TW200538087A - Anti-inflammatory and analgesic plaster - Google Patents

Abstract

The present invention provides an anti-inflammatory and analgesic plaster with excellent transdermal absorption and low irritation to skin. The plaster constituted by rubber-based adhesive is characterized in that the medicine layer therein contains diclofenac sodium, an organic acid which is solid at room temperature, and crotamiton. More specifically, the anti-inflammatory and analgesic plaster constituted by rubber-based adhesive, wherein the medicin layer contains diclofenac sodium, an organic acid which is solid at room temperature and crotamiton, is obtained by mixing and dissolving the organic acid and diclofenac sodium in crotamiton, followed by kneading the resulting solution with the rubber-based adhesive.

Description

‘200538087 IX. Description of the invention: [Technical field to which the invention belongs] The present invention relates to a percutaneous absorption patch containing an anti-inflammatory and analgesic agent, which has excellent stability and percutaneous absorption, and has less irritation to the skin. Specifically, the present invention relates to an anti-inflammatory and analgesic patch composed of a rubber-based adhesive which is characterized by containing diphenanthrene sodium, organic acid which is solid at room temperature, and clomiton. [Previous technology] ^ Sodium digassing (chemical name: 2-[(2, 6-dichlorophenyl) amino] sodium phenylacetate) was developed by Saliman et al. Of Ciba-Geigy, Switzerland in 1965. 7 Non-steroidal anti-inflammatory agent issued, it has a medicinal effect on chronic rheumatoid arthritis, deformable arthritis, or analgesia, antipyretics, etc. when taken orally, and its 0.1% eye drops are suitable for preventing inflammation after surgery. use. On the other hand, recent research has shown that the topical 1% gel is used for the treatment of deformed joints or muscle pain. The dosage, when taken orally, is based on sodium diclofenac, 75-1000 mg per day. Although diclofenac sodium is an excellent non-steroidal anti-inflammatory and analgesic, there are problems with side effects such as gastrointestinal disorders when administered orally. In recent years, various topical applications of diclofenac sodium have been developed in recent years. ^. Recently: Japan has also approved tapes containing sodium bifenfenate as medicine; Oral, diclofenac sodium-containing cataplasms, diclofenac diethyl salt-containing cataplasms, and patches are also available abroad. Female However, diclofenac is almost insoluble in ethers and relatively soluble in water. Therefore, the transdermal absorption is insufficient, and various improvement methods have been introduced7. 200538087 For example, containing right 雔 # μ · accumulated in soft support ^ separation and pressure of organic acids ㈣ 收 收 收 收 收 性 ^ ^ ^ ^ diclofenac solubility and percutaneous absorption η " < 4 Fire Analgesic Patch (for anti-inflammatory drugs ^, contains high non-steroidal properties, and & so, *, B-g subclasses dissolve diclofenac in base ingredients ", ^ also high Topical agent (refer to Patent Document 2); contains trowel · 夂 ， ·, clomitone and 2-ethylheptanoic acid, nonanoic acid, octanoic acid, and carbon atoms such as I and linoleic acid are 6 /醅 Α @ w 王 18 and the liquid fat in suspension μ ^ Characteristic of diclofenac-containing dressings at noon reading (refer to the patent by dispersing diclofenac sodium, osmium in the paste taken from the patch) by ? Κ polyacrylic acid ester, φ gold less selected 摞 1 glycerol vinegar or clomiton medium oils, (ui) fatty acids that are liquid at normal temperature, (iv) f affinity surfactant and (v) Diclofenac sodium-containing patch solution containing sodium diclofenac containing water as a characteristic (see patent document d drug, clomitone, rubber adhesive, flowing stone sacrifice and support Body composition 'good-to-use patch (refer to Patent Document 5); drug-releasing property composed of anti-inflammatory analgesic, clomiton, and phenethyl__isoprene_benzene block copolymer Anti-inflammatory and analgesic dressing with excellent and persistent properties (Tukao Patent Document 6); diclofenac sodium percutaneously composed of an adhesive paste containing diphenanthrene sodium, organic acids, succinate, and polyhydric alcohol fatty acid vinegar Oil-based analgesic and anti-inflammatory local action type patch with high absorption (refer to Patent Document 7), etc. In addition, there are also those containing sodium bischlorate and organic acid (weight ratio of 1 ·· 0.1 to 1: 5 · 0) Drug storage layer, Diclofenac sodium diffusion control film and a lipophilic adhesive layer that can be applied to the skin, which are characterized by a systemic injection of 317002 6 200538087 and the application of the patch, among which Used are acids, linolenic acid, isostearic acid, myristic acid, linoleic acid, and ethanol (refer to patent document s). Γ 4, citric acid, herbicide development, but transdermal absorption Sexually pleasing and less irritating to each other and the skin, save 1 character over time Both safety and stability are excellent. "Effective has not been fully developed." The "secret phase agent" has so far been patent documents: Lu patent document 1: Japanese BS BS 6bu. 426 patent document 2. Japanese Patent Laid-Open No. 62-181 Patent Document No. 226 3: Japanese Patent Publication No. 7-89853 Patent Document 4 · Japanese Patent Publication No. 6-21 9940 Patent Document 5: Japanese Patent Application No. 9-291 028 Patent Document 6: Japanese Patent Application No. 4-321624 Patent Document 7: Japanese Patent Application Laid-Open No. 2002-338462 • Patent Document 8 · Japanese Patent Application No. 1 322595 [Summary of the Invention] The object of the present invention is to provide a skin with excellent percutaneous absorption and stability, and low irritation to the skin. Anti-inflammatory analgesic dressing. In addition, it is to provide a diclofenac sodium external preparation which does not cause crystallization of active ingredients under long-term storage, and has excellent storage stability. Method _ The researcher of the present invention researches and develops with excellent effectiveness and safety in addition to 317002 7 200538087 == studies, and found that when solid organic acids are used, when using solid organic acids, the formulation's experience = nature Defective, the precipitation of organic acids has been prepared. Therefore, an improvement method for direct prevention is sought. First, the results of a review of various solvents found that clomitone has excellent precipitation prevention effects. More = less than found that the preparation of the present invention compared with the previous use (clonomiton + multiple = the previous technology 'can significantly reduce the irritation to the skin, and the fentanyl and organic acids no longer crystallize in the preparation The teacher found that the base composition of sodium fenatine with high transdermal absorption and its