JP2723919B2 - Oral pharmaceutical composition containing cyclic amine derivative - Google Patents
Oral pharmaceutical composition containing cyclic amine derivativeInfo
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- JP2723919B2 JP2723919B2 JP63219790A JP21979088A JP2723919B2 JP 2723919 B2 JP2723919 B2 JP 2723919B2 JP 63219790 A JP63219790 A JP 63219790A JP 21979088 A JP21979088 A JP 21979088A JP 2723919 B2 JP2723919 B2 JP 2723919B2
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- cyclic amine
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Description
【発明の詳細な説明】 〔産業上の利用分野〕 本発明は、環状アミン誘導体を含有する経口用医薬品
組成物に関する。Description: TECHNICAL FIELD The present invention relates to an oral pharmaceutical composition containing a cyclic amine derivative.
詳しくは、環状アミン誘導体と、有機酸と、セルロー
ス系水溶性高分子又はポリビニルピロリドンとを含有し
てなる中性領域において良好な溶出性を示すことを特徴
とする経口用医薬品組成物に関する。More specifically, the present invention relates to an oral pharmaceutical composition characterized by exhibiting good dissolution in a neutral region containing a cyclic amine derivative, an organic acid, and a cellulose-based water-soluble polymer or polyvinylpyrrolidone.
本出願人は先に医薬として優れた作用を有する下記一
般式（Ｉ）で表される環状アミン誘導体及びその薬理学
的に許容できる塩を提案した（PCT/JP86/00502号）。The present applicant has previously proposed a cyclic amine derivative represented by the following formula (I) and a pharmacologically acceptable salt thereof having excellent action as a medicament (PCT / JP86 / 00502).
〔Ａは低級アルキル基、低級アルコキシ基、水酸基又は
ハロゲン原子から選択された同一又は相異なる１又は２
以上の置換基により置換されても良い置換もしくは無置
換のナフチル基、Ｂはハロゲン原子、低級アルキル基又
は低級アルコキシ基から選択された同一又は相異なる１
又は２の置換基により置換されてもよい置換又は無置換
のフェニル基、Ｘは式 で示される基、式−CH2−で示される基、式 で示される基、又は式 で示される基、Ｙは式 で示される基、式−Ｏ−で示される基、式−NH−で示さ
れる基、又は式−CH2−で示される基を意味する。〕 上記一般式（Ｉ）で表される環状アミン誘導体のう
ち、次式（II）に表される化合付が薬理実験及び毒性試
験において、特に医薬品として好ましい結果を与えてい
る。 [A is the same or different 1 or 2 selected from a lower alkyl group, a lower alkoxy group, a hydroxyl group or a halogen atom;
A substituted or unsubstituted naphthyl group which may be substituted by the above substituents, B is the same or different 1 selected from a halogen atom, a lower alkyl group or a lower alkoxy group;
Or a substituted or unsubstituted phenyl group optionally substituted by 2 substituents, X is a group represented by the formula A group represented by the formula: -CH 2- , a group represented by the formula: A group represented by or a formula And Y is a group represented by the formula Means a group represented by - a group represented by a group represented by formula -O-, a group represented by formula -NH-, or Formula -CH 2. Among the cyclic amine derivatives represented by the general formula (I), the combination represented by the following formula (II) gives particularly favorable results as pharmaceuticals in pharmacological experiments and toxicity tests.
（式中、Halはハロゲン原子を意味する） しかしながら、これらの環状アミン誘導体は難溶性で
あり経口用医薬品として製剤化するのは困難であった。 (In the formula, Hal represents a halogen atom.) However, these cyclic amine derivatives are hardly soluble and difficult to formulate as an oral drug.
上記の式（II）で表される環状アミン誘導体の代表的
な化合物である下記式（III） で表される化合物（以下、化合物Ａと略記する）は、虚
血後細胞障害保護作用及び学習障害改善作用を有する化
合物で、この虚血脳保護作用から脳血管性痴呆、知的機
能障害などの治療薬として効果が期待される薬物であ
る。The following formula (III) which is a typical compound of the cyclic amine derivative represented by the above formula (II) (Hereinafter abbreviated as compound A) is a compound having a post-ischemic cell damage-protecting action and a learning-disorder-improving action. It is a drug that is expected to be effective as a therapeutic agent.
