JP2016088853A - Fexofenadine and NSAID-containing pharmaceutical composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a stable pharmaceutical composition containing fexofenadine or a salt thereof and loxoprofen or a salt thereof.SOLUTION: The invention provides a pharmaceutical composition containing fexofenadine or a salt thereof and loxoprofen or a salt thereof and a basic compound having acid neutralization ability.SELECTED DRAWING: None

Description

  The present invention relates to a pharmaceutical composition containing fexofenadine and NSAID.

  Fexofenadine is a compound having an antihistaminic action and is generally used for allergic rhinitis, urticaria, and pruritus associated with skin diseases (eczema / dermatitis, cutaneous pruritus, atopic dermatitis). Hydrochloride is orally administered at 60 mg once a day (Non-patent Document 1). In Japan, fexofenadine hydrochloride simple ingredient "allergic rhinitis drug" was put on the market as a switch OTC drug at the end of 2012.

On the other hand, various compounds such as ibuprofen and loxoprofen have been developed as non-steroidal anti-inflammatory analgesics (NSAIDs). In general, ibuprofen is administered at a dose of 600 mg per day for the purpose of rheumatoid arthritis, arthralgia and arthritis, neuralgia and neuritis, back and back pain, cervical arm syndrome, uterine adnexitis, dysmenorrhea, erythema and its symptoms. Orally administered in divided doses (Non-patent Document 2). In Japan, the antipyretic analgesic, which is a simple component of ibuprofen, was marketed as a switch OTC drug at the end of 1985, and was subsequently combined with a “common cold medicine (cold medicine)” containing ibuprofen and other analgesic ingredients and ibuprofen. An antipyretic analgesic is being marketed.
Further, although it is known that a combination of fexofenadine or a salt thereof and ibuprofen is effective for darkening under the eyes, swelling and swelling (Patent Document 1), a mixture of ibuprofen and fexofenadine is mixed. The stability when stored has not been studied so far.

  Loxoprofen is generally used for rheumatoid arthritis, osteoarthritis, low back pain, shoulder periarthritis, neck-shoulder arm syndrome, toothache, acute upper respiratory tract inflammation, anti-inflammatory, analgesic and antipyretic after surgery, post-traumatic injury, and post-extraction. As an effective agent, 60 mg of loxoprofen sodium anhydride is orally administered once (Non-patent Document 3). In Japan, loxoprofen sodium simple ingredient “pyretic analgesic” was launched as a switch OTC drug in 2011, following the example of ibuprofen, and from the viewpoint of promoting self-medication, loxoprofen and its salts were formulated. Expectations for the launch of combination drugs such as “common cold medicine (cold medicine)” and “antipyretic analgesics” are increasing.

Special table 2011-521948 gazette

The 16th revision Japanese Pharmacopoeia commentary Yodogawa Shoten Co., Ltd. C-3867-3871 The 16th revision Japanese Pharmacopoeia Commentary Yodogawa Shoten Co., Ltd. C-573-577 The 16th revision Japanese Pharmacopoeia Manual Sasakawa Shoten Co., Ltd. C-5359-5364

As a result of investigation by the present inventor, it was found that when fexofenadine or a salt thereof and NSAID are mixed and stored, solidification, melting, etc. occur unexpectedly, resulting in a problem in storage stability.
Therefore, the problem to be solved by the present invention is to provide a stable pharmaceutical composition containing fexofenadine or a salt thereof and NSAID.

  As a result of intensive studies, the present inventors have selected from xanthine derivatives, tranexamic acid or salts thereof, basic compounds having acid neutralizing ability, and ascorbic acid or salts thereof in addition to fexofenadine or a salt thereof and NSAID. The present invention has been completed by finding that the above-mentioned solidification, melting, and the like are suppressed by allowing one or more types to coexist.

That is, this invention provides the pharmaceutical composition containing the following components (A)-(C).
(A) Fexofenadine or a salt thereof (B) NSAID
(C) one or more selected from xanthine derivatives, tranexamic acid or salts thereof, basic compounds having acid neutralizing ability, and ascorbic acid or salts thereof

  The present invention also provides a stabilizer for a pharmaceutical composition containing fexofenadine or a salt thereof and NSAID, a xanthine derivative, tranexamic acid or a salt thereof, a basic compound having acid neutralizing ability, and ascorbic acid Or the stabilizer which uses 1 or more types chosen from the salt as an active ingredient is provided.

  Furthermore, the present invention allows at least one selected from xanthine derivatives, tranexamic acid or a salt thereof, a basic compound having an acid neutralizing ability, and ascorbic acid or a salt thereof together with fexofenadine or a salt thereof and an NSAID. The present invention provides a method for suppressing the interaction between fexofenadine or a salt thereof and NSAID.

The pharmaceutical composition of the present invention is excellent in storage stability.
Moreover, the stabilizer of this invention can stabilize the pharmaceutical composition containing fexofenadine or its salt, and NSAID.

  The pharmaceutical composition of the present invention comprises (A) fexofenadine or a salt thereof, (B) an NSAID, and (C) a xanthine derivative, tranexamic acid or a salt thereof, a basic compound having acid neutralizing ability, and ascorbic acid or 1 type or more chosen from the salt is contained.

<Component (A)>
The fexofenadine or a salt thereof used in the present invention includes not only fexofenadine itself, but also a pharmaceutically acceptable salt of fexofenadine, and a solvate of these with water, alcohol or the like. These are known compounds, and can be produced by known methods, or commercially available products can be used. Among these, fexofenadine hydrochloride is preferable, and Japanese Pharmacopoeia fexofenadine hydrochloride is more preferable.

  The content of fexofenadine or a salt thereof in the pharmaceutical composition of the present invention is not particularly limited, and may be determined by appropriately examining the daily dose according to the sex, age, symptoms, etc. of the user. Well, for example, 10 to 1000 mg, preferably 30 to 500 mg, more preferably 50 to 200 mg of fexofenadine hydrochloride can be contained per day. The daily dose may be taken once or twice. As a dose per time, 20-100 mg is preferable as fexofenadine hydrochloride, and 30 mg and 60 mg are more preferable.

  Moreover, as content of fexofenadine or its salt, 0.1-30 mass% is preferable with respect to the pharmaceutical composition total mass of this invention, 0.5-27.5 mass% is more preferable, 1- 1 20 mass% is more preferable, and 2-10 mass% is further more preferable.

