JP6009967B2 - Solid preparation - Google Patents

Description

  The present invention relates to a solid preparation containing loxoprofen or a salt thereof and tranexamic acid or a salt thereof.

  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), and its excellent antipyretic analgesic action is expected to be incorporated into a general cold medicine.

  Tranexamic acid, on the other hand, has antiplasmin, antiallergic and anti-inflammatory effects, and is associated with increased tendency to systemic fibrinolysis, bleeding tendency, tonsillitis, sore throat, and sore throat. It is a known ingredient that is used for symptoms such as swelling and mouth pain in stomatitis, and also used for melasma, senile pigment spots, post-inflammation pigmentation, etc. (Non-Patent Documents 2 and 3). It is also included in general cold medicine.

  Combinations of these loxoprofen and tranexamic acid are already known. For example, Patent Document 1 discloses a pharmaceutical composition exhibiting excellent efficacy or effect in which gastrointestinal disorders caused by loxoprofen are reduced by combining loxoprofen and tranexamic acid. Things are disclosed. Patent Document 2 discloses that tranexamic acid suppresses the interaction between loxoprofen and interactive components such as clemastine. Patent Document 3 discloses a soft capsule in which a capsule skin is filled with a content in which loxoprofen and tranexamic acid are uniformly suspended.

JP 2010-83882 A JP 2011-246437 A JP 2009-242360 A

The 16th revised Japanese Pharmacopoeia Manual Sasakawa Shoten Co., Ltd. C-5359-5364 The 16th revised Japanese Pharmacopoeia Manual Sasakawa Shoten Co., Ltd. C-3090-3095 OTC Handbook 2008-09 Academic Information Distribution Center Co., Ltd. Pages 693-694

However, at present, the problems in the case of formulating a combination of loxoprofen and tranexamic acid as a solid preparation have not been studied so far.
Therefore, the present inventor conducted intensive studies to formulate a combination of loxoprofen and tranexamic acid as a solid preparation, and found that a disintegration delay occurs immediately after the production of the solid preparation. If the disintegration of the solid preparation is delayed, the release of the drug is delayed, so that the drug effect may be delayed and non-uniform. As a method of eliminating such disintegration delay and speeding up disintegration, a method of reducing the formulation hardness can be considered, but the decrease in the formulation hardness leads to embrittlement and new problems such as cracking and chipping during transportation of the solid formulation May cause.

  Accordingly, an object of the present invention is to provide a solid preparation containing loxoprofen or a salt thereof and tranexamic acid or a salt thereof and having high hardness and good disintegration.

  Therefore, the present inventor has made further studies in order to solve the above-mentioned problems, and in addition to loxoprofen or a salt thereof and tranexamic acid or a salt thereof, by further containing magnesium oxide, high hardness and good disintegration are said. The present invention has been completed by finding that a solid preparation having conflicting properties can be obtained.

That is, the present invention provides a solid preparation containing loxoprofen or a salt thereof, tranexamic acid or a salt thereof, and magnesium oxide.
Moreover, this invention provides the hardness enhancer of the solid formulation which uses magnesium oxide as an active ingredient.
Furthermore, this invention provides the disintegration promoter of the solid formulation which uses magnesium oxide as an active ingredient.
Furthermore, this invention provides the hardness and disintegration regulator of a solid formulation which uses magnesium oxide as an active ingredient.

  Although the solid preparation of the present invention contains loxoprofen or a salt thereof and tranexamic acid or a salt thereof, they have contradictory properties of high hardness and good disintegration. Therefore, it is possible to simultaneously achieve a rapid drug effect and ensure sufficient formulation strength.

  In the present invention, “loxoprofen or a salt thereof” includes not only loxoprofen itself but also a pharmaceutically acceptable salt of loxoprofen, and further a solvate of loxoprofen or a pharmaceutically acceptable salt thereof with water, alcohol or the like. It is. These are known compounds, and can be produced by known methods, or 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 content of loxoprofen or a salt thereof in the solid preparation of the present invention is not particularly limited, and may be determined by appropriately examining according to the sex, age, symptoms, etc. of the user. For example, 10 to 300 mg, more preferably 30 to 240 mg, particularly preferably 60 to 180 mg in terms of loxoprofen sodium anhydride can be contained per day.
In the present invention, loxoprofen or a salt thereof is preferably contained in an amount of 0.1 to 50% by mass in terms of anhydrous loxoprofen sodium, more preferably 1 to 30% by mass, based on the total mass of the solid preparation. 5 to 20% by mass is particularly preferable.