しかしながら、化合物Ａは難溶性化合物で中性領域で
はほとんど溶けない化合物である。即ち、化合物Ａの溶
解性を検討したところ、この溶解度は、pH3で5mg/mlで
あるが、pH4.5以上では0.1μg/ml以下である。酸性領域
では溶解度はやや上昇するが、ヒトの胃液酸度は生理的
要因により変動し、しかも個体差の大きいことが知られ
ており、特に高齢者の場合、低酸症、無酸症の比率が高
いことから、難溶性化合物のバイオアベラビリティーが
低下しやすいと言われている。However, compound A is a compound which is hardly soluble in a neutral region and hardly soluble. That is, when the solubility of Compound A was examined, the solubility was 5 mg / ml at pH 3, but 0.1 μg / ml or less at pH 4.5 or more. It is known that the solubility slightly increases in the acidic region, but the acidity of gastric juice in humans fluctuates due to physiological factors, and it is known that there are large individual differences.Especially in the case of the elderly, the ratio of hypoxia and anoxia is low. It is said that the bioavailability of a poorly soluble compound is apt to be reduced due to its high value.
従って、消化管内において、上記の如き環状アミン誘
導体の吸収率は非常に低く、速やかな薬効は期待できな
い。Therefore, the absorption rate of the above-mentioned cyclic amine derivative in the gastrointestinal tract is extremely low, and rapid drug efficacy cannot be expected.
難溶性化合物の溶解性向上の手法としては、塩の選
択、多形の利用、非晶質化、包接化、微粉砕、溶媒和
物、固体表面吸着、固体分散等、多くの報告がある。し
かしながら、これらの方法を環状アミン誘導体に適用し
た場合、経時的安定性あるいは実用性の面で難がある。There are many reports on techniques for improving the solubility of hardly soluble compounds, such as selection of salts, use of polymorphs, amorphization, inclusion, pulverization, solvates, solid surface adsorption, and solid dispersion. . However, when these methods are applied to cyclic amine derivatives, there are difficulties in terms of stability over time or practicality.
本発明者らは、環状アミン誘導体の中性領域における
溶解性を向上させる技術について鋭意検討を行った結
果、環状アミン誘導体に有機酸とセルロース系水溶性高
分子又はポリビニルピロリドンとを共存せしめることに
よって所期の目的が達成されることを見出し、本発明を
完成させた。The present inventors have conducted intensive studies on a technique for improving the solubility of the cyclic amine derivative in the neutral region.As a result, the cyclic amine derivative was allowed to coexist with an organic acid and a cellulose-based water-soluble polymer or polyvinylpyrrolidone. The inventor has found that the intended purpose is achieved, and has completed the present invention.
即ち、本発明は、上記一般式（Ｉ）で表される環状ア
ミン誘導体１重量部に対して、クエン酸、酒石酸、コハ
ク酸、リンゴ酸、フマール酸、アジピン酸及びアスコル
ビン酸からなる群から選ばれる少なくとも１種の有機酸
を0.05〜1.2重量部、ヒドロキシプロピルメチルセルロ
ース、ヒドロキシプロピルセルロース及びメチルセルロ
ースからなる群から選ばれる少なくとも１種のセルロー
ス系水溶性高分子又はポリビニルピロリドンを0.05〜1.
2重量部配合してなることを特徴とする経口用医薬品組
成物を提供するものである。That is, the present invention relates to 1 part by weight of the cyclic amine derivative represented by the general formula (I), selected from the group consisting of citric acid, tartaric acid, succinic acid, malic acid, fumaric acid, adipic acid and ascorbic acid. 0.05 to 1.2 parts by weight of at least one organic acid, and at least one cellulose-based water-soluble polymer selected from the group consisting of hydroxypropylmethylcellulose, hydroxypropylcellulose and methylcellulose or polyvinylpyrrolidone at 0.05 to 1.