<Component (B)>
The NSAID used in the present invention is not particularly limited, but actarit, acemethacin, ampiroxicam, ampenac, ibuprofen, indomethacin, etodolac, ketoprofen, zaltoprofen, diclofenac, sulindac, celecoxib, thiaprofenic acid, tenoxicam, naproxen, piroxicam, probnica , Flurbiprofen, mefenamic acid, medicoxib, meloxicam, mofezolac, lefecoxib, loxoprofen, lobenzalit, lornoxicam, salts thereof, and the like, and these may be used alone or in combination of two or more. Good. NSAID can be produced by a known method, or a commercially available product can be used.
Among these, preferred specific examples include ibuprofen, loxoprofen, and salts thereof.

(Ibuprofen or its salt)
As said ibuprofen or its salt, Japanese pharmacopoeia ibuprofen is preferable.
The content of ibuprofen or a salt thereof in the pharmaceutical composition of the present invention is not particularly limited, and may be determined by appropriately examining the dose per day according to the sex, age, symptoms, etc. of the user, For example, 10-3000 mg per day, 10-3000 mg, preferably 30-2000 mg, more preferably 100-600 mg can be included. The daily dose may be taken once or divided into appropriate times. The dose per dose is preferably 60 to 200 mg as ibuprofen, more preferably 100 mg and 200 mg.
Moreover, as content of ibuprofen or its salt, 5-60 mass% is preferable with respect to the pharmaceutical composition total mass of this invention, 10-55 mass% is more preferable, 20-50 mass% is further more preferable.
The mass ratio of fexofenadine or a salt thereof to ibuprofen or a salt thereof in the pharmaceutical composition is preferably 1: 0.1 to 1:20, more preferably 1: 0.5 to 1:10. 1: 1 to 1: 5 are more preferable.

(Loxoprofen or its salt)
The 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. Among these, loxoprofen sodium hydrate (chemical name: Monosodium 2- [4-[(2-oxocyclopentyl) methyl] phenyl] propanoate dihydrate) is preferable, and Japanese Pharmacopoeia loxoprofen sodium hydrate is more preferable.
The content of loxoprofen or a salt thereof in the pharmaceutical composition of the present invention is not particularly limited, and may be determined by appropriate examination according to the sex, age, symptoms, etc. of the user, for example, loxoprofen per day. An amount that can be taken is 10 to 300 mg, preferably 30 to 240 mg, more preferably 60 to 180 mg in terms of sodium anhydride. The daily dose may be taken once or divided into appropriate times. The dose per dose is preferably 30 to 120 mg, more preferably 60 mg in terms of loxoprofen sodium anhydride.
Moreover, as content of loxoprofen or its salt, 0.5-40 mass% is preferable in conversion of loxoprofen sodium anhydride with respect to the pharmaceutical composition total mass of this invention, 1-35 mass% is more preferable, 2 -25% by mass is more preferable, and 3-15% by mass is more preferable.
The mass ratio in the pharmaceutical composition of fexofenadine or a salt thereof and loxoprofen or a salt thereof (in terms of loxoprofen sodium anhydride) is preferably 1: 0.1 to 1:15, and 1: 0.5 ˜1: 10 is more preferred, and 1: 1 to 1: 5 is even more preferred.

<Ingredient (C)>
Component (C) of the present invention is at least one selected from xanthine derivatives, tranexamic acid or salts thereof, basic compounds having acid neutralizing ability, and ascorbic acid or salts thereof.

(Xanthine derivative)
The xanthine derivative used in the pharmaceutical composition of the present invention is preferably a compound represented by the following general formula (I), a salt or a double salt of the compound.

[Wherein, R ¹ and R ² each independently represent a hydrogen atom or a methyl group. R ³ represents a hydrogen atom, a methyl group, a monohydroxypropyl group or a dihydroxypropyl group. ]

In R ³ described above, the monohydroxypropyl group is preferably a 2-hydroxypropyl group. The dihydroxypropyl group is preferably a 2,3-dihydroxypropyl group.
In the general formula (I),
(1) R ¹ is a methyl group, R ² is a methyl group, and R ³ is a methyl group means caffeine.
(2) R ¹ is a methyl group, R ² is a methyl group, and R ³ is a hydrogen atom means theophylline.
(3) R ¹ is a hydrogen atom, R ² is a methyl group, and R ³ is a methyl group means theobromine.
(4) R ¹ is a methyl group, R ² is a hydrogen atom, and R ³ is a methyl group means paraxanthine.
(5) A compound in which R ¹ is a methyl group, R ² is a methyl group, and R ³ is a 2-hydroxypropyl group means proxyphylline.
(6) The case where R ¹ is a methyl group, R ² is a methyl group, and R ³ is a 2,3-dihydroxypropyl group means diprofylline.
The compounds of the general formula (I), especially the above-mentioned compounds are known, and in the present invention, commercially available products can be used in addition to those produced by known methods.
In addition, as the caffeine and theophylline, those in which a double salt is formed (sodium benzoate caffeine (double salt of sodium benzoate and caffeine), aminophylline (double salt of theophylline and ethylenediamine)) or the like may be used. it can.

  As the xanthine derivative used in the pharmaceutical composition of the present invention, caffeine is preferable from the viewpoint of the use of the pharmaceutical composition of the present invention as an antipyretic analgesic, a general cold medicine, and the like and storage stability. Specific examples of the caffeine include caffeine hydrate, anhydrous caffeine, sodium benzoate caffeine and caffeine citrate. Among these, caffeine hydrate, anhydrous caffeine, and sodium benzoate caffeine are preferable from the viewpoint of storage stability.

  The content of the xanthine derivative in the pharmaceutical composition of the present invention may be determined by appropriately examining the dose per day according to the sex, age, symptoms, etc. of the user, for example, per day, The amount that can be taken is 10 to 1000 mg, preferably 20 to 800 mg, more preferably 40 to 600 mg.

Moreover, as content of a xanthine derivative, 1-65 mass% is preferable with respect to the pharmaceutical composition total mass of this invention, 1-60 mass% is more preferable, 5-50 mass% is more preferable, 10-50 % By mass is more preferred, and 20-50% by mass is more preferred.
The mass ratio of fexofenadine or a salt thereof and a xanthine derivative in the pharmaceutical composition is preferably 1: 0.1 to 1:10, more preferably 1: 0.5 to 1: 5, and more preferably 1 : 1-1: 3 is more preferable.

