JP6654682B2 - Antipyretic analgesics - Google Patents

Description

  The present invention relates to an antipyretic analgesic drug, and more specifically, contains ibuprofen, allyl isopropylacetyl urea and caffeine as active pharmaceutical ingredients, and mixes these active pharmaceutical ingredients in a specific ratio to form a container. The present invention relates to an antipyretic analgesic drug, which is hermetically packaged with an antipyretic analgesic preparation which suppresses the generation of cloudiness and odor.

  The antipyretic analgesic containing ibuprofen, allylisopropylacetyl urea and anhydrous caffeine was released as an Ibu A tablet (manufactured by SSP) on September 1, 1990. It is widely used as an antipyretic analgesic containing ibuprofen, which overcomes the weakness of somewhat weak and works quickly and effectively. The Ibu A tablet contains 150 mg, 60 mg and 80 mg of ibuprofen, allyl isopropyl acetyl urea and anhydrous caffeine as active pharmaceutical ingredients in two tablets, respectively, and the same amount of ibuprofen and allyl isopropyl as the Ibu A tablet. Many antipyretic analgesics containing acetyl urea and anhydrous caffeine have been sold in Japan as over-the-counter drugs, and further contain antacids such as magnesium oxide, magnesium metasilicate aluminate, and dried aluminum hydroxide gel. Including antipyretic analgesics, there are over 30 antipyretic analgesics.

  By the way, it is known that ibuprofen has a relatively low melting point of 75 to 77 ° C. and is sublimable, so that recrystallization is formed on the inner wall of a closed container such as a glass bottle, and clouding (whisker) occurs. I have. It is also known that caffeine is sublimable and therefore fogged in the storage container, and that caffeine grows as needle-like crystals on the surface of the preparation or in the storage container. When other active pharmaceutical ingredients or excipients are mixed with these sublimable active pharmaceutical ingredients, the melting point of the active pharmaceutical ingredients is lowered, so that it is known that the active pharmaceutical ingredients are more easily sublimated than when the active pharmaceutical ingredients are blended alone. Have been.

  In addition, solid preparations such as the above-mentioned antipyretic analgesics are usually stored in sealed containers such as PTP packages, plastic bottles, glass bottles, and the like, and are sold in a package that ensures stability. However, in the case of a solid preparation containing an active pharmaceutical ingredient that tends to sublimate, fogging may occur inside a sealed container such as a glass bottle or a PTP container during storage of the product, and the active pharmaceutical ingredient may be opened when the sealed container is opened. It is also known to have an unpleasant odor from the origin, which causes a problem of a decrease in commercial value. In particular, over-the-counter medicines that are stocked and sold in stores may be exposed to various harsh environments depending on the operating conditions of air conditioning in the store, sunlight irradiation, seasonal and morning and evening temperature and humidity fluctuations, etc. External deterioration may occur outside.

  As a method for preventing whisker of ibuprofen, which is an active pharmaceutical ingredient which is easily sublimated, a method of coating sugar-coated ibuprofen-containing tablets with an amount of 5 to 60% of uncoated tablets (Patent Literature 1), and a method of preventing ibuprofen-containing uncoated tablets There has been reported a method of coating a plain tablet with a saccharide, such as a method of forming a saccharide layer between the outer tablet and the outer film coating (Patent Document 2). In addition, a method of directly performing film coating on an ibuprofen-containing uncoated tablet has also been reported. Examples of the composition of the film coating solution include propylene glycol, glycerin or copolyvidone, a water-soluble polymer base (Patent Document 3), and a water-soluble polymer. Polymers and triacetin (Patent Literature 4), polyvinyl alcohol and silicic acid (Patent Literature 5), polyvinyl alcohol, paraffin, carnauba wax, and a specific amount of titanium oxide (Patent Literature 6) are disclosed.

  Further, as a method for preventing whisker of ibuprofen, substances such as polyvinylpyrrolidone, magnesium oxide, sodium hydrogencarbonate (Patent Document 7), and desiccants such as silica gel and calcium chloride (Patent Document 7) A method has been reported in which reference 8) is coexistent with the same preparation and stored in a closed container. Also, a method has been reported in which an acid selected from citric acid, tartaric acid, malic acid, and succinic acid is added in powder form to ibuprofen-containing powder and mixed (Patent Document 9).