An object of the present invention is to provide a pharmaceutical composition for oral use characterized by being blended in 2 parts by weight.
本発明において用いられる環状アミン誘導体としては
上記一般式（Ｉ）で表される環状アミン誘導体及びその
薬理学的に許容できる塩が挙げられる。Examples of the cyclic amine derivative used in the present invention include a cyclic amine derivative represented by the above general formula (I) and a pharmaceutically acceptable salt thereof.
一般式（Ｉ）において、Ａ又はＢの置換置としての低
級アルキル基としては炭素数１〜６の直鎖もしくは分枝
状のアルキル基、例えばメチル、エチル、ｎ−プロピ
ル、ｎ−ブチル、イソプロピル、イソブチル、１−メチ
ルプロピル、tert−ブチル、ｎ−ペンチル、１−エチル
プロピル、イソアミル、ｎ−ヘキシルなどが挙げられ、
好ましくはメチル基又はエチル基である。また、Ａ又は
Ｂの置換基としての低級アルコキシ基としては、上記の
低級アルキル基から誘導されたアルコキシ基が挙げられ
るが、好適な例としては、例えばメトキシ、エトキシ、
プロポキシ、イソプロポキシ、ブトキシ、イソブトキシ
基などが挙げられる。また、Ａ又はＢの置換基としての
ハロゲン原子としては、フッ素、臭素、ヨウ素、塩素な
どが挙げられる。In the general formula (I), the lower alkyl group as a substituent for A or B is a straight-chain or branched alkyl group having 1 to 6 carbon atoms, for example, methyl, ethyl, n-propyl, n-butyl, isopropyl , Isobutyl, 1-methylpropyl, tert-butyl, n-pentyl, 1-ethylpropyl, isoamyl, n-hexyl and the like,
Preferably it is a methyl group or an ethyl group. Examples of the lower alkoxy group as a substituent of A or B include an alkoxy group derived from the above lower alkyl group. Preferred examples include methoxy, ethoxy,
And propoxy, isopropoxy, butoxy and isobutoxy groups. Examples of the halogen atom as a substituent for A or B include fluorine, bromine, iodine, and chlorine.
また、環状アミン誘導体の薬理学的に許容できる塩と
は、慣用の無毒性塩類であり、例えば塩酸塩、臭化水素
酸塩、硫酸塩、燐酸塩などの無機酸塩、例えば酢酸塩、
マレイン酸塩、酒石酸塩、メタンスルホン酸塩、ベンゼ
ンスルホン酸塩などの有機酸塩又はアルギニン、アスペ
ラギン酸などのアミノ酸との塩などが挙げられる。The pharmacologically acceptable salt of the cyclic amine derivative is a conventional non-toxic salt, for example, an inorganic acid salt such as hydrochloride, hydrobromide, sulfate, phosphate, for example, acetate,
Organic acid salts such as maleate, tartrate, methanesulfonate, and benzenesulfonate, and salts with amino acids such as arginine and asperarginic acid, and the like.
前記一般式（Ｉ）で表される環状アミン誘導体として
好ましい化合物は前記一般式（II）で表される化合物で
あり、前記一般式（III）で表される化合物（化合物
Ａ）が特に好ましい。Preferred compounds as the cyclic amine derivative represented by the general formula (I) are the compounds represented by the general formula (II), and the compound represented by the general formula (III) (compound A) is particularly preferred.
本発明において用いられる有機酸は、クエン酸、酒石
酸、コハク酸、リンゴ酸、フマール酸、アジピン酸及び
アスコルビン酸からなる群から選ばれる少なくとも１種
である。本発明の組成物中のこれら有機酸の配合量は、
環状アミン誘導体の含有率により異なるが、後記実験例
において示される如く、環状アミン誘導体１重量部に対
し、0.05〜1.2重量部が適当である。また、本発明に係
る有機酸はそれぞれ単独に使用しても良いが、２つ以上
の有機酸を共存せしめて使用することもできる。The organic acid used in the present invention is at least one selected from the group consisting of citric acid, tartaric acid, succinic acid, malic acid, fumaric acid, adipic acid and ascorbic acid. The amount of these organic acids in the composition of the present invention is:
Although it depends on the content of the cyclic amine derivative, 0.05 to 1.2 parts by weight is appropriate for 1 part by weight of the cyclic amine derivative as shown in the experimental examples described later. The organic acids according to the present invention may be used alone, or two or more organic acids may be used together.
