JP2012510447A - エゼチミブおよびシンバスタチンを含む医薬組成物 - Google Patents
エゼチミブおよびシンバスタチンを含む医薬組成物 Download PDFInfo
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- JP2012510447A JP2012510447A JP2011537993A JP2011537993A JP2012510447A JP 2012510447 A JP2012510447 A JP 2012510447A JP 2011537993 A JP2011537993 A JP 2011537993A JP 2011537993 A JP2011537993 A JP 2011537993A JP 2012510447 A JP2012510447 A JP 2012510447A
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- ezetimibe
- simvastatin
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- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 1
- 229960004844 lovastatin Drugs 0.000 description 1
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 1
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- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
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Abstract
Description
(1)シンバスタチンおよびエゼチミブを含む剤形を調製するための方法であって:
a)シンバスタチンを含有する第1組成物を提供する段階と、
b)エゼチミブを含有する第2組成物を提供する段階と、
c)少なくとも2つ、好ましくは2つの別個の区画を含む剤形を形成する段階とを含み、
1つの区画は第1または第2組成物のいずれかを使用して形成され、もう1つの区画はそれぞれの他の組成物を用いて形成され、区画は直接接触しており、および
区画の各々はそれぞれに1つの層を構成する方法。
崩壊剤は、カルメロースカルシウム、カルボキシメチルスターチナトリウム、クロスカルメロースナトリウム塩(架橋セルロースカルボキシメチルエーテルナトリウム塩)、デンプン、例えばナトリウムスターチグリコレートもしくはコーンスターチ、架橋ポリビニルピロリドン(クロスポビドン)、および低置換ヒドロキシプロピルセルロースからなる群から選択され、特に好ましくは、崩壊剤は、ナトリウムスターチグリコレートおよびクロスカルメロースナトリウム塩からなる群から選択される;
潤滑剤は、ステアリン酸、タルク、ナトリウムステアリルフマレートおよびマグネシウムステアレートからなる群から選択され、特に好ましくは、潤滑剤はマグネシウムステアレートである;
結合剤は、ポリビニルピロリドン(ポビドン)、ビニルピロリドンと他のビニル誘導体(コポビドン)とのコポリマー、ヒドロキシプロピルメチルセルロース、メチルセルロース、ヒドロキシプロピルセルロース、アラビアゴム末、ゼラチン、グアールゴム、カルボマー、例えばカーボポール、ポリメタクリレートおよびデンプンからなる群から選択され、特に好ましくは、結合剤はヒドロキシプロピルメチルセルロースおよびコポビドンからなる群から選択される;
希釈剤は、炭水化物、例えばグルコースのような単糖類、スクロースのようなオリゴ糖類、無水ラクトースおよびラクトース一水和物、ならびにソルビトール、マンニトール、エリスロ−ル、およびキシリトールのような糖アルコールから選択され、特に好ましくは、希釈剤はソルビトールである;
流動促進剤は、コロイド状シリカ、疎水性コロイド状シリカおよびマグネシウムトリシリケート、例えばタルカムからなる群から選択され、特に好ましくは、潤滑剤はコロイド状シリカおよび疎水性コロイド状シリカからなる群から選択される;および/または
甘味料は、アスパルテーム、サッカリンナトリウム、グリシルリジン酸二カリウム、アスパルテーム、ステビア、タウマチンなどからなる群から選択される。
単層錠剤
比較のために、両方の有効成分、シンバスタチンおよびエゼチミブが単層錠剤内、すなわち1つの共通コンポーネント内に存在する剤形を製造した。
エゼチミブ、シンバスタチン、ケイ化微結晶セルロース、ラクトース、クロスカルメロースナトリウム、ヒドロキシプロピルメチルセルロースおよびコロイド状シリカを均質に混合した。マグネシウムステアレートを加え、この混合物を再び混合し、単層錠剤に圧縮した。
二層錠剤
1つの実施例によって、両方の有効成分であるシンバスタチンおよびエゼチミブが相違する成分の例としての二層錠剤の相違する層内に各々存在する剤形を製造した。
シンバスタチン、ケイ化微結晶セルロース、ラクトース、クロスカルメロースナトリウム、ヒドロキシプロピルメチルセルロースおよびコロイド状シリカを均質に混合した。マグネシウムステアレートを加え、この混合液を再び混合し、二層錠剤成形機の第1ホッパー内に充填した。
