JP7160395B2 - メロキシカムを含有する固体医薬組成物及びその使用 - Google Patents
メロキシカムを含有する固体医薬組成物及びその使用 Download PDFInfo
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- JP7160395B2 JP7160395B2 JP2021077528A JP2021077528A JP7160395B2 JP 7160395 B2 JP7160395 B2 JP 7160395B2 JP 2021077528 A JP2021077528 A JP 2021077528A JP 2021077528 A JP2021077528 A JP 2021077528A JP 7160395 B2 JP7160395 B2 JP 7160395B2
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- meloxicam
- dosage form
- cyclodextrin
- pharmaceutical composition
- solid pharmaceutical
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- 230000032258 transport Effects 0.000 description 1
- 206010044652 trigeminal neuralgia Diseases 0.000 description 1
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Description
本出願は、2017年5月10日出願の米国仮特許出願第62/504,105号、及び、2017年7月25日出願の米国仮特許出願第62/536,466号の利益、並びに、2018年1月4日出願の国際出願番号PCT/US2018/012433号の利益を主張し、これらの先行する全ての特許出願の全体が参照により本明細書に組み込まれる。
(a)腸溶性コーティングによって囲まれている又は囲まれていない、デクスケトプロフェン、
(b)重炭酸ナトリウム若しくは重炭酸カリウム及び/又は炭酸ナトリウム若しくは炭酸カリウム、及び、
(c)腸溶性コーティングによって囲まれている又は囲まれておらず、シクロデキストリンを用いて製剤化されている又は製剤化されていない、フロバトリプタン、
を含む医薬組成物に関する。
実施形態2 1)実施形態1の包接錯体又は2)メロキシカムと、カーボネート又はバイカーボネートとを含む剤形。
実施形態3 前記シクロデキストリンは置換β-シクロデキストリンを含む、前記包接錯体を含む実施形態2の剤形。
実施形態4 前記置換β-シクロデキストリンはスルホブチルエーテルβ-シクロデキストリン(SBEβCD)又はヒドロキシプロピルβ-シクロデキストリン(HPβCD)である、実施形態3の剤形。
実施形態5 前記シクロデキストリンは前記SBEβCDである、実施形態4の剤形。
実施形態6 前記SBEβCDはβ-シクロデキストリンの各分子について約6個~約7個のスルホブチルエーテル基を有する、実施形態5の剤形。
実施形態7 前記メロキシカム及び前記SBEβCDは約0.8から約1.2のモル比を有する、実施形態6の剤形。
実施形態8 前記メロキシカム及び前記SBEβCDは約1のモル比を有する、実施形態6の剤形。
実施形態9 バイカーボネートを含有する、実施形態2、3、4、5、6、7、又は8の剤形。
実施形態10 前記バイカーボネートは重炭酸ナトリウムを含む、実施形態9の剤形。
実施形態11 経口剤形である、実施形態2、3、4、5、6、7、8、9、又は10の剤形。
実施形態12 前記剤形中に約50mgから約200mgの前記SBEβCDが存在する、実施形態2、3、4、5、6、9、10、又は11の剤形。
実施形態13 前記カーボネート又は前記バイカーボネートは約400mgから約600mgの範囲の量で存在する、実施形態2、3、4、5、6、7、8、9、10、11、又は12の剤形。
実施形態14 メロキシカムのTmaxが、カーボネートも、バイカーボネートも、シクロデキストリンも含まない剤形と比べて、減らされている、実施形態2、3、4、5、6、7、8、9、10、11、12、又は13の剤形。
実施形態15 前記メロキシカムのTmaxは、患者において投与後約10分から約180分の範囲内の時点で達成される、実施形態14の方法。
実施形態16 カーボネートも、バイカーボネートも、シクロデキストリンも含まない剤形よりも高いメロキシカムの経口生物学的利用能を有する、実施形態2、3、4、5、6、7、8、9、10、11、12、13、14、又は15の剤形。
実施形態17 制酸剤をさらに含む、実施形態2、3、4、5、6、7、8、9、10、11、12、13、14、15、又は16の剤形。