  In the present invention, “tranexamic acid or a salt thereof” includes tranexamic acid itself, a pharmaceutically acceptable salt of tranexamic acid, and a solvent of tranexamic acid or a pharmaceutically acceptable salt thereof, water, alcohol, and the like. Japanese products are also included. Tranexamic acid or a salt thereof is a known compound, and can be produced by a known method or a commercially available product. Specific examples include tranexamic acid and sodium tranexamic acid, but tranexamic acid (chemical name: trans-4- (Aminomethyl) cyclohexanecarboxylic acid) is preferred.

  The content of tranexamic acid or a salt thereof in the solid preparation of the present invention is not particularly limited, and may be determined by appropriately examining according to the sex, age, symptoms, etc. of the user. For example, an amount that can be taken per day is 50 to 2000 mg, more preferably 70 to 750 mg, particularly preferably 400 to 750 mg in terms of free form of tranexamic acid. In the present invention, tranexamic acid or a salt thereof is preferably contained in an amount of 5 to 70% by mass, more preferably 10 to 50% by mass, in terms of the free form of tranexamic acid, based on the total mass of the solid preparation. It is particularly preferable to contain 15 to 45% by mass.

  In the present invention, the particle diameter, specific volume and the like of “magnesium oxide” are not particularly limited, and may be heavy magnesium oxide or light magnesium oxide. In the present invention, magnesium oxide described in the 16th revision Japanese Pharmacopoeia is preferable. Magnesium oxide may be produced by a known method or may be a commercially available product. Furthermore, as the said commercial item, you may use what is marketed as a mixture with another compound. Furthermore, as the said commercial item, you may use what is marketed as a mixture with another compound. Specific examples of commercially available magnesium oxide include magnesium oxide manufactured by Kyowa Chemical Industry.

  The content of magnesium oxide contained in the solid preparation of the present invention is not particularly limited, and may be determined by appropriately examining from the viewpoints of hardness and disintegration of the solid preparation. In the present invention, from the viewpoint of obtaining high hardness and quick disintegration, the content is preferably 1 to 50% by mass, more preferably 5 to 40% by mass with respect to the total mass of the solid preparation. What contains 30 mass% is especially preferable.

The content ratio of loxoprofen or a salt thereof and magnesium oxide contained in the solid preparation of the present invention is not particularly limited, and may be determined appropriately from the viewpoints of hardness and disintegration of the solid preparation. In the present invention, from the viewpoint of obtaining high hardness and rapid disintegration, 0.1 to 10 parts by mass of magnesium oxide is preferable with respect to 1 part by mass of loxoprofen or a salt thereof (in terms of anhydrous loxoprofen sodium), and 0.5 to 5 mass parts is more preferable, and what contains 1-2 mass parts is especially preferable.
In addition, the content ratio of tranexamic acid or a salt thereof and magnesium oxide contained in the solid preparation of the present invention is not particularly limited, and may be determined by appropriately examining from the viewpoint of hardness and disintegration of the solid preparation. In the present invention, from the viewpoint of obtaining high hardness and quick disintegration, 0.05 to 2 parts by mass of magnesium oxide is preferable with respect to 1 part by mass of tranexamic acid or a salt thereof (in terms of free form of tranexamic acid). 1-1 mass parts is more preferable, and 0.2-0.8 mass parts is especially preferable.

  In the solid preparation of the present invention, drugs other than those described above as pharmaceutical ingredients, such as antipyretic analgesics, antihistamines, antitussives, noscapines, bronchodilators, expectorants, hypnotic sedatives, vitamins, anti-inflammatory agents, gastric mucosa You may contain 1 type, or 2 or more types chosen from the group which consists of a protective agent, an anticholinergic agent, a herbal medicine, Chinese medicine prescription, etc.

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

  Antihistamines include, for example, azelastine hydrochloride, alimemazine tartrate, istipendil hydrochloride, iproheptin hydrochloride, ebastine, epinastine hydrochloride, emedastine fumarate, oxatomide, olopatadine hydrochloride, carbinoxamine diphenyldisulfonate, carbibi Noxamine maleate, d-chlorpheniramine maleate, dl-chlorpheniramine maleate, ketotifen fumarate, difeterol hydrochloride, difeterol phosphate, diphenylpyraline hydrochloride, diphenylpyralineteocric acid Salt, diphenhydramine hydrochloride, diphenhydramine salicylate, diphenhydramine tannate, cyproheptadine hydrochloride hydrate, cetirizine hydrochloride, triprolidine hydrochloride, tripelenamine hydrochloride, Dilamine hydrochloride, fexofenadine, phenetadine hydrochloride, promethazine hydrochloride, promethazine methylene disalicylate, bepotastine besylate, homochlorcyclidine hydrochloride, mequitazine, methodirazine hydrochloride, mebhydroline napadisilate , Loratadine and the like.

