JP2004083579A - Antipyretic composition - Google Patents
Antipyretic composition Download PDFInfo
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- JP2004083579A JP2004083579A JP2003186658A JP2003186658A JP2004083579A JP 2004083579 A JP2004083579 A JP 2004083579A JP 2003186658 A JP2003186658 A JP 2003186658A JP 2003186658 A JP2003186658 A JP 2003186658A JP 2004083579 A JP2004083579 A JP 2004083579A
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- antipyretic
- salt
- ketotifen
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- phenylpropionic acid
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Abstract
Description
【0001】
【発明の属する技術分野】
本発明は、フェニルプロピオン酸系解熱消炎鎮痛剤とケトチフェンとを含有する解熱剤組成物に関する。
【0002】
【従来の技術】
フェニルプロピオン酸系解熱消炎鎮痛剤は、解熱剤として広範囲に使用されている。この中でも、例えば本邦では、ロキソプロフェン、イブプロフェン、アルミノプロフェン、チアプロフェン、フェノプロフェン又はプラノプロフェン等は、感冒などの急性上気道炎の解熱にも投与されている。
【0003】
一方、抗ヒスタミン剤は感冒などの上気道炎に伴う鼻汁等を抑えるためにも投与され、非ステロイド解熱消炎鎮痛剤と併用されることもある。
【0004】
フェニルプロピオン酸系解熱消炎鎮痛剤とケトチフェンとの公知併用例としては、
1)ロキソプロフェンとケトチフェンとの併用で鼻閉症状を有する患者の嗅覚改善に優れた効果のある旨の記載(特許文献1参照)、
2)イブプロフェン、リン酸コデイン、フマル酸ケトチフェン、無水カフェインの配合剤Aと、これにフマル酸ケトチフェンを除いた配合剤Bとの比較の結果、AがBに較べ鎮咳効果が優れる旨の記載(特許文献2参照)が挙げられる。
【0005】
また、本発明に関連すると思われるその他の公知併用例としては、
3)ロキソプロフェンと、抗ヒスタミン剤のマレイン酸カルビノキサミンとの併用で、解熱作用が増強(特許文献3参照)する旨の開示が挙げられる。
【0006】
【特許文献1】
特開2001−199882号公報
【特許文献2】
特開平10−45595号公報
【特許文献3】
特開2000−143505号公報
【0007】
【発明が解決しようとする課題】
しかし、ロキソプロフェンが、どの抗ヒスタミン剤と併用しても解熱作用が増強するわけではなく、さらにまた、フェニルプロピオン酸系解熱消炎鎮痛剤とケトチフェンとの併用により解熱作用が増強したという報告は存在しない。
【0008】
そこで本発明者らは、非ステロイド解熱消炎鎮痛剤と併用して解熱作用が顕著に増強する薬剤の組合せを見出すべく、研究を行った。
【0009】
その結果、フェニルプロピオン酸系解熱消炎鎮痛剤とケトチフェンとの併用により解熱効果が増強されることを見出して本発明を完成させた。
【0010】
【課題を解決するための手段】
本発明は、
(1)フェニルプロピオン酸系解熱消炎鎮痛剤とケトチフェンとを含有する解熱剤組成物であり、好適には、
(2)ロキソプロフェン及び/又はイブプロフェンと、ケトチフェンとを含有する解熱剤組成物であり、またさらに
(3)感冒剤に用いることを特徴とする、(1)又は(2)記載の解熱剤組成物である。
【0011】
ケトチフェンとは、ケトチフェンまたはその薬理上許容される塩を示す。
【0012】
ここで、薬理上許容される塩としては、例えば、フッ化水素酸塩、塩酸塩、臭化水素酸塩、ヨウ化水素酸塩のようなハロゲン化水素酸塩;硝酸塩、過塩素酸塩、硫酸塩、リン酸塩等の無機酸塩;メタンスルホン酸塩、トリフルオロメタンスルホン酸塩、エタンスルホン酸塩のような低級有機スルホン酸塩;ベンゼンスルホン酸塩、p−トルエンスルホン酸塩等のようなアリールスルホン酸塩;オルニチン酸塩、グルタミン酸塩のようなアミノ酸塩;及びフマル酸、コハク酸、クエン酸、酒石酸、シュウ酸、マレイン酸のようなカルボン酸塩を挙げられ、好適にはフマル酸塩が挙げられる。
【0013】
