JP2841857B2 - Long-term stable oral pharmaceutical preparation - Google Patents

Long-term stable oral pharmaceutical preparation

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Publication number
JP2841857B2
JP2841857B2 JP2336272A JP33627290A JP2841857B2 JP 2841857 B2 JP2841857 B2 JP 2841857B2 JP 2336272 A JP2336272 A JP 2336272A JP 33627290 A JP33627290 A JP 33627290A JP 2841857 B2 JP2841857 B2 JP 2841857B2
Authority
JP
Japan
Prior art keywords
weight
polyethylene glycol
bisoprolol
mannitol
long
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
JP2336272A
Other languages
Japanese (ja)
Other versions
JPH04202131A (en
Inventor
欣吾 中島
英明 人見
尚志 米山
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Tanabe Seiyaku Co Ltd
Original Assignee
Tanabe Seiyaku Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Tanabe Seiyaku Co Ltd filed Critical Tanabe Seiyaku Co Ltd
Priority to JP2336272A priority Critical patent/JP2841857B2/en
Publication of JPH04202131A publication Critical patent/JPH04202131A/en
Application granted granted Critical
Publication of JP2841857B2 publication Critical patent/JP2841857B2/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Description

【発明の詳細な説明】 〔技術分野〕 本発明はビソプロロールを含有する長期間安定な経口
用医薬製剤に関する。
Description: TECHNICAL FIELD The present invention relates to a long-term stable oral pharmaceutical preparation containing bisoprolol.

〔従来技術〕(Prior art)

ビソプロロール〔化学名:1−〔p−〔(2−イソプロ
ポキシエトキシ)メチル〕フェノキシ〕−3−イソプロ
ピルアミノ−2−プロパノール〕(以下、ビソプロロー
ルと称する。)は、強力なβ−受容体遮断作用を有し、
心臓、循環系及び脈管系疾患の治療・予防薬として優れ
た薬剤である(特公昭62−10220号)。
Bisoprolol [chemical name: 1- [p-[(2-isopropoxyethoxy) methyl] phenoxy] -3-isopropylamino-2-propanol] (hereinafter referred to as bisoprolol) has a strong β-receptor blocking action. Has,
It is an excellent drug for treating and preventing heart, circulatory and vascular diseases (Japanese Patent Publication No. 62-10220).

しかしながら、この化合物は加水分解しやすく、通常
この分野で汎用される賦形剤や結合剤等を用いて製剤し
た場合には、吸湿水分によって該化合物が加水分解を起
こし、製剤中の含量が低下するという問題がある。
However, this compound is easily hydrolyzed, and when formulated using excipients or binders commonly used in this field, the compound is hydrolyzed by moisture absorption and the content in the formulation decreases. There is a problem of doing.

〔本発明が解決しようとする課題〕 本発明の目的はビソプロロールを含有する安定な経口
用製剤を提供しようとするものである。
[Problem to be solved by the present invention] An object of the present invention is to provide a stable oral preparation containing bisoprolol.

〔課題を解決するための手段〕[Means for solving the problem]

本発明は、ビソプロロールまたはその薬理的に許容し
うる塩にアンニット及びポリエチレングリコールを配合
してなる、長期間安定な経口用医薬製剤及びその製法で
ある。
The present invention relates to a long-term stable oral pharmaceutical preparation comprising bisoprolol or a pharmaceutically acceptable salt thereof and annit and polyethylene glycol, and a method for producing the same.

従来マンニットは賦形剤として又、ポリエチレングリ
コールは結合剤として公知の物質であるが、ビソプロロ
ールにこれらを組合せて配合した場合、該医薬活性成分
の加水分解が抑制されるという知見は全く知られていな
かったものである。
Conventionally, mannitol is a known substance as an excipient, and polyethylene glycol is a known substance as a binder.However, when bisoprolol is combined with these substances, it is completely known that the hydrolysis of the pharmaceutically active ingredient is suppressed. That was not.