本発明において用いられるセルロース系水溶性高分子
は、ヒドロキシプロピルメチルセルロース、ヒドロキシ
プロピルセルロース及びメチルセルロースからなる群か
ら選ばれる少なくとも１種である。The cellulose-based water-soluble polymer used in the present invention is at least one selected from the group consisting of hydroxypropylmethylcellulose, hydroxypropylcellulose and methylcellulose.
本発明の組成物中のセルロース系水溶性高分子又はポ
リビニルピロリドンの配合量は、環状アミン誘導体の含
有率により異なるが、後記実験例において示されるごと
く、環状アミン誘導体１重量部に対し、0.05〜1.2重量
部が適当である。これらセルロース系水溶性高分子又は
ポリビニルピロリドンの使用量は製剤総重量との兼ね合
いによって適宜変えることができる。The amount of the cellulosic water-soluble polymer or polyvinylpyrrolidone in the composition of the present invention varies depending on the content of the cyclic amine derivative. However, as shown in the experimental examples described later, 0.05 to 1 part by weight of the cyclic amine derivative is used. 1.2 parts by weight is suitable. The amount of the cellulose-based water-soluble polymer or polyvinylpyrrolidone used can be appropriately changed depending on the total weight of the preparation.
また、本発明に係るセルロース系水溶性高分子又はポ
リビニルピロリドンは、それぞれ単独に使用してもよい
が、２種以上のセルロース系水溶性高分子又はポリビニ
ルピロリドンを共存せしめて使用することもできる。In addition, the cellulose-based water-soluble polymer or polyvinylpyrrolidone according to the present invention may be used alone, or two or more cellulose-based water-soluble polymers or polyvinylpyrrolidone may be used together.
本発明医薬品組成物は、具体的には、主として固型製
剤として使用される。固型製剤とするために必要な他の
残分、例えば、賦形剤、崩壊剤、滑沢剤等を加えること
は自由であり、通常の方法によって製造し、粒剤及び錠
剤として製剤化することが可能である。即ち、環状アミ
ン誘導体にセルロース系水溶性高分子又はポリビニルピ
ロリドンと乳糖とを混合させた後、有機酸を適量の水に
溶解して加え、更に、必要に応じて水を加えて練合し造
粒し、乾燥後、ステアリン酸マグネシウム等の滑沢剤を
加え、常法により錠剤化することができる。Specifically, the pharmaceutical composition of the present invention is mainly used as a solid preparation. It is free to add other residues necessary for forming a solid preparation, for example, excipients, disintegrants, lubricants, etc., manufactured by a usual method, and formulated as granules and tablets. It is possible. That is, after mixing a cyclic amine derivative with a cellulose-based water-soluble polymer or polyvinylpyrrolidone and lactose, an organic acid is dissolved in an appropriate amount of water and added, and if necessary, water is added and kneaded. After granulating and drying, a lubricating agent such as magnesium stearate is added, and the mixture can be tableted by a conventional method.
以下、実施例により本発明を更に詳細に説明するが、
これらの実施例は本発明の代表的な組成物を開示するも
ので、いかなる場合も本発明はこれらの実施例により制
限されるものではない。Hereinafter, the present invention will be described in more detail by examples,
These examples disclose representative compositions of the present invention, and in no way the present invention is limited by these examples.
実施例１ 化合物A5重量部、ヒドロキシプロピルメチルセルロー
ス４重量部及び乳糖85重量部を撹拌混合機内で混合した
後、酒石酸５重量部を適量の水に溶解して注加し、必要
により更に水を加えて造粒した。Example 1 Compound A (5 parts by weight), hydroxypropyl methylcellulose (4 parts by weight) and lactose (85 parts by weight) were mixed in a stirrer, and then tartaric acid (5 parts by weight) was dissolved in an appropriate amount of water and poured. And granulated.