フェニルプロピオン酸系解熱消炎鎮痛剤としては、例えば、フェニルプロピオン酸骨格を持つ解熱作用、消炎作用及び/又は鎮痛作用を持つ薬剤のことで、例えば、アルミノプロフェン、イブプロフェン、オキサプロジン、ザルトプロフェン、チアプロフェン(酸)、ナブメトン、ナプロキセン、フェノプロフェン(カルシウム)、プラノプロフェン、フルルビプロフェン又はロキソプロフェン(ナトリウム)が挙げられ、好適には、アルミノプロフェン、イブプロフェン、チアプロフェン(酸)、フェノプロフェン(カルシウム)、プラノプロフェン又はロキソプロフェン(ナトリウム)が挙げられ、さらに好適には、イブプロフェン又はロキソプロフェン(ナトリウム)が挙げられる。
【0014】
ロキソプロフェンとは、ロキソプロフェン、その薬理上許容される塩及び/又はその水和物をしめす。
【0015】
ここで、その薬理上許容される塩とは、ナトリウム塩、カリウム塩、リチウム塩のようなアルカリ金属塩、カルシウム塩、マグネシウム塩のようなアルカリ土類金属塩、アルミニウム塩、鉄塩、亜鉛塩、銅塩、ニッケル塩、コバルト塩等の金属塩;アンモニウム塩のような無機塩、t−オクチルアミン塩、ジベンジルアミン塩、モルホリン塩、グルコサミン塩、フェニルグリシンアルキルエステル塩、エチレンジアミン塩、N−メチルグルカミン塩、グアニジン塩、ジエチルアミン塩、トリエチルアミン塩、ジシクロヘキシルアミン塩、N,N’−ジベンジルエチレンジアミン塩、クロロプロカイン塩、プロカイン塩、ジエタノールアミン塩、N−ベンジル−フェネチルアミン塩、ピペラジン塩、テトラメチルアンモニウム塩、トリス(ヒドロキシメチル)アミノメタン塩のような有機塩等のアミン塩を挙げる事ができ、好適にはナトリウム塩が挙げられる。
【0016】
これらのうち、好適にはロキソプロフェンナトリウム・2水和物である。
【0017】
【発明の実施の形態】
フェニルプロピオン酸系解熱消炎鎮痛剤のうち、イブプロフェン又はロキソプロフェン等は第十四改正日本薬局方に収載されており、容易に入手しうる。
【0018】
フマル酸ケトチフェンは医薬品として市販されており、(株)ワイ・アイ・シーより入手し得る。
【0019】
本発明の解熱薬が固形製剤の場合において含有される、フェニルプロピオン酸系解熱消炎鎮痛剤の重量%は通常、0.01乃至30%であり、好適には、0.1乃至10%であり、また、ケトチフェンの重量%は通常、0.0001乃至0.5%であり、好適には、0.001乃至0.2%である。
【0020】
本発明の解熱薬が液剤の場合において含有される、フェニルプロピオン酸系解熱消炎鎮痛剤の含有量は通常、0.1乃至100mg/mLであり、好適には、1乃至50mg/mLであり、また、ケトチフェンの含有量は通常、0.001乃至2mg/mLであり、好適には、0.01乃至1mg/mLである。
【0021】
本発明においては、上記有効成分の他、必要に応じてカフェイン類、鎮咳薬、去痰薬、ビタミン類、生薬などを本発明の効果を損なわない範囲で配合することができる。
【0022】
本発明の解熱剤の具体的な剤形としては、例えば、錠剤、細粒剤(散剤を含む)、カプセル、液剤(シロップ剤を含む)等をあげることができ、各剤形に適した添加剤や基材を適宜使用し、日本薬局方等に記載された通常の方法に従い、製造することができる。
【0023】
上記各剤形において、その剤形に応じ、通常使用される各種添加剤を使用することもできる。
【0024】
例えば、錠剤の場合、乳糖、結晶セルロース等を賦形剤として、メタケイ酸アルミン酸マグネシウム又は酸化マグネシウム等を安定化剤として、ヒドロキシプロピルセルロース等をコーテイング剤として、ステアリン酸マグネシウム等を滑沢剤として、使用することができ、
細粒剤及びカプセル剤の場合、乳糖又は精製白糖等を賦形剤として、メタケイ酸アルミン酸マグネシウム又は酸化マグネシウム等を安定化剤として、トウモロコシデンプン等を吸着剤として、ヒドロキシプロピルセルロース等を結合剤として、使用することができる。
【0025】
上記各剤形において、必要に応じ、クロスポビドン等の崩壊剤;ポリソルベート等の界面活性剤;ケイ酸カルシウム等の吸着剤;三二酸化鉄、カラメル等の着色剤;安息香酸ナトリウム等の安定剤;pH調節剤;香料;等を添加することもできる。
【0026】
【実施例】
以下に、実施例等を示し、本発明をさらに詳細に説明するが、本発明の範囲はこれらに限定されるものではない。
(実施例1)錠剤
(1)成分
【0027】
【表1】
(2)製法
上記成分及び分量をとり、日局製剤総則「錠剤」の項に準じて錠剤を製する。
(実施例2)細粒剤
(1)成分
【0028】
【表2】
(2)製法
上記成分及び分量をとり、日局製剤総則「顆粒剤」の項に準じて細粒剤を製する。
実施例(3)カプセル剤
(1)成分
【0029】
【表3】
(2)製法
上記成分及び分量をとり、日局製剤総則「顆粒剤」の項に準じて細粒剤を製した後、カプセルに充てんして硬カプセル剤を製する。
実施例(4)シロップ剤
(1)成分
【0030】