本発明において、医薬活性成分であるビソプロロール
は遊離塩基であってもよく、また無機酸や有機酸などの
酸付加塩であってもよい。無機酸付加塩としては、例え
ば硫酸塩、硝酸塩、塩酸塩、臭化水素酸塩またはオルト
燐酸塩などがあげられ、有機酸付加塩としては、例えば
ギ酸塩、酢酸塩、プロピオン酸塩、ピバリン酸塩、ジエ
チル酢酸塩、マロン酸塩、コハク酸塩、ピメリン酸塩、
フマル酸塩、マレイン酸塩、乳酸塩、酒石酸塩、リンゴ
酸塩、安息香酸塩、サリチリ酸塩、2−フェニルプロピ
オン酸塩、クエン酸塩、グルコン酸塩、アスコルビン酸
塩、ニコチン酸塩、イソニコチン酸塩、メタンスルホン
酸塩、エタンスルホン酸塩、エタンジスルホン酸塩、2
−ヒドロキシエタンスルホン酸塩、ベンゼンスルホン酸
塩、p−トルエンスルホン酸塩またはナフタレンモノス
ルホン酸塩ナフタレンジスルホン酸塩などがあげられ
る。
In the present invention, bisoprolol which is a pharmaceutically active ingredient may be a free base or may be an acid addition salt such as an inorganic acid or an organic acid. Examples of the inorganic acid addition salts include sulfate, nitrate, hydrochloride, hydrobromide and orthophosphate, and examples of the organic acid addition salts include formate, acetate, propionate, and pivalic acid. Salt, diethyl acetate, malonate, succinate, pimelate,
Fumarate, maleate, lactate, tartrate, malate, benzoate, salicylate, 2-phenylpropionate, citrate, gluconate, ascorbate, nicotinate, isoform Nicotinate, methanesulfonate, ethanesulfonate, ethanedisulfonate, 2
-Hydroxyethanesulfonate, benzenesulfonate, p-toluenesulfonate or naphthalene monosulfonate naphthalenedisulfonic acid salt.

本発明で使用されるマンニットは、経口投与用製剤に
通常用いられるものであればよく、特に限定されない。
The mannitol used in the present invention is not particularly limited as long as it is one usually used in a preparation for oral administration.

また、ポリエチレングリコールも、経口投与用製剤に
通常用いられるものであればよく、特に限定されない
が、例えば平均分子量が1,000〜20,000、好ましくは4,0
00〜6,000のものが好適に使用できる。
In addition, polyethylene glycol may be any one that is usually used in a formulation for oral administration, and is not particularly limited.For example, the average molecular weight is 1,000 to 20,000, preferably 4,0.
Those having a size of from 00 to 6,000 can be suitably used.

マンニット、ポリエチレグリコールおよび医薬活性成
分は、それぞれマンニットを約50〜90重量%、とりわけ
約60〜80重量%、ポリエチレングリコールを約5〜30重
量%、とりわけ約8〜15重量%、医薬活性成分を約1〜
30重量%、とりわけ約2〜20重量%の範囲で配合するの
が好ましい。
Mannitol, polyethylene glycol and the pharmaceutically active ingredient are each about 50-90% by weight, especially about 60-80% by weight, polyethylene glycol about 5-30% by weight, especially about 8-15% by weight, pharmaceutically active ingredient. About 1 to
It is preferred that the amount be 30% by weight, especially about 2 to 20% by weight.

本発明の製剤においては、その剤型に応じて更に他の
賦形剤あるいは滑沢剤を使用することもできる。賦形剤
としては経口用製剤に通常用いられるものであればいず
れも使用でき、これら賦形剤としては例えば乳糖、デン
プン、ソルビット、結晶セルロース、第二リン酸カルシ
ウム、クエン酸カルシウム、白糖、硫酸カルシウム等が
挙げられ、とりわけソルビットが好適に使用できる。こ
れらの賦形剤は約10〜25重量%の範囲で用いるのが好ま
しい。又滑沢剤も経口用製剤に通常用い得るものであれ
ばよく、例えばタルク、ステアリン酸マグネシウム、ス
テアリン酸カルシウム、ステアリン酸、ワックス等があ
げられる。滑沢剤は約0.1〜3.0重量%の範囲で用いるの
が好ましい。
In the preparation of the present invention, other excipients or lubricants can be used depending on the dosage form. As the excipient, any of those usually used in oral preparations can be used. Examples of these excipients include lactose, starch, sorbit, crystalline cellulose, dibasic calcium phosphate, calcium citrate, sucrose, calcium sulfate and the like. And sorbit is particularly preferably used. These excipients are preferably used in the range of about 10 to 25% by weight. Also, the lubricant may be any one which can be usually used in an oral preparation, and examples thereof include talc, magnesium stearate, calcium stearate, stearic acid, and wax. Lubricants are preferably used in the range of about 0.1-3.0% by weight.