  On the other hand, as a method for preventing whisker of caffeine, a specific substance is added to caffeine, for example, hydrated silicon dioxide (Patent Document 10), antacid and hydrated silicon dioxide (Patent Document 11), polyvinylpyrrolidone ( Patent Document 12) and a method for producing granules and tablets by adding and mixing glycyrrhizic acids (Patent Document 13) and the like to caffeine are disclosed. In addition, there has been reported a method in which a high molecular weight polymer is added to caffeine and kneading and extrusion treatment (Patent Document 14) or extrusion treatment with a multi-screw extruder (Patent Document 15) is performed.

  Further, as a method for preventing whisker of caffeine, there is a method of performing wet granulation by controlling the water content of caffeine under the condition of equilibrium relative humidity of 75% or less (Patent Document 16), or granulating a drug other than caffeine, A method of adding caffeine as a powder to this granular drug has been reported (Patent Document 17).

  In addition, as a method for preventing fogging of a preparation containing both ibuprofen and caffeine with whiskers, a method of coating carboxymethylcellulose on uncoated tablets containing these components, or adding carboxymethylcellulose to ibuprofen and caffeine is used. There has been reported a method of granulating by using the method (Patent Document 18).

  However, when these methods are applied to antipyretic analgesic preparations marketed as over-the-counter medicines containing ibuprofen, allylisopropylacetylurea and anhydrous caffeine, any of these methods are insufficiently effective or severe. It did not show any effect under the environment. In addition, the above-described method has a problem that it is difficult to adopt the method because of its complicated manufacturing process and high cost.

JP 2002-179559 A JP-A-2002-241275 JP 2003-183181 A JP 2007-31281 A JP 2009-7295A JP 2010-189378 A JP-A-8-193027 JP-A-8-333247 JP 2011-231105 A JP-A-5-339158 JP-A-8-301664 JP-A-2000-247870 JP-A-8-310953 JP-A-2004-26750 WO95 / 13794 JP 2011-207877 A JP-A-4-5234 JP 2005-162619 A

  Therefore, an object of the present invention is to provide a technique capable of suppressing the occurrence of whiskers and the generation of unpleasant odor associated therewith in an antipyretic analgesic preparation containing ibuprofen, allylisopropylacetylurea and caffeine more simply than the prior art. It is to provide.

  The present inventors have studied the formulation of an antipyretic analgesic formulation containing ibuprofen, allylisopropylacetylurea and caffeine in order to solve the above-mentioned problems. The present inventors have found that only by increasing the ratio of ibuprofen in the mass ratio of the components, it is possible to reduce fogging when stored in a closed container and unpleasant odor at the time of opening, and completed the present invention.

  That is, the present invention is an antipyretic analgesic drug, which is obtained by sealingly packaging an antipyretic analgesic formulation containing ibuprofen, allylisopropylacetyl urea and caffeine at a mass ratio of 10: 3: 4, respectively.

  Further, the present invention is the above antipyretic analgesic, wherein the antipyretic analgesic further contains one or more selected from antacids, vitamins, and crude drugs.

  ADVANTAGE OF THE INVENTION According to this invention, when an antipyretic analgesic preparation containing ibuprofen, allyl isopropyl acetyl urea, and caffeine is stored in a closed container, it can suppress generation | occurrence | production of cloudiness and generation | occurrence | production of an unpleasant odor. Therefore, the commercial value of this antipyretic analgesic drug can be increased.

  The antipyretic analgesic preparation used in the antipyretic analgesic drug of the present invention contains ibuprofen, allylisopropylacetyl urea and caffeine in a unit preparation at a ratio of 10: 3: 4 (hereinafter referred to as “the present preparation”). ), If necessary, may contain other active pharmaceutical ingredients and formulation additives.

The chemical name of ibuprofen contained in the preparation of the present invention is (2RS) -2- [4- (2-methylpropyl) phenyl] propanoic acid (English name: (2RS) -2- [4- (2-methylpropyl)). phenyl] propanoic acid), a molecular formula of C ₁₃ H ₁₈ O ₂ , a molecular weight of 206.28, and a melting point of 75 to 77 ° C., a phenylpropionic acid-based nonsteroidal anti-inflammatory drug, and prostaglandin. It exerts anti-inflammatory, analgesic and antipyretic effects by inhibiting gin biosynthesis.

