JP2006001920A - Medicinal preparation - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a medicinal preparation excellent in both analgesic and anti-inflammatory effects and safety, and capable of being used by patients without having anxiety as a generic medicine. <P>SOLUTION: This medicinal preparation contains (a) 1 pt. wt. propionic acid derivative-based non-steroidal anti-inflammatory agent (such as ibuprofen, etc.), (b) 0.3-0.7 pt. wt. non-pyrin-based antipyretic analgesic agent (such as acetoaminophen, etc.) and (c) 0.05-10 pt. wt. at least one selected from an antiplasmin agent (such as tranexamic acid, etc.) and an anti-inflammatory enzymatic agent (such as lysozyme chloride, etc.). The ratio of the (c) component to the 1 pt. wt. (b) non-pyrin-based antipyretic analgesic agent is allowed to be 0.1-20 pt. wt. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a novel pharmaceutical formulation containing an anti-inflammatory drug such as ibuprofen.

  The idea of “self-medication”, in which every citizen is always interested in their own health and is involved in the prevention and treatment of illness, has become a major trend in medical care in the world, regardless of whether it is a developed country or a developing country.・ In Japan, where the aging of society is rapidly progressing, the necessity of preventing the failure of the medical insurance system has been screamed. Given this social background, over-the-counter drugs most commonly used for self-medication are purchased at pharmacies and drug stores at the patient's own discretion. High safety is required. In particular, antipyretic analgesics and cold medicines have an extremely large number of users, and the appearance of general antipyretic analgesics and cold medicines that are excellent in terms of safety as well as analgesic / anti-inflammatory effects is desired.

  Ibuprofen is a non-steroidal antipyretic analgesic agent that has antipyretic, analgesic and anti-inflammatory effects and is now widely used around the world, but its analgesic effect is relatively mild, and stomach discomfort, Since side effects such as gastric pain are likely to occur, compounding with various medicinal ingredients has been attempted for the purpose of enhancing the analgesic effect of ibuprofen itself and reducing its gastrointestinal disorders.

  For example, Japanese Examined Patent Publication No. 64-8602 (Patent Document 1) discloses a combined antipyretic analgesic in which ibuprofen and an aniline derivative antipyretic analgesic such as busetine are combined. Japanese Patent Publication No. 1-24131 (Patent Document) 2) discloses a pharmaceutical composition containing ibuprofen and caffeine, and Japanese Patent Application Laid-Open No. 5-148139 (Patent Document 3) discloses 0.01 to 30 weights per 1 part by weight of ibuprofen. An antipyretic analgesic is disclosed in which a part of acetaminophen and 0.05 to 100 parts by weight of magnesium-based antacid are blended with 1 part by weight of ibuprofen and acetaminophen. JP-A-9-48728 (Patent Document 4) discloses an antipyretic analgesic agent containing ibuprofen and tranexamic acid, and the ratio of tranexamic acid is 0.1 to 10 times that of ibuprofen. Has been.

  Japanese Laid-Open Patent Publication No. 7-188004 (Patent Document 5) discloses a common cold medicine containing ibuprofen and lysozyme chloride. This document describes an example of a tablet containing 450 g of ibuprofen, 600 g of acetaminophen and 90 g of lysozyme chloride. JP-A-10-259130 (Patent Document 6) discloses (a) one or two drugs selected from bromhexine hydrochloride, ambroxol hydrochloride and lysozyme chloride, (b) ibuprofen, and (c) noscapine. Or an oral administration preparation comprising a salt thereof and (d) acetaminophen, the drug (a), (b) ibuprofen, (e) an antihistamine, and (d) acetaminophen. Formulations for oral administration are disclosed. This document describes an example of blending 300 g of ibuprofen, 300 g of acetaminophen and 60 g of lysozyme, and an example of blending 150 g of ibuprofen, 600 g of acetaminophen and 60 g of lysozyme chloride.

  Furthermore, JP-A-11-158066 (Patent Document 7) relating to the present applicant discloses a pharmaceutical preparation in which 0.40 to 0.60 parts by weight of acetaminophen is blended with 1 part by weight of ibuprofen. Yes. This pharmaceutical preparation can enhance the analgesic effect of ibuprofen and reduce gastrointestinal disorders.