本発明の製剤は、医薬活性成分であるビソプロロール
またはその薬理的に許容しうる塩にマンニット及びポリ
エチレングリコールを配合して造粒し、要すれば更に所
望の剤型に成型することにより製することができる。上
記の操作はいずれもこの技術分野における常法により実
施することができ、例えば加熱造粒法、湿式造粒法又は
乾式造粒法により行うことができる。加熱造粒法による
ときは医薬活性成分、マンニット及びポリエチレングリ
コールを混合し、適宜加熱混合したのち冷却し、必要な
場合には粉砕することにより実施できる。加熱温度とし
ては約60〜90℃、とりわけ約70〜85℃であるのが好まし
い。マンニット以外の賦形剤を更に併用する場合は、上
記混合時に同時に加えればよい。又、湿式造粒法による
場合は、医薬活性成分及びマンニットもしくはそれらの
混合物をポリエチレングリコール含有溶液で練合し市販
の造粒装置等により造粒し、乾燥することにより実施す
ることができる。練合の際使用する溶媒としては例えば
メタノール、エタノール、水、あるいはこれらの混合物
等があげられる。更に、乾式造粒法によるときは市販の
乾式造粒機を用いて実施することができる。
The preparation of the present invention is produced by blending mannitol and polyethylene glycol with a pharmaceutically active ingredient bisoprolol or a pharmacologically acceptable salt thereof, granulating the mixture, and, if necessary, further molding it into a desired dosage form. be able to. Any of the above operations can be performed by a conventional method in this technical field, for example, a heating granulation method, a wet granulation method, or a dry granulation method. In the case of the heat granulation method, it can be carried out by mixing a pharmaceutically active ingredient, mannitol and polyethylene glycol, appropriately heating and mixing, cooling, and, if necessary, pulverizing. The heating temperature is preferably about 60-90 ° C, especially about 70-85 ° C. When an excipient other than mannitol is further used, it may be added at the same time as the above mixing. In the case of wet granulation, it can be carried out by kneading a pharmaceutically active ingredient and mannitol or a mixture thereof with a polyethylene glycol-containing solution, granulating the mixture with a commercially available granulating apparatus or the like, and drying. Examples of the solvent used in kneading include methanol, ethanol, water, and mixtures thereof. Furthermore, when using the dry granulation method, it can be carried out using a commercially available dry granulator.

かくして得られた固化物は所望の粒度となるように市
販の粉砕機等を用いて粉砕する。粒度は使用目的によっ
ても異なるが概ね約50〜1,500μm、とりわけ約100〜80
0μmが適当である。
The solidified product thus obtained is pulverized using a commercially available pulverizer or the like so as to have a desired particle size. The particle size varies depending on the purpose of use, but is generally about 50 to 1,500 μm, especially about 100 to 80 μm.
0 μm is appropriate.

かくして得られた粉砕物は要すれば更に整粒、打錠等
の常法により所望の剤型とすることができる。更に打錠
等の製剤時には必要に応じて滑沢剤を使用するのが好ま
しい。かくして経口投与に適した製剤とすることができ
る。かかる剤型としては例えば散剤、顆粒剤、細粒剤、
錠剤等があげられ、更にこれらの最終製品には着色剤、
芳香剤などの補助剤を任意に含ませることができる。
The pulverized product thus obtained can be further made into a desired dosage form by a conventional method such as sizing and tableting, if necessary. Further, it is preferable to use a lubricant as needed at the time of formulation such as tableting. Thus, a formulation suitable for oral administration can be obtained. Such dosage forms include, for example, powders, granules, fine granules,
Tablets and the like, and furthermore, these final products include coloring agents,
Auxiliaries such as fragrances can optionally be included.

以下に、実験例及び実施例を挙げて更に本発明を説明
する。
Hereinafter, the present invention will be further described with reference to Experimental Examples and Examples.