【表4】
(2)製法
上記成分及び分量をとり、日局製剤総則「シロップ剤」の項に準じてシロップ剤を製した後、褐色ガラス瓶に充てんしてシロップ剤を製する。
(試験例 1 )解熱効果
(1)被験物質
被験物質は、試験前日もしくは当日に0.5%トラガント液で懸濁液にして調製した。前日に調製した場合は、使用時まで冷蔵庫に保管する。被験物質の投与液量は、体重1Kgあたり2.5mLとし、対照群には同量の0.5%トラガント液を投与した。
(2)動物
Wister−Imamichi雄性ラット5週齢(動物繁殖研究所より購入)を、温度20〜26℃、湿度30〜70%、照明時間7時〜19時に制御された環境制御飼育装置(日本クレア製)内で、ステンレス製ラット飼育ゲージに5〜6匹入れ、飼料(マウス・ラット飼育用F−2、船橋農場製)および水フィルターを通した水道水を自由に摂取させて、5〜9日間の予備飼育後、試験前日に肉眼的に健康状態を観察し良好な動物を選別して絶食(約20時間、水は自由摂取)させる。
(3)方法
(a)イーストによる発熱の誘発
イースト液は、ビール酵母(イースト、シグマ化学)に生理食塩液(大塚製薬)を加えて25%濃度に調製し、試験前日にラットの背部皮下にイースト液を2.0mL投与して発熱を誘発させる。
(b)群分け
イースト投与約20時間後に、サーミスタ温度計(MGAIII 日本光電工業製)を直腸内に約5Cm挿入して体温を測定する。イースト非投与群の体温も同様に測定する。イースト非投与群(5匹)の平均直腸温より1.5℃以上発熱したイースト投与ラットを選び、発熱温が平均化するように群分けする(1群5匹)。
(c)被験物質の解熱作用
被験物質は、(b)の体温測定約1時間後に経口投与し、投与後1.0および2.0時間後の直腸温を測定する。この測定値から、イースト非投与群の平均直腸温を差し引いた値を発熱強度とする。対象群も同様にして直腸温を測定する。
【0031】
発熱抑制率は次式より求める。
抑制率(%)=[1−A/B]×100
A:被験物質投群の平均発熱強度
B:対照群の平均発熱強度
(4)試験結果
(a)被験物質(単剤)の無作用量
各被験物質において薬効が現れない用量を、無作用量として予め調べた(表5)。
【0032】
【表5】
(b)被験物質(イブプロフェン及びロキソプロフェン単剤と併用剤)のID50
イブプロフェン及びロキソプロフェンナトリウム単剤(いずれも0.33、1.0、3.3mg/Kg)の用量と抑制率との回帰により算出したID50、イブプロフェン及びロキソプロフェンナトリウム(いずれも0.33、1.0、3.3mg/Kg)とフマル酸ケトチフェンの無作用量(1mg/Kg)との配合物質の用量と抑制率との回帰から算出したID50を表6、表7に示す。
【0033】
【表6】
【0034】
【表7】
ケトチフェンと、イブプロフェン又はロキソプロフェンナトリウムとを組み合わせることにより、解熱効果の増強が認められた。
【0035】
【発明の効果】
本発明のフェニルプロピオン酸系解熱消炎鎮痛剤とケトチフェンとを含有する解熱剤組成物は、優れた解熱効果があり、有用である。[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to an antipyretic composition containing a phenylpropionic acid-based antipyretic anti-inflammatory analgesic and ketotifen.
[0002]
[Prior art]
Phenylpropionic acid-based antipyretic analgesics are widely used as antipyretics. Among them, for example, in Japan, loxoprofen, ibuprofen, aluminoprofen, thiaprofen, fenoprofen, pranoprofen and the like are also administered for the resolution of acute upper respiratory inflammation such as cold.
[0003]
On the other hand, antihistamines are also administered to suppress nasal discharge and the like associated with upper respiratory inflammation such as the common cold, and are sometimes used in combination with nonsteroidal antipyretic and antiphlogistic analgesics.
[0004]