(Tranexamic acid or its salt)
Tranexamic acid or a salt thereof used in the pharmaceutical composition of the present invention includes tranexamic acid itself, a pharmaceutically acceptable salt of tranexamic acid, and further, tranexamic acid or a pharmaceutically acceptable salt thereof, water, alcohol, etc. And solvates thereof. These are known compounds, and can be produced by known methods, or commercially available products can be used. Among such tranexamic acids or salts thereof, tranexamic acid is preferred from the viewpoint of use of the pharmaceutical composition of the present invention as an antipyretic analgesic, a general cold medicine, etc., and storage stability. Japanese Pharmacopoeia tranexamic acid Is preferred.

  The content of tranexamic acid or a salt thereof in the pharmaceutical composition of the present invention may be determined by appropriately examining the daily dose according to the sex, age, symptoms, etc. of the user, for example, tranexam An amount that can be taken is 50 to 2000 mg, preferably 70 to 750 mg, more preferably 400 to 750 mg per day in terms of free form of acid.

Moreover, as content of tranexamic acid or its salt, 10-60 mass% is preferable with respect to the pharmaceutical composition total mass of this invention, 15-50 mass% is more preferable, 20-45 mass% is further more preferable.
The mass ratio in the pharmaceutical composition of fexofenadine or a salt thereof and tranexamic acid or a salt thereof (in terms of tranexamic acid free form) is preferably 1: 1 to 1:10, and is preferably 1: 2 to 1: 5 is more preferable, and 1: 3 to 1: 4 is even more preferable.

(Basic compound with acid neutralization ability)
The basic compound having acid neutralizing ability used in the pharmaceutical composition of the present invention means a basic compound having acid neutralizing ability. Here, the “acid neutralizing ability” can be determined by conducting a test according to the antacid test method described in the 16th revised Japanese Pharmacopoeia General Test Method.
In the present invention, examples of the basic compound having acid neutralizing ability include alkaline earth metals such as magnesium, aluminum and calcium and / or earth metal basic inorganic compounds, and alkali metal bases such as sodium and potassium. Inorganic compounds, basic inorganic compounds such as amine basic inorganic compounds; alkaline earth metals such as magnesium, aluminum and calcium and / or earth metal basic organic compounds, alkali metal basic such as sodium and potassium Examples include basic organic compounds such as organic compounds and amine-based basic organic compounds. In addition, the basic compound which has acid neutralization ability may be individual, and may combine 2 or more types. These are known compounds, and can be produced by known methods, or commercially available products can be used.

The alkaline earth metal and / or earth metal basic inorganic compound is not particularly limited. For example, magnesium silicate, magnesium aluminate silicate, magnesium aluminum silicate, magnesium oxide, magnesium hydroxide, magnesium hydroxide, Co-precipitation product of potassium aluminum sulfate, magnesium carbonate, synthetic hydrotalcite, magnesium aluminate metasilicate, dry aluminum hydroxide gel, synthetic aluminum silicate, synthetic aluminum silicate, hydroxypropyl starch, crystalline cellulose, magnesium magnesium hydroxide , Aluminum hydroxide gel, Aluminum hydroxide / sodium bicarbonate coprecipitation product, Aluminum hydroxide / magnesium carbonate mixed dry gel, Aluminum hydroxide / magnesium carbonate / calcium carbonate coprecipitation Narubutsu, bentonite, calcium silicate, calcium carbonate, precipitated calcium carbonate, calcium hydrogen phosphate, magnesium such as anhydrous calcium hydrogen phosphate, metal inorganic salts selected from aluminum and calcium and the like.
Further, the alkali metal basic inorganic compound is not particularly limited. For example, dry sodium carbonate, sodium hydroxide, sodium hydrogen carbonate, sodium carbonate hydrate, tetrasodium pyrophosphate, trisodium phosphate, sodium hydrogen phosphate Inorganic salts of metals selected from sodium and potassium such as hydrate, anhydrous sodium pyrophosphate, anhydrous sodium hydrogen phosphate, potassium hydroxide, potassium hydrogen carbonate, potassium carbonate and the like.

  Among the basic inorganic compounds with acid neutralization ability as described above, coprecipitation of magnesium silicate, magnesium aluminate silicate, magnesium aluminum silicate, magnesium oxide, magnesium hydroxide, magnesium hydroxide and potassium aluminum sulfate , Magnesium carbonate, Synthetic hydrotalcite, Magnesium aluminate metasilicate, Dry aluminum hydroxide gel, Synthetic aluminum silicate, Synthetic aluminum silicate, Hydroxypropyl starch, Crystalline cellulose, Magnesium aluminate hydroxide, Aluminum hydroxide gel, Water Aluminum oxide / sodium bicarbonate coprecipitation product, aluminum hydroxide / magnesium carbonate mixed dry gel, aluminum hydroxide / magnesium carbonate / calcium carbonate coprecipitation product, bentonite, calcium silicate Um, calcium carbonate, precipitated calcium carbonate, calcium hydrogen phosphate, calcium hydrogen phosphate anhydrous, sodium bicarbonate is preferred.

In addition, the alkaline earth metal and / or earth metal-based basic organic compound is not particularly limited, and examples thereof include aldioxa, dihydroxyaluminum aminoacetate, sucralfate hydrate, and calcium pantothenate.
In addition, the alkali metal basic organic compound is not particularly limited. For example, sodium citrate hydrate, disodium succinate hexahydrate, DL-sodium tartrate, sodium L-tartrate, copper chlorophyllin sodium, polyacrylic Examples include sodium acid, 5′-ribonucleotide disodium, and copper chlorophyllin potassium.
The amine basic organic compound is not particularly limited, and examples thereof include aminoacetic acid, L-arginine, and meglumine.
Among the basic organic compounds having acid neutralizing ability as described above, aldioxa, dihydroxyaluminum aminoacetate and sucralfate hydrate are preferable.

  In the present invention, as the basic compound, a crude drug containing a basic compound such as bandit bone, stone decision, or oyster (oyster) may be used.

  In the present invention, preferred specific examples of the basic compound having acid neutralizing ability include aminoacetic acid, dry aluminum hydroxide gel, magnesium aluminate silicate, magnesium silicate, calcium silicate, magnesium aluminum silicate, One or more types selected from the group consisting of synthetic hydrotalcite, magnesium oxide, magnesium hydroxide, magnesium carbonate, precipitated calcium carbonate, anhydrous calcium hydrogen phosphate and magnesium aluminate metasilicate are included, and more preferably, interaction suppression In terms of aminoacetic acid, dry aluminum hydroxide gel, magnesium aluminate silicate, magnesium silicate, calcium silicate, synthetic hydrotalcite, magnesium oxide, magnesium hydroxide, magnesium carbonate, precipitated calcium carbonate, anhydrous phosphoric acid water One or more selected from the group consisting of calcium and magnesium aluminometasilicate and the like. Among these, what has magnesium as a structural component is preferable.