実施形態18 前記制酸剤はプロトンポンプ阻害剤である、実施形態17の剤形。
実施形態19 前記プロトンポンプ阻害剤はエソメプラゾールである、実施形態18の剤形。
実施形態20 前記剤形中に約30mgから約50mgのエソメプラゾールが存在する、実施形態19の剤形。
実施形態21 実施形態2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、又は20の剤形を、治療の必要な患者に、経口投与することを含む、メロキシカムの経口投与方法。
実施形態22 前記剤形は疼痛を治療するために投与される、実施形態21の方法。
実施形態23 前記剤形は炎症性疼痛を治療するために投与される、実施形態21の方法。
実施形態24 前記剤形は、骨関節炎、関節リウマチ、又は若年性関節リウマチを治療するために投与される、実施形態21の方法。
実施形態25 実施形態2、3、4、5、6、7、8、9、10、11、12、13、14、又は15の剤形を、治療の必要な患者に、静脈内投与することを含む、メロキシカムの静脈内投与方法。
実施形態26 シクロデキストリン内にフロバトリプタンがある包接錯体。
実施形態2-2 前記包接錯体であって、前記シクロデキストリンが、スルホブチルエーテルβ-シクロデキストリン(SBEβCD)又はヒドロキシプロピルβ-シクロデキストリン(HPβCD)を含む、包接錯体を含む実施形態2-1の剤形。
実施形態2-3 前記シクロデキストリンは、前記SBEβCDであり、β-シクロデキストリンの各分子について約6個~約7個のスルホブチルエーテル基を有する、実施形態2-2の剤形。
実施形態2-4 バイカーボネートをさらに含有する、実施形態2-3の剤形。
実施形態2-5 前記バイカーボネートは重炭酸ナトリウムを含む、実施形態2-4の剤形。
実施形態2-6 前記フロバトリプタン及び前記SBEβCDは約0.8から約1.2のモル比を有する、実施形態2-3の剤形。
実施形態2-7 バイカーボネートを含有する、実施形態2-6の剤形。
実施形態2-8 前記バイカーボネートは重炭酸ナトリウムを含む、実施形態2-7の剤形。
実施形態2-9 経口剤形である、実施形態2-1の剤形。
実施形態2-10 前記包接錯体であって、単位剤形中に約50mgから約200mgの前記SBEβCDが存在する、包接錯体を含む実施形態2-2の剤形。
実施形態2-11 前記フロバトリプタンと、前記カーボネート又は前記バイカーボネートとを含む実施形態2-1の剤形。
実施形態2-12 フロバトリプタンのTmaxが、カーボネートも、バイカーボネートも、シクロデキストリンも含まない剤形と比べて、減らされている、実施形態2-1の剤形。
実施形態2-13 フロバトリプタンのTmaxは、患者において投与後約10分から約180分の範囲内の時点で達成される、実施形態2-1の剤形。
実施形態2-14 カーボネートも、バイカーボネートも、シクロデキストリンも含まない剤形よりも高いフロバトリプタンの経口生物学的利用能を有する、実施形態2-1の剤形。
実施形態2-15 前記カーボネート又は前記バイカーボネートは約400mgから約600mgの範囲の量で単位剤形中に存在する、実施形態2-11の剤形。
実施形態2-16 前記カーボネート又は前記バイカーボネートは重炭酸ナトリウムである、実施形態2-15の剤形。
実施形態2-17 NSAIDをさらに含む、実施形態2-11の剤形。
実施形態2-18 前記NSAIDは、デクスケトプロフェン又はメロキシカムである、実施形態2-17の剤形。
実施形態2-19 前記NSAIDは、デクスケトプロフェンである、実施形態2-18の剤形。
実施形態2-20 単位剤形中に約10mgから約50mgのデクスケトプロフェンが存在する、実施形態2-19の剤形。
実施形態2-21 実施形態2-1の剤形を治療の必要な患者に経口投与することを含む、フロバトリプタンの経口投与方法。
実施形態2-22 前記剤形は前記包接錯体を含み、前記シクロデキストリンはSBEβCDであり、さらに、前記剤形はバイカーボネートをさらに含む、実施形態2-21の方法。
実施形態2-23 前記バイカーボネートは重炭酸ナトリウムである、実施形態2-22の方法。
実施形態2-24 単位剤形が約300mgから約600mgの重炭酸ナトリウムを含有する、実施形態2-23の方法。
実施形態2-25 前記剤形はNSAIDをさらに含む、実施形態2-22の方法。
実施形態2-26 前記NSAIDは、デクスケトプロフェン、メロキシカム、ナプロキセン、イブプロフェン、又はセレコキシブである、実施形態2-25の方法。
実施形態2-27 前記剤形は疼痛を治療するために投与される、実施形態2-21の方法。
実施形態2-28 前記剤形は炎症性疼痛を治療するために投与される、実施形態2-21の方法。
