JP5835865B2 - Loxoprofen-containing pharmaceutical composition - Google Patents

Description

  The present invention relates to a pharmaceutical composition containing loxoprofen and tranexamic acid.

Loxoprofen is a type of non-steroidal anti-inflammatory analgesic (NSAID), including rheumatoid arthritis, osteoarthritis, low back pain, shoulder periarthritis, cervical-shoulder arm syndrome, toothache, acute upper respiratory inflammation, post-surgical / post-traumatic It is known as effective for anti-inflammatory, analgesic and antipyretic after tooth extraction (Non-patent Document 1).
Loxoprofen is considered to cause less gastrointestinal disorders (gastric mucosal irritation, ulcer formation in the small intestine) as side effects than other NSAIDs such as ketoprofen, naproxen, and indomethacin. However, in fact, loxoprofen is not completely free from gastrointestinal disorders, and measures to reduce gastrointestinal disorders caused by loxoprofen are being studied. For example, a composition in which loxoprofen is combined with a herbal medicine (Patent Document 1), a proton pump inhibitor (Patent Document 2), or an antacid (Patent Document 3) having a gastric / gastric mucosa protecting action is known.

Tranexamic acid, on the other hand, has antiplasmin, antiallergic and anti-inflammatory effects and is thought to be associated with increased systemic fibrinolysis, soreness, tonsillitis, sore throat, and sore throat. It is a drug used for symptoms such as swelling and oral pain in stomatitis (Non-Patent Document 2), and also used for liver spots, senile pigment spots, post-inflammation pigmentation, etc. (Non-Patent Document 3).
However, it is not known how the action on the gastrointestinal tract changes when tranexamic acid and loxoprofen are used in combination.

JP 2004-161667 A Special table 2007-522217 gazette JP 2006-52210 A

Fifteenth revised Japanese Pharmacopoeia explanation book Yodogawa Shoten Co., Ltd. C-4790-4759 Fifteenth revised Japanese Pharmacopoeia explanation book Yodogawa Shoten Co., Ltd. C-2743-2749 OTC Handbook 2008-09 Academic Information Distribution Center Co., Ltd. Pages 693-694

  An object of the present invention is to provide a new means for reducing or suppressing a digestive tract disorder caused by loxoprofen.

  The present inventors diligently studied about the reduction and suppression measures of the gastrointestinal tract disorder of loxoprofen. When loxoprofen or a salt thereof is combined with tranexamic acid or a salt thereof, the gastrointestinal tract disorder caused by the loxoprofen is reduced or suppressed. The present invention has been completed by finding out what can be done.

That is, the present invention provides a pharmaceutical composition containing loxoprofen or a salt thereof and tranexamic acid or a salt thereof.
The present invention also provides an agent for reducing or suppressing gastrointestinal disorders caused by loxoprofen or a salt thereof containing tranexamic acid or a salt thereof as an active ingredient.

  Tranexamic acid reduces gastrointestinal disorders caused by loxoprofen. Therefore, by using a pharmaceutical composition containing loxoprofen or a salt thereof and tranexamic acid or a salt thereof, there is no risk of gastrointestinal tract disorder, and an excellent NSAID effect of loxoprofen is exhibited, and an excellent antiplasmin of tranexamic acid Since it can also have an effect | action etc., it can become an outstanding pharmaceutical composition. Tranexamic acid is useful as an active ingredient for reducing or suppressing gastrointestinal disorders caused by loxoprofen.

The present invention relates to a pharmaceutical composition containing loxoprofen or a salt thereof and tranexamic acid or a salt thereof.
The loxoprofen or a salt thereof contained in the pharmaceutical composition of the present invention includes not only loxoprofen but also a pharmaceutically acceptable salt of loxoprofen, and further a solvate with water, alcohol and the like. These can be produced by known methods, and commercially available products can be used. In the present invention, loxoprofen or a salt thereof is preferably loxoprofen sodium hydrate (chemical name: Monosodium 2- [4-[(2-oxocyclopentyl) methyl] phenyl] propanoate dihydrate).

  The tranexamic acid or salt thereof contained in the pharmaceutical composition of the present invention includes not only tranexamic acid, but also pharmaceutically acceptable salts of tranexamic acid, and solvates with water, alcohol and the like. These can be produced by known methods, and commercially available products can be used. In the present invention, tranexamic acid or a salt thereof is preferably tranexamic acid.