manufacturing method. Also, "the present invention is related to the wide range of anti-inflammatory armor pain patches made of rubber-based adhesives" with a drug layer. An anti-inflammatory and analgesic patch containing diclofenac sodium, an organic acid that is solid at room temperature, and clomiton. It is specifically about mixing and dissolving clomiton in solid form at room temperature. There are _ and diphenanthrene sodium, and the solution layer and the rubber-based adhesive are kneaded together. The agent layer contains diclofenac sodium, an organic acid that is solid at room temperature, and miromitone. An anti-inflammatory and analgesic patch composed of an adhesive. In addition, the present invention also relates to mixing and dissolving an organic acid and amphoteric sodium which are solid at room temperature in clomitone, and then mixing the solution with a rubber Adhesive is kneaded to form diphenfenac in the drug layer A method for producing an anti-inflammatory and analgesic patch composed of a solid organic acid and clomiton-based rubber-based adhesive at room temperature. The anti-inflammatory and analgesic patch of the present invention comprises a support and a drug-containing layer It is composed of an adhesive layer and a release film. The release film is peeled off during use, and the adhesive layer containing the adhesive layer < adhesive layer is applied to the skin. 317002 200538087 I The adhesive layer of the patch of the present invention contains at least diclofenac Sodium, Croweton, organic acids that are solid at room temperature, and rubber-based adhesives. The adhesive layer can be formed as a single layer by mixing the above components, or it can be composed of a rubber-based adhesive and a drug-containing drug layer. In this Miaoming, the so-called solid state among organic acids that are solid at temperature refers to those that are solid at room temperature. Specifically, the organic acids that are solid at room temperature in the present invention refer to Organic acids with a melting point above room temperature, usually a melting point above 30 r. In the present invention, the preferred types of organic acids that are solid at room temperature are, for example, citric acid, tartaric acid, lactic acid, and ethanol. Acid, succinic acid, maleic acid One or two or more carboxylic acids are selected from the group consisting of fumaric acid, malic acid, etc. ^ In the invention, the preferred organic acid type that is solid at room temperature is, for example, selected from citric acid, tartaric acid, One or two or more types of organic carboxylic acids which are solid at room temperature in the group consisting of lactic acid, glycolic acid, and malic acid. More preferably, the types of organic acids which are solid at temperature are selected from citric acid, and One or more of the tartaric acid and malic acid groups are organic hydroxycarboxylic acids that are solid at room temperature. Specific examples of the preferred organic hydroxy acid that is solid at room temperature are citric acid, Tartaric acid, etc. In the present invention, the amount of organic acid that is solid at room temperature may be used as long as it can improve the transdermal absorption of diphenanthrene sodium. The possibility of crystallization is increased, and a large amount of solvent is required. The preferred blending amount is based on 1 part by weight of bisfenfen sodium as an active ingredient, using 0.01 to 10 parts by weight, 0.1 to 5 parts by weight, or 0.1 to 1 part by weight, more preferably 〇 3 to] parts by weight. In addition, for the entire adhesive layer in the 317002 9 200538087 patch of the present invention, the blending ratio is 0.05 to 10% by weight, preferably 0. 5% by weight, or 2% by weight. In April this year, to prevent crystallization of organic acids that were solid at room temperature, the solvent system used was a solvent that could almost completely dissolve diphenanthrene sodium and organic acids at room temperature. Examples of the solvent include methyl group, clomitone, methanol, and the like. In consideration of the mutual solubility between the solvent and the rubber-based adhesive in the patch of the present invention, the stability of the adhesive layer, etc., the solvent is preferably N-methylrotaxone or clomiton. The formulation of a solvent as described above prevents the precipitation of crystals of organic acids. However, the present invention has found that the use of clomitone is optimal from the viewpoint of skin irritation (see Comparative Example 2 described later). Regarding the precipitation of the succinic acid + 〇 acid in the present invention, it is sufficient to use 'as long as it can prevent organics without restrictions'-generally for the entire adhesive layer ^ to 20% by mass, preferably 2 to 10% by mass, It is particularly preferable to use about 2 to 8% by mass. The rubber-based adhesive of the adhesive layer in the patch of the present invention is a non-aqueous composition composed of a thinner or a two-component rubber, which is mainly composed of non-aqueous ^ anhydrous = two-component composition containing natural and / or synthetic silk, And sticking Ou Zhi: Yue Yue and softener 'different according to purpose' can add other additives. : Invented the rubber in the adhesive layer of the patch = can be exemplified by the choice of self-polymerized polyisocyanate, polyisobutyl roast, polybutylene. 'Cai'-one or more of the group consisting of butadiene-stupid ethylene block copolymers, styrene-vinyl pentoxide + ethylene roasted block copolymers, styrene-butadiene, stupid ethylene rubber Among them, 317002 10 200538087 is preferred. The present ethylene-isoprene-stupid ethylene block copolymer, polyisobutylene and the like. The proportion of the natural and / or synthetic rubber in the entire rubber-adhesive layer is 10 to 40% by mass, and about 20 to 40% by mass is preferred. The nature of the rubber-based adhesive used in the adhesive layer of the & patch application is not limited as long as it is a general user: it is widely used, for example, poly-resin, rosin-cool Resin, hydrogenated rosin II: Second purpose: and hydrocarbon resin, hope resin, petroleum resin, etc. / "The ratio of the raw resin in the rubber-based adhesive composition is 10 to 40% by mass. It is used in the rubber-based adhesive in the adhesive layer of the invention patch ==== # It can be used by the public, and there is no particular limitation, it can make /: two: m liquid polyisobutylene, animal and vegetable oil, etc. The ratio of the softener in the entire rubber layer is 30 to 70% by mass. In the adhesive layer of the inventive patch, various additives can be blended in fashion. Examples of the additives include drugs, absorption enhancers, colonizers, demulsifiers, ultraviolet absorbers, and fragrances. , Pigments, etc .: The drug refers to the addition of sodium diphenfenate so that its therapeutic multiplication can be expected, such as capsicum ingredients (capsaicin, etc.), vanillyl nonanoate, etc.