However, even with the above-mentioned prior art, ibuprofen-containing pharmaceutical preparations are excellent in both analgesic / anti-inflammatory effects and safety, and can be used as a general over-the-counter drug with sufficient peace of mind. I can not say.
Japanese Patent Publication No. 64-8602 (Claims) Japanese Patent Publication No. 1-24131 (Claims) JP-A-5-148139 (Claims) JP-A-9-48728 (Claims) JP-A-7-188004 (Claims, Examples) JP-A-10-259130 (Claims and Examples) JP 11-158066 A (Claims)

  Accordingly, an object of the present invention is to provide a pharmaceutical preparation which is further excellent in two main effects of analgesia and anti-inflammation and is reduced in gastrointestinal disorders as an over-the-counter medicine as an antipyretic analgesic or a cold medicine. .

  Another object of the present invention is to provide a pharmaceutical preparation containing ibuprofen suitable for self-medication.

  As a result of intensive studies to achieve the above-mentioned problems, the present inventors have (a) a propionic acid derivative-based non-steroidal anti-inflammatory drug (such as ibuprofen) and (b) a non-pyrine antipyretic analgesic (such as acetaminophen) Attempts to formulate various medicinal ingredients into a combination containing a specific ratio of at least one selected from (c1) antiplasmin drugs (such as tranexamic acid) and (c2) anti-inflammatory enzyme drugs (such as lysozyme chloride) It was found that the anti-inflammatory effect can be further enhanced by blending at a specific ratio. The present invention has been completed by further studying these findings.

  That is, the pharmaceutical preparation of the present invention comprises (a) a propionic acid derivative non-steroidal anti-inflammatory drug (such as ibuprofen), (b) a non-pyrine antipyretic analgesic (such as acetaminophen), and (c) (c1) Containing at least one component selected from an antiplasmin drug (such as tranexamic acid) and (c2) an anti-inflammatory enzyme drug (such as lysozyme chloride), and (a) 1 part by weight of a non-steroidal anti-inflammatory drug ( b) 0.3 to 0.7 parts by weight of non-pyrine antipyretic analgesic and (c) 0.05 to 10 parts by weight of component. In this pharmaceutical preparation, (b) 0.4 to 0.6 parts by weight of a non-pyrine antipyretic analgesic and (c) component 0.06 to 6 parts by weight with respect to 1 part by weight of (a) a nonsteroidal anti-inflammatory drug. May be included. Moreover, 0.1-20 weight part may be sufficient as the ratio of (c) component with respect to 1 weight part of (b) non-pyrine antipyretic analgesics. More specifically, at least one selected from (b) 0.4 to 0.6 parts by weight of (b) acetaminophen, (c) tranexamic acid and lysozyme chloride with respect to 1 part by weight of (a) ibuprofen. -6 parts by weight may be included.

  The pharmaceutical preparation of the present invention can further improve analgesic / anti-inflammatory effects, and is excellent in both analgesic / anti-inflammatory effects and safety. Therefore, it is suitable for self-medication as an over-the-counter medicine for antipyretic analgesics and cold medicines.

  (A) Propionic acid derivative-based non-steroidal anti-inflammatory drugs include propionic acid derivatives such as ibuprofen, ketoprofen, flurbiprofen, flurbiprofen axetyl, oxaprozin, fenoprofen, thiaprofenic acid, naproxen, pranopro Examples include phen, loxoprofen, aluminoprofen, zaltoprofen, and salts thereof. These medicinal ingredients can be used alone or in combination of two or more. A preferred medicinal component (a) is ibuprofen. Ibuprofen is a substance having the chemical name of 2- (4-isobutylphenyl) propionic acid, and is a medicinal ingredient listed in “14th revised Japanese pharmacopoeia” (hereinafter referred to as “Pharmacopeia”) and the like.

  (B) Examples of non-pyrine antipyretic analgesics include acetaminophen, dimethothiazine mesylate or salts thereof. These medicinal ingredients can be used alone or in combination of two or more. A preferred component (b) is acetaminophen. Acetaminophen is a substance having the chemical name of N- (4-hydroxyphenyl) acetamide, which has an analgesic action and the like and is a medicinal ingredient listed in the pharmacopoeia.