実験例 ビソプロロール・1/2フマル酸塩を下記第1表に示す
賦形剤、結合剤及び滑沢剤と組合せた場合における安定
性を試験した。
Experimental Example Stability was tested when bisoprolol 1/2 fumarate was combined with the excipients, binders and lubricants shown in Table 1 below.

実験は各物質を所定の比率で混合し、常法により製し
た錠剤を60℃、1ヵ月間保存し、保存後の活性薬剤の残
存量を測定し残存率を算出した。結果は第1表に示す通
りである。
In the experiment, each substance was mixed at a predetermined ratio, tablets prepared by a conventional method were stored at 60 ° C. for one month, and the residual amount of the active drug after storage was measured to calculate the residual ratio. The results are as shown in Table 1.

実施例1 ビソプロロール・1/2フマル酸塩5重量部、マンニッ
ト84重量部を混合し、撹拌造粒機(品川式混合機)に入
れ、これにポリエチレングリコール(平均分子量6000)
10重量部を含むエタノール(60℃にて加温して溶解)を
加えて練合する。練合物を20メッシュのJIS標準篩で処
理し、篩を通過したものを40℃で2時間乾燥する。乾燥
後ステアリン酸マグネシウム1重量部を加えて混合し、
混合物を回転式打錠機(直径6.5mm)で圧縮成形するこ
とにより、1錠当たり100mgの錠剤を得る。
Example 1 5 parts by weight of bisoprolol 1/2 fumarate and 84 parts by weight of mannitol were mixed, and the mixture was placed in a stirring granulator (Shinagawa mixer), and polyethylene glycol (average molecular weight: 6000) was added thereto.
Ethanol containing 10 parts by weight (dissolved by heating at 60 ° C.) is added and kneaded. The kneaded material is treated with a 20 mesh JIS standard sieve, and the material that has passed through the sieve is dried at 40 ° C. for 2 hours. After drying, add and mix 1 part by weight of magnesium stearate,
The mixture is compressed on a rotary tablet press (6.5 mm diameter) to give 100 mg tablets per tablet.

実施例2 ビソプロロール・1/2フマル酸塩5重量部、マンニッ
ト76重量部を混合し、撹拌造粒機(品川式混合機)に入
れ、これにポリエチレングリコール(平均分子量6000)
15重量部を含むエタノール(60℃にて加温して溶解)を
加えて練合する。練合物を20メッシュのJIS標準篩で処
理し、篩を通過したものを40℃で2時間乾燥する。乾燥
後ステアリン酸マグネシウム1重量部及びタルク3重量
部を加えて混合する。以下実施例1と同様にして1錠当
たり100mgの錠剤を得る。
Example 2 5 parts by weight of bisoprolol 1/2 fumarate and 76 parts by weight of mannitol were mixed, and the mixture was placed in a stirring granulator (Shinagawa mixer), and polyethylene glycol (average molecular weight 6000) was added thereto.
15 parts by weight of ethanol (dissolved by heating at 60 ° C.) is added and kneaded. The kneaded material is treated with a 20 mesh JIS standard sieve, and the material that has passed through the sieve is dried at 40 ° C. for 2 hours. After drying, 1 part by weight of magnesium stearate and 3 parts by weight of talc are added and mixed. Thereafter, a tablet of 100 mg per tablet is obtained in the same manner as in Example 1.

実施例3 ビソプロロール・1/2フマル酸塩10重量部、マントニ
ット99重量部及びポリエチレングリコール(平均分子量
6000)10重量部を混合し、高速撹拌造粒機(ハイスピー
ドミキサー)に入れ、外浴温度75℃にて加熱造粒する。
造粒物を室温まで冷却し、20メッシュのJIS標準篩で処
理し、篩を通過したものにステアリン酸マグネシウム1
重量部を加えて混合する。混合物を回転式打錠機(直径
7mm)で圧縮成形することにより、1錠当たり120mgの錠
剤を得る。
Example 3 10 parts by weight of bisoprolol 1/2 fumarate, 99 parts by weight of mantonit and polyethylene glycol (average molecular weight
6000) 10 parts by weight are mixed, put into a high-speed stirring granulator (high-speed mixer), and heat-granulated at an external bath temperature of 75 ° C.
The granulated product was cooled to room temperature, treated with a 20-mesh JIS standard sieve, and passed through a sieve with magnesium stearate 1
Add parts by weight and mix. The mixture is turned on a rotary tablet press (diameter
7 mm) to give tablets of 120 mg per tablet.