  The blending ratio of loxoprofen or a salt thereof and tranexamic acid or a salt thereof in the pharmaceutical composition of the present invention is 0.1 to 0.1 parts by weight of tranexamic acid with respect to 1 part by mass of loxoprofen sodium anhydride from the viewpoint of reducing or suppressing gastrointestinal disorders. 25 mass parts is preferable, 0.2-15 mass parts is more preferable, 0.5-10 mass parts is further more preferable.

In addition, the dosage of the components contained in the pharmaceutical composition of the present invention may be determined by appropriate examination. In the case of oral administration, loxoprofen or a salt thereof is used as a daily dosage in terms of loxoprofen sodium anhydride. 10-300 mg is preferable, 30-180 mg is more preferable, and 60-180 mg is further more preferable.
Tranexamic acid or a salt thereof is preferably 50 to 2000 mg, more preferably 70 to 750 mg, and still more preferably 400 to 750 mg as a daily dose in terms of tranexamic acid.
These dosages can be appropriately increased or decreased depending on age, sex, symptoms, etc., and may be taken in 1 to 4 times a day.

  The ratio of loxoprofen or a salt thereof contained in the pharmaceutical composition of the present invention may be determined by appropriate examination according to the above-mentioned daily dose. For example, loxoprofen sodium anhydrate with respect to the whole pharmaceutical composition 1-97 mass% is preferable in conversion, 5-90 mass% is more preferable, and 7-80 mass% is further more preferable.

  Further, the ratio of tranexamic acid or a salt thereof contained in the pharmaceutical composition of the present invention may be determined by appropriate examination according to the above-mentioned daily dose. 1-70 mass% is preferable as an acid, 5-60 mass% is more preferable, and 7-50 mass% is further more preferable.

  In the pharmaceutical composition of the present invention, as a pharmaceutical ingredient, a drug other than loxoprofen or a salt thereof and tranexamic acid or a salt thereof, such as an antipyretic analgesic, an antihistamine, an antitussive, a noscapine, a bronchodilator, an expectorant, a hypnotic sedative , Vitamins, anti-inflammatory agents, gastric mucosa protective agents, anticholinergic agents, herbal medicines, Chinese herbal formulas, caffeine, xanthine components and the like may be included.

  Examples of antipyretic analgesics include aspirin, aspirin aluminum, acetaminophen, ibuprofen, ethenzamide, sazapyrine, salicylamide, lactylphenetidine, sodium salicylate, isopropylantipyrine, and thiaramide hydrochloride.

  Examples of the antihistamine include chlorpheniramine such as dl-chlorpheniramine maleate and d-chlorpheniramine maleate or a salt thereof; azelastine hydrochloride, isothipentyl hydrochloride, iproheptin hydrochloride, clemastine fumarate, ketotifen Fumarate, diphenylpyraline hydrochloride, diphenhydramine hydrochloride, dipheterol hydrochloride, triprolidine hydrochloride, tripelenamine hydrochloride, tondilamine hydrochloride, phenetazine hydrochloride, promethazine hydrochloride, methodirazine hydrochloride, diphenhydramine salicylate, carbinoxamine diphenyl Disulfonate, alimemazine tartrate, diphenhydramine tannate, diphenylpyraline theocuroate, mebhydroline napadisylate, promethazine methylene disali Le salts, carbitol Roh hexa Min maleate, mequitazine, epinastine hydrochloride, diphenylmethane Te roll phosphates include emetine Das Chin fumarate salt.

  Antitussives include, for example, codeines such as codeine phosphate and dihydrocodeine phosphate; tipepidine such as tipepidine citrate and tipipedin hibenzate; or salts thereof; dextromethorphan hydrobromide, dextromethorphan and phenolphthalate Dextromethorphan or its salts such as phosphorus salts; aloclamide hydrochloride, cloperastine hydrochloride, carbetapentane enoate, dibutate sodium, cloperastine phendizoate, dimemorphan phosphate, eprazinone hydrochloride, etc. Is mentioned.

  Examples of noscapine include noscapine hydrochloride and noscapine.

  Examples of bronchodilators include ephedrines such as methylephedrine, dl-methylephedrine hydrochloride, 1-methylephedrine hydrochloride, dl-methylephedrine saccharin salt, pseudoephedrine hydrochloride, pseudoephedrine sulfate, and the like; trimethquinol hydrochloride; Examples include phenylpropanolamine hydrochloride, phenylephrine hydrochloride, methoxyphenamine hydrochloride and the like.