  (C) Examples of the antiplasmin drug (c1) include tranexamic acid, epsilon aminocaproic acid, and salts thereof. These medicinal ingredients can be used alone or in combination of two or more. A preferred component (c1) is tranexamic acid. Tranexamic acid is a substance having the chemical name of trans-4- (aminomethyl) cyclohexanecarboxylic acid, which has anti-bleeding action, anti-allergic action, anti-inflammatory action, etc., and is a medicinal ingredient listed in the pharmacopoeia. is there.

  Examples of the anti-inflammatory enzyme (c2) include lysozyme chloride, semi-alkaline proteinase, serrapeptase, bromelain, and salts thereof. These medicinal ingredients can be used alone or in combination of two or more. A preferred component (c2) is lysozyme chloride. Lysozyme chloride is a hydrochloride of a basic polypeptide obtained from chicken egg white and has an anti-inflammatory action, a bleeding-inhibiting action, a squeezing action, and the like, and is a medicinal ingredient listed in the pharmacopoeia and the like.

  As the salts of the medicinal components (a), (b) and (c), various physiologically or pharmaceutically acceptable salts can be used, and the acid or base forming the salt depends on the type of medicinal component. For example, inorganic acid (hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, etc.), organic acid (organic carboxylic acid, eg, acetic acid, trichloroacetic acid, trifluoroacetic acid, maleic acid, fumaric acid, etc. Hydroxycarboxylic acids such as carboxylic acid, succinic acid, citric acid and tartaric acid; organic sulfonic acids such as alkane sulfonic acids such as methane sulfonic acid and ethane sulfonic acid, arene sulfonic acids such as benzene sulfonic acid and toluene sulfonic acid) Inorganic salts (alkali metal hydroxides such as ammonia, sodium hydroxide, potassium hydroxide, alkali metal carbonates, calcium hydroxide, magnesium hydroxide) Alkaline earth metal hydroxides, alkaline earth metal carbonates such as um, aluminum salts), organic bases (alkyl amines, alkanolamines, such as polyamines such as alkylene amines), and others. The medicinal components (a), (b), and (c) may be racemates, optically active substances ((R) isomers, (S) isomers, diastereomers, etc.).

  In the present invention, in addition to (a) a propionic acid derivative non-steroidal anti-inflammatory drug and (b) a non-pyrine antipyretic analgesic, (c) an antiplasmin drug (c1) and an anti-inflammatory enzyme drug (c2) are selected. In combination with at least one component, the anti-inflammatory activity is greatly improved. As the component (c), one of the antiplasmin drug (c1) and the anti-inflammatory enzyme drug (c2) may be used alone, or both components may be used in combination. In addition, as the component (c), a plurality of components selected from the same category (c1) or (c2) may be used in combination. For example, when lysozyme chloride is used as the anti-inflammatory enzyme (c2), it may be used in combination with other anti-inflammatory enzyme (c2) (for example, bromelain, serrapeptase, semi-alkaline proteinase, etc.).

  In the pharmaceutical preparation of the present invention, the ratio of (b) non-pyrine antipyretic analgesic (eg, acetaminophen) is 0.3 parts per 1 part by weight of (a) non-steroidal anti-inflammatory drug (eg, ibuprofen). To 0.7 parts by weight (for example, 0.35 to 0.65 parts by weight), preferably 0.4 to 0.6 parts by weight (for example, 0.45 to 0.55 parts by weight), and more preferably 0. It is about 4 to 0.55 parts by weight (for example, 0.4 to 0.5 parts by weight).