実施例4 ビソプロロール・1/2フマル酸塩5重量部、マンニッ
ト144.5重量部及びソルビット30重量部を混合し、撹拌
造粒機(品川式混合機)に入れ、これにポリエチレング
リコール(平均分子量6000)20重量部を含むエタノール
(60℃にて加温して溶解)を加えて練合する。練合物を
40℃で15分間乾燥後、練合物を破砕する。再び40℃で2
時間乾燥後、32メッシュのJIS標準篩で処理する。篩を
通過したものに含水二酸化ケイ素0.5重量部を加えて混
合し散剤を得る。
Example 4 5 parts by weight of bisoprolol 1/2 fumarate, 144.5 parts by weight of mannitol and 30 parts by weight of sorbite were mixed, and the mixture was placed in a stirring granulator (Shinagawa mixer), and polyethylene glycol (average molecular weight: 6000) was added thereto. ) Add 20 parts by weight of ethanol (dissolved by heating at 60 ° C) and knead. Kneaded material
After drying at 40 ° C. for 15 minutes, the kneaded material is crushed. Again at 40 ° C 2
After drying for an hour, it is treated with a 32 mesh JIS standard sieve. 0.5 parts by weight of hydrous silicon dioxide is added to the mixture that has passed through the sieve, and mixed to obtain a powder.

実施例5 実施例4で得た顆粒をゼラチン硬カプセルに充填し
て、カプセル剤を得る。
Example 5 The granules obtained in Example 4 are filled into hard gelatin capsules to obtain capsules.

実施例6 ビソプロロール・1/2フマル酸塩5重量部、マンニッ
ト164.5重量部及びポリエチレングリコール(平均分子
量6000)30重量部を混合し、高速撹拌造粒機(ハイスピ
ードミキサー)に入れ、外浴温度75℃にて加熱造粒す
る。造粒物を室温まで冷却し、12メッシュのJIS標準篩
で処理する。篩を通過したものに含水二酸化ケイ素0.5
重量部を加えて混合し顆粒剤を得る。
Example 6 5 parts by weight of bisoprolol 1/2 fumarate, 164.5 parts by weight of mannitol and 30 parts by weight of polyethylene glycol (average molecular weight: 6000) were mixed, and the mixture was placed in a high-speed stirring granulator (high-speed mixer), followed by an external bath. Heat granulation at a temperature of 75 ° C. The granulated product is cooled to room temperature and treated with a 12 mesh JIS standard sieve. Water-containing silicon dioxide 0.5
The parts by weight are added and mixed to obtain granules.

〔発明の効果〕〔The invention's effect〕

かくして得られる本発明の経口用医薬製剤は、医薬活
性成分であるビソプロロールまたはその薬理的に許容し
うる塩にマンニット及びポリエチレングリコールを配合
することにより、該活性薬剤を長期間安定に存在せしめ
ることができ、医薬用製剤として優れた性質を有するも
のである。
The oral pharmaceutical preparation of the present invention thus obtained can stably exist the active agent for a long period of time by blending mannitol and polyethylene glycol with bisoprolol, which is a pharmaceutically active ingredient, or a pharmaceutically acceptable salt thereof. It has excellent properties as a pharmaceutical preparation.

また、本発明の製剤、殊に錠剤においては、消化管内
における錠剤からの主薬の溶出が極めて速く、そのため
通常錠剤において必要とされる崩壊剤を使用する必要が
ないという利点をも有するものである。
In addition, the preparation of the present invention, particularly a tablet, has the advantage that the active ingredient elutes from the tablet in the gastrointestinal tract very quickly, so that it is not necessary to use a disintegrant, which is usually required in tablets. .