Moreover, as a basic compound which has the said acid neutralization ability, what can be used as an antacid is mentioned as a preferable specific example. Specific examples of basic compounds having acid neutralizing ability that can be used as antacids include, for example, aminoacetic acid, dry aluminum hydroxide gel, magnesium aluminate silicate, magnesium silicate, synthetic aluminum silicate, synthesis Hydrotalcite, magnesium oxide, dihydroxyaluminum aminoacetate, magnesium hydroxide magnesium, aluminum hydroxide gel, dry aluminum hydroxide gel, aluminum hydroxide / magnesium carbonate mixed dry gel, aluminum hydroxide / sodium bicarbonate coprecipitation product Coprecipitation product of aluminum hydroxide / calcium carbonate / magnesium carbonate, magnesium hydroxide, coprecipitation product of magnesium hydroxide / potassium aluminum sulfate, magnesium carbonate, sodium hydrogen carbonate, precipitated calcium carbonate, Magnesium aluminometasilicate, anhydrous calcium hydrogen phosphate, calcium hydrogen phosphate, cuttlefish bone, stone Ke'Akira, Borei like.
Antacids are broadly classified into absorbent antacids and local antacids due to their properties. In the present invention, local antacids are preferred from the viewpoint of preventing alkalosis.

  The content of the basic compound having acid neutralizing ability in the pharmaceutical composition of the present invention may be determined by appropriately examining the daily dose according to the sex, age, symptoms, etc. of the user. . For example, 1 to 20000 mg per day, preferably 10 to 10000 mg, more preferably 20 to 5000 mg can be included.

In addition, when using aminoacetic acid as a basic compound which has acid neutralization ability, the quantity which can be taken | dosed 1-2000 mg per day is preferable, and the quantity which can be taken | dosed 10-900 mg is more preferable.
When using aldioxa, the quantity which can be taken | dosed 10-800 mg per day is preferable, and the quantity which can be taken | dosed 30-400 mg is more preferable.
When using the bandage bone, the amount that can be taken 10 to 6000 mg per day is preferable, and the amount that can be taken 30 to 3000 mg is more preferable.
When using dry aluminum hydroxide gel, the quantity which can be taken | dosed 10-6000 mg per day is preferable, and the quantity which can be taken | dosed 30-3000 mg is more preferable.
When using magnesium aluminate silicate, the quantity which can be taken | dosed 10-8000 mg per day is preferable, and the quantity which can be taken | dosed 30-4000 mg is more preferable.
When using calcium silicate, the quantity which can be taken | dosed 1-600 mg per day is preferable, and the quantity which can be taken | dosed 30-300 mg is more preferable.
When using magnesium silicate, the quantity which can be taken | dosed 10-12000 mg per day is preferable, and the quantity which can be taken | dosed 30-6000 mg is more preferable.
When using magnesium aluminum silicate, the quantity which can be taken | dosed 1-500 mg per day is preferable, and the quantity which can be taken | dosed 20-225 mg is more preferable.
When using synthetic aluminum silicate, the quantity which can be taken | dosed 10-20000 mg per day is preferable, and the quantity which can be taken | dosed 30-10000 mg is more preferable.
When using synthetic aluminum silicate / hydroxypropyl starch / crystalline cellulose, the amount that can be taken 10 to 3500 mg per day is preferable, and the amount that can be taken 30 to 1800 mg is more preferable.
When using synthetic hydrotalcite, the quantity which can be taken | dosed 10-8000 mg per day is preferable, and the quantity which can be taken | dosed 30-4000 mg is more preferable.
When using magnesium oxide, the quantity which can be taken | dosed 10-2000 mg per day is preferable, and the quantity which can be taken | dosed 30-1000 mg is more preferable.
When using dihydroxyaluminum amino acetate, the quantity which can be taken | dosed 10-6000 mg per day is preferable, and the quantity which can be taken | dosed 30-3000 mg is more preferable.
When using alumina magnesium hydroxide, the quantity which can be taken | dosed 10-8000 mg per day is preferable, and the quantity which can be taken | dosed 30-4000 mg is more preferable.
When using aluminum hydroxide gel, the quantity which can be taken | dosed 10-6000 mg per day in conversion of dry aluminum hydroxide gel is preferable, and the quantity which can be taken | dosed 30-3000 mg is more preferable.
When using an aluminum hydroxide / sodium hydrogen carbonate coprecipitation product, the amount that can be taken 10 to 4000 mg per day is preferable, and the amount that can be taken 30 to 2000 mg is more preferable.
When using an aluminum hydroxide / magnesium carbonate mixed dry gel, the amount that can be taken 10 to 6000 mg per day is preferred, and the amount that can be taken 30 to 3000 mg is more preferred.
When using the aluminum hydroxide / magnesium carbonate / calcium carbonate coprecipitation product, the amount that can be taken 10 to 8000 mg per day is preferable, and the amount that can be taken 30 to 4000 mg is more preferable.
When using magnesium hydroxide, the quantity which can be taken | dosed 10-5000 mg per day is preferable, and the quantity which can be taken | dosed 30-2400 mg is more preferable.
When using the coprecipitation product of magnesium hydroxide and potassium aluminum sulfate, the amount that can be taken 10 to 4000 mg per day is preferable, and the amount that can be taken 30 to 2000 mg is more preferable.
When using sucralfate hydrate, the quantity which can be taken | dosed 10-6500 mg per day is preferable, and the quantity which can be taken | dosed 30-3250 mg is more preferable.
When using stone decision, the quantity which can be taken | dosed 10-6000 mg per day is preferable, and the quantity which can be taken | dosed 30-3000 mg is more preferable.
When using sodium hydrogencarbonate, the quantity which can be taken | dosed 10-10000 mg per day is preferable, and the quantity which can be taken | dosed 30-5000 mg is more preferable.
When using calcium carbonate, the quantity which can be taken | dosed 10-1500 mg per day is preferable, and the quantity which can be taken | dosed 30-700 mg is more preferable.
When using magnesium carbonate, the quantity which can be taken | dosed 10-4000 mg per day is preferable, and the quantity which can be taken | dosed 30-2000 mg is more preferable.
When using precipitated calcium carbonate, the quantity which can be taken | dosed 10-6000 mg per day is preferable, and the quantity which can be taken | dosed 30-3000 mg is more preferable.
When using bentonite, the quantity which can be taken | dosed 1-200 mg per day is preferable, and the quantity which can be taken | dosed 10-100 mg is more preferable.
When using a oyster (oyster), the quantity which can be taken | dosed 10-6000 mg per day is preferable, and the quantity which can be taken | dosed 30-3000 mg is more preferable.
When using anhydrous calcium hydrogenphosphate, the quantity which can be taken | dosed 10-5000 mg per day is preferable, and the quantity which can be taken | dosed 30-2400 mg is more preferable.
When using magnesium aluminate metasilicate, the quantity which can be taken | dosed 10-8000 mg per day is preferable, and the quantity which can be taken | dosed 30-4000 mg is more preferable.
When using calcium hydrogenphosphate, the quantity which can be taken | dosed 10-9000 mg per day is preferable, and the quantity which can be taken | dosed 30-4500 mg is more preferable.