: Cold sensation agents such as senanol, essential oil ingredients, others (plant extracts, tocopherol acetate, etc.). X The above-mentioned absorption accelerators such as oleic acid can be exemplified by aliphatic alcohol fatty acids such as oleyl alcohol; fatty acid metal salts such as sodium stearate; fatty acid can be exemplified by the above-mentioned fillers such as silicic anhydride, aluminum silicate, etc. η 317002 * 200538087 The support of the patch of the present invention can use polyethylene, polypropylene, polybutadiene, ethylene-vinyl acetate copolymer, vinyl acetate-vinyl chloride copolymer, polyvinyl chloride, polyamide, poly Films, flakes, sheet-like porous ", sheet-like bodies, woven fabrics, woven fabrics, non-woven fabrics, paper, or the above-mentioned laminates of synthetic resins such as cool, Shilong, cellulose derivatives, and polyurea. Among them: in terms of ensuring the applicability of money to the skin, weaving cloth # In addition, those having self-supporting properties are more preferred in terms of the operation point of the patch. An adhesive layer having a thickness of 10 to 500 #m can be coated or stretched on the support, and the thickness is preferably 30 to 300 // m. For the release film of the patch of the present invention, a sheet-like material composed of% ester, polypropylene baking, polyethylene, polystyrene, polyisocyanate, or its laminated body is subjected to a mold release treatment (Shi Shixi treatment specialty) Is better. The manufacturing method of the patch of the present invention can be manufactured according to the general manufacturing method of a non-aqueous or anhydrous tincture patch. Among the preferred manufacturing methods, the method is to mix and dissolve them in Krypton separately at room temperature. The solid organic acid and sodium diclofenac are mixed, and the solution is mixed with the prepared rubber-based adhesive = to make a composition for the adhesive layer, and then spread on the f support by coating and other methods. Then, it produced by attaching a release film. When necessary, it is cut to a suitable size to become a product. It can also be produced by mixing and dissolving organic acids and diclofenac with clomiton. According to the present invention, it is found that the mismatched diclofenac sodium and the solid at room temperature are 317002 12 200538087 organic acid in rubber-based adhesives, and provide a patch with excellent percutaneous absorption of diclofenac sodium as an active ingredient. The formulation can also be used as a patch for diclofenac sodium with excellent percutaneous absorption, stability over time, and less irritation to the skin. Therefore, the patch of the present invention can provide the active ingredient of diphenanthrene sodium with excellent transdermal absorption, excellent stability over time, and less anti-inflammatory and analgesic effect on the skin. Practical patch with excellent safety, stability and stability. 'X' The patch of the present invention can be prepared by a simple and stable method by using a clomiton solution containing an active ingredient and an absorption promoter and a rubber-based adhesive. [Embodiment] The present invention is specifically described below by way of examples, but the present invention is not limited directly. / 、 Example 1 φ Permeability Test Example 1 Solubility test The researcher of Mao Ming took citric acid as an example as a willow at room temperature: to explore various solvents for sodium amphoteric acid and room temperature. Solid = solubility of Θ organic acid. The results are shown in Table 丨. , 317002 13 200538087 Table diisopropyl adipate g diethyl malonate g oleic acid polyoxyethylene hardened castor seed oil