As a known combination example of a phenylpropionic acid-based antipyretic anti-inflammatory analgesic and ketotifen,
1) A statement that the combination of loxoprofen and ketotifen is effective for improving the sense of smell in patients with nasal obstruction (see Patent Document 1).
2) As a result of comparison of the combination A of ibuprofen, codeine phosphate, ketotifen fumarate and anhydrous caffeine with the combination B excluding ketotifen fumarate, it is described that A has a superior antitussive effect as compared with B (See Patent Document 2).
[0005]
Further, as other known combination examples considered to be related to the present invention,
3) There is a disclosure that the combined use of loxoprofen and carbinoxamine maleate as an antihistamine enhances the antipyretic effect (see Patent Document 3).
[0006]
[Patent Document 1]
JP 2001-199882 A [Patent Document 2]
Japanese Patent Application Laid-Open No. H10-45595 [Patent Document 3]
JP 2000-143505 A
[Problems to be solved by the invention]
However, there is no report that loxoprofen enhances the antipyretic effect even when used in combination with any antihistamine, and furthermore, the antipyretic effect is enhanced by using a phenylpropionic acid-based antipyretic and anti-inflammatory analgesic in combination with ketotifen.
[0008]
Therefore, the present inventors conducted research to find a combination of drugs that significantly enhance antipyretic action in combination with a nonsteroidal antipyretic and anti-inflammatory analgesic.
[0009]
As a result, they have found that the combined use of a phenylpropionic acid-based antipyretic anti-inflammatory analgesic and ketotifen enhances the antipyretic effect, and completed the present invention.
[0010]
[Means for Solving the Problems]
The present invention
(1) An antipyretic composition containing a phenylpropionic acid-based antipyretic anti-inflammatory analgesic and ketotifen, and preferably,
(2) The antipyretic composition according to (1) or (2), which is an antipyretic composition containing loxoprofen and / or ibuprofen and ketotifen, and further (3) is used as a common cold agent. .