エゼチミブ、シンバスタチン、ケイ化微結晶セルロース、ラクトース、クロスカルメロースナトリウム、ヒドロキシプロピルメチルセルロースおよび疎水性コロイド状シリカを均質に混合した。マグネシウムステアレートを加え、この混合物を再び混合し、単層錠剤に圧縮した。
シンバスタチン、微結晶セルロース、ラクトース、クロスカルメロースナトリウム、ヒドロキシプロピルメチルセルロースおよび疎水性コロイド状シリカを均質に混合した。マグネシウムステアレートを加え、この混合液を再び混合し、二層錠剤成形機の第1ホッパー内に充填した。
Claims (16)
- シンバスタチンおよびエゼチミブを含む剤形を調製するための方法であって:
a)シンバスタチンを含有する第1組成物を提供する段階と、
b)エゼチミブを含有する第2組成物を提供する段階と、
c)少なくとも2つの別個の区画を含む剤形を形成する段階とを含み、
1つの区画は第1または第2組成物のいずれかを使用して形成され、もう1つの区画はそれぞれの他の組成物を用いて形成され、前記区画は直接接触しており、および区画の各々はそれぞれに1つの層を構成する方法。 - 剤形が、この各々が1つの層を構成する2つの別個の区画からなる錠剤である、請求項1に記載の方法。
- 段階(a)から(c)が空気の存在下で実施される、請求項1または2に記載の方法。
- 第1組成物が第1層を形成し、第2組成物が第2層を形成し、第2層が第1層上に圧縮される、請求項1から3のいずれかに記載の方法。
- 第1および第2組成物には1つ以上の賦形剤が各々添加され、抗酸化剤および/または酸素吸収剤の添加は除外される、請求項1から4のいずれか一項に記載の方法。
- 段階(c)の錠剤上にはコーティングが適用されない、請求項1から5のいずれかに記載の方法。
- シンバスタチンおよびエゼチミブを含有する剤形を調製するための方法であって、直接圧縮の使用を含む方法。
- 第1および第2組成物の提供が造粒段階を含有していない、請求項1から7のいずれか一項に記載の方法。
- 請求項1から8のいずれかによる方法によって得られた剤形。
- 少なくとも2つの別個の区画を含む剤形であって、1つの区画はシンバスタチンを含有し、もう1つの区画はエゼチミブを含有し、前記区画は直接接触しており、区画の各々はそれぞれに1つの層を構成する剤形。
- 剤形が、コーティング層を含んでいない、請求項10に記載の剤形。
- 少なくとも2つの層は追加して1つ以上の賦形剤を含有する、請求項10または11に記載の剤形。
- 1つおよび他の区画は同一タイプの賦形剤を含有する、請求項10から12のいずれかに記載の剤形。
- 剤形が、二層錠剤である、請求項10から13のいずれかに記載の剤形。
- 高コレステロール血症の予防または治療において使用するための剤形の2つの別個の区画内に存在するシンバスタチンおよびエゼチミブの組み合わせを含む複合剤形であって、前記区画は直接接触しており、区画の各々はそれぞれ1つの層を構成する複合剤形。
- 複合剤形が、二層錠剤である、請求項15に記載の複合剤形。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP08170384A EP2204170A1 (en) | 2008-12-01 | 2008-12-01 | Pharmaceutical composition comprising ezetimibe and simvastatin |
EP08170384.5 | 2008-12-01 | ||
PCT/EP2009/066033 WO2010063667A2 (en) | 2008-12-01 | 2009-11-30 | Pharmaceutical composition comprising ezetimibe and simvastatin |
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JP2012510447A true JP2012510447A (ja) | 2012-05-10 |
JP5651123B2 JP5651123B2 (ja) | 2015-01-07 |
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JP2011537993A Expired - Fee Related JP5651123B2 (ja) | 2008-12-01 | 2009-11-30 | エゼチミブおよびシンバスタチンを含む医薬組成物 |
Country Status (8)
Country | Link |
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US (1) | US20120027854A1 (ja) |
EP (2) | EP2204170A1 (ja) |
JP (1) | JP5651123B2 (ja) |
CN (1) | CN102300561B (ja) |
AU (1) | AU2009324243B2 (ja) |
CA (1) | CA2745248C (ja) |
SI (1) | SI2370061T1 (ja) |
WO (1) | WO2010063667A2 (ja) |
Cited By (2)