N-fluorenyl-2-D ratio slightly burned g with benzyl alcohol cromidone diethyl ester ^ diisopropyl diacetate isopropyl myristate dilute oil base — _ polyethylene glycol monolaurate Alcohol --- --- Distilled water In the above, a solvent having a base may form cool with diclofenac during storage. Therefore, it is not suitable as a solvent for the preparation of the present invention, and therefore is not in the selection range. As a result, 耻, s & 疋 N methyl-2-pyrrolidone and clomidol were selected as the best solvents. Example 2 Manufacture of the patch (1) of the present invention A patch 317002 200538087 (1) of the present invention composed of the composition shown below was produced according to the following method. First of all, 1 part of diclofenac sodium is dissolved in 3 parts of clomiton with heating, and 0.4 part of citric acid is heated and dissolved in 1 part of clomiton. The two solutions are combined into one solution. Glycerin fatty acid ester (product of Nikko Pharmaceutical Co., Ltd.) was added to the above solution and mixed to form a homogeneous solution. The styrene-isoprene-styrene block copolymer (sis), polybutylene difluoride, liquid stone sacrificial acid, and alicyclic petroleum resin were mixed, and the mixture was heated and refined. The clomiton solution prepared above is mixed therein, and the mixture is uniformly mixed to form an adhesive layer composition. 2. Apply and spread the adhesive composition obtained above on the support, cut it into an appropriate size to obtain a patch (丨). IΜΛ_ Dimethanol Sodium Cromiton Cromiton Citrate Glycerol Fatty Acid Ethylene Diene-Isoamidine (SIS) Polyisobutylene (PIB) Liquid Stone Worm Cycloaliphatic Petroleum Resin Comparative Example 1 Comparative Sticker The dressing (1) was prepared according to the method described in Example 2 and consisted of ~ points consisting of the following ancestors: 1 3 0 · 1 2 14 14 32. 32 ·

