JP2019137703A - Hifプロリルヒドロキシラーゼ阻害剤の医薬製剤 - Google Patents
Hifプロリルヒドロキシラーゼ阻害剤の医薬製剤 Download PDFInfo
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- JP2019137703A JP2019137703A JP2019104562A JP2019104562A JP2019137703A JP 2019137703 A JP2019137703 A JP 2019137703A JP 2019104562 A JP2019104562 A JP 2019104562A JP 2019104562 A JP2019104562 A JP 2019104562A JP 2019137703 A JP2019137703 A JP 2019137703A
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- Prior art keywords
- light stabilizer
- capsule
- item
- isoquinoline
- iron oxide
- Prior art date
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Abstract
Description
本出願は、35U.S.C.§119(e)の下、2013年6月6日に出願された米国仮特許出願第61/831,909に対する利益を主張し、これはその全体が参考として本明細書に援用される。
本開示は、[(4−ヒドロキシ−1−メチル−7−フェノキシ−イソキノリン−3−カルボニル)−アミノ]−酢酸、薬学的に許容される添加剤、および有効量の光安定化剤を含む医薬製剤を提供することによって、化合物Aおよびその他の光安定性を提供する必要性を満たす。一実施形態では、医薬製剤は、[(4−ヒドロキシ−1−メチル−7−フェノキシ−イソキノリン−3−カルボニル)−アミノ]−酢酸の光分解生成物を約0.2%w/w未満(活性医薬成分(「API」)の量に対して)含む。別の実施形態では、光安定化剤は、約200から約550nmの間の波長範囲の光を遮断する。
本発明は、例えば、以下の項目を提供する。
(項目1)
[(4−ヒドロキシ−1−メチル−7−フェノキシ−イソキノリン−3−カルボニル)−アミノ]−酢酸、薬学的に許容される添加剤、および有効量の光安定化剤を含む医薬製剤であって、[(4−ヒドロキシ−1−メチル−7−フェノキシ−イソキノリン−3−カルボニル)−アミノ]−酢酸の光分解生成物を約0.2%w/w未満([(4−ヒドロキシ−1−メチル−7−フェノキシ−イソキノリン−3−カルボニル)−アミノ]−酢酸の量に対して)含む医薬製剤。
(項目2)
[(4−ヒドロキシ−1−メチル−7−フェノキシ−イソキノリン−3−カルボニル)−アミノ]−酢酸、薬学的に許容される添加剤、および有効量の光安定化剤を含む医薬製剤であって、該光安定化剤が二酸化チタンおよび少なくとも1種の追加の色素を含む、医薬製剤。
(項目3)
前記光安定化剤が、約200から約550nmの間の波長範囲の光を遮断する、項目1または2に記載の医薬製剤。
(項目4)
前記色素が、黒色色素、青色色素、緑色色素、赤色色素、橙色色素、黄色色素、およびこれらの組合せからなる群から選択される、項目2に記載の医薬製剤。
(項目5)
前記色素が、赤色色素、橙色色素、黄色色素、およびこれらの組合せからなる群から選択される、項目4に記載の医薬製剤。
(項目6)
前記色素が、Allura Red AC、Allura Red ACアルミニウムレーキ、酸化鉄赤、酸化鉄黄、Sunset Yellow FCF、Sunset Yellow FCFアルミニウムレーキ、インジゴチン、インジゴチンアルミニウムレーキ、およびこれらの組合せからなる群から選択される、項目4に記載の医薬製剤。
(項目7)
[(4−ヒドロキシ−1−メチル−7−フェノキシ−イソキノリン−3−カルボニル)−アミノ]−酢酸を約20mgから約200mg含む、項目1から6のいずれか一項に記載の医薬製剤。
(項目8)
[(4−ヒドロキシ−1−メチル−7−フェノキシ−イソキノリン−3−カルボニル)−アミノ]−酢酸を約20mg、約50mg、または約100mg含む、項目7に記載の医薬製剤。
(項目9)
[(4−ヒドロキシ−1−メチル−7−フェノキシ−イソキノリン−3−カルボニル)−アミノ]−酢酸を約20mgまたは約50mg含む、項目7に記載の医薬製剤。
(項目10)