乾燥して篩下後、ステアリン酸マグネシウム１重量部
を加えて混合し、慣用の打錠機で錠剤とした。After drying and sieving, 1 part by weight of magnesium stearate was added and mixed, and formed into tablets using a conventional tableting machine.
実施例２ 化合物A5重量部、ヒドロキシプロピルメチルセルロー
ス４重量部及び乳糖79重量部を予め混合した後、酒石酸
1.5重量部を適量の水に溶解して注加し、必要により更
に水を加えて造粒した。Example 2 Compound A (5 parts by weight), hydroxypropyl methylcellulose (4 parts by weight) and lactose (79 parts by weight) were mixed in advance, and tartaric acid was added.
1.5 parts by weight were dissolved in an appropriate amount of water and poured, and water was further added as needed to perform granulation.
乾燥して篩下後、結晶セルロース５重量部、トウモロ
コシ澱粉５重量部、ステアリン酸マグネシウム0.5重量
部を加えて混合し、慣用の打錠機で錠剤とした。After drying and sieving, 5 parts by weight of crystalline cellulose, 5 parts by weight of corn starch, and 0.5 parts by weight of magnesium stearate were added and mixed, and tableted with a conventional tableting machine.
以下に記載する実験例をもって本発明の効果を説明す
る。The effects of the present invention will be described with reference to the following experimental examples.
実験例１ 実施例１において得られた錠剤を検体試料とした。Experimental Example 1 The tablet obtained in Example 1 was used as a sample.
別に、検体試料よりヒドロキシプロピルメチルセルロ
ースを除いて同様に製剤化したものを対照試料（１）、
検体試料より酒石酸を除いて同様に製剤化したものを対
照試料（２）とした。Separately, a control sample (1) was prepared in the same manner except that hydroxypropylmethylcellulose was removed from the test sample.
A control sample (2) was prepared in the same manner except that tartaric acid was removed from the test sample.
検体試料及び対照試料（１）、（２）をそれぞれ１錠
とり、第11改正日本薬局方一般試験法の溶出試験法第２
法（パドル法、回転数100rpm）に従って試験を実施し
た。Take one tablet each of the sample sample and the control sample (1) and (2), and use the dissolution test method 2 of the Japanese Pharmacopoeia 11th Edition
The test was performed according to the method (paddle method, rotation speed 100 rpm).
試験液は、崩壊試験法第２液500mlを用い、経時的にN
o.3ガラスフィルターを通して一定量を採取し、吸光光
度法により定量した。結果を図１に示す。The test solution used was 500 ml of the second solution of the disintegration test method, and N
o. A fixed amount was collected through a glass filter and quantified by an absorption spectrophotometric method. The results are shown in FIG.
図１は溶出曲線を示し、 （２）の結果である。FIG. 1 shows the elution curve, This is the result of (2).
図１より本発明の医薬品組成物は明らかに良好な溶出
性を有することが明らかである。From FIG. 1, it is clear that the pharmaceutical composition of the present invention has a clearly good dissolution property.
実験例２ 実施例１において、酒石酸の代わりにクエン酸、コハ
ク酸、リンゴ酸、フマール酸、アジピン酸又はアスコル
ビン酸をそれぞれ用いて、実施例１と同様に錠剤を製造
した。Experimental Example 2 A tablet was produced in the same manner as in Example 1, except that citric acid, succinic acid, malic acid, fumaric acid, adipic acid or ascorbic acid were used instead of tartaric acid.
得られた錠剤について実験例１と同様に溶出率を求め
た。その結果を図２に示す。The dissolution rate of the obtained tablets was determined in the same manner as in Experimental Example 1. The result is shown in FIG.
図２において、 はアスコルビン酸をそれぞれ用いた場合の溶出率を示
す。In FIG. Indicates the elution rate when ascorbic acid was used.