Ethylene-styrene block copolymer 4 Dissolve Dissolve Dissolve Dissolve 317002 15 200538087 Comparative patch (l). Ingredients Diclofenac Sodium 1 Dissolve Cromiton 4 Dissolve Glycerin Fatty Acid 2 Dissolve Styrene-Isoprene-Stupid Ethylene Block Copolymer (SIS) 14 Polyisobutylene (PIB) 14 Liquid Paraffin 32.5 Fat Ring family petroleum resin 32.5 Example 3 Production of the patch (2) of the present invention According to the method described in Example 2, the patch (2) of the present invention having the following composition was produced. Composition_ Parts Dissolved Dissolved Disodium Diphenanthrene Sodium 1 Cromiton 3 Citric Acid 0.4 Cromiton 1 Styrene-Isoprene-Styrene Block Copolymer (SIS) 14 Polyisobutylene (PIB) 14 Liquid paraffin 33 .; Month privately-made Yasawa petroleum resin 33 .: 317002 • 200538087 Example 4 Production of the patch (3) of the present invention According to the method described in Example 2, the present invention having the following composition was produced Patch (3). Composition ^-Diclofenac sodium 1 Dissolve clomiton 3 Dissolve tartaric acid 0.4 Dissolve clomiton 1 Dissolve glycerin fatty acid Scope 2 Styrene-isoprene-styrene block copolymer (SIS) 14 Polyisobutylene (PIB) 14 Liquid Stone 32. 3 Alicyclic Petroleum Resin 32.3 According to the method described in Example 2, a comparative patch (2) having the following composition was produced. Comparative Example Composition ___ diclofenac sodium N-fluorenyl-2-pyrrolidone citric acid N-methyl-2-D bisalone

Dissolve 2 Dissolve the dissolve and dissolve 3】 7〇〇2] 7 • 200538087 Styrene-isoprene-styrene-styrene block copolymer (SIS) 14 Polyisobutylene (PIB) 14 Liquid paraffin 32.3 Alicyclic Petroleum resin 32.3 Example 5 Production of the patch (4) of the present invention According to the method described in Example 2, a patch (4) of the present invention was prepared according to the present invention. Composition ___ One serving of diclofenac sodium 1 dissolve clomiton 3 dissolve tartaric acid 0. 28 dissolve clomiton 1 dissolve glycerin fatty acid ester 2 styrene-isoprene-benzyl ethylene block copolymer (SIS) 14 poly Isobutylene (PIB) 14 Liquid paraffin 32. 36 Alicyclic petroleum resin 32. 36 Example 6 Production of the patch (5) of the present invention is made according to the present invention with the following composition: the method described in Example 2 , Ming's patch (5). 317002 18 200538087

Composition • ~------------------- Diclofenac Sodium Cromiton Crotamiton Citrate Glycerin fatty acid ester Phenyl-isoprene-styrene block Copolymer (SIS) Polyisobutylene (PIB) Liquid paraffin hydrogenated rosin ester resin Example 7 parts 3

1 2 Dissolve Dissolve Dissolve 141432 · 3 32 · 3 Examination Example 2 Skin penetration test in test tube (in vitro) Test method: Take the skin of the body part of the nude mouse and carefully remove the fat from the dermis side. The dermal side constitutes a receptor groove, and a 37 ° C circulating water container is installed in the peripheral part. A patch was applied to the stratum corneum side, and a phosphate buffer solution was passed through the receptor tank at a rate of 1 mL / hr, and the buffer solution was collected every 4 hours. From this sample, the drug concentration was quantified by HPLC, and the permeation rate (Flux) at each collection time was calculated according to the following formula. Transmission rate = [Concentration of sample (# g / mL) x 4 hours flow rate (mL)] / Area of application of the preparation (cm2) x 4 hours Test conditions: Animals and skin: Nude mice (female, 8 weeks old) Part of the skin (to the dermis) of the shaved body side 19 317002 ^ 200538087. Number of cases: 4