前記光安定化剤が、二酸化チタンおよびAllura Red ACアルミニウムレーキを含む、項目1から9のいずれか一項に記載の医薬製剤。
(項目11)
前記光安定化剤が、酸化鉄赤および二酸化チタンを含む、項目1から9のいずれか一項に記載の医薬製剤。
(項目12)
前記光安定化剤が、Allura Red AC、酸化鉄黄、および二酸化チタンを含む、項目1から9のいずれか一項に記載の医薬製剤。
(項目13)
前記光安定化剤が、酸化鉄赤、Allura Red AC、酸化鉄黄、および二酸化チタンを含む、項目1から9のいずれか一項に記載の医薬製剤。
(項目14)
前記光安定化剤が、酸化鉄赤、酸化鉄黄、および二酸化チタンを含む、項目1から9のいずれか一項に記載の医薬製剤。
(項目15)
前記光安定化剤が、酸化鉄黄および二酸化チタンを含む、項目1から9のいずれか一項に記載の医薬製剤。
(項目16)
項目1から9のいずれか一項に記載の医薬製剤を含む固体剤形であって、カプセル、錠剤、ビーズ、顆粒、ペレット、ロゼンジ、丸薬、またはガムから選択される固体剤形。
(項目17)
錠剤である、項目16に記載の固体剤形。
(項目18)
カプセルである、項目16に記載の固体剤形。
(項目19)
[(4−ヒドロキシ−1−メチル−7−フェノキシ−イソキノリン−3−カルボニル)−アミノ]−酢酸、薬学的に許容される添加剤、および有効量の光安定化剤を含む錠剤。(項目20)
錠剤コアおよびコーティングを含む、項目19に記載の錠剤。
(項目21)
前記光安定化剤が、前記錠剤または前記錠剤コアにブレンドされている、項目19または20に記載の錠剤。
(項目22)
前記錠剤コアが、[(4−ヒドロキシ−1−メチル−7−フェノキシ−イソキノリン−3−カルボニル)−アミノ]−酢酸および前記薬学的に許容される添加剤を含み、前記コーティングが前記光安定化剤を含む、項目20に記載の錠剤。
(項目23)
前記光安定化剤が、二酸化チタンと、Allura Red AC、Allura Red ACアルミニウムレーキ、酸化鉄赤、酸化鉄黄、Sunset Yellow FCF、Sunset Yellow FCFアルミニウムレーキ、インジゴチン、インジゴチンアルミニウムレーキ、およびこれらの組合せからなる群から選択される少なくとも1種の追加の色素とを含む、項目21または22に記載の錠剤。
(項目24)
前記光安定化剤が、二酸化チタンおよびAllura Red ACアルミニウムレーキを含む、項目23に記載の錠剤。
(項目25)
前記光安定化剤が、少なくとも約0.1mg/cm2の二酸化チタンと、
少なくとも約0.1mg/cm2のAllura Red AC、
少なくとも約0.1mg/cm2の、アルミニウムレーキ状Allura Red AC、
少なくとも約0.004mg/cm2の酸化鉄赤、
少なくとも約0.009mg/cm2の酸化鉄黄、
少なくとも約0.01mg/cm2のSunset Yellow FCF、および
少なくとも約0.01mg/cm2の、アルミニウムレーキ状Sunset Yellow FCF
からなる群から選択される少なくとも1種の追加の色素と
を含み、
ここで、光安定化剤の量は該錠剤コアの表面積に対するものである、項目22に記載の錠剤。
(項目26)
前記光安定化剤が、約0.1から約2mg/cm2の二酸化チタンと、
約0.1から約0.4mg/cm2のAllura Red AC、
約0.1から約0.4mg/cm2の、アルミニウムレーキ状Allura Red AC、
約0.004から約0.4mg/cm2の酸化鉄赤、
約0.009から約0.2mg/cm2の酸化鉄黄、
約0.01から0.03mg/cm2のSunset Yellow FCF、および
約0.01から0.03mg/cm2の、アルミニウムレーキ状Sunset Yellow FCF
からなる群から選択される少なくとも1種の追加の色素と
を含み、
ここで、光安定化剤の量は該錠剤コアの表面積に対するものである、項目22に記載の錠剤。
(項目27)
錠剤コアおよびコーティングを含む錠剤であって、該錠剤コアが[(4−ヒドロキシ−1−メチル−7−フェノキシ−イソキノリン−3−カルボニル)−アミノ]−酢酸および薬学的に許容される添加剤を含み、該コーティングが有効量の光安定化剤を含み、該コーティングが、約3%から約8%w/w(該錠剤コアの重量に対して)の量で存在する錠剤。
(項目28)
前記錠剤コアが、約22%から約28%w/wの[(4−ヒドロキシ−1−メチル−7−フェノキシ−イソキノリン−3−カルボニル)−アミノ]−酢酸(該錠剤コアの重量に対して)および薬学的に許容される添加剤を含む、項目27に記載の錠剤。
(項目29)