The chemical name of allylisopropylacetylurea contained in the preparation of the present invention is 2-isopropyl-4-pentenoylurea (English name: 2-Isopropyl-4-pentenoylurea), and the molecular formula is C ₉ H ₁₆ N. ₂ O ₂ , its molecular weight is 184.24 and its melting point is 193-198 ° C., a mild sedative, which relieves pain by eliminating pain reactions such as painful anxiety, discomfort and fear. In addition, it enhances the action of analgesics.

Further, as the caffeine contained in the preparation of the present invention, anhydrous caffeine, caffeine hydrate or a mixture thereof can be used. Among them, anhydrous caffeine has a chemical name of 1,3,7-trimethyl-1H-purine-2,6 (3H, 7H) -dione (English name: 1,3,7-Trimethyl-1H-purine-2, 6 (3H, 7H) is -Dione), its molecular formula _{is C 8 H 10 N 4 O 2} , molecular weight, 194.19, melting point is 235-238 ° C.. Caffeine hydrate has a chemical name of 1,3,7-trimethyl-1H-purine-2,6 (3H, 7H) -dione monohydrate (English name: 1,3,7-Trimethyl-). 1H-purine-2,6 (3H, 7H) -dione monohydrate, whose molecular formula is C ₈ H ₁₀ N ₄ O ₂ .H ₂ O, its molecular weight is 212.21, and melting point is 235 to 238 ° C. (After drying). Both of them have a central nervous system excitatory effect, activate the nerve function, eliminate pain reactions such as discomfort, alleviate pain, and further contract cerebral blood vessels for vascular headache. It shows an analgesic effect.

  As described above, the preparation of the present invention contains ibuprofen, allylisopropylacetylurea and caffeine in a unit preparation at a ratio of ibuprofen: allylisopropylacetylurea: caffeine = 10: 3: 4. Specifically, for example, when 50 mg of ibuprofen is blended in one tablet in the form of a tablet, 15 mg of allylisopropylacetyl urea and 20 mg of caffeine are blended in one tablet. When 75 mg of ibuprofen is blended in one tablet, 22.5 mg of allylisopropylacetyl urea and 30 mg of caffeine are blended in one tablet. Similarly, when 100 mg of ibuprofen is mixed in one tablet, 30 mg of allylisopropylacetylurea and 40 mg of caffeine are mixed, and when 150 mg of ibuprofen is mixed in one tablet, 45 mg of allylisopropylacetylurea and 60 mg of caffeine are mixed. When 200 mg of ibuprofen is blended in one tablet, 60 mg of allylisopropylacetyl urea and 80 mg of caffeine are blended in one tablet.

  In the preparation of the present invention, an antacid may be added, if necessary, in addition to the above-mentioned each pharmaceutical component. Examples of the antacid include aminoacetic acid (glycine), magnesium silicate, synthetic aluminum silicate, synthetic hydrotalcite, magnesium oxide, dihydroxyaluminum aminoacetate (aluminum glycinate), aluminum hydroxide gel, and dry water. Aluminum oxide gel, aluminum hydroxide / magnesium carbonate mixed dry gel, co-precipitated product of aluminum hydroxide / sodium hydrogen carbonate, co-precipitated product of aluminum hydroxide / calcium carbonate / magnesium carbonate, magnesium hydroxide / potassium aluminum sulfate Coprecipitated product, magnesium carbonate, magnesium metasilicate aluminate, magnesium aluminate, magnesium hydroxide alumina, magnesium hydroxide, sodium hydrogen carbonate, precipitated calcium carbonate, anhydrous hydrogen phosphate calcium Um, calcium hydrogen phosphate and the like. These may be added alone or in combination of two or more.

  Although the amount of these antacids varies depending on the type of antacid, it is preferable to use 10 to 5000 mg, more preferably 16 to 4000 mg, for 450 to 600 mg of ibuprofen. More specifically, when aminoacetic acid or a coprecipitated product of aluminum hydroxide and sodium hydrogencarbonate is used as an antacid for 450 mg to 600 mg of ibuprofen, about 30 to 900 mg, magnesium silicate, synthetic silica About 100 to 3000 mg when using aluminum oxide, aluminum hydroxide and magnesium carbonate mixed dry gel, about 133 to 4000 mg when using synthetic hydrotalcite, and about 16 to 500 mg when using magnesium oxide When using dihydroxyaluminum / aminoacetate, coprecipitated product of aluminum hydroxide / calcium carbonate / magnesium carbonate, magnesium metasilicate aluminate, precipitated calcium carbonate or calcium hydrogen phosphate, about 50 to 1500 mg Aluminum When using an aluminum gel or a dry aluminum hydroxide gel, about 33 to 1000 mg of a dry aluminum hydroxide gel is used. When using a coprecipitated product of magnesium hydroxide and aluminum potassium sulfate, about 60 to 1800 mg, magnesium carbonate, When using magnesium aluminate silicate and magnesium aluminate hydroxide, about 66 to 2000 mg, when using magnesium hydroxide and anhydrous calcium hydrogen phosphate, about 40 to 1200 mg, when using sodium hydrogen carbonate, It is preferable to be about 83 to 2500 mg.