更に本発明によれば、ビソプロロールが結合剤として
役立つため、従来成型性が劣るといわれているマンニッ
ト及びステッキング等の打錠障害を起こしやすいポリエ
チレングリコールを用いているにもかかわらず、その製
剤化に際し何ら障害を生ずることなく良好な製剤を得る
ことができるので、簡単でしかも経済的に長期間安定な
経口用医薬製剤を得ることができる。
Furthermore, according to the present invention, since bisoprolol serves as a binder, polyethylene glycol which is apt to cause tableting troubles such as mannitol and sticking, which is conventionally considered to be inferior in moldability, is used. Since a good formulation can be obtained without any obstacles during the preparation, a simple and economically stable oral pharmaceutical formulation can be obtained for a long period of time.

フロントページの続き (58)調査した分野(Int.Cl.6,DB名) A61K 31/135 A61K 47/26 A61K 47/34 C07C 215/00 A61K 31/045 A61K 31/765 CA(STN) REGISTRY(STN) WPIDS(STN)Continued on the front page (58) Fields surveyed (Int.Cl. 6 , DB name) A61K 31/135 A61K 47/26 A61K 47/34 C07C 215/00 A61K 31/045 A61K 31/765 CA (STN) REGISTRY ( STN) WPIDS (STN)

Claims (4)

(57)【特許請求の範囲】(57) [Claims] 【請求項1】ビソプロロールまたはその薬理的に許容し
うる塩にマンニットおよびポリエチレングリコールを配
合してなる長期間安定な経口用医薬製剤。
1. A long-term stable oral pharmaceutical preparation comprising mannitol and polyethylene glycol mixed with bisoprolol or a pharmaceutically acceptable salt thereof.
【請求項2】1〜30重量%のビソプロロール・1/2フマ
ル酸塩、50〜90重量%のマンニットおよび5〜30重量%
のポリエチレングリコールを配合してなる請求項1記載
の製剤。
2. 1-30% by weight of bisoprolol 1/2 fumarate, 50-90% by weight of mannitol and 5-30% by weight
2. The preparation according to claim 1, which comprises polyethylene glycol.
【請求項3】ポリエチレングリコールの平均分子量が1,
000〜20,000である請求項2記載の製剤。
3. The polyethylene glycol having an average molecular weight of 1,
The preparation according to claim 2, wherein the amount is from 000 to 20,000.
【請求項4】ビソプロロールまたはその薬理的に許容し
うる塩にマンニットおよびポリエチレングリコールを配
合して造粒し、要すれば更に所望の剤型に成型すること
を特徴とする長期間安定な経口用医薬製剤の製法。
4. A long-term stable oral preparation characterized by blending mannitol and polyethylene glycol with bisoprolol or a pharmacologically acceptable salt thereof and granulating the mixture and, if necessary, further molding it into a desired dosage form. Of pharmaceutical preparations for medical use.
JP2336272A 1990-11-29 1990-11-29 Long-term stable oral pharmaceutical preparation Expired - Lifetime JP2841857B2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2336272A JP2841857B2 (en) 1990-11-29 1990-11-29 Long-term stable oral pharmaceutical preparation

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP2336272A JP2841857B2 (en) 1990-11-29 1990-11-29 Long-term stable oral pharmaceutical preparation

Publications (2)

Publication Number Publication Date
JPH04202131A JPH04202131A (en) 1992-07-22
JP2841857B2 true JP2841857B2 (en) 1998-12-24

Family

ID=18297396

Family Applications (1)

Application Number Title Priority Date Filing Date
JP2336272A Expired - Lifetime JP2841857B2 (en) 1990-11-29 1990-11-29 Long-term stable oral pharmaceutical preparation

Country Status (1)

Country Link
JP (1) JP2841857B2 (en)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PE20130200A1 (en) * 2003-04-08 2013-03-09 Novartis Ag PHARMACEUTICAL COMPOSITION CONTAINING AN S1P RECEPTOR AGONIST AND A SUGAR ALCOHOL
US20070158227A1 (en) * 2004-01-30 2007-07-12 Satoshi Amano Plaster enclosing packaging bag
EP1728791A4 (en) * 2004-03-25 2008-12-10 Astellas Pharma Inc Composition for solid pharmaceutical preparation of solifenacin or salt thereof
WO2006095542A1 (en) * 2005-03-04 2006-09-14 Kureha Corporation Pharmaceutical composition comprising amine compound

Also Published As

Publication number Publication date
JPH04202131A (en) 1992-07-22

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