実験例３ 実施例２において、ヒドロキシプロピルメチルセルロ
ース（HPMC）の代わりに、ヒドロキシプロピルセルロー
ス（HPC）、メチルセルロース（MC）、ポリビニルピロ
リドン（PVP）をそれぞれ用いて実施例２と同様に錠剤
を製造した。Experimental Example 3 In Example 2, tablets were produced in the same manner as in Example 2 except that hydroxypropylcellulose (HPC), methylcellulose (MC), and polyvinylpyrrolidone (PVP) were used instead of hydroxypropylmethylcellulose (HPMC).
得られた錠剤について実験例１と同様に溶出率を求め
た。その結果を図３に示す。The dissolution rate of the obtained tablets was determined in the same manner as in Experimental Example 1. The result is shown in FIG.
図３において、 はPVPをそれぞれ用いた場合の溶出率を示す。In FIG. Indicates the elution rate when PVP was used.
実験例４ 実施例２において、酒石酸の配合量を化合物A1重量部
に対し、0,0.05,0.1,0.2,0.3重量部にそれぞれ変え、以
下実施例２と同様の方法で錠剤を製造した。Experimental Example 4 In Example 2, tablets were produced in the same manner as in Example 2 except that the amount of tartaric acid was changed to 0, 0.05, 0.1, 0.2, and 0.3 parts by weight with respect to 1 part by weight of compound A.
得られた錠剤について、実験例１と同様の方法で溶出
率を求めた。その結果を図４に示す。The dissolution rate of the obtained tablets was determined in the same manner as in Experimental Example 1. FIG. 4 shows the results.
図４において、 の場合の結果である。In FIG. It is a result in the case of.
図４の結果から明らかな如く、酒石酸の配合量は環状
アミン誘導体１重量部に対して0.05重量部以上で完全に
効果が示される。As is clear from the results in FIG. 4, the effect is completely exhibited when the amount of tartaric acid is 0.05 parts by weight or more based on 1 part by weight of the cyclic amine derivative.
実験例５ 実施例１において、ヒドロキシプロピルメチルセルロ
ースの配合量を化合物A1重量部に対して、0,0.05,0.1,
0.2,0.4,0.8,1.2重量部にそれぞれ変え、以下実施例１
と錠の方法で錠剤を製造した。Experimental Example 5 In Example 1, the compounding amount of hydroxypropylmethylcellulose was 0,0.05,0.1,
Example 1 was changed to 0.2, 0.4, 0.8, and 1.2 parts by weight, respectively.
And tablets were manufactured by the tablet method.
得られた錠剤について、実験例１と同様の方法で溶出
率を求めた。その結果を図５に示す。The dissolution rate of the obtained tablets was determined in the same manner as in Experimental Example 1. The result is shown in FIG.
図５において、 はヒドロキシプロピルメチルセルロースの配合量が０、 の場合の結果である。In FIG. Is 0 in the amount of hydroxypropyl methylcellulose, It is a result in the case of.
図５に示す結果から明らかな如く、ヒドロキシプロピ
ルメチルセルロースの配合量が環状アミン誘導体１重量
部に対して0.05重量部以上で効果が示される。As is apparent from the results shown in FIG. 5, the effect is exhibited when the amount of hydroxypropylmethylcellulose is 0.05 parts by weight or more based on 1 part by weight of the cyclic amine derivative.
図１〜図５はそれぞれ実験例１〜５の結果を示すグラフ
である。1 to 5 are graphs showing the results of Experimental Examples 1 to 5, respectively.