  Antitussives include, for example, aloclamide hydrochloride, eprazinone hydrochloride, carbetapentane enoate, cloperastine hydrochloride, cloperastine phendizoate, codeine, codeine phosphate hydrate, dihydrocodeine, dihydrocodeine phosphate, dibub Examples thereof include sodium sodium, dimemorphan phosphate, tipepidine citrate, tipepidine hibenzate, dextromethorphan, dextromethorphan hydrobromide hydrate, dextromethorphan phenolphthalein salt and the like.

Examples of noscapine include noscapine hydrochloride and noscapine.
Examples of bronchodilators include trimethquinol hydrochloride, phenylpropanolamine hydrochloride, phenylephrine hydrochloride, pseudoephedrine hydrochloride, pseudoephedrine sulfate, 1-methylephedrine hydrochloride, dl-methylephedrine hydrochloride, l-methylephedrine. Saccharin salt, dl-methylephedrine saccharin salt, methoxyphenamine hydrochloride and the like can be mentioned.

  As an expectorant, for example, ambroxol hydrochloride, ammonia fennel, ethylcysteine hydrochloride, ammonium chloride, carbocysteine, guaifenesin, potassium guaiacolsulfonate, potassium cresolsulfonate, bromhexine hydrochloride, methylcysteine hydrochloride, Examples thereof include l-menthol and lysozyme hydrochloride.

Examples of the hypnotic sedative include allyl isopropyl acetyl urea and bromvalerylurea.
Vitamins include vitamin B1, vitamin B2, vitamin B5, vitamin B6, vitamin B12, vitamin C, hesperidin and derivatives thereof, and salts thereof (for example, thiamine, thiamine chloride hydrochloride, thiamine nitrate, dicetiamine hydrochloride) , Cetothiamine hydrochloride, fursultiamine, fursultiamine hydrochloride, octothiamine, chicotiamine, thiamine disulfide, bisibutiamine, bisbenchamine, prosultiamine, benfotiamine, riboflavin, riboflavin phosphate, riboflavin butyrate, Sodium riboflavin phosphate, panthenol, panthetin, sodium pantothenate, pyridoxine hydrochloride, pyridoxal phosphate, cyanocobalamin, mecobalamin, ascorbic acid, ascorbic acid Thorium, calcium ascorbate, hesperidin, etc.).

  Examples of anti-inflammatory agents include glycyrrhizic acid and derivatives thereof and salts thereof (for example, dipotassium glycyrrhizinate, monoammonium glycyrrhizinate), seaprose, semi-alkaline proteinase, serrapeptase, proctase, pronase, bromelain and the like.

  Examples of the gastric mucosa protective agent include gefarnate, cetraxate hydrochloride, sofalcone, teprenone, methylmethionine sulfonium chloride and the like.

  Anticholinergic agents 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, butyl scopolamine bromide, belladonna alkaloid, belladonna extract, belladonna total alkaloid, iodide isopropamide, iodide diphenylpiperidinomethyldioxolane, funnel extract, funnel root, funnel root total Examples include alkaloid citrate.

  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), gadgets (garbage), valerian grass (kashikoshi), chamomile, caronin (karojin), kyokyo (kikyo), kyonin (kyojin), kokushi (枸杞) Child), Kukoyo (Kashiwaha), Keigai (Kashiwa), Keihi (Katsuhashi), Ketsumeishi (Kemeko), Gentiana, Gennoshouko (current evidence), Koubushi (Katsukiko), Gooh (oxen yellow), Goshi (Gomiko), Saishin ( Spicy, Salamander, Zion, Zipoppi, Peonies, Shako, Shajin, Shazenshi, Shazenso, Car Grass), animal gall (including yutan (bear gall)), gyoza (ginger), giraffe (earth dragon), shin ii (spicy potato), sexan (stone urn), senega, senkyu (river cucumber), zenko (maehu) ), Sembli (Senri), Sojutsu (蒼朮), Sohakuhi (mulberry bark), Soyo (Soba), Taisan (Daegu), Chiksetsu carrot (Bamboo ginseng), Clove (clove), Chimpi (Chen), Toki ( Toko (Togyo), Nantenjitsu (Nan Tenji), Carrot (Ginseng), Baimo (Scarlet mother), Bacmondou (Wheat Gate Winter), Hange (Halfsummer), Bankouka (Banka Flower), Hampi (Antinas) ), Peony (white bean), peanut (white cocoon), bukuryo (pepper), button pi (peony skin), mao (mao), rokjo (deer moth), and their extracts (extract, tincture, dried extract, etc.) Etc.

