JP6081376B2 - アンギオテンシンii拮抗作用を有する化合物を含有する固形医薬組成物 - Google Patents
アンギオテンシンii拮抗作用を有する化合物を含有する固形医薬組成物 Download PDFInfo
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- JP6081376B2 JP6081376B2 JP2013551847A JP2013551847A JP6081376B2 JP 6081376 B2 JP6081376 B2 JP 6081376B2 JP 2013551847 A JP2013551847 A JP 2013551847A JP 2013551847 A JP2013551847 A JP 2013551847A JP 6081376 B2 JP6081376 B2 JP 6081376B2
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- solid pharmaceutical
- magnesium
- pharmaceutical composition
- angiotensin
- compound
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- 239000007787 solid Substances 0.000 title claims description 27
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- 102000005862 Angiotensin II Human genes 0.000 title claims description 18
- 101800000733 Angiotensin-2 Proteins 0.000 title claims description 18
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- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 14
- 230000008485 antagonism Effects 0.000 claims description 10
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- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 claims description 6
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 14
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- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
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- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
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- RMMXLENWKUUMAY-UHFFFAOYSA-N telmisartan Chemical compound CCCC1=NC2=C(C)C=C(C=3N(C4=CC=CC=C4N=3)C)C=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C(O)=O RMMXLENWKUUMAY-UHFFFAOYSA-N 0.000 description 4
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- FNAQSUUGMSOBHW-UHFFFAOYSA-H calcium citrate Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O FNAQSUUGMSOBHW-UHFFFAOYSA-H 0.000 description 3
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
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- 229910001629 magnesium chloride Inorganic materials 0.000 description 3
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- WMFHUUKYIUOHRA-UHFFFAOYSA-N (3-phenoxyphenyl)methanamine;hydrochloride Chemical compound Cl.NCC1=CC=CC(OC=2C=CC=CC=2)=C1 WMFHUUKYIUOHRA-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- 239000005485 Azilsartan Substances 0.000 description 2
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- 239000001736 Calcium glycerylphosphate Substances 0.000 description 2
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- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