Permeable container ·· Longitudinal flow container preparation ·· 10 mm diameter round moon bean solution · 50 m MU saccharic acid buffer solution, p η 7.4 Test temperature: 37 ° C A summary of the composition of the patch and the comparative patch is shown in Table 2. Table 2 Example 1 Comparative Example Example 2 Example 3 Diclofenac Sodium 0.000 cromiton 〇 〇 〇 〇 〇 〇 φ 益 »〇 〇 no tartaric acid no without no glycerin fatty acid ester. No results are shown in Fig. 1. In the figure, the horizontal axis indicates time, and the vertical axis indicates transmission speed (// g / cm2 / hr). The black square () shows the patch (丨) of the present invention (Example 2), the black diamond (♦) shows the patch (2) (Example 3) of the present invention, and the black circle (#) shows the present invention The patch (3) (Example 4) and the black triangle (▲) show the patch (1) for comparison (Comparative Example 丨). From the results, it is found that the present invention is extremely excellent in the transdermal absorbability of a patch prepared by preparing an organic acid which is solid at room temperature. Implementation Example 8 Implementation Example 3 317002 -200538087 Stability Test The implementation examples 4 and 5 will be used to maintain stability. That is, Baoguang # 's patch was evaluated for its test sample according to the following method. The Ιρργγ soil i agent was quantified at 25 ° C, 4 ° C, and 1 month later using the oral HPLC method to calculate the content after 1 month. Once fz Chen degrees, take the pre-saved content as the post, as shown in Table 3.

Lane to initial ratio (%). The "° Fruit reduction" The patch of Example 4 containing a large amount of tartaric acid has superior storage stability. Example 9 Experimental example 4 Safety test The patches of Example 2 and Comparative Example 2 were respectively applied to the inner sides of the upper wrists of healthy normal adult males (3 persons) and peeled off after 24 hours. The skin condition was observed 1 hour after peeling, and scored according to the following criteria. Also, the ratio of the number of persons who had any skin reaction was taken as the positive rate (%). + + Erythema + edema, rash + obvious erythema appears ± slight erythema appears 21 317002 200538087-no response The results are shown in Table 4 below.

+ + Safety test results of the patch of the present invention ^

1 Total number of positive rates throughout Example 2 Comparative Example 2 0 10 τ0

According to the results of the application of the patch, the skin shows that the present invention using clomitone has little irritation. Industrial feasibility The invention can be applied to a transdermal absorbent patch containing anti-inflammatory analgesics, stability and transdermal absorption, and less irritation to the skin, which is extremely useful in the industry. [Schematic description] 1 jly 1 The results of the percutaneous absorption test of the patch of the present invention and the patch of the comparative example. 22 317002

Claims (1)

'200538087 10. Scope of patent application: 1-An anti-inflammatory and analgesic patch, an anti-inflammatory and analgesic patch composed of rubber-based adhesives, which is characterized in that the pharmaceutical layer contains diphthyl sodium (Jhclofenac s〇dlum) ), Organic acids and crotamiton that are solid at room temperature. 2. If = please apply the anti-inflammatory and analgesic patch according to item i of the patent, which is a mixture of organic acid and sodium diclofenac dissolved in clomitone at room temperature: solid solution, and then this solution and rubber adhesive Produced by mixing. 3 .: Apply for the anti-inflammatory and analgesic patch of item 1 or item 2 of the patent scope, and the rubber adhesive is selected from the group consisting of polyisoprene, polyisobutylene, succinate, and acetoin-butyl One or two or more of two groups consisting of stilbene-styrene ethyl benzene block copolymer, styrene-styrene block copolymer, and natural rubber. Γ Γ Patent is the anti-inflammatory and analgesic, depot of any one of items 1 to 3, wherein the organic acid which is solid at room temperature is an organic hydroxy acid at room temperature. Post = Special :: Wai :: Any of the items from item 4 to item 4 of the anti-inflammatory analgesic sand /, medium, and organic acids that are solid at temperature are selected from lemon: 石: stone acid, lactic acid, glycolic acid, One or two or more members of the group consisting of succinic acid, maleic acid, and fumaric acid. Zhongshen: The anti-inflammatory and analgesic patch of Li Target Wei No. 4 or No. 5, whose organic acid is tartaric acid which is solid at 5 to temperature. ^ 17002