In the preparation of the present invention, if necessary, vitamin B ₁ , vitamin B ₂ , vitamin C, hesperidin and derivatives thereof and salts thereof, and ground dragon, licorice, calyx, peonies, buttonpi, valerian, ginger, Crude drugs such as cocks can also be added.

  In producing the preparation of the present invention, in addition to the above-described components, excipients, binders, disintegrants, lubricants and the like that can be generally used in the field of preparation can be used. . The formulation additives that can be incorporated in the formulation of the present invention include, in addition to excipients, binders, disintegrants, and lubricants, various carriers, stabilizing (stabilizing) agents, surfactants, plasticizers, lubricants, Solubilizing agent, reducing agent, buffering agent, sweetener, base, adsorbent, corrigent, suspending agent, antioxidant, brightener, coating agent, skin, wetting agent, wetting control Agents, fillers, defoamers, fresheners, colorants, flavors, fragrances, sugar coatings, tonicity agents, softeners, emulsifiers, thickeners, thickeners, foaming agents, pH adjusters , Diluents, dispersants, disintegration aids, disintegration extenders, fragrances, moisture inhibitors, preservatives, preservatives, solubilizers, dissolution aids, solvents, flow agents, antistatic agents, extenders, humectants, Pharmaceutical additives such as humectants can be mentioned. Examples of such additives include the Japanese Pharmacopoeia 1204 No. 1 (Pharmaceutical Affairs Law), the Pharmaceutical Additives Dictionary 2007 (edited by the Japan Pharmaceutical Excipients Association, Yakuji Nippo) and the Eighth Edition Food Additives Official Standard Product Association).

  Among the above pharmaceutical additives, excipients include, for example, lactose, starch, corn starch, pregelatinized starch, partially pregelatinized starch, crystalline cellulose, low-substituted hydroxypropylcellulose, hydroxypropylcellulose, purified sucrose, sugar alcohols Light anhydrous silicic acid, calcium silicate, titanium oxide, precipitated calcium carbonate and the like. One or two or more of these excipients can be used.

  As the binder, for example, gelatin, gum arabic powder, methylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, hydroxypropylcellulose, hypromellose, polyvinylpyrrolidone, polyvinyl alcohol, polyvinyl alcohol / acrylic acid / methyl methacrylate copolymer, polyvinyl Acrylic acid derivatives such as alcohol / polyethylene glycol / graft copolymer, pullulan, dextrin, carboxymethylcellulose calcium, carboxymethylcellulose sodium, methacrylic acid copolymer, shellac, carboxyvinyl polymer, sodium carboxymethyl starch, carboxymethylethylcellulose, cellulose acetate phthalate, etc. No. One or more of these binders can be used.

  Further, examples of the disintegrant include croscarmellose sodium, crospovidone, cross-linked insolvable polyvinylpyrrolidone, carmellose calcium, sodium carboxymethyl starch, potato starch, corn starch, pregelatinized starch and the like. One or two or more of these disintegrants can be used.

  Furthermore, examples of the lubricant include talc, stearic acid, magnesium stearate, sucrose fatty acid esters, polyethylene glycol and the like. One or more of these lubricants can be used.