Moreover, as content of the basic compound which has acid neutralization ability, 1-99 mass% is preferable with respect to the pharmaceutical composition total mass of this invention, 10-95 mass% is more preferable, 15-90 mass% Is more preferable, 15-85 mass% is further more preferable, and 20-80 mass% is especially preferable.
The mass ratio in the pharmaceutical composition of fexofenadine or a salt thereof and a basic compound having acid neutralizing ability is preferably 1: 0.1 to 1: 100, and 1: 0.5 to 1 : 50 is more preferred, 1: 1 to 1:40 is more preferred, and 1: 1 to 1:35 is even more preferred.

(Ascorbic acid or its salt)
Ascorbic acid or a salt thereof used in the pharmaceutical composition of the present invention includes ascorbic acid itself, a pharmaceutically acceptable salt of ascorbic acid, further ascorbic acid or a pharmaceutically acceptable salt thereof, water, alcohol, etc. And solvates thereof. These are known compounds, and can be produced by known methods, or commercially available products can be used. Among such ascorbic acid or a salt thereof, ascorbic acid and sodium ascorbate are preferable from the viewpoint of use of the pharmaceutical composition of the present invention as an antipyretic analgesic or a general cold medicine and storage stability. Pharmacopoeia ascorbic acid is preferred.

  The content of ascorbic acid or a salt thereof in the pharmaceutical composition of the present invention may be determined by appropriately examining the daily dose according to the sex, age, symptoms, etc. of the user. Ascorbic acid can be contained in an amount of 10 to 1000 mg, preferably 30 to 750 mg, and more preferably 50 to 500 mg per day.

Moreover, as content of ascorbic acid or its salt, 5-75 mass% is preferable with respect to the pharmaceutical composition total mass of this invention, 10-70 mass% is more preferable, 20-65 mass% is further more preferable, 30-65 mass% is further more preferable.
The mass ratio in the pharmaceutical composition of fexofenadine or a salt thereof and ascorbic acid or a salt thereof (ascorbic acid-free body equivalent) is preferably 1: 2 to 1: 7, and is preferably 1: 3 to 1: 6 is more preferable, and 1: 4 to 1: 5 is more preferable.

The pharmaceutical composition of the present invention can be formulated into various dosage forms by using known formulation additives according to known methods described in the 16th revised Japanese Pharmacopoeia General Rules for Preparations. The dosage form of the pharmaceutical composition may be an oral pharmaceutical composition or a parenteral pharmaceutical composition, and is not particularly limited, but is preferably a solid preparation. Specific examples of solid preparations include, for example, tablets (orally disintegrating tablets, chewable tablets, dispersible tablets, dissolving tablets; including oral tablets such as troches, sublingual tablets, buccal tablets, adhesive tablets, and gums) Examples include oral preparations such as capsules, pills, granules, fine granules, powders, dry syrups, oral jelly, and parenteral preparations such as suppositories, vaginal tablets, and vaginal suppositories. A formulation is preferred.
In addition, the pharmaceutical composition of the present invention may be coated with a sugar coating or a film coating by a known method. Further, fexofenadine or a salt thereof and NSAID may be granulated. Storage stability is further improved by granulating.

  In addition, the pharmaceutical composition of the present invention includes drugs other than the above components (A) to (C), such as antihistamines, antitussives, noscapines, bronchodilators, expectorants, hypnotic sedatives, vitamins, anti-inflammatory agents , One or more selected from the group consisting of a gastric mucosa protective agent, an anticholinergic agent, a herbal medicine, a Kampo prescription, and the like may be included.

  Antihistamines include, for example, azelastine hydrochloride, alimemazine tartrate, istipendil hydrochloride, iproheptin hydrochloride, epinastine hydrochloride, emedastine fumarate, carbinoxamine diphenyl disulfonate, carbinoxamine maleate, clemastine fumarate. Acid salt, dl-chlorpheniramine maleate, d-chlorpheniramine maleate, ketotifen fumarate, dipheterol hydrochloride, dipheterol phosphate, diphenylpyraline hydrochloride, diphenylpyraline theocrate, diphenhydramine Hydrochloride, diphenhydramine tannate, triprolidine hydrochloride, tripelenamine hydrochloride, tondylamine hydrochloride, phenetazine hydrochloride, promethazine hydrochloride, mequitazine, methodirazine hydrochloride, mebhydro N'napajishiru salts include emetine Das Chin fumarate salt.

  Antitussives include, for example, aloclamide hydrochloride, eprazinone hydrochloride, carbetapentane enoate, cloperastine hydrochloride, cloperastine phendizoate, codeine phosphate, dihydrocodeine phosphate, dibutarate sodium, dimemorphan Examples thereof include phosphate, dextromethorphan hydrobromide, dextromethorphan / phenol phthaline salt, tipepidine citrate, and tipepidine hibenzate.

  Examples of noscapine include noscapine hydrochloride and noscapine.

  Examples of bronchodilators include trimethquinol hydrochloride, phenylpropanolamine hydrochloride, phenylephrine hydrochloride, pseudoephedrine hydrochloride, pseudoephedrine sulfate, methylephedrine, dl-methylephedrine hydrochloride, l-methylephedrine hydrochloride, dl. -Methylephedrine saccharin salt, methoxyphenamine hydrochloride, etc. are mentioned.

