agent is added while the mixer is rotating to knead all formulations. In addition, as for the temperature at the time of kneading | mixing, it is desirable that it is 10-60 degreeC, Preferably it is 20-50 degreeC. The external patch of the present invention is obtained by uniformly applying the hydrous plaster composition thus obtained to at least one surface of a support by a roll sand or knife coat method. . In addition, the external patch of the present invention can be produced according to the above method. For example, in the case of an external patch, the above components are kneaded to prepare a paste, which is applied to the support. If necessary, it can be obtained by coating a facing such as a polyethylene film.

  The plaster layer may be formed on the entire surface of the support, or may be formed partially or intermittently.

Next, although an Example and a comparative example are shown and this invention is demonstrated concretely, this invention is not restrict | limited to the following Example.
[Examples 1 to 14 and Comparative Examples 1 to 8] Each component shown in Tables 1 and 2 was mixed and stirred by a Henschel mixer according to a conventional method to prepare a patch, and immediately one sheet (140 × 100 mm) The patches of Examples and Comparative Examples were produced by spreading and cutting into a knit so as to be 14 g per hit, and the following evaluation was performed. The results are shown in Tables 1 and 2.
Anti-inflammatory effect <Method for evaluating edema-suppressing effect>
A specimen was affixed to the right hind paw of a rat (Wistar strain, male 5 weeks old) (10 mice per group) 3 hours before the injection of the inflammation agent. Note that no sample was applied to the control group. Next, 0.1 mL of 1% carrageenin (λ Carrageenin, Minsei Rikagaku Co.) solution was injected subcutaneously into the right hind paw to cause inflammation.
Immediately after the inflammation occurred, the volume of the foot was measured with a volume measuring device (manufactured by Ugo Basile). Then, measurement was performed 30 minutes and 4 hours after the initiation of flame, and the edema rate and the inhibition rate were calculated by the following formulas.

Edema rate E (%) = {(Vt−Vo) / Vo} × 100
Vt: foot volume t hours after carrageenin injection
Vo: Foot volume immediately after carrageenin injection Edema suppression rate I (%) = {(Ec−Et) / Ec} × 100
Et: edema rate at time t after sample application group Ec: edema rate at time t after control group
Analgesic effect <Method for evaluating pain suppression test>
The pain threshold was measured with an analgesy meter on the right footpad of a rat (Wistar strain, male 5 weeks old) (10 mice per group), and then the specimen was attached to the right footpad. Note that no sample was applied to the control group. The specimen was removed 4 hours after application, and 0.1 mL of 10% brewer's yeast suspension was injected subcutaneously into the right foot. The pain threshold of the right footpad was measured 30 minutes and 4 hours after the brewer's yeast injection, and the pain threshold rate was calculated from the pain threshold before the specimen was applied.

Pain threshold ratio = (pain threshold after brewer's yeast treatment / pain threshold before brewer's yeast treatment) × 100
Pain threshold ratio increase rate (%) = (average pain threshold ratio of each sample administration group−average pain threshold ratio of control group)
/ Average pain threshold ratio of control group × 100
Skin irritation test Male rabbits were subjected to the test. Prior to sample administration, rabbits with good health were selected, and after hair removal with a clipper on the back, 10 animals were selected for use.
The sample was cut to a size of 2.5 × 2.5 cm and attached to the rabbit hair removal back, and the specimen was removed after 24 hours.
The skin reaction was observed 24 hours after removing the specimen. Judgment was made according to the criteria shown below, and an average value was calculated. It was judged that the skin irritation was low when the average skin irritation score was 4.0 or more.
Criterion: Rating 5 No erythema
4 Very weak erythema
3 Clear erythema
2 Medium to strong erythema
1 Extremely strong erythema

Claims (4)

A hydrous anti-inflammatory analgesic patch for external use containing glycolic salicylate and / or methyl salicylate and lidocaine. The hydrated external anti-inflammatory analgesic patch according to claim 1, further comprising menthol and / or a blood flow promoter. The hydrous external anti-inflammatory analgesic patch according to claim 1 or 2, further comprising 0.1 to 5% by mass of an oily compound having a melting point of 40 ° C or lower and / or glycol. The hydrous external anti-inflammatory analgesic patch according to claims 1 to 3, comprising a crosslinked polyacrylic acid and / or a salt thereof as a plaster base.