  Chinese herbal prescriptions include Kakonto (Kakkonto), Keishito (Katsurayu), Kousosan (Kososan), Psychokeito (Saiko Keitou), Shosai Koto (Koshisaikoyu), Shosei Ryuto (Sho Seiryuto) ), Bakumondou (Bakumon Fuyuto), Hangekoubokuto (Hankatsu Kobokuto), Maoutou (Maoyuto) and the like.

  In the present invention, the “solid preparation” specifically includes tablets (including orally disintegrating tablets, chewable tablets, effervescent tablets); granular preparations such as pills, granules, fine granules, powders; Examples of the dosage form include capsules obtained by encapsulating the preparation in capsules. The solid preparation of the present invention is particularly useful as a tablet because it has high hardness and good disintegration.

In the present invention, the “solid preparation” can be produced by a known method described in, for example, the 16th revised Japanese Pharmacopoeia General Rules for Preparations.
Specifically, when the dosage form of the solid preparation is a granular preparation such as a pill, granule, fine granule or powder, in addition to loxoprofen or a salt thereof, tranexamic acid or a salt thereof, magnesium oxide, an excipient or Known formulation such as extrusion granulation, tumbling granulation, stirring granulation, fluidized bed granulation, spray granulation, melt granulation, crush granulation, etc. using appropriate formulation additives such as binders and disintegrants It can manufacture by granulating by the granule method. In addition, the obtained granulated material can also be coat | covered with a coating agent by a well-known method.
When the dosage form of the solid preparation is a tablet, directly compress a mixture of loxoprofen or a salt thereof, tranexamic acid or a salt thereof, magnesium oxide, and appropriate preparation additives such as excipients, binders and disintegrants. It can be produced by (direct powder compression method) or by compressing the above granulated product (semi-dry granule compression method, dry granule compression method, wet granule compression method, etc.). In compression, a lubricant may be further used as a preparation additive.
Moreover, what is necessary is just to fill the above-mentioned granulated material into a capsule, when the dosage form of a solid formulation is a capsule.

Specific examples of formulation additives that can be used in producing the solid formulation of the present invention include excipients, binders, disintegrants, lubricants, and the like.
Examples of the excipient include calcium citrate, crystalline cellulose, calcium silicate, light anhydrous silicic acid, wheat starch, rice starch, corn starch, lactose hydrate, sucrose, glucose hydrate, mannitol, anhydrous phosphorus Examples thereof include calcium oxyhydrogen phosphate and calcium hydrogen phosphate hydrate.
Examples of the binder include crystalline cellulose, methylcellulose, hydroxypropylcellulose, hypromellose, carmellose sodium, wheat starch, rice starch, corn starch, dextrin, partially pregelatinized starch, pullulan, gum arabic, agar, gelatin, tragacanth, Examples include sodium alginate, povidone, and polyvinyl alcohol.
Content of a binder is 0.1-15 mass% normally, Preferably it is 0.5-10 mass%, More preferably, it is 1-5 mass%.
Examples of the disintegrant include carboxymethyl starch sodium, carmellose, carmellose calcium, croscarmellose sodium, crospovidone and the like.
Content of a disintegrating agent is 0.1-20 mass% normally, Preferably it is 0.5-15 mass%, More preferably, it is 1-10 mass%.
Examples of the lubricant include calcium stearate, magnesium stearate, talc, and sodium stearyl fumarate.
The content of the lubricant is usually 0.01 to 10% by mass, preferably 0.1 to 5% by mass, and more preferably 0.5 to 2.5% by mass.

  Examples of the route of administration of the solid preparation of the present invention include oral and parenteral such as vagina. In the present invention, an oral administration preparation is preferred. In addition, the solid preparation of the present invention can be taken before meals, between meals, after meals, before going to bed, etc. in about 1 to 4 times per day.

  Since the solid preparation of the present invention contains loxoprofen or a salt thereof, which is a kind of NSAID, and tranexamic acid having an anti-inflammatory action, 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, joint pain, muscle pain), etc., and is useful as a general cold medicine (cold medicine) or antipyretic analgesic.