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JP2018115139A (ja) * | 2017-01-20 | 2018-07-26 | ニプロ株式会社 | エゼチミブ含有医薬組成物の製造方法 |
JP2020094025A (ja) * | 2018-12-11 | 2020-06-18 | 日本ジェネリック株式会社 | アジルサルタンとアムロジピンベシル酸塩含有固形製剤及び固形製剤の製造方法 |
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WO2011002424A2 (en) * | 2009-07-02 | 2011-01-06 | Bilgic Mahmut | Solubility and stability enchancing pharmaceutical formulation |
CN103236829B (zh) * | 2013-03-27 | 2016-03-09 | 杭州远方仪器有限公司 | 一种方波发生电路 |
CN103340852A (zh) * | 2013-07-01 | 2013-10-09 | 北京阜康仁生物制药科技有限公司 | 含有依折麦布和阿托伐他汀的药物组合物 |
HU231036B1 (hu) * | 2013-09-30 | 2019-12-30 | Egis Gyógyszergyár Nyilvánosan Működő Részvénytársaság | Koleszterin bioszintézis gátló hatóanyagot és koleszterin abszorpciót gátló hatóanyagot tartalmazó kombinációs gyógyszerkészítmény |
CN104382896A (zh) * | 2014-11-04 | 2015-03-04 | 万全万特制药江苏有限公司 | 含有依折麦布和辛伐他汀的药物组合物 |
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- 2009-11-30 JP JP2011537993A patent/JP5651123B2/ja not_active Expired - Fee Related
- 2009-11-30 EP EP09760531.5A patent/EP2370061B1/en not_active Not-in-force
- 2009-11-30 WO PCT/EP2009/066033 patent/WO2010063667A2/en active Application Filing
- 2009-11-30 US US13/132,055 patent/US20120027854A1/en not_active Abandoned
- 2009-11-30 CN CN200980155564.XA patent/CN102300561B/zh not_active Expired - Fee Related
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Cited By (3)
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JP2018115139A (ja) * | 2017-01-20 | 2018-07-26 | ニプロ株式会社 | エゼチミブ含有医薬組成物の製造方法 |
JP2020094025A (ja) * | 2018-12-11 | 2020-06-18 | 日本ジェネリック株式会社 | アジルサルタンとアムロジピンベシル酸塩含有固形製剤及び固形製剤の製造方法 |
JP7109748B2 (ja) | 2018-12-11 | 2022-08-01 | 日本ジェネリック株式会社 | アジルサルタンとアムロジピンベシル酸塩含有固形製剤及び固形製剤の製造方法 |
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CA2745248C (en) | 2016-12-20 |
JP5651123B2 (ja) | 2015-01-07 |
US20120027854A1 (en) | 2012-02-02 |
CA2745248A1 (en) | 2010-06-10 |
WO2010063667A3 (en) | 2010-08-05 |
AU2009324243B2 (en) | 2015-02-05 |
SI2370061T1 (sl) | 2014-03-31 |
AU2009324243A1 (en) | 2011-07-07 |
EP2204170A1 (en) | 2010-07-07 |
CN102300561A (zh) | 2011-12-28 |
EP2370061A2 (en) | 2011-10-05 |
EP2370061B1 (en) | 2013-10-23 |
CN102300561B (zh) | 2014-07-16 |
WO2010063667A2 (en) | 2010-06-10 |
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