  As an expectorant, for example, bromhexine such as bromhexine hydrochloride or a salt thereof; potassium guaiacol sulfonate, guaifenesin, potassium cresolsulfonate, ammonium chloride, l-menthol, ammonia fennel, ethylcysteine hydrochloride, methylcysteine hydrochloride , Ambroxol hydrochloride, carbocysteine and the like.

  Examples of the hypnotic sedative include bromvalerylurea and allylisopropylacetylurea.

Vitamins include vitamin B ₁ , vitamin B ₂ , vitamin B ₅ , vitamin B ₆ , vitamin B ₁₂ , vitamin C, hesperidin and derivatives thereof, and salts thereof (for example, thiamine, thiamine chloride hydrochloride, thiamine nitrification) , Dicetiamine hydrochloride, cetothiamine hydrochloride, fursultiamine, fursultiamine hydrochloride, octothiamine, chicotiamine, thiamine disulfide, bisbutiamine, bisbenchamine, prosultiamine, benfotiamine, riboflavin, riboflavin phosphate , Riboflavin butyrate, sodium riboflavin phosphate, panthenol, panthetin, calcium pantothenate, sodium pantothenate, pyridoxine hydrochloride, pyridoxal phosphate, cyanocobalamin, mecobalamin, Ascorbic acid, sodium ascorbate, calcium ascorbate, hesperidin, etc.).

  Anti-inflammatory agents include lysozyme chloride, serrapeptase, bromelain, semi-alkaline proteinase, pronase, seaprose, proctase, glycyrrhizic acid and its derivatives and salts thereof (for example, dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, etc.) .

As gastric mucosa protective agents, aminoacetic acid, magnesium silicate, synthetic aluminum silicate, synthetic hydrotalcite, magnesium oxide, dihydroxyaluminum aminoacetate (aluminum glycinate), aluminum hydroxide gel, aluminum hydroxide / magnesium carbonate Mixed dried gel, aluminum hydroxide / sodium bicarbonate coprecipitation product, aluminum hydroxide / calcium carbonate / magnesium carbonate coprecipitation product, magnesium hydroxide / potassium aluminum sulfate coprecipitation product, magnesium carbonate, metasilicic acid Magnesium aluminate, aldioxa, copper chlorophyllin sodium, copper chlorophyllin potassium, methylmethionine sulfonium chloride, sucralfate, cetraxate hydrochloride, sofalcone, gefarnate, te Lennon and the like.
Anticholinergics include oxyphencyclimine hydrochloride, dicyclomine hydrochloride, methixene hydrochloride, scopolamine hydrobromide, datsura extract, tipidium bromide, methyl atropine bromide, methyl anisotropin bromide, methyl scopolamine bromide, methyl-1- Hyoscyamine bromide, methylbenactidium bromide, pirenzepine hydrochloride, butylscopolamine bromide, belladonna extract, belladonna total alkaloid, iodopropamide, diphenylpiperidinomethyldioxolane iodide, funnel extract, funnel root, funnel root total alkaloid citric acid Examples include salts.

  Herbal medicines include Akamegashiwa (red buds), Asenyaku (Asen Yaku), Inyo-kaku (Ryokan), Fennel (Yongxiang), Engosaku (Yancho), Ogon (Yellow), Ousei (Yellow), Oubak (Yellow), Spruce (Cherry bark), auren (yellow ream), onji (distant), gajutsu (weather), valerian (kashikusa), chamomile, caronin (karojin), licorice (licorice), kyokyo (kikyo), kyonin (kyojin) ), Kukoshi (Kushiko), Kukoyo (Kashiwaha), Keigai (Kashiwagi), Keihi (Kinshikashi), Ketsumeishi (Keiko), Gentiana, Gennoshouko (current evidence), Kobushi (Katsukiko), Gouou (cow yellow), Dust ( Goshiko, Saishin, Sansho, Shion, Zikopi, Hakuyaku, Shakuyaku, Shako, Shajin, Shazenshi ), Shazenso (car in front of the car), Beast gall (including Yutan (bear gall)), Syougyo (ginger), Giryu (land dragon), Shinyi (spicy potato), Sexan (stone wall), Senega, Senkyu (river kyu), Zenko (mae-hu), assembly (Senhwa), Sojutsu (蒼朮), Sohakuhi (mulberry white skin), Soyo (Soyo), Taisan (Otsuchi) Chikutsutsujinjin (Takebushi ginseng), clove (chome), chimpi (Chen) , Toki (homecoming), Tokon (Nanten), Nantenjitsu (Nan Tenji), Carrot (Ginseng), Baimo (Shell), Bakumondou (Bakumon winter), Hange (half-summer), Bankouka (Bankaka), Hampi (Anti-nasal), peony (white bean), peanut (white moth), bukuryo (、), button pi (peony skin), borei (oyster), maou (mao yellow), rokjo (deer moth) and other extracts and their extracts ( Extract, tincture, dried extract, etc.) I can get lost.