  In addition, the proportion of the component (c) (for example, at least one selected from tranexamic acid and lysozyme chloride) is 0.05 to 1 part by weight with respect to 1 part by weight of the (a) nonsteroidal anti-inflammatory drug (for example, ibuprofen). 10 parts by weight (for example 0.05 to 7 parts by weight), preferably 0.05 to 8 parts by weight (for example 0.05 to 6 parts by weight), more preferably 0.06 to 6 parts by weight (for example 0 0.06 to 5 parts by weight). The ratio of the component (c) is 0.5 to 5 parts by weight (for example, 0.6 to 5 parts by weight), particularly 0.7 to 5 parts by weight with respect to 1 part by weight of the (a) nonsteroidal anti-inflammatory drug. It may be about a part. Combining the components in the above proportions, compared to a combination of (a) a non-steroidal anti-inflammatory drug (eg ibuprofen) and (b) a non-pyrine antipyretic analgesic (eg acetaminophen) in the same proportion Excellent anti-inflammatory activity.

  In addition, the ratio of the component (c) to 1 part by weight of (b) a non-pyrine antipyretic analgesic (for example, acetaminophen) is, for example, 0.1 to 20 parts by weight (for example, 0.1 to 17 parts by weight), Preferably, it may be about 0.12 to 15 parts by weight. When both the antiplasmin drug (c1) and the anti-inflammatory enzyme drug (c2) are used as the component (c), the weight ratio of the anti-plasmin drug (c1) and the anti-inflammatory enzyme drug (c2) is, for example, the former (c1 ) / The latter (c2) = 0.1 / 1 to 15/1, preferably about 0.3 / 1 to 10/1 (for example, 0.5 / 1 to 8/1).

  The ratio of the above-mentioned medicinal ingredients is determined based on typical medicinal ingredients listed in the pharmacopoeia, and pharmaceutically active optical isomers (optically active substances) are used as medicinal ingredients. In this case, the amount of optical isomer used can be selected according to the degree of pharmacological activity. For example, it is assumed that the optical isomer has twice the activity with respect to the racemic body (or mixture) having pharmacological activity, and the usage amount of the optical isomer is 0.5 parts by weight. The ratio can be corrected assuming that it corresponds to parts by weight. Specifically, in place of the ibuprofen, a pharmaceutically active optical isomer of ibuprofen (for example, S-ibuprofen) can be used. In this case, 0.5 parts by weight of the optical isomer is It corresponds to 1 part by weight. Therefore, when the optical isomer of ibuprofen is used, the ratio can be calculated by regarding the ratio of ibuprofen as 0.5 parts by weight.

  In addition to the components (a), (b), and (c), other medicinal ingredients that can be blended in antipyretic analgesics and cold medicines can be appropriately blended in the pharmaceutical preparation of the present invention. The medicinal component that can be blended may be any medicinal component that does not adversely affect the analgesic / anti-inflammatory activity and safety of the pharmaceutical preparation of the present invention. For example, “Manufacture (import) of antipyretic analgesics for over-the-counter drugs” Approval Criteria "[general medicines Japan Pharmaceutical Collection 2002-03, 13th edition, Jiho Co., Ltd., 92-94 pages, issued July 30, 2001] Drug manufacturing (import) approval criteria "[general drug Japan Pharmaceutical Collection 2002-03, 13th edition, Jiho Co., Ltd., page 1-4, issued July 30, 2001] Can be mentioned.

  In addition to those based on the above approval criteria, a medicinal component suitable for the use of antipyretic analgesics and cold medicines should also not adversely affect the analgesic / anti-inflammatory activity and safety of the pharmaceutical preparation of the present invention. If necessary, it can be appropriately blended.

Examples of such medicinal ingredients include vitamins (fat-soluble vitamins such as vitamins A, D, E, K, and U; water-soluble vitamins such as vitamins B, C, and P), antipyretic / analgesic / anti-inflammatory. Drugs (pyrine antipyretic analgesics such as sulpyrine; salicylic acid drugs such as sodium salicylate and aspirin; phenamic acid drugs such as flufenamic acid and mefenamic acid; arylacetic acid drugs such as diclofenac sodium and indomethacin; phenylbutazone and oxyphenylbuta Pyrazolidine drugs such as zon, pyrimidine drugs such as bucolome, oxicam drugs such as piroxicam, isopropylantipyrine), antihistamines (eg clemastine fumarate, diphenhydramine hydrochloride, chlorpheniramine maleate), antitussive expectorant (phosphorus) Acid codin Antitussives such as dihydrocodine phosphate, cloperastine, dextromethorphan, and benzonate; expectorants, for example, mucosa such as bromhexine hydrochloride, L-cysteine hydrochloride, L-methylcysteine hydrochloride, acetylcysteine, and mucus such as carbocysteine repair agent, hydrochloric ambroxol mucus lubricating agents, such as soles, etc.), bronchodilators or asthma drug (pseudoephedrine, ephedrine hydrochloride, methylephedrine hydrochloride terbutaline, isoproterenol, salbutamol, beta _2, such as terbutaline - adrenoceptor Examples include body stimulants, theophylline, aminophylline, xanthine drugs such as proxyphylline, cromoglycic acid, etc.), caffeine, antacids, amino acids, herbal medicines and the like. These medicinal ingredients can be used alone or in combination of two or more. In the present invention, antihistamines, caffeines, and magnesium-based antacids are not necessarily required.