実施形態2-29 前記剤形は、骨関節炎、関節リウマチ、又は若年性関節リウマチを治療するために投与される、実施形態2-21の方法。
実施形態P-2 1)前記メロキシカム又は前記トリプタンと、2)前記SBEβCDとの包接錯体を含む、実施形態P-1の剤形。
実施形態P-3 約10mgから約20mgのメロキシカムを含有する、実施形態P-1又はP-2の剤形。
実施形態P-4 約15mgのメロキシカムを含有する、実施形態P-3の剤形。
実施形態P-5 前記SBEβCDは、β-シクロデキストリンの各分子について約6個~約7個のスルホブチルエーテル基を有する、実施形態P-1、P-2、P-3、又はP-4の剤形。
実施形態P-6 約50mgから約200mgの前記SBEβCDを含有する、実施形態P-1、P-2、P-3、P-4、又はP-5の剤形。
実施形態P-7 前記トリプタンはリザトリプタンである、実施形態P-1、P-2、P-3、P-4、P-5、又はP-6の剤形。
実施形態P-8 約5mgから約20mgのリザトリプタンを含有する、実施形態P-7の剤形。
実施形態P-9 約10mgのリザトリプタンを含有する、実施形態P-8の剤形。
実施形態P-10 約100mgのSBEβCDを含有する、実施形態P-6の剤形。
実施形態P-11 前記バイカーボネートは重炭酸ナトリウムを含む、実施形態P-1、P-2、P-3、P-4、P-5、P-6、P-7、P-8、P-9、又はP-10の剤形。
実施形態P-12 約400mgから約600mgのバイカーボネートを含有する、実施形態P-10の剤形。
実施形態P-13 約500mgの重炭酸ナトリウムを含有する、実施形態P-12の剤形。
実施形態P-14 前記経口剤形は、約3時間未満のメロキシカムのミーンTmaxを有することを示されたものである、実施形態P-1、P-2、P-3、P-4、P-5、P-6、P-7、P-8、P-9、P-10、P-11、又はP-12の剤形。
実施形態P-15 前記経口剤形は、約2時間未満のメロキシカムのミーンTmaxを有することを示されたものである、実施形態P-14の剤形。
実施形態P-16 前記経口剤形は、約1時間未満のメロキシカムのミーンTmaxを有することを示されたものである、実施形態P-14の剤形。
実施形態P-17 前記経口剤形は、哺乳類に投与された場合、前記基準剤形と比べて、増加したメロキシカムの生物学的利用能を有する、実施形態P-1、P-2、P-3、P-4、P-5、P-6、P-7、P-8、P-9、P-10、P-11、P-12、P-13、P-14、P-15、又は、P-16の剤形。
実施形態P-18 前記経口剤形は、哺乳類に投与された場合、前記基準剤形と比べて、改善したメロキシカムの薬物動態を有する、実施形態P-1、P-2、P-3、P-4、P-5、P-6、P-7、P-8、P-9、P-10、P-11、P-12、P-13、P-14、P-15、P-16、又はP-17の剤形。
実施形態P-19 前記経口剤形は、哺乳類に投与された場合、前記基準剤形と比べて、増加したトリプタンの生物学的利用能を有する、実施形態P-1、P-2、P-3、P-4、P-5、P-6、P-7、P-8、P-9、P-10、P-11、P-12、P-13、P-14、P-15、P-16、P-17、又はP-18の剤形。
実施形態P-20 前記経口剤形は、哺乳類に投与された場合、前記基準剤形と比べて、改善したトリプタンの薬物動態を有する、実施形態P-1、P-2、P-3、P-4、P-5、P-6、P-7、P-8、P-9、P-10、P-11、P-12、P-13、P-14、P-15、P-16、P-17、P-18、又はP-19の剤形。
実施形態P-21 実施形態P-1、P-2、P-3、P-4、P-5、P-6、P-7、P-8、P-9、P-10、P-11、P-12、P-13、P-14、P-15、P-16、P-17、P-18、P-19、又はP-20の剤形を、トリプタン又はNSAIDによる治療が必要な哺乳類又はヒトに経口投与することを含む、トリプタン又はNSAIDの薬物動態を改善する方法。
実施形態P-22 実施形態P-1、P-2、P-3、P-4、P-5、P-6、P-7、P-8、P-9、P-10、P-11、P-12、P-13、P-14、P-15、P-16、P-17、P-18、P-19、又はP-20の剤形を、それらを必要とする哺乳類又はヒトに経口投与することを含む、疼痛を治療する方法。
実施形態P-23 前記疼痛は片頭痛である、実施形態P-22の方法。
実施形態P-24 前記疼痛は炎症性疼痛である、実施形態P-22の方法。
酸性培地のpHでの様々な量の炭酸カリウム(K2CO3)及び重炭酸ナトリウム(NaHCO3)の影響を調べた。酸性培地は胃条件を模すよう選ばれた。0.01N HCl溶液(pH2)50mlにK2CO3又はNaHCO3を添加した。K2CO3又はNaHCO3の添加後に、この溶液のpHを測定した。その後、この混合物に脱イオン水(240mL)を加え、再び、pHを測定した。結果を表1から表4に示す。