The present invention also provides:
Hardness enhancer for solid preparations containing magnesium oxide as an active ingredient,
The present invention provides a disintegration accelerator for solid preparations containing magnesium oxide as an active ingredient, and a hardness and disintegration regulator for solid preparations containing magnesium oxide as an active ingredient.
In this case, the meaning of each wording, the amount of each component used, and the like are the same as in the case of the solid preparation.
Moreover, as shown in the below-mentioned Example, in addition to loxoprofen or its salt and tranexamic acid or its salt, the solid formulation provided with high hardness and favorable disintegration can be obtained by further containing magnesium oxide. Therefore, the hardness enhancer, disintegration accelerator, hardness and disintegration regulator of the present invention are used for enhancing the hardness, promoting disintegration, controlling hardness and disintegration of a solid preparation containing loxoprofen or a salt thereof and tranexamic acid or a salt thereof. , Each particularly suitable.

  EXAMPLES The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples.

[Test Example 1]
The tablets of Reference Examples 1 to 3 were produced according to the following method, and the disintegration time was measured immediately after production.
The disintegration test results of each tablet are shown in Table 1 together with the types of compounding ingredients and the compounding amount (mg) per tablet.
<Reference Example 1>
Loxoprofen sodium hydrate 885.3 parts by mass, tranexamic acid 1820 parts by mass, crystalline cellulose 1300 parts by mass, hydroxypropylcellulose 148.2 parts by mass and carmellose calcium 247 parts by mass were put into a high-speed agitation granulator and mixed. Then, 352 parts by mass of purified water was added and kneaded. The obtained granulated product was put into a fluid bed dryer and dried, and then granulated using a granulator. After putting 4171 parts by mass of the obtained sized product and 41.9 parts by mass of magnesium stearate into a mixer, mixing was performed, and then 1.2 tons of tableting was performed using a tableting machine equipped with a 9.0 mm diameter punch. Tableting was performed with tableting pressure to obtain tablets with a mass of 341.9 mg per tablet.
<Reference Example 2>
A tablet with a mass of 201.9 mg per tablet was obtained in the same manner as in Reference Example 1 except that no tranexamic acid was used.
<Reference Example 3>
Tablets having a mass per tablet of 273.8 mg were obtained in the same manner as in Reference Example 1 except that loxoprofen sodium hydrate was not added.

<Measurement of disintegration time (disintegration test)>
About the tablet obtained by the reference examples 1-3, the disintegration time was measured using the disintegration test apparatus (NT-40H: Toyama Sangyo Co., Ltd. product). Water (1000 mL, 37 ° C.) was used as the test solution, the disintegration time of 6 tablets was measured for each example, and the average value was calculated.

From the test results shown in Table 1, the disintegration time was 16.6 minutes and 0 for the tablet containing Loxoprofen sodium hydrate alone (Reference Example 2) and the tablet containing Tranexamic acid alone (Reference Example 3), respectively. It was revealed that the disintegration time exceeded 30 minutes in the tablet containing both loxoprofen sodium hydrate and tranexamic acid (Reference Example 1), while it was as fast as 0.8 minutes.
From the above test results, it became clear that the disintegration delay of the solid preparation occurs by combining loxoprofen or a salt thereof and tranexamic acid or a salt thereof in combination.

[Test Example 2]
The tablets of Example 1 and Comparative Example 1 were produced according to the following method, and the tablet hardness and disintegration time were measured immediately after production.
The test results for each tablet are shown in Table 1 together with the types of compounding ingredients and the compounding amount (mg) per tablet.
<Example 1>
Loxoprofen sodium hydrate 885.3 parts by mass, tranexamic acid 1820 parts by mass, magnesium oxide 1300 parts by mass, hydroxypropylcellulose 148.2 parts by mass and carmellose calcium 247 parts by mass were put into a high-speed agitation granulator and mixed. Then, 352 parts by mass of purified water was added and kneaded. The obtained granulated product was put into a fluid bed dryer and dried, and then granulated using a granulator. After putting 4171 parts by mass of the obtained sized product and 41.9 parts by mass of magnesium stearate into a mixer and mixing them, using a tableting machine with a 9.0 mm diameter punch, tableting pressure: 1 Tableting was performed at 0.0, 1.2, 1.4, 1.6, or 1.8 tons to obtain tablets having a mass per tablet of 341.9 mg.
<Comparative Example 1>
Tablets having a mass per tablet of 341.9 mg were obtained in the same manner as in Example 1 except that magnesium oxide was replaced with 1300 parts by mass of crystalline cellulose.