[0011]
Ketotifen refers to ketotifen or a pharmacologically acceptable salt thereof.
[0012]
Here, pharmacologically acceptable salts include, for example, hydrofluorides, hydrochlorides, hydrobromides, hydrohalides such as hydroiodates; nitrates, perchlorates, Inorganic salts such as sulfates and phosphates; lower organic sulfonates such as methanesulfonate, trifluoromethanesulfonate and ethanesulfonate; such as benzenesulfonate and p-toluenesulfonate; Aryl sulfonates; amino acid salts such as ornithate and glutamate; and carboxylate salts such as fumaric acid, succinic acid, citric acid, tartaric acid, oxalic acid and maleic acid, and preferably fumaric acid. Salts.
[0013]
The phenylpropionic acid-based antipyretic and anti-inflammatory analgesics include, for example, drugs having an antipyretic, anti-inflammatory and / or analgesic action having a phenylpropionic acid skeleton, and include, for example, aluminoprofen, ibuprofen, oxaprozin, zaltoprofen, thiaprofen ( Acid), nabumetone, naproxen, fenoprofen (calcium), pranoprofen, flurbiprofen or loxoprofen (sodium), preferably aluminoprofen, ibuprofen, tiaprofen (acid), fenoprofen ( Calcium), pranoprofen or loxoprofen (sodium), and more preferably, ibuprofen or loxoprofen (sodium).
[0014]
Loxoprofen refers to loxoprofen, a pharmacologically acceptable salt thereof and / or a hydrate thereof.
[0015]
Here, the pharmacologically acceptable salt includes alkali metal salts such as sodium salt, potassium salt and lithium salt, alkaline earth metal salts such as calcium salt and magnesium salt, aluminum salt, iron salt and zinc salt. Metal salts such as copper salts, nickel salts, and cobalt salts; inorganic salts such as ammonium salts, t-octylamine salts, dibenzylamine salts, morpholine salts, glucosamine salts, phenylglycine alkyl ester salts, ethylenediamine salts, N- Methylglucamine salt, guanidine salt, diethylamine salt, triethylamine salt, dicyclohexylamine salt, N, N'-dibenzylethylenediamine salt, chloroprocaine salt, procaine salt, diethanolamine salt, N-benzyl-phenethylamine salt, piperazine salt, tetramethyl salt Ammonium salt, tris (hydro An amine salt such as an organic salt such as (xmethyl) aminomethane salt can be mentioned, and a sodium salt is preferable.
[0016]
Of these, loxoprofen sodium dihydrate is preferred.
[0017]
BEST MODE FOR CARRYING OUT THE INVENTION
Among the phenylpropionic acid-based antipyretic anti-inflammatory analgesics, ibuprofen, loxoprofen and the like are listed in the Japanese Pharmacopoeia, 14th Edition, and can be easily obtained.
[0018]
Ketotifen fumarate is commercially available as a pharmaceutical and can be obtained from YIC.
[0019]
In the case where the antipyretic of the present invention is a solid preparation, the weight% of the phenylpropionic acid-based antipyretic anti-inflammatory drug is usually 0.01 to 30%, preferably 0.1 to 10%. Also, the weight percentage of ketotifen is usually 0.0001 to 0.5%, preferably 0.001 to 0.2%.
[0020]
When the antipyretic drug of the present invention is contained in a liquid preparation, the content of the phenylpropionic acid-based antipyretic anti-inflammatory analgesic is usually 0.1 to 100 mg / mL, preferably 1 to 50 mg / mL, In addition, the content of ketotifen is usually 0.001 to 2 mg / mL, and preferably 0.01 to 1 mg / mL.
[0021]
In the present invention, caffeines, antitussives, expectorants, vitamins, crude drugs, and the like can be added as necessary, in addition to the above-mentioned active ingredients, as long as the effects of the present invention are not impaired.