  These medicinal ingredients can be selected according to the intended efficacy of the pharmaceutical preparation of the present invention. For example, among the medicinal ingredients, a component having an inhibitory action on vascular permeability enhancement, such as a vitamin P component or a component of a vitamin P preparation (hesperidin or hesperetin) is a component that uses the pharmaceutical preparation of the present invention for cold medicine As preferred. The amount of such component used is, for example, 0.01 to 5 parts by weight (for example, 0.03 to 1 part by weight), preferably 0.05 to 0.7 parts per 1 part by weight of component (a). It may be about parts by weight (for example, 0.1 to 0.5 parts by weight). Examples of medicinal ingredients suitable for antipyretic analgesics include analgesic antipyretic drugs (such as isopropylantipyrine), and effective ingredients suitable for use as cold medicines include antihistamines (such as clemastine fumarate) and antitussive expectorant. Drugs (bromhexine hydrochloride, L-cysteine derivatives, etc.), bronchodilators or asthma drugs (pseudoephedrine, ephedrine hydrochloride, etc.) and the like can be mentioned.

  In the present specification, the pharmaceutical preparation means a preparation suitable for oral administration (oral administration preparation). Orally administered preparations may be solid preparations (tablets, pills, fine granules, granules, powders, hard capsules, soft capsules, troches, dry syrups) and liquids (syrups, liquids and suspensions). It may be a turbidity agent. The pharmaceutical preparation includes preparations with controlled release of medicinal ingredients (for example, immediate-release preparations and sustained-release preparations).

  The pharmaceutical preparation of the present invention can be formulated by a conventional method by combining the components (a), (b) and (c) with a carrier (preparation additive suitable for the pharmaceutical preparation). That is, the pharmaceutical preparation of the present invention is produced, for example, according to the method for producing tablets, granules, powders, hard capsules, soft capsules, troches, dry syrups, syrups, liquids and suspensions described in the pharmacopoeia. can do. The solid preparation can be usually prepared using at least one carrier (particularly, at least an excipient) selected from a binder, an excipient, and a disintegrant. For example, a granule can be prepared by granulating a medicinal component and a carrier component by extrusion granulation, spray granulation or the like, and adjusting the size as necessary. Tablets can be produced by mixing and compressing the granulated product and additives, and if necessary, coating by a method known per se that imparts taste masking, enteric properties or durability. Capsules can be prepared by filling capsules with granules. Depending on the dosage form, the liquid preparation is a medicinal component and a liquid carrier component (such as water) and, if necessary, an additive (emulsifier, dispersant or suspending agent, preservative, stabilizer, corrigent, pH adjusting agent, buffering agent, etc. ) And can be sterilized if necessary.

  Examples of the carrier (preparation additive) include additives usually used in the manufacture of the above-mentioned pharmaceutical preparations. For example, the Pharmacopoeia and “Pharmaceutical Additives Encyclopedia” (Pharmaceutical Daily Newspaper, January 1994) Excipients, binders, disintegrants, lubricants, coating agents, etc. listed on the 14th).