  As an expectorant, for example, ambroxol hydrochloride, ammonia fennel, ethylcysteine hydrochloride, ammonium chloride, carbocysteine, guaifenesin, potassium guaiacolsulfonate, potassium cresolsulfonate, bromhexine hydrochloride, methylcysteine hydrochloride, And lysozyme hydrochloride.

  Examples of the hypnotic sedative include allyl isopropyl acetyl urea and bromovalerylurea.

Examples of vitamins include vitamin B ₁ , vitamin B ₂ , vitamin B ₅ , vitamin B ₆ , vitamin B ₁₂ , 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, bisivethiamine, bisbenchamine, prosultiamine, benfotiamine, riboflavin, riboflavin phosphate, riboflavin Butyrate, sodium riboflavin phosphate, panthenol, pantethine, calcium pantothenate, sodium pantothenate, pyridoxine hydrochloride, pyridoxal phosphate, cyanocobalamin, mecobalamin, hesper Lysine, etc.).

  Examples of the anti-inflammatory agent include glycyrrhizic acid and derivatives thereof and salts thereof (for example, dipotassium glycyrrhizinate and 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, for example, oxyphencyclimine hydrochloride, dicyclomine hydrochloride, methixene hydrochloride, scopolamine hydrobromide, datsura extract, tipidium bromide, methyl atropine bromide, methyl anisotropin bromide, methyl scopolamine bromide, methyl- l-hyostiamine bromide, methylbenactidium bromide, pirenzepine hydrochloride, belladonna alkaloid, belladonna extract, belladonna total alkaloid, iodide isopropamide, diphenylpiperidinomethyldioxolane iodide, funnel extract, funnel root, funnel root total alkaloid quench Examples include acid salts.

  Herbal medicines include, for example, akamegashiwa (red buds), asenyaku (asenyaku), inyoukaku (horny lamb), fennel (yuka), turmeric (depressed gold), engosaku (yenkogyo), enmaiso (extended herb), ogon (yellow jade) ), Ousei (yellow spirit), Owaku (yellow twilight), Spruce (cherry bark), Auren (yellow ream), Onji (distant), Gajutsu (weather), valerian (deer grass), chamomile, caronin (karojin), Licorice, licorice, bellflowers, kokushi (coconut), cucumber (cucumber leaves), keigai (cocoon), keihi (cinnamon), ketsumeishi (actual child), gentian, gennoshouko (current evidence), Koubushi (Kosuke), Gooh (Gyuhuang), Goshi (Gomiko), Saishin (Spicy), Salamander (Sambu), Zion (Purple), Zykopi (Peel), Peonies (Glue), Ji Jakkou, Shajin, Shazenshi (car forerunner), Shazenso (car forerunner), Beast gall (including yutan (gum gal)), Shakyo (ginger), Giryu (land dragon), Xinyi ), Sexan (Ishizuchi), Senega, Senkyu (Ryukyu), Zenko (Mae-Hu), Senburi (Senshu), Sojutsu (蒼朮), Sohakuhi (Mulberry white skin), Soyo (Soba), Taisan (Oiso), Chixetsu Carrot (Takebushi Ginseng), Clove (Chiko), Chimp (Chan), Toki (Toki), Tokon (Nanten), Carrot (Ginseng), Baimo (Shell), Bacmond (Wheat) Gate winter), mint (thin load), Hange (half-summer), bankouka (Banka), Hampi (anti-nose), peony (white bean), peanut (white moth), bukuryo (茯苓), button pi (peony skin), maou (Mao), herbal medicines such as Lokujo (deer) These extracts (extract, tincture, dry extract, etc.) and the like.

  The Kampo prescription includes, for example, Kakkon-to, Katsue-yu, Koso-san, Saiko-Kei-to, Sho-saiko-to, Shosei-ryu, Mumon-tou-yu, Hanka-kopaku-to, Mao-to, and the like.

  And the pharmaceutical composition of this invention is excellent in storage stability. Thereby, even after being stored for a long time or after being stored under harsh conditions, the effects and functions of fexofenadine and NSAID are sufficiently exerted, and xanthine derivatives, tranexamic acid or salts thereof, acids The effect | action and function which 1 or more types chosen from the basic compound which has neutralization ability, and ascorbic acid or its salt are also show | played.

  The pharmaceutical composition of the present invention contains NSAID having an action as an antipyretic analgesic and fexofenadine having an antihistamine action or a salt thereof. For this reason, the pharmaceutical composition of the present invention is preferably used as a general cold medicine (cold medicine), etc. As its efficacy and effect, various symptoms of cold (throat pain, chills, fever, headache, joints) Pain, muscle pain) and the like.

  In the method for suppressing the interaction between fexofenadine or a salt thereof and NSAID of the present invention, “to coexist” means that fexofenadine or a salt thereof and NSAID are the same regardless of the order of mixing. It means that a state existing in the system (for example, in the same closed system in the composition) is directly or indirectly created. Specifically, the state existing in the closed system means that fexofenadine or a salt thereof and NSAID exist in a container that can be used as a container for food, supplements, pharmaceuticals, health foods, and the like. State. As a container, regardless of a fixed shape and an irregular shape, examples of the fixed shape container include a bottle, a can, and a box. Examples of the amorphous container include bags (pillow packaging, stick packaging, PTP packaging, SP packaging, etc.) and the like. Of these containers, bottles and bags are preferable from the viewpoint of easy storage. As a mode of coexisting in this manner, a mode in which fexofenadine or a salt thereof and NSAID are contained in the pharmaceutical composition is preferable.

  EXAMPLES Hereinafter, although an Example is given and this invention is demonstrated in detail, this invention is not limited to these Examples.

Test Example 1 Examination of storage stability of fexofenadine and NSAID (1)
1 part by weight of ibuprofen was placed in a glass bottle and stored at 80 ° C. Moreover, 1 part by mass of loxoprofen sodium hydrate and 1 part by mass of fexofenadine hydrochloride were put in glass bottles and stored at 50 ° C.
About these, the state of the sample 1 hour later, 2 hours later, 3 hours later, 4 hours later, and 6 hours after storage start was observed and evaluated with the naked eye. The results are shown in Table 1.

  As shown in Table 1, when ibuprofen was stored alone, ibuprofen solidified in the bottle. On the other hand, when loxoprofen sodium hydrate and fexofenadine hydrochloride were each stored alone, no change in state was observed from immediately after the start of storage even after 6 hours.