  The preparation of the present invention described above is provided as an internal solid preparation such as a tablet, a caplet, a hard capsule, an orally disintegrating tablet, a chewable tablet, a fine granule, a granule, and a dry syrup. Further, a film preparation or sugar coating may be applied as necessary to obtain a coating preparation of the above preparation. These dosage forms include the usual formulation methods (Kyosuke Tsuda and Hisashi Ueno, “Basic Drug Development Lecture XI, Pharmaceutical Manufacturing Method (upper), (lower)”, Jinjinshokan, published in 1971; Yu Nakai Yoshinori, "Pharmaceutical Engineering Handbook", Jinjinshokan, 1983; Yoshinobu Nakai, "Development of Pharmaceuticals, Unit Operation and Machinery of Drugs", Hirokawa Shoten, 1989; Mitsuru Hashida, "Oral Preparations" And "Evaluation and Evaluation of Pharmaceuticals", Pharmaceutical Times Publishing Co., 1995; Mitsuru Hashida, "Prescription Design of Oral Administration Formulations", Pharmaceutical Times Publishing Co., Ltd., 1995). Further, fine particles such as microcapsules, nanocapsules, microspheres, nanospheres, and the like may be used.

  The dosage of the preparation of the present invention is the same as that of the conventional product, and it is usually preferable to limit the dose to three times a day and to take as little as possible on an empty stomach with water or lukewarm water.

  The antipyretic analgesic preparation of the present invention thus obtained can be made into the antipyretic analgesic drug of the present invention by storing it in a sealed container such as a glass bottle, a plastic bottle, PTP packaging, or aluminum heat seal packaging. In this case, the generation of fogging and unpleasant odor can be suppressed.

  Next, the present invention will be described in more detail with reference to Examples and Comparative Examples, but the present invention is not limited thereto.

Example 1
Production of film coated tablets:
(1) 300 g of ibuprofen, 90 g of allylisopropylacetyl urea, 120 g of anhydrous caffeine, 60 g of corn starch, 255 g of crystalline cellulose, 30 g of light anhydrous silicic acid, 150 g of low-substituted hydroxypropylcellulose and 63 g of talc, and a high-speed stirring granulator Then, purified water was added to perform wet granulation. After sieving, after drying in a fluidized bed, the mixture was passed through a 24-mesh sieve, and 12 g of talc was mixed therewith to produce granules for tableting. According to a conventional method, the tablets were compression-molded with a rotary tableting machine so as to be 360 mg per tablet to obtain plain tablets. A film coating agent composed of hypromellose, titanium oxide, macrogol, and water (7: 2.5: 0.5: 90) is sprayed on the uncoated tablet with a ventilation type coating apparatus, and the diameter of the film is approximately 9 mm, and the film is 365 mg / tablet. Invention 1 was obtained as a coated tablet.

(2) 660 g of ibuprofen, 198 g of allylisopropylacetyl urea, 264 g of anhydrous caffeine, 330 g of magnesium oxide and 481.8 g of low-substituted hydroxypropylcellulose were mixed by a high-speed stirring granulator, and purified water was added and kneaded. Next, it was extruded and granulated with a 0.6 mm screen, and then dried with a fluidized bed drier. 1758 g of the dried granules were weighed out, and 165.6 g of crystalline cellulose, 120 g of croscarmellose sodium, 16.2 g of light anhydrous silicic acid, 24 g of talc, and 16.2 g of magnesium stearate were mixed to prepare granules for tableting. According to a conventional method, the tablet was compression-molded with a rotary tableting machine so as to be 350 mg per tablet to obtain an uncoated tablet. A film coating agent composed of hydroxypropylmethylcellulose, titanium oxide, macrogol and water (7: 2.5: 0.5: 90) is sprayed on the uncoated tablet with a ventilation type coating apparatus, and the diameter is about 9 mm, 360 mg / tablet. Inventive product 2 was obtained as a film-coated tablet.

Comparative example 1
A film-coated tablet was obtained in the same manner as in Example 1 (1) except that the used ibuprofen was changed to 225 g, the mass of the uncoated tablet was changed to 335 mg, and the mass of the film-coated tablet was changed to 340 mg. This was designated as Comparative Product 1.

  In the same manner as in Example 1 (2) above, except that the amount of ibuprofen used was changed to 495 g, the amount of the dried granules used was changed to 1608 g, the mass of the uncoated tablet was changed to 325 mg, and the mass of the film-coated tablet was changed to 335 mg. I got This was designated as Comparative Product 2.

  Table 1 shows the compositions of the respective components per film-coated tablet of the invention products 1 and 2 and the comparison products 1 and 2.

Test example 1
Storage test:
The invention products 1 and 2 and the comparison products 1 and 2 were hermetically sealed for each tablet in a PTP package of 10 tablets per sheet, and two sheets were put in a paper box. After heating and blowing them at 40 ° C. for 8 hours, and then blowing them at room temperature (23 ° C.) for 16 hours, this was repeated for 6 months and stored. The cloudiness of the transparent portion of the PTP package after storage was evaluated according to the following evaluation criteria. Table 2 shows the results.