  Among the carrier components or additives, examples of the excipient include starches such as corn starch (corn starch), polysaccharides such as crystalline cellulose; saccharides such as lactose, sucrose, glucose, mannitol, and sorbitol. Binders include polysaccharides such as pregelatinized starch, agar, gum arabic, and dextrin; synthetic polymers such as polyvinylpyrrolidone, polyvinyl alcohol, carboxyvinyl polymer, and polylactic acid; methylcellulose, ethylcellulose, sodium carboxymethylcellulose (CMC), hydroxy Examples thereof include cellulose ethers such as ethyl cellulose, hydroxypropyl cellulose, and hydroxypropyl methylcellulose. Examples of the disintegrant include calcium carbonate, carboxymethylcellulose calcium (carmellose calcium), crospovidone, and low-substituted hydroxypropylcellulose. Examples of the lubricant include talc, magnesium stearate, polyethylene glycol 6000, and the like. Disintegration aids, lipids (oils and fats such as hydrogenated vegetable oils, phospholipids, etc.), macrogol, flavoring agents, masking agents, coloring agents, fragrances and the like can also be used.

  Examples of the coating agent include saccharides, cellulose derivatives such as ethyl cellulose and hydroxymethyl cellulose, polyoxyethylene glycol, cellulose acetate phthalate, hydroxypropyl methylcellulose phthalate, and Eudragit (methacrylic acid / acrylic acid copolymer). The coating agent may be an enteric component such as hydroxypropylmethylcellulose phthalate, or may be a gastric component composed of a polymer (such as Eudragit) containing a basic component such as dialkylaminoalkyl (meth) acrylate. .

  In the present invention, polyethylene glycol is not always necessary.

  The pharmaceutical preparation of the present invention is usually orally administered in 1 to several times a day, but the content of (a) non-steroidal anti-inflammatory drug (for example, ibuprofen) in the pharmaceutical preparation of the present invention is: (A) In the case of an adult, the dose of a non-steroidal anti-inflammatory drug (for example, ibuprofen) is 100 to 1000 mg / day, preferably 200 to 800 mg / day, more preferably about 300 to 600 mg / day. It is good to mix. (A) The dose of a non-steroidal anti-inflammatory drug (for example, ibuprofen) can be appropriately increased or decreased depending on the age, weight, and symptoms of patients including children. In addition, the content of (b) a non-pyrine antipyretic analgesic (for example, acetaminophen) in the pharmaceutical preparation of the present invention depends on the blending amount of the component (a) (for example, ibuprofen). For example, (b) component (for example, aminophen) is blended in the above proportion (for example, 0.4 to 0.6 parts by weight, preferably 0.4 to 0.5 parts by weight) with respect to 1 part by weight of ibuprofen). . Furthermore, the amount of the component (c) (for example, at least one selected from tranexamic acid and lysozyme chloride) in the pharmaceutical preparation of the present invention depends on the blending amount of the component (a) (for example, ibuprofen). ) The aforementioned ratio (for example, 0.06 to 6 parts by weight) of (c) component (for example, at least one selected from tranexamic acid and lysozyme chloride) with respect to 1 part by weight of non-steroidal anti-inflammatory drug (for example, ibuprofen) , Preferably 0.06 to 5 parts by weight).

  The pharmaceutical preparation of the present invention has a particularly enhanced anti-inflammatory effect as compared with a combination drug of a specific ratio of ibuprofen and acetaminophen disclosed in the prior application by the applicant of the present invention. Headache, toothache, post-extraction pain, sore throat , Joint pain, neuralgia, low back pain, muscle pain, stiff shoulder pain, bruise pain, fracture pain, sprain pain, menstrual pain, trauma pain, and other cold symptoms (sore throat, chills, fever, headache) , Joint pain, muscle pain, etc.).

  Hereinafter, the present invention will be described in more detail based on test examples and examples, but the present invention is not limited to these examples.

Test Example 1 Anti-inflammatory effect by rat carrageenan footpad edema method (1)
As a test drug, a combination drug of ibuprofen: acetaminophen = 1: 0.5 by weight ratio (hereinafter also referred to as “two-component combination drug”), and ibuprofen: acetaminophen: tranexamic acid = 1: 0.5 by weight ratio. : 0.5 compounding agent (hereinafter also referred to as “3-component compounding agent A”), ibuprofen: acetaminophen: tranexamic acid = 1: 0.5: 4.5 compounding agent (hereinafter “3-component compounding”) Anti-bacterial agent using rat carrageenan footpad edema method according to the method of Pichat et al. [Arzneim.-Forsch./Drug Res. 48 (I), 173-178 (1998)] using tranexamic acid alone. Inflammatory effects were tested.