メロキシカムを含有し且つシクロデキストリン、K2CO3、又はNaHCO3が配合されている錠剤を、作成し、溶解度を調べた。メロキシカムのみを含有する錠剤(MOBIC(登録商標))も、購入し、溶解度を調べた。調べた錠剤を表5に列記する。メロキシカムとシクロデキストリンとを含有する錠剤では、メロキシカム/シクロデキストリンの包接錯体の形態のメロキシカムを用いた。この包接錯体は、メロキシカムとシクロデキストリンとをpH調整済水溶液中で混合することにより形成した。この溶液のpHは緩衝剤を用いて調整した。その後、得られた溶解性のメロキシカム/シクロデキストリンの包接錯体を、噴霧乾燥した。この噴霧乾燥分散物を、シクロデキストリンを含有する錠剤の作成に用いた。
1)実施例2の記載に従って調製されたメロキシカムを含むSBEβCDの包接錯体と、2)重炭酸ナトリウムとを含有する二層錠剤を調製した(SBEβCD-メロキシカム/バイカーボネート)。第1層は、メロキシカム15mgとSBEβCD100mgとの包接錯体、及び、重炭酸ナトリウム100mgを含有していた。第2層は、エソメプラゾール40mg及び重炭酸ナトリウム400mgを含有していた。
1)メロキシカムを含むSBEβCDの包接錯体と、2)リザトリプタンと、3)重炭酸ナトリウムとを含有する単層錠剤を調整した(SBEβCD-メロキシカム/リザトリプタン/バイカーボネート)。この単層錠剤は、メロキシカム20mgと、リザトリプタン10mgと、重炭酸ナトリウム500mgとを含有していた。包接錯体は、実施例3の包接錯体と同様である。
Claims (25)
- メロキシカム及びスルホブチルエーテルβ-シクロデキストリン(SBEβCD)の包
接錯体と、
重炭酸ナトリウムと、
リザトリプタンとを含む固体医薬組成物であって、
前記固体医薬組成物は、それを必要とする非ヒト哺乳類又はヒトに直接経口投与するためのものである、
固体医薬組成物。 - 約10mgから約50mgのメロキシカムを含有する、請求項1に記載の固体医薬組成物。
- 約10mgから約20mgのメロキシカムを含有する、請求項1又は2に記載の固体医薬組成物。
- 約20mgのメロキシカムを含有する、請求項1から3のいずれか1項に記載の固体医薬組成物。
- 前記SBEβCDは、β-シクロデキストリンの各分子について6個~7個のスルホブ
チルエーテル基を有する、請求項1から4のいずれか1項に記載の固体医薬組成物。 - 約50mgから約200mgの前記SBEβCDを含有する、請求項1から5のいずれか1項に記載の固体医薬組成物。
- 約100mgから約200mgの前記SBEβCDを含有する、請求項1から6のいずれか1項に記載の固体医薬組成物。
- 約100mgの前記SBEβCDを含有する、請求項1から7のいずれか1項に記載の固体医薬組成物。
- 約5mgから約20mgのリザトリプタンを含有する、請求項1から8のいずれか1項に記載の固体医薬組成物。
- 約10mgから約20mgのリザトリプタンを含有する、請求項1から9のいずれか1項に記載の固体医薬組成物。
- 約10mgのリザトリプタンを含有する、請求項1から10のいずれか1項に記載の固体医薬組成物。
- 約400mgから約1000mgの重炭酸ナトリウムを含有する、請求項1から11のいずれか1項に記載の固体医薬組成物。
- 約400mgから約600mgの重炭酸ナトリウムを含有する、請求項1から12のいずれか1項に記載の固体医薬組成物。
- 約500mgの重炭酸ナトリウムを含有する、請求項1から13のいずれか1項に記載の固体医薬組成物。
- メロキシカムは遊離酸形態である、請求項1から14のいずれか1項に記載の固体医薬組成物。
- リザトリプタンはリザトリプタン安息香酸塩である、請求項1から15のいずれか1項に記載の固体医薬組成物。
- 前記固体医薬組成物の剤形は錠剤形態である、請求項1から16のいずれか1項に記載の固体医薬組成物。
- 前記剤形は単層錠剤である、請求項17に記載の固体医薬組成物。
- 前記剤形は二層錠剤である、請求項17に記載の固体医薬組成物。
- 前記メロキシカムと前記リザトリプタンとは異なる層内に存在する、請求項19に記載の固体医薬組成物。
- 重炭酸ナトリウムは両方の層内に存在する、請求項19又は20に記載の固体医薬組成物。
- 非ヒト哺乳類又はヒトの疼痛を治療するための、請求項1から21のいずれか1項に記載の固体医薬組成物。
- 前記疼痛は片頭痛である、請求項22に記載の固体医薬組成物。
- 前記疼痛は炎症性疼痛である、請求項22に記載の固体医薬組成物。
- 非ヒト哺乳類又はヒトの疼痛を治療するための医薬の製造における、請求項1から21のいずれか1項に記載の固体医薬組成物の使用。
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