Test Example 2 Examination of storage stability of a mixture of fexofenadine and NSAID (1)
400 parts by mass of ibuprofen was put in a glass bottle and stored at 80 ° C. (Comparative Example 1). Similarly, a mixture of 400 parts by weight of ibuprofen and 120 parts by weight of fexofenadine hydrochloride was put in another glass bottle and stored at 80 ° C. (Comparative Example 2).
About these comparative examples 1 and 2, the state of the sample 1 hour later, 2 hours later, 3 hours later, 4 hours later, and 6 hours immediately after the start of storage was visually observed and evaluated. The results are shown in Table 2.

  As shown in Table 2, when ibuprofen was stored alone, the powder remained solidified (Comparative Example 1), whereas when a mixture of ibuprofen and fexofenadine hydrochloride was stored, it melted. It was found that there was a serious problem with respect to storage stability (Comparative Example 2).

Test Example 3 Examination of storage stability of a mixture of fexofenadine and NSAID (2)
400 parts by mass of ibuprofen and 120 parts by mass of fexofenadine hydrochloride were further mixed with 300 parts by mass of magnesium aluminate metasilicate, and the mixture was placed in a glass bottle and stored at 80 ° C. (Example 1).
Further, 400 parts by mass of ibuprofen and 120 parts by mass of fexofenadine hydrochloride were mixed with 500 parts by mass of ascorbic acid, and the mixture was placed in a glass bottle and stored at 80 ° C. (Example 2).
Further, 400 parts by mass of ibuprofen and 120 parts by mass of fexofenadine hydrochloride were mixed with 420 parts by mass of tranexamic acid, and the mixture was put in a glass bottle and stored at 80 ° C. (Example 3).
Regarding Examples 1 to 3, the state of the samples immediately after the start of storage, 1 hour, 2 hours, 3 hours, 4 hours, and 6 hours was observed and evaluated with the naked eye. The results are shown in Table 3.

  As shown in Table 3, a mixture of three components in which magnesium aluminate metasilicate, ascorbic acid or tranexamic acid is added to ibuprofen and fexofenadine hydrochloride maintains the state immediately after the start of storage, and the aluminate metasilicate It has been found that the use of magnesium, ascorbic acid or tranexamic acid eliminates the storage stability problem in a mixture of ibuprofen and fexofenadine hydrochloride.

Test Example 4 Examination of storage stability of a mixture of fexofenadine and NSAID (3)
The mixtures of Comparative Example 3 and Examples 4 to 12 shown below were prepared, put into glass bottles, and stored at 50 ° C.
Comparative Example 3: A mixture of 204.3 parts by mass of loxoprofen sodium hydrate (180 parts by mass in terms of anhydrous loxoprofen sodium) and 120 parts by mass of fexofenadine hydrochloride.
Example 4: A mixture of 204.3 parts by mass of loxoprofen sodium hydrate, 120 parts by mass of fexofenadine hydrochloride and 2000 parts by mass of magnesium carbonate.
Example 5: A mixture of 204.3 parts by mass of loxoprofen sodium hydrate, 120 parts by mass of fexofenadine hydrochloride and 1500 parts by mass of magnesium aluminate metasilicate.
Example 6: Mixture of 204.3 parts by mass of loxoprofen sodium hydrate, 120 parts by mass of fexofenadine hydrochloride and 300 parts by mass of magnesium aluminate metasilicate.
Example 7: Mixture of 204.3 parts by mass of loxoprofen sodium hydrate, 120 parts by mass of fexofenadine hydrochloride and 500 parts by mass of magnesium oxide.
Example 8: A mixture of 204.3 parts by mass of loxoprofen sodium hydrate, 120 parts by mass of fexofenadine hydrochloride and 4000 parts by mass of synthetic hydrotalcite.
Example 9: Mixture of 204.3 parts by mass of loxoprofen sodium hydrate, 120 parts by mass of fexofenadine hydrochloride and 400 parts by mass of synthetic hydrotalcite.
Example 10: Mixture of 204.3 parts by mass of loxoprofen sodium hydrate, 120 parts by mass of fexofenadine hydrochloride and 150 parts by mass of anhydrous caffeine.
Example 11: A mixture of 204.3 parts by mass of loxoprofen sodium hydrate, 120 parts by mass of fexofenadine hydrochloride and 300 parts by mass of sodium caffeine benzoate.
Example 12: Mixture of 204.3 parts by mass of loxoprofen sodium hydrate, 120 parts by mass of fexofenadine hydrochloride and 500 parts by mass of ascorbic acid.
About the mixture of these comparative examples 3 and Examples 4-12, the state of the sample immediately after the start of storage, 1 hour, 2 hours, 3 hours, 18 hours, 24 hours and 42 hours was observed with the naked eye. evaluated. The results are shown in Table 4.

As shown in Table 4, it was found that when a mixture of loxoprofen sodium hydrate and fexofenadine hydrochloride was stored, it solidified and caused storage stability problems (Comparative Example 3).
On the other hand, a mixture of three components obtained by adding a third component such as magnesium carbonate used in Examples 4 to 12 to loxoprofen sodium hydrate and fexofenadine hydrochloride maintains the state immediately after the start of storage. It has been found that the use of a third component such as magnesium carbonate eliminates the storage stability problem in the mixture of loxoprofen and fexofenadine hydrochloride (Examples 4 to 12).

Production Example 1 Tablet (Tablet containing 204.3 mg of loxoprofen, 120 mg of fexofenadine hydrochloride and 2000 mg of magnesium carbonate)
Loxoprofen sodium hydrate (manufactured by Yamato Pharmaceutical Co., Ltd .: trade name: Japanese Pharmacopoeia Loxoprofen sodium hydrate) 408.6 parts by mass, fexofenadine hydrochloride 240 parts by mass, magnesium carbonate 4000 parts by mass, hydroxypropyl cellulose (manufactured by Nippon Soda) : Trade name HPC-M) 145.8 parts by mass, carmellose calcium (product name: ECG505) 486 parts by mass, crystalline cellulose (product name: Theolas PH-101) 1771 parts by mass, 243 parts by mass of purified water was added and kneaded to obtain a granulated product. The resulting granulated product is sized and mixed with 4811.4 parts by mass of the sized product and 48.1 parts by mass of magnesium stearate (trade name: magnesium stearate (vegetable) manufactured by Taihei Chemical Industry). Tablets were obtained.