[0022]
Specific dosage forms of the antipyretic agent of the present invention include, for example, tablets, fine granules (including powders), capsules, liquids (including syrups), and additives suitable for each dosage form. It can be produced according to a usual method described in the Japanese Pharmacopoeia or the like, using an appropriate material and a base material.
[0023]
In each of the above dosage forms, various commonly used additives can be used depending on the dosage form.
[0024]
For example, in the case of tablets, lactose, crystalline cellulose or the like as an excipient, magnesium metasilicate aluminate or magnesium oxide as a stabilizer, hydroxypropyl cellulose or the like as a coating agent, magnesium stearate or the like as a lubricant Can be used,
In the case of fine granules and capsules, lactose or purified sucrose is used as an excipient, magnesium aluminate metasilicate or magnesium oxide is used as a stabilizer, corn starch is used as an adsorbent, and hydroxypropyl cellulose is used as a binder. As can be used.
[0025]
In each of the above dosage forms, if necessary, a disintegrating agent such as crospovidone; a surfactant such as polysorbate; an adsorbent such as calcium silicate; a coloring agent such as iron sesquioxide and caramel; a stabilizer such as sodium benzoate; pH adjusters; fragrances; and the like can also be added.
[0026]
【Example】
Hereinafter, the present invention will be described in more detail by way of Examples and the like, but the scope of the present invention is not limited thereto.
Example 1 Tablet (1) Ingredient
[Table 1]
(2) Production method The above components and amounts are taken, and a tablet is produced in accordance with the “Tablets” section of the Japanese Pharmacopoeia General Rules for Preparations.
(Example 2) Fine granule (1) component
[Table 2]
(2) Production method The above components and amounts are taken, and a fine granule is produced in accordance with the section of the Japanese Pharmacopoeia General Rules for Granules.
Example (3) Capsule (1) Ingredient
[Table 3]
(2) Production method The above components and amounts are taken, fine granules are produced in accordance with the section of the Japanese Pharmacopoeia General Rules for Granules, and then filled into capsules to produce hard capsules.
Example (4) Syrup (1) Ingredient
[Table 4]
(2) Production method Take the above components and amounts, prepare a syrup according to the Japanese Pharmacopoeia General Rules for Syrups, and fill in a brown glass bottle to produce a syrup.
(Test Example 1 ) Antipyretic Effect (1) Test Substance A test substance was prepared as a suspension in a 0.5% tragacanth solution the day before or on the day of the test. If prepared the day before, keep in refrigerator until use. The dose of the test substance was 2.5 mL per 1 kg of body weight, and the control group received the same volume of 0.5% tragacanth solution.
(2) Animal Wister-Imamichi male rat, 5 weeks old (purchased from the Animal Breeding Laboratory), an environmental control breeding device controlled at a temperature of 20 to 26 ° C., a humidity of 30 to 70%, and an illumination time of 7:00 to 19: 5-6 animals in a stainless steel rat breeding gauge and allowed to freely ingest feed (mouse / rat breeding F-2, manufactured by Funabashi Farm) and tap water through a water filter. After pre-breeding for 9 days, the animals are visually observed on the day before the test, and good animals are selected and fasted (approximately 20 hours, with free access to water).
(3) Method (a) Induction of Fever by Yeast A yeast solution was prepared to a concentration of 25% by adding physiological saline (Otsuka Pharmaceutical) to brewer's yeast (yeast, Sigma Chemical) and subcutaneously on the back of the rat on the day before the test. Inject 2.0 mL of yeast solution to induce fever.
(B) Grouping About 20 hours after administration of yeast, a thermistor thermometer (MGAIII manufactured by Nihon Kohden Kogyo) is inserted into the rectum by about 5 cm, and the body temperature is measured. The body temperature of the yeast non-administration group is measured in the same manner. Yeast-administered rats having a fever of 1.5 ° C. or more from the average rectal temperature of the non-yeast-administered group (5 animals) are selected and divided into groups so that the exothermic temperatures are averaged (5 animals per group).