  That is, 6 rats per group fasted overnight were used, 9.7 mg / kg of the 2-component formulation was 12.93 mg / kg of the 3-component formulation A (9.7 mg / kg of the 2-component formulation, and tranexamic acid 3 38.8 mg / kg) (38.8 mg / kg), 39.8 mg / kg (containing 29.1 mg / kg of tranexamic acid) and 29.1 mg / kg of tranexamic acid, respectively. Orally administered. One hour later, 1% λ carrageenan was subcutaneously administered to the left hind footpad, and after 3 hours, the footpad volume was measured to measure anti-inflammatory activity.

  As a result, both the three-component compounding agent A and the same compounding agent B showed better anti-inflammatory activity than the two-component compounding agent. On the other hand, anti-inflammatory activity was not observed with tranexamic acid alone.

Test Example 2 Anti-inflammatory effect by rat carrageenan footpad edema method (2)
As a test drug, a two-component formulation, ibuprofen: acetaminophen: tranexamic acid = 1: 0.5: 1.17 in a weight ratio (hereinafter also referred to as “three-component formulation C”), and ibuprofen in a weight ratio : Acetaminophen: Lysozyme chloride = 1: 0.5: Anti-inflammatory by rat carrageenan footpad edema method according to Test Example 1 using a compounding agent (hereinafter also referred to as “three-component compounding agent D”) The effect was tested.

  That is, 6 rats per group fasted overnight were used, 11-28 mg / kg of 2-component formulation was 20.05 mg / kg of 3-component formulation C (tranexamic acid was added to 11.28 mg / kg of 2-component formulation) 8.77 mg / kg) and 3-component combination D 16.92 mg / kg (2-component combination 11.28 mg / kg combined with lysozyme chloride 5.64 mg / kg) were orally administered. One hour later, 1% λ carrageenan was subcutaneously administered to the left hind footpad, and after 3 hours, the footpad volume was measured to measure anti-inflammatory activity. The administration group of only 1% CMC and physiological saline was the carrageenin non-administration group, and the group in which 1% λ carrageenin was subcutaneously administered to the left hind paw 1 hour after oral administration of 1% CMC was defined as the control group.

  Table 1 shows the average footpad volume and edema inhibition rate of 6 mice in each group. The edema inhibition rate was determined by the following formula.

Edema suppression rate (%) = 100 × [1− (A−B) / (C−B)]
A: Toe volume of test drug administration group B: Toe volume of carrageenin non-administration group C: Toe volume of control group

  As is clear from Table 1, the three-component compounding agents C and D both exhibit excellent anti-inflammatory activity compared to the two-component compounding agent.

Example 1
Formulation example in one tablet (total amount: 170 mg): ibuprofen 75 mg, acetaminophen 32.5 mg, tranexamic acid 32.5 mg, corn starch 23 mg, and low-substituted hydroxypropylcellulose 7 mg
About the said prescription, the tablet was manufactured according to the well-known method of a pharmacopoeia general rule description.

Example 2
Formulation in one tablet (total amount: 160 mg): ibuprofen 60 mg, acetaminophen 30 mg, tranexamic acid 30 mg, hesperidin 10 mg and corn starch 23 mg and low-substituted hydroxypropylcellulose 7 mg
About the said prescription, the tablet was manufactured according to the well-known method of a pharmacopoeia general rule description.

Example 3
Formulation in one capsule (total amount 180 mg): ibuprofen 75 mg, acetaminophen 32.5 mg, tranexamic acid 32.5 mg, corn starch 38 mg and magnesium stearate 2 mg
About the said prescription, the capsule was manufactured according to the well-known method described in a pharmacopoeia general rule.