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- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
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Description
バルサルタンを含有する錠剤を以下の表1に記載の処方により製造した。バルサルタン(特許文献1)800g、炭酸マグネシウム100g、低置換度ヒドロキシプロピルセルロース770g、結晶セルロース100g、軽質無水ケイ酸100gおよびステアリン酸マグネシウム30gを容器回転形混合機(筒井理化学器械株式会社製S−3形)に投入して混合し、この混合物に対し、ローラーコンパクター(フロイント産業株式会社製TF−MINI)を用いて、圧密力60kg/cm2およびローラースピード4rpmにて圧密化を行った。圧密化された混合圧縮体を整粒機(株式会社ダルトン製P−02S型)に通して顆粒状とし(乾式造粒)、低置換度ヒドロキシプロピルセルロース50g、軽質無水ケイ酸10g、タルク20gおよびステアリン酸マグネシウム20gを添加・混合し、この混合物を打錠機(株式会社菊水製作所製VIRGO)に投入し、直径8.5mmの杵を用いて打錠圧7kN/cm2にて1錠質量200mgとなるように打錠を行い、素錠(核錠部)を得た。次いで、この素錠をフィルムコーティング機(フロイント産業株式会社製HCT−48N)に投入し、ヒドロキシプロピルメチルセルロース128g、ポリエチレングリコール16gおよび酸化チタン16gを精製水1600gに溶解した液を、1錠あたり8mgの固形分がコーティングされるように素錠に噴霧してフィルムコーティングを行い、錠剤を得た。
バルサルタンを含有する錠剤を以下の表2に記載の処方により製造した。実施例1の炭酸マグネシウムを沈降炭酸カルシウムに替えたこと以外は、実施例1と同様に製造した。
バルサルタンを含有する錠剤を以下の表3に記載の処方により製造した。バルサルタン(特許文献1)200g、炭酸マグネシウム25g、低置換度ヒドロキシプロピルセルロース210gおよび結晶セルロース25gを攪拌造粒機(株式会社パウレック製VG−05)に投入して混合し、さらにヒドロキシプロピルセルロース15gを精製水に溶解した液を添加して湿式造粒を行った。得られた造粒物に低置換度ヒドロキシプロピルセルロース12.5g、軽質無水ケイ酸2.5g、タルク5gおよびステアリン酸マグネシウム5gを添加・混合し、この混合物を打錠機(株式会社菊水製作所製VIRGO)に投入し、直径8.5mmの杵を用いて打錠圧6kN/cm2にて打錠を行い、素錠(核錠部)を得た。次いで、この素錠をフィルムコーティング機(フロイント産業株式会社製HCT−48N)に投入し、ヒドロキシプロピルメチルセルロース32g、ポリエチレングリコール4gおよび酸化チタン4gを精製水400gに溶解した液を素錠に噴霧してフィルムコーティングを行い、錠剤を得た。
バルサルタンを含有する錠剤を以下の表4に記載の処方により製造した。実施例3の炭酸マグネシウムを酸化マグネシウムに替えたこと以外は、実施例3と同様に製造した。
バルサルタンを含有する錠剤を以下の表5に記載の処方により製造した。バルサルタン(特許文献1)800g、低置換度ヒドロキシプロピルセルロース870g、結晶セルロース100g、軽質無水ケイ酸100gおよびステアリン酸マグネシウム30gを容器回転形混合機(筒井理化学器械株式会社製S−3形)に投入して混合し、この混合物に対し、ローラーコンパクター(フロイント産業株式会社製TF−MINI)を用いて、圧密力60kg/cm2およびローラースピード4rpmにて圧密化を行った。圧密化された混合圧縮体を整粒機(株式会社ダルトン製P−02S型)に通して顆粒状とし(乾式造粒)、低置換度ヒドロキシプロピルセルロース50g、軽質無水ケイ酸10g、タルク20gおよびステアリン酸マグネシウム20gを添加・混合し、この混合物を打錠機(株式会社菊水製作所製VIRGO)に投入し、直径8.5mmの杵を用いて打錠圧7kN/cm2にて1錠質量200mgとなるように打錠を行い、素錠(核錠部)を得た。次いで、この素錠をフィルムコーティング機(フロイント産業株式会社製HCT−48N)に投入し、ヒドロキシプロピルメチルセルロース128g、ポリエチレングリコール16gおよび酸化チタン16gを精製水1600gに溶解した液を、1錠あたり8mgの固形分がコーティングされるように素錠に噴霧してフィルムコーティングを行い、錠剤を得た。
実施例1〜4および比較例1で得られた錠剤および「ディオバン(登録商標)錠80mg」(ノバルティス社製)(比較例2)について、保存前後でバルサルタンの溶出試験を行った。試験液は900mLとし、パドル回転数50rpmにて、30分後の溶出率(%)を測定した。なお、「ディオバン(登録商標)錠80mg」は、バルサルタンのほか、ヒドロキシプロピルセルロース、セルロース、無水ケイ酸、タルク、ステアリン酸マグネシウム、ヒプロメロース、マクロゴールおよび酸化チタンの8成分を含有する。
Claims (2)
- アンギオテンシンII拮抗作用を有する化合物およびアルカリ土類金属塩を含有する固形医薬組成物であって、
該アルカリ土類金属塩が、酸化マグネシウムおよび炭酸マグネシウムからなる群から選択される少なくとも1種の化合物であり、
該アルカリ土類金属塩の含有量が該組成物の質量を基準として2質量%から7質量%であり、そして
該アンギオテンシンII拮抗作用を有する化合物がバルサルタンである、固形医薬組成物。 - 前記アンギオテンシンII拮抗作用を有する化合物の含有量が前記組成物の質量を基準として30質量%以上である、請求項1に記載の固形医薬組成物。
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