Production Example 2 Tablet (Tablet containing 204.3 mg of loxoprofen, 120 mg of fexofenadine hydrochloride and 300 mg of magnesium aluminate metasilicate)
Magnesium carbonate was replaced with magnesium aluminate metasilicate in the same manner as in Production Example 1 to obtain a tablet having the following composition.
Loxoprofen 204.3 parts by weight Fexofenadine hydrochloride 120 parts by weight Magnesium aluminate metasilicate 300 parts by weight Hydroxypropyl cellulose 48.6 parts by weight Carmellose calcium 162 parts by weight Crystalline cellulose 738.9 parts by weight Magnesium stearate 16.2 parts by weight Part

Production Example 3 Tablet (tablet containing 204.3 mg of loxoprofen, 120 mg of fexofenadine hydrochloride and 500 mg of magnesium oxide)
Magnesium carbonate was replaced with magnesium oxide, and tablets having the following composition were obtained in the same manner as in Production Example 1.
Loxoprofen 204.3 parts by weight Fexofenadine hydrochloride 120 parts by weight Magnesium oxide 500 parts by weight Hydroxypropyl cellulose 48.6 parts by weight Carmellose calcium 162 parts by weight Crystalline cellulose 738.9 parts by weight Magnesium stearate 16.2 parts by weight

Production Example 4 Tablet (tablet containing 204.3 mg of loxoprofen, 120 mg of fexofenadine hydrochloride and 4000 mg of synthetic hydrotalcite)
Magnesium carbonate was replaced with synthetic hydrotalcite, and tablets having the following composition were obtained in the same manner as in Production Example 1.
Loxoprofen 204.3 parts by weight Fexofenadine hydrochloride 120 parts by weight Synthetic hydrotalcite 4000 parts by weight Hydroxypropyl cellulose 48.6 parts by weight Carmellose calcium 162 parts by weight Crystalline cellulose 738.9 parts by weight Magnesium stearate 16.2 parts by weight

Production Example 5 Tablet (tablet containing 204.3 mg of loxoprofen, 120 mg of fexofenadine hydrochloride and 150 mg of anhydrous caffeine)
Magnesium carbonate was replaced with anhydrous caffeine, and tablets having the following composition were obtained in the same manner as in Production Example 1.
Loxoprofen 204.3 parts by weight Fexofenadine hydrochloride 120 parts by weight Anhydrous caffeine 150 parts by weight Hydroxypropyl cellulose 48.6 parts by weight Carmellose calcium 162 parts by weight Crystalline cellulose 738.9 parts by weight Magnesium stearate 16.2 parts by weight

Production Example 6 Tablet (tablet containing 204.3 mg of loxoprofen, 120 mg of fexofenadine hydrochloride and 300 mg of sodium caffeine benzoate)
Magnesium carbonate was replaced with sodium benzoate caffeine, and tablets having the following composition were obtained in the same manner as in Production Example 1.
Loxoprofen 204.3 parts by weight Fexofenadine hydrochloride 120 parts by weight Sodium caffeine benzoate 300 parts by weight Hydroxypropyl cellulose 48.6 parts by weight Carmellose calcium 162 parts by weight Crystalline cellulose 738.9 parts by weight Magnesium stearate 16.2 parts by weight Part

Production Example 7 Tablet (tablet containing 204.3 mg of loxoprofen, 120 mg of fexofenadine hydrochloride and 500 mg of ascorbic acid)
Magnesium carbonate was replaced with ascorbic acid, and tablets of the following composition were obtained in the same manner as in Production Example 1.
Loxoprofen 204.3 parts by weight Fexofenadine hydrochloride 120 parts by weight Ascorbic acid 500 parts by weight Hydroxypropyl cellulose 48.6 parts by weight Carmellose calcium 162 parts by weight Crystalline cellulose 738.9 parts by weight Magnesium stearate 16.2 parts by weight

Production Example 8 Tablet (tablet containing 400 mg of ibuprofen, 120 mg of fexofenadine hydrochloride and 300 mg of magnesium aluminate metasilicate)
Loxoprofen sodium hydrate was replaced with ibuprofen, and tablets having the following composition were obtained in the same manner as in Production Example 2.
Ibuprofen 400 parts by weight Fexofenadine hydrochloride 120 parts by weight Magnesium aluminate metasilicate 300 parts by weight Hydroxypropyl cellulose 48.6 parts by weight Carmellose calcium 162 parts by weight Crystalline cellulose 739.2 parts by weight Magnesium stearate 16.2 parts by weight

Production Example 9 Tablet (tablet containing 400 mg of ibuprofen, 120 mg of fexofenadine hydrochloride and 500 mg of ascorbic acid)
In the same manner as in Production Example 8, tablets with the following composition were obtained by replacing magnesium aluminate metasilicate with ascorbic acid.
Ibuprofen 400 parts by weight Fexofenadine hydrochloride 120 parts by weight Ascorbic acid 500 parts by weight Hydroxypropyl cellulose 48.6 parts by weight Carmellose calcium 162 parts by weight Crystalline cellulose 739.2 parts by weight Magnesium stearate 16.2 parts by weight

Production Example 10 Tablet (tablet containing 400 mg of ibuprofen, 120 mg of fexofenadine hydrochloride and 420 mg of tranexamic acid)
In the same manner as in Production Example 8, tablets with the following composition were obtained by replacing magnesium aluminate metasilicate with tranexamic acid.
Ibuprofen 400 parts by weight Fexofenadine hydrochloride 120 parts by weight Tranexamic acid 420 parts by weight Hydroxypropyl cellulose 48.6 parts by weight Carmellose calcium 162 parts by weight Crystalline cellulose 739.2 parts by weight Magnesium stearate 16.2 parts by weight

  ADVANTAGE OF THE INVENTION According to this invention, the sublimation of the sublimation drug can be suppressed and the pharmaceutical composition containing the sublimation drug excellent in storage stability can be provided. Since loxoprofen or a salt thereof, which functions as a sublimation inhibitor for a sublimation drug, has an antipyretic analgesic action, the pharmaceutical composition of the present invention not only exhibits the action of a sublimation drug, but also exhibits an antipyretic analgesic action. is there.

Claims (4)

  A pharmaceutical composition comprising fexofenadine or a salt thereof, loxoprofen or a salt thereof and a basic compound having an acid neutralizing ability.   The pharmaceutical composition according to claim 1, wherein the loxoprofen or a salt thereof is loxoprofen sodium hydrate.   The pharmaceutical composition according to claim 1 or 2, wherein the content of loxoprofen or a salt thereof is 10 to 300 mg as a daily dose in terms of anhydrous loxoprofen sodium.   The pharmaceutical composition according to any one of claims 1 to 3, wherein the dosage form is a solid preparation.