Example 4
Formulation in 1 capsule (total amount 170 mg): ibuprofen 60 mg, acetaminophen 30 mg, tranexamic acid 30 mg, hesperidin 10 mg, corn starch 38 mg and magnesium stearate 2 mg
About the said prescription, the capsule was manufactured according to the well-known method described in a pharmacopoeia general rule.

Example 5
Formulation in one granule (total amount 640 mg): 75 mg ibuprofen, 32.5 mg acetaminophen, 32.5 mg tranexamic acid, 200 mg lactose, 295 mg crystalline cellulose and 5 mg low substituted hydroxypropylcellulose
About the said prescription, the granule was manufactured according to the well-known method of description in a pharmacopoeia general rule.

Example 6
Formulation in one granule (total amount: 630 mg): ibuprofen 60 mg, acetaminophen 30 mg, tranexamic acid 30 mg, hesperidin 10 mg, lactose 200 mg, crystalline cellulose 295 mg and low-substituted hydroxypropylcellulose 5 mg
About the said prescription, the granule was manufactured according to the well-known method of description in a pharmacopoeia general rule.

Example 7
Formulation in one granule (total amount: 600 mg): ibuprofen 60 mg, acetaminophen 30 mg, lysozyme chloride 15 mg, lactose 200 mg, crystalline cellulose 290 mg and low-substituted hydroxypropylcellulose 5 mg
About the said prescription, the granule was manufactured according to the well-known method of description in a pharmacopoeia general rule.

Example 8
Formulation in one granule (total amount 640 mg): ibuprofen 75 mg, acetaminophen 32.5 mg, tranexamic acid 32.5 mg, lysozyme chloride 32.5 mg, hesperidin 10 mg, lactose 200 mg, crystalline cellulose 295 mg and low-substituted hydroxypropylcellulose 5mg
About the said prescription, the granule was manufactured according to the well-known method of description in a pharmacopoeia general rule.

Example 9
Formulation in one granule (total amount: 640 mg): ibuprofen 75 mg, acetaminophen 32.5 mg, tranexamic acid 25 mg, lysozyme chloride 7.5 mg, hesperidin 10 mg, lactose 200 mg, crystalline cellulose 295 mg and low-substituted hydroxypropylcellulose 5 mg
About the said prescription, the granule was manufactured according to the well-known method of description in a pharmacopoeia general rule.

Example 10
Formulation in one granule (total amount 640 mg): ibuprofen 75 mg, acetaminophen 32.5 mg, tranexamic acid 7.5 mg, lysozyme chloride 25 mg, hesperidin 10 mg, lactose 200 mg, crystalline cellulose 295 mg and low-substituted hydroxypropylcellulose 5 mg
About the said prescription, the granule was manufactured according to the well-known method of description in a pharmacopoeia general rule.

Claims (5)

  (A) a propionic acid derivative-based non-steroidal anti-inflammatory drug, (b) a non-pyrine antipyretic analgesic, and (c) at least one component selected from an antiplasmin drug and an anti-inflammatory enzyme drug, A pharmaceutical preparation comprising (b) 0.3 to 0.7 parts by weight of a non-pyrine antipyretic analgesic and (c) 0.05 to 10 parts by weight of the component per 1 part by weight of the non-steroidal anti-inflammatory drug.   (A) It contains 0.4 to 0.6 parts by weight of (b) a non-pyrine antipyretic analgesic and (c) 0.06 to 6 parts by weight of the component per 1 part by weight of the nonsteroidal anti-inflammatory drug. 1. The pharmaceutical preparation according to 1.   (B) The pharmaceutical preparation according to claim 1, wherein the ratio of the component (c) to 1 part by weight of the non-pyrine antipyretic analgesic is 0.1 to 20 parts by weight.   The pharmaceutical preparation according to claim 1, wherein the nonsteroidal anti-inflammatory drug is ibuprofen, the non-pyrine antipyretic analgesic is acetaminophen, the antiplasmin drug is tranexamic acid, and the anti-inflammatory enzyme drug is lysozyme chloride.   (A) with respect to 1 part by weight of ibuprofen, (b) acetaminophen 0.4 to 0.6 parts by weight, (c) at least one selected from tranexamic acid and lysozyme chloride 0.06 to 6 parts by weight The pharmaceutical preparation according to claim 1.