<Evaluation criteria for cloudiness>
(Evaluation) (Content)
-: No fogging is observed
±: Almost no fogging
+: Fogging is observed ++: Strong fogging is observed +++: Extremely fogging is observed

  From these results, it was found that the preparation of the present invention having ibuprofen, allylisopropylacetyl urea and caffeine at a mass ratio of 10: 3: 4, respectively, showed no fogging, whereas the same component had a different ratio (15: 3: 4). 6: 8) It became clear that fogging occurred in the comparative product used.

Test example 2
Odor generation test:
The invention products 1 and 2 and the comparison products 1 and 2 were each placed in a colorless and transparent glass bottle of 50 tablets, sealed, and stored at 50 ° C. for 10 days. The odor immediately after opening the lid of the glass bottle was evaluated according to the following evaluation criteria. Table 3 shows the results.

<Odor evaluation criteria>
(Evaluation) (Content)
-: No unpleasant odor
±: Almost no unpleasant odor
+: There is an unpleasant odor ++: There is a strong unpleasant odor

  As is clear from these results, the formulation of the present invention having ibuprofen, allylisopropylacetyl urea and caffeine at a mass ratio of 10: 3: 4, respectively, has no or almost no unpleasant odor when opened. On the other hand, a comparative product using the same components in different ratios had a strong unpleasant odor upon opening.

Example 2
Production of tablets:
400 g of ibuprofen, 120 g of allylisopropylacetylurea, 160 g of anhydrous caffeine, 160 g of crystalline cellulose, 40 g of light anhydrous silicic acid, 120 g of low-substituted hydroxypropylcellulose and 50 g of talc were weighed, and purified water was added using a high-speed stirring granulator. Then, wet granulation was performed. After sieving, after drying in a fluidized bed, the mixture was passed through a 24-mesh sieve, and 10 g of talc was mixed with the mixture to prepare granules for tableting. Inventive product 3 was obtained by compression molding with a rotary tableting machine so as to obtain 530 mg per tablet according to a conventional method.

Comparative Example 2
Tablets were obtained in the same manner as in Example 2 except that the amount of ibuprofen used was changed to 300 g and the mass per tablet was changed to 480 mg. This was designated as Comparative Product 3.

  Table 4 shows the composition of each component per tablet of Invention Product 3 and Comparative Product 3.

Test example 3
Storage test and odor generation test:
Inventive product 3 and comparative product 3 are each hermetically sealed in a PTP package of 10 tablets per sheet, and two sheets are placed in a paper box and stored in the same manner as in Test Example 1. The same evaluation criteria as in the above storage test The cloudiness was evaluated. Inventive product 3 and comparative product 3 were each sealed in a colorless and transparent glass bottle of 50 tablets, stored in the same manner as in Test Example 2, and evaluated for odor according to the same evaluation criteria as in the above-mentioned odor generation test. Table 5 shows the results.

  From this experiment, it was found that the preparation of the present invention containing ibuprofen, allylisopropylacetyl urea and caffeine at a weight ratio of 10: 3: 4 did not cause any fogging even in PTP packaging, and had almost no unpleasant odor. On the other hand, it was revealed that a comparative product using the same components in different ratios caused strong fogging and a strong unpleasant odor was felt upon opening.

  According to the present invention, in an antipyretic analgesic preparation containing ibuprofen, allyl isopropylacetyl urea and caffeine, by changing the mixing ratio, when stored easily in a sealed container, fogging and unpleasant odor are prevented or reduced. can do.

Therefore, the present invention makes it possible to easily prevent fogging and unpleasant odor and prevent a decrease in commercial value, and thus can be widely used in the manufacture of antipyretic analgesics using a solid antipyretic analgesic.

Claims (3)

An antipyretic analgesic drug obtained by sealingly packaging an antipyretic analgesic preparation containing ibuprofen, allylisopropylacetyl urea and caffeine in a mass ratio of 10: 3: 4, respectively, in a mixed state . Antipyretic analgesics made agent further, antacids, vitamins, antipyretic analgesic medicament according to claim 1, further comprising at least one member selected from crude drugs.   The antipyretic analgesic according to claim 1 or 2, wherein the sealed package is a PTP package, a glass bottle, a plastic bottle or an aluminum pillow package.