(C) Antipyretic action of test substance The test substance is orally administered about 1 hour after the measurement of body temperature in (b), and the rectal temperature is measured 1.0 and 2.0 hours after the administration. The value obtained by subtracting the average rectal temperature of the non-yeast-administered group from this measured value is defined as the heat generation intensity. Rectal temperature is measured in the same manner for the control group.
[0031]
The heat generation suppression rate is obtained from the following equation.
Suppression rate (%) = [1-A / B] × 100
A: Average heat intensity of test substance-administered group B: Average heat intensity of control group (4) Test results (a) No effect amount of test substance (single agent) (Table 5).
[0032]
[Table 5]
(B) ID 50 of test substance (ibuprofen and loxoprofen alone and in combination)
ID 50 calculated by regression between the dose of ibuprofen and loxoprofen sodium alone (0.33, 1.0, 3.3 mg / Kg each) and the inhibition rate, ibuprofen and loxoprofen sodium (0.33, 1.0. Tables 6 and 7 show the ID 50 calculated from the regression between the dose of the compound and the inhibition rate of the no-effect level (1 mg / Kg) of the ketotifen fumarate (0, 3.3 mg / Kg).
[0033]
[Table 6]
[0034]
[Table 7]
The combination of ketotifen and ibuprofen or loxoprofen sodium was found to enhance the antipyretic effect.
[0035]
【The invention's effect】
The antipyretic composition containing the phenylpropionic acid-based antipyretic analgesic and the ketotifen of the present invention has an excellent antipyretic effect and is useful.
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Cited By (8)
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WO2006006577A1 (en) * | 2004-07-13 | 2006-01-19 | Sankyo Company, Limited | Loxoprofen-containing composition for oral administration |
JP2006052210A (en) * | 2004-07-13 | 2006-02-23 | Sankyo Co Ltd | Loxoprofen-containing oral composition |
WO2007040188A1 (en) * | 2005-10-03 | 2007-04-12 | Sankyo Company, Limited | Medicinal composition for inhibiting the excessive formation of goblet cells |
WO2009075324A1 (en) * | 2007-12-12 | 2009-06-18 | Teikoku Seiyaku Co., Ltd. | Loxoprofen-containing aqueous plaster |
JP2012214512A (en) * | 2006-04-27 | 2012-11-08 | Daiichi Sankyo Healthcare Co Ltd | Antihistamine-containing pharmaceutical composition for suppressing goblet cell hyperplasia |
JP2013006830A (en) * | 2011-05-20 | 2013-01-10 | Taisho Pharmaceutical Co Ltd | Method for producing loxoprofen-containing preparation |
JP2014118348A (en) * | 2012-12-13 | 2014-06-30 | Shionogi & Co Ltd | Loxoprofen containing pharmaceutical composition |
JP2020100610A (en) * | 2018-12-25 | 2020-07-02 | 小林製薬株式会社 | Oral pharmaceutical composition |
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JP2016027058A (en) * | 2004-07-13 | 2016-02-18 | 第一三共株式会社 | Loxoprofen-containing oral composition 6 |
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WO2007040188A1 (en) * | 2005-10-03 | 2007-04-12 | Sankyo Company, Limited | Medicinal composition for inhibiting the excessive formation of goblet cells |
JP2012214512A (en) * | 2006-04-27 | 2012-11-08 | Daiichi Sankyo Healthcare Co Ltd | Antihistamine-containing pharmaceutical composition for suppressing goblet cell hyperplasia |
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JP2013006830A (en) * | 2011-05-20 | 2013-01-10 | Taisho Pharmaceutical Co Ltd | Method for producing loxoprofen-containing preparation |
JP2014118348A (en) * | 2012-12-13 | 2014-06-30 | Shionogi & Co Ltd | Loxoprofen containing pharmaceutical composition |
JP2020100610A (en) * | 2018-12-25 | 2020-07-02 | 小林製薬株式会社 | Oral pharmaceutical composition |
JP7229012B2 (en) | 2018-12-25 | 2023-02-27 | 小林製薬株式会社 | Pharmaceutical composition for internal use |
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