  The Kampo prescriptions include Kakkon-yu, Katsue-yu, Kosou-san, Saiko-Kei-do, Sho-saiko-to, Shosei-ryu, Mumon-tou-yu, Hanka-kopaku-to, Mao-to, and the like.

  Examples of caffeine include caffeine, anhydrous caffeine, and sodium benzoate caffeine.

  Examples of the xanthine component include aminophylline, diprofylline, theophylline, proxyphylline and the like.

  Note that the dose of a drug other than loxoprofen or a salt thereof and tranexamic acid or a salt thereof contained in the pharmaceutical composition of the present invention may be determined by appropriately examining, for example, administration of chlorpheniramine or a salt thereof. In the case of oral administration, the daily dose is preferably 0.1 to 20 mg. In addition, the dose of codeine is preferably 2 to 60 mg as a daily dose when administered orally, and the dose of tipepidine or a salt thereof is 1 to 300 mg as a daily dose when administered orally. Preferably, when administered orally, the dosage of ephedrine is preferably 5 to 500 mg as a daily dosage, and when administered orally, the dosage of dextromethorphan or a salt thereof is 0. 1 to 270 mg is preferable, the dosage of bromhexine or a salt thereof is preferably 0.1 to 50 mg as a daily dosage, and the dosage of mao (mao) is 0 as a daily dosage when orally administered. .1 to 25 g (concentration in bulk drug substance) is preferable, and the dose of caffeine is preferably 10 to 600 mg as a daily dose when orally administered.

  The pharmaceutical composition of the present invention can be produced by a known method described in the 15th revision Japanese Pharmacopoeia General Rules for Preparation, etc., and includes excipients, binders, disintegrants, lubricants, etc. It can be manufactured using pharmaceutical additives.

  The dosage form of the pharmaceutical composition of the present invention is not particularly limited, and examples thereof include capsules, pills, granules, fine granules, powders, tablets, liquids, syrups, jellies, and lozenges. Orally administered preparations such as topical preparations, ointments, creams, gel creams, poultices, transdermal preparations, patches, liniments, lotions, suppositories and the like. In the present invention, a preparation for oral administration is preferable, and a solid preparation is more preferable. The solid preparation may be coated with sugar coating, film coating or the like by a known method.

  Since the pharmaceutical composition of the present invention contains loxoprofen, which is a kind of NSAID, and tranexamic acid having an antiplasmin action and the like, headache, toothache, pain after tooth extraction, sore throat, ear pain, joint pain, neuralgia, low back pain, Muscle pain, stiff shoulder pain, bruise pain, fracture pain, sprain pain, menstrual pain, menstrual pain, pain relief, chills, antipyretic fever, cold symptoms, sore throat, chills, fever, headache, It is effective or effective for joint pain, muscle pain), sore throat, tonsillitis (sore throat, sore throat), stomatitis, and the like.

By containing tranexamic acid or a salt thereof, the pharmaceutical composition of the present invention is excellent because there is no risk of gastrointestinal disturbance caused by loxoprofen.
Tranexamic acid or a salt thereof may be aluminoprofen other than loxoprofen, ampiroxicam, ampenac sodium, indomethacin, etodolac, epilysole, oxaprozin, ketoprofen, zaltoprofen, diclofenac, sulindac, celecoxib, thiaprofenic acid, thiaramide, tenoxicam, tolfenamic acid Gastrointestinal disorders (gastric mucosal irritation, in the small intestine) as side effects of other NSAIDs such as nabumetone, naproxen, piroxicam, pranoprofen, flufenamic acid, flurbiprofen, progouritacin, mefenamic acid, meloxicam, mofezolac, lornoxicam Ulcer formation etc.) can be expected to be reduced or suppressed.

  Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited thereto.

Example 1. Loxoprofen-induced gastrointestinal disorder control test (1)
Using Wistar rats (Std: Wistar / ST, male, 8 weeks old, body weight 205.7-231.3 g), the test was carried out as 6 animals per group. Rats were fasted from the day before the test (16 hours or longer). Water intake was free up to 1 hour before the start of the test, and then water was stopped.
As a test drug, tranexamic acid (TXA) was suspended in a 0.5% methylcellulose (MC) solution and orally administered in predetermined amounts (100, 400 mg / 5 mL / kg). In the control group, only the solvent (0.5% MC) was orally administered in the same volume (5 mL / kg).
One hour after administration of the test drug, loxoprofen sodium hydrate 100 mg / 2 mL physiological saline / kg was orally administered to each group of rats to induce gastric mucosal damage. Five hours after administration of loxoprofen sodium hydrate, the rats were euthanized by cervical dislocation, the cardia was ligated, and the stomach was removed. After injecting 10 mL of 1% formalin solution into the stomach from the pyloric region and ligating the pyloric region, the entire stomach was immersed in the formalin solution for about 20 minutes and fixed lightly.
Evaluation of the degree of gastric mucosal damage is performed by measuring the length (mm) of individual damage (erosion) occurring in the glandular stomach portion under a stereomicroscope after incising the stomach along the large curvature. The total damage per rat was calculated as the ulcer index (UI).
Taking the ulcer index of the control group as 100%, the ulcer suppression rate (%) in the test drug was calculated. The results are shown in Table 1.

  As is apparent from Table 1, tranexamic acid alleviated gastric mucosal damage caused by loxoprofen.

Example 2 Loxoprofen-induced gastrointestinal tract disorder inhibition test (2)
Wistar rats (Std: Wistar / ST, male, 8 weeks old, body weight 197.1 to 217.3 g) were used, and tranexamic acid (TXA) and d-chlorpheniramine maleate (CM) were used as test drugs. The test was carried out in the same manner as in Example 1 by using a suspension in 0.5% methylcellulose (MC) solution and orally administering a predetermined amount ((TXA 400 mg + CM 3 mg) / 5 mL / kg). The ulcer suppression rate (%) in the test drug was calculated, and the results are shown in Table 2.

  As is clear from Tables 1 and 2, when tranexamic acid and d-chlorpheniramine maleate were used in combination, gastric mucosal damage caused by loxoprofen was further reduced as compared with the case where tranexamic acid alone was administered. Therefore, it has been found that chlorpheniramine or a salt thereof enhances the gastric mucosal disorder inhibitory action of tranexamic acid and is preferable as a concomitant drug.

Example 3 Loxoprofen-induced gastrointestinal disorder control test (3)
Wistar rats (Std: Wistar / ST, male, 8 weeks old, weight 209.3 to 226.9 g) were used, and tranexamic acid (TXA) and anhydrous caffeine (Caf) were added to 0.5% methylcellulose as test drugs. The test was carried out in the same manner as in Example 1 by orally administering a predetermined amount ((TXA 400 mg + Caf 100 mg) / 5 mL / kg) using the suspension in the (MC) solution. The ulcer inhibition rate (%) in the test drug was calculated, and the results are shown in Table 3.

  As is clear from Tables 1 and 3, when tranexamic acid and caffeine anhydride were used in combination, gastric mucosal damage caused by loxoprofen was further reduced as compared with the case where tranexamic acid alone was administered. Therefore, it has been found that caffeine enhances the gastric mucosal disorder inhibiting action of tranexamic acid and is preferable as a concomitant drug.