───────────────────────────────────────────────────── フロントページの続き (56)参考文献 特開 昭62−283926（ＪＰ，Ａ) 特開 昭62−123117（ＪＰ，Ａ) 特開 昭63−126825（ＪＰ，Ａ) 米国特許4921863（ＵＳ，Ａ) ────────────────────────────────────────────────── (5) References JP-A-62-283926 (JP, A) JP-A-62-123117 (JP, A) JP-A-63-126825 (JP, A) US Pat. , A)
Claims (1)
ハロゲン原子から選択された同一又は相異なる１又は２
以上の置換基により置換されても良い置換もしくは無置
換のナフチル基、Ｂはハロゲン原子、低級アルキル基又
は低級アルコキシ基から選択された同一又は相異なる１
又は２の置換基により置換されてもよい置換又は無置換
のフェニル基、Ｘは式 で示される基、式−CH2−で示される基、式 で示される基、又は式 で示される基、Ｙは式 で示される基、式−Ｏ−で示される基、式−NH−で示さ
れる基、又は式−CH2−で示される基を意味する。〕 で表される環状アミン誘導体１重量部に対して、クエン
酸、酒石酸、コハク酸、リンゴ酸、フマール酸、アジピ
ン酸及びアスコルビン酸からなる群から選ばれる少なく
とも１種の有機酸を0.05〜1.2重量部、ヒドロキシプロ
ピルメチルセルロース、ヒドロキシプロピルセルロース
及びメチルセルロースからなる群から選ばれる少なくと
も１種のセルロース系水溶性高分子又はポリビニルピロ
リドンを0.05〜1.2重量部配合してなることを特徴とす
る経口用医薬品組成物。(1) General formula [A is the same or different 1 or 2 selected from a lower alkyl group, a lower alkoxy group, a hydroxyl group or a halogen atom;
A substituted or unsubstituted naphthyl group which may be substituted by the above substituents, B is the same or different 1 selected from a halogen atom, a lower alkyl group or a lower alkoxy group;
Or a substituted or unsubstituted phenyl group optionally substituted by 2 substituents, X is a group represented by the formula A group represented by the formula: -CH 2- , a group represented by the formula: A group represented by or a formula And Y is a group represented by the formula Means a group represented by - a group represented by a group represented by formula -O-, a group represented by formula -NH-, or Formula -CH 2. With respect to 1 part by weight of the cyclic amine derivative represented by the formula, at least one organic acid selected from the group consisting of citric acid, tartaric acid, succinic acid, malic acid, fumaric acid, adipic acid and ascorbic acid is added in an amount of 0.05 to 1.2. Oral pharmaceutical composition comprising 0.05 to 1.2 parts by weight of at least one cellulose-based water-soluble polymer selected from the group consisting of hydroxypropylmethylcellulose, hydroxypropylcellulose and methylcellulose or polyvinylpyrrolidone. Stuff.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63219790A JP2723919B2 (en) | 1988-09-02 | 1988-09-02 | Oral pharmaceutical composition containing cyclic amine derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63219790A JP2723919B2 (en) | 1988-09-02 | 1988-09-02 | Oral pharmaceutical composition containing cyclic amine derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH0267219A JPH0267219A (en) | 1990-03-07 |
| JP2723919B2 true JP2723919B2 (en) | 1998-03-09 |
Family
ID=16741062
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP63219790A Expired - Fee Related JP2723919B2 (en) | 1988-09-02 | 1988-09-02 | Oral pharmaceutical composition containing cyclic amine derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2723919B2 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010026993A1 (en) * | 2008-09-03 | 2010-03-11 | 武田薬品工業株式会社 | Method for improving absorbability of preparation, and preparation having improved absorbability |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4921863A (en) | 1988-02-17 | 1990-05-01 | Eisai Co., Ltd. | Cyclic amine derivatives |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS62123117A (en) * | 1985-11-22 | 1987-06-04 | Nippon Chemiphar Co Ltd | Nicardipine hydrochloride composition for oral administration |
| JPS62283926A (en) * | 1986-06-02 | 1987-12-09 | Nippon Chemiphar Co Ltd | Long-acting composition of nicardipine hydrochloride |
| DE3776269D1 (en) * | 1986-11-03 | 1992-03-05 | Schering Corp | LABETALOL TABLET WITH DELAYED DELIVERY OF ACTIVE SUBSTANCES. |
-
1988
- 1988-09-02 JP JP63219790A patent/JP2723919B2/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4921863A (en) | 1988-02-17 | 1990-05-01 | Eisai Co., Ltd. | Cyclic amine derivatives |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0267219A (en) | 1990-03-07 |
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