<Measurement of tablet hardness>
About the tablet obtained in Example 1 and Comparative Example 1, tablet hardness was measured using a tablet hardness meter (PHARMA TEST PTB-311: Japan Machinery Co., Ltd.). For each example, the tablet hardness of 20 tablets was measured for each tableting pressure condition, and the average value was calculated.
<Measurement of disintegration time (disintegration test)>
For the tablets obtained in Example 1 and Comparative Example 1, the disintegration time was measured using a disintegration test apparatus (NT-40H: manufactured by Toyama Sangyo Co., Ltd.). Water (1000 mL, 37 ° C.) was used as a test solution, and the disintegration time of 6 tablets tableted with 1.2 tons of tableting pressure was measured for each example, and the average value was calculated.

From the test results shown in Table 2, in addition to loxoprofen sodium hydrate and tranexamic acid, the tablet of Example 1 further containing magnesium oxide is composed of crystalline cellulose, which is said to have high hardness because it has good moldability. Even when compared with the tablet of Comparative Example 1 contained, high hardness was obtained at all tableting pressures. In addition, it was revealed that the tablet of Example 1 rapidly disintegrates despite having high hardness and exhibits good disintegration properties.
From the above test results, it was revealed that the solid preparation containing loxoprofen or a salt thereof, tranexamic acid or a salt thereof, and magnesium oxide has high hardness and good disintegration.

[Production Example 1]
Tablets containing the following ingredients per tablet were produced by a conventional method.
Loxoprofen sodium hydrate 60mg
Tranexamic acid 140mg
Magnesium oxide 100mg
Anhydrous caffeine 80mg
Allyl isopropyl acetyl urea 60mg
Lactose Appropriate amount Crystalline cellulose Appropriate amount Croscarmellose sodium 30mg
Hydroxypropylcellulose 30mg
Hydrous silicon dioxide 12mg
Anhydrous calcium hydrogen phosphate 15mg
Magnesium stearate

[Production Example 2]
Tablets containing the following ingredients per tablet were produced by a conventional method.
Loxoprofen sodium hydrate 60mg
Acetaminophen 130mg
Tranexamic acid 140mg
Magnesium oxide 100mg
Anhydrous caffeine 80mg
Allyl isopropyl acetyl urea 60mg
Lactose Appropriate amount Crystalline cellulose Appropriate amount Croscarmellose sodium 40mg
Hydroxypropylcellulose 40mg
Hydrous silicon dioxide 16mg
Anhydrous calcium hydrogen phosphate 24mg
Magnesium stearate

[Production Example 3]
Tablets containing the following ingredients per tablet were produced by a conventional method.
Loxoprofen sodium hydrate 60mg
Ethenzamid 84mg
Tranexamic acid 140mg
Magnesium oxide 100mg
Anhydrous caffeine 50mg
Bromvalerylurea 200mg
Lactose Appropriate amount Crystalline cellulose Appropriate amount Croscarmellose sodium 45mg
Hydroxypropylcellulose 45mg
Hydrous silicon dioxide 18mg
Anhydrous calcium hydrogen phosphate 27mg
Magnesium stearate

[Production Example 4]
According to a conventional method, tablets containing the following components per 3 tablets (daily dose) were produced.
Tranexamic acid 750mg
Clemastine fumarate 1.34 mg (1 mg as clemastine)
Bromhexine hydrochloride 12mg
Loxoprofen sodium hydrate 180mg
Methylephedrine hydrochloride 60mg
Dihydrocodeine phosphate 24mg
Magnesium oxide 100mg
Thiamine nitrate 25mg
Riboflavin 12mg
Lactose Appropriate amount Crystalline cellulose Appropriate amount Macrogol 30mg
Croscarmellose sodium 80mg
Polyvinyl alcohol 1mg
Light anhydrous silicic acid 24mg
Sucrose fatty acid ester 20mg
Hardened oil 10mg
Magnesium stearate

  ADVANTAGE OF THE INVENTION According to this invention, the solid formulation which contains loxoprofen or its salt, and tranexamic acid or its salt, was equipped with high hardness and favorable disintegration, and was excellent in quality can be provided, and can be utilized in pharmaceutical industry etc.

Claims (2)

  A solid preparation containing loxoprofen or a salt thereof, tranexamic acid or a salt thereof, and magnesium oxide.   The solid preparation according to claim 1, which is a tablet.