Example 4 Loxoprofen-induced gastrointestinal tract disorder inhibition test (4)
Wistar rats (Std: Wistar / ST, male, 8 weeks old, body weight 202.5 to 229.6 g) were used, and tranexamic acid (TXA) and dl-methylephedrine hydrochloride (ME) were treated with 0.1% as test drugs. A predetermined amount ((TXA 400 mg + ME 60 mg) / 5 mL / kg) was orally administered using a suspension in a 5% methylcellulose (MC) solution.
Gastric mucosal injury was induced by oral administration of loxoprofen sodium hydrate 120 mg / 2 mL saline / kg.
Except for the above, the test was performed in the same manner as in Example 1. The ulcer inhibition rate (%) in the test drug was calculated, and the results are shown in Table 4.
Similarly, dl-methylephedrine hydrochloride 60 mg / 5 ml / kg, dihydrocodeine phosphate (DP) 24 mg / 5 mL / kg, tipepidine hibenzate (TH) 75 mg / 5 mL / kg, dextromethorphan bromide Instead of the solution prepared to be 48 mg / 5 mL / kg of hydrate (DH), the test was carried out by oral administration of these, and the ulcer suppression rate (%) in each test drug was calculated. Are also shown in Table 4.

  As is clear from Tables 1 and 4, when tranexamic acid and dl-methylephedrine hydrochloride, dihydrocodeine phosphate, tipepidine hibenzate, or dextromethorphan hydrobromide are used in combination, tranexamic acid alone is administered. The gastric mucosal damage caused by loxoprofen was further alleviated than that. Therefore, it has been found that ephedrines, codeines, tipepidine or a salt thereof, dextromethorphan or a salt thereof enhances the gastric mucosal disorder inhibitory action of tranexamic acid and is preferable as a concomitant drug.

Example 5 FIG. Loxoprofen-induced gastrointestinal tract disorder inhibition test (5)
Wistar rats (Std: Wistar / ST, male, 8 weeks old, body weight 210.0-227.6 g) were used, and tranexamic acid (TXA) and bromhexine hydrochloride (BH) were added to 0.5% methylcellulose as test drugs. The test was conducted in the same manner as in Example 4 by orally administering a predetermined amount ((TXA 400 mg + BH 4 mg) / 5 mL / kg) using the suspension in the (MC) solution. The ulcer suppression rate (%) in the test drug was calculated, and the results are shown in Table 5.

  As can be seen from Tables 1 and 5, when tranexamic acid and bromohexine hydrochloride were used in combination, gastric mucosal damage caused by loxoprofen was further reduced as compared with the case where tranexamic acid alone was administered. Therefore, it was found that bromhexine or a salt thereof is preferable as a concomitant drug because it enhances the gastric mucosal disorder inhibitory action of tranexamic acid.

The present invention provides a pharmaceutical composition containing loxoprofen or a salt thereof and tranexamic acid or a salt thereof, and the pharmaceutical composition of the present invention includes loxoprofen, a kind of NSAID, and tranexam having an antiplasmin action. Contains acid.
Therefore, the pharmaceutical composition of the present invention has a headache, toothache, pain after extraction, sore throat, ear pain, joint pain, neuralgia, low back pain, muscle pain, stiff shoulder pain, bruise pain, fracture pain, sprain pain, menstrual pain ( Menstrual pain) / traumatic pain relief, chills / pyretic fever, cold symptoms (throat pain, chills, fever, headache, joint pain, muscle pain) and sore throat / tonsillitis (throat is And sore throat) and stomatitis.
According to the present invention, tranexamic acid alleviated gastrointestinal disorders caused by loxoprofen. Therefore, a gastrointestinal disorder caused by loxoprofen is reduced, and a pharmaceutical composition exhibiting the above-described excellent efficacy or effect can be provided and is useful.

Claims (8)

A pharmaceutical composition containing loxoprofen or a salt thereof and tranexamic acid or a salt thereof (except when a dry aluminum hydroxide gel is included) . The pharmaceutical composition according to claim 1, wherein gastrointestinal disorders caused by loxoprofen are reduced or suppressed. The pharmaceutical composition according to claim 1 or 2, wherein the loxoprofen or a salt thereof is loxoprofen sodium hydrate. The pharmaceutical composition according to claim 3 , comprising loxoprofen sodium hydrate in an amount of 10 to 300 mg per day in terms of anhydrous loxoprofen sodium. The pharmaceutical composition according to any one of claims 1 to 4 , comprising tranexamic acid or a salt thereof as a daily dose of 50 to 2000 mg in terms of tranexamic acid. The pharmaceutical composition according to any one of claims 1 to 5, which is a preparation for oral administration. The pharmaceutical composition according to any one of claims 1 to 5, which is a solid preparation. An agent for reducing or suppressing gastrointestinal disorders caused by loxoprofen or a salt thereof containing tranexamic acid or a salt thereof as an active ingredient (except when a dry aluminum hydroxide gel is included) .