前記薬学的に許容される添加剤が、ラクトース一水和物、微結晶質セルロース、ポビドン、クロスカルメロースナトリウム、およびステアリン酸マグネシウムを含む、項目28に記載の錠剤。
(項目30)
前記錠剤コアが、約20mgから約200mgの[(4−ヒドロキシ−1−メチル−7−フェノキシ−イソキノリン−3−カルボニル)−アミノ]−酢酸を含む、項目28または29に記載の錠剤。
(項目31)
前記錠剤コアが、約20mg、約50mg、または約100mgの[(4−ヒドロキシ−1−メチル−7−フェノキシ−イソキノリン−3−カルボニル)−アミノ]−酢酸を含む、項目30に記載の錠剤。
(項目32)
前記光安定化剤が、二酸化チタンと、Allura Red AC、Allura Red ACアルミニウムレーキ、酸化鉄赤、酸化鉄黄、Sunset Yellow FCF、Sunset Yellow FCFアルミニウムレーキ、インジゴチン、インジゴチンアルミニウムレーキ、およびこれらの組合せからなる群から選択される少なくとも1種の追加の色素とを含む、項目27に記載の錠剤。
(項目33)
前記光安定化剤が、二酸化チタンおよびAllura Red ACアルミニウムレーキを含む、項目32に記載の錠剤。
(項目34)
前記コーティングが、約0.1から約0.4mg/cm2の二酸化チタンと、約0.1から約0.4mg/cm2のアルミニウムレーキ状Allura Red ACとを含み、ここで、二酸化チタンおよびアルミニウムレーキ状Allura Red ACの量は前記錠剤コアの表面積に対するものである、項目33に記載の錠剤。
(項目35)
前記錠剤コアが、約20mg、約50mg、または約100mgの[(4−ヒドロキシ−1−メチル−7−フェノキシ−イソキノリン−3−カルボニル)−アミノ]−酢酸、ラクトース一水和物、微結晶質セルロース、ポビドン、クロスカルメロースナトリウム、およびステアリン酸マグネシウムを含み、前記光安定化剤が、0.1から約0.4mg/cm2の二酸化チタンおよび約0.1から約0.4mg/cm2のアルミニウムレーキ状Allura Red ACを含み、ここで、二酸化チタンおよびアルミニウムレーキ状Allura Red ACの量は該錠剤コアの表面積に対するものである、項目27に記載の錠剤。
(項目36)
[(4−ヒドロキシ−1−メチル−7−フェノキシ−イソキノリン−3−カルボニル)−アミノ]−酢酸、薬学的に許容される添加剤、および有効量の光安定化剤を含むカプセル。
(項目37)
カプセル充填物およびカプセルシェルを含み、該カプセル充填物が、[(4−ヒドロキシ−1−メチル−7−フェノキシ−イソキノリン−3−カルボニル)−アミノ]−酢酸および前記薬学的に許容される添加剤を含み、該カプセルシェルが前記光安定化剤を含む、項目36に記載のカプセル。
(項目38)
前記光安定化剤が、二酸化チタンと、Allura Red AC、酸化鉄赤、酸化鉄黄、およびこれらの組合せからなる群から選択される少なくとも1種の追加の色素とを含む、項目37に記載のカプセル。
(項目39)
前記光安定化剤が、酸化鉄赤および二酸化チタンを含む、項目38に記載のカプセル。(項目40)
前記光安定化剤が、Allura Red AC、酸化鉄黄、および二酸化チタンを含む、項目38に記載のカプセル。
(項目41)
前記光安定化剤が、酸化鉄赤、Allura Red AC、酸化鉄黄、および二酸化チタンを含む、項目38に記載のカプセル。
(項目42)
前記光安定化剤が、酸化鉄赤、酸化鉄黄、および二酸化チタンを含む、項目38に記載のカプセル。
(項目43)
前記光安定化剤が、酸化鉄黄および二酸化チタンを含む、項目38に記載のカプセル。(項目44)
前記カプセルシェルが、約1.8%から約6%w/wの光安定化剤(該カプセルシェルの重量に対して)を含む、項目37に記載のカプセル。
(項目45)
前記カプセルシェルが、約2%から約3.5%w/wの光安定化剤(該カプセルシェルの重量に対して)を含む、項目37に記載のカプセル。
(項目46)
前記カプセルシェルがゼラチンシェルである、項目37に記載のカプセル。
(項目47)
カプセル充填物およびカプセルシェルを含むカプセルであって、該カプセル充填物が、約12%から約15%w/wの[(4−ヒドロキシ−1−メチル−7−フェノキシ−イソキノリン−3−カルボニル)−アミノ]−酢酸(該カプセル充填物の重量に対して)および薬学的に許容される添加剤を含み、該カプセルシェルが、有効量の光安定化剤を含むカプセル。
(項目48)
前記薬学的に許容される添加剤が、ラクトース一水和物、微結晶質セルロース、ポビドン、クロスカルメロースナトリウム、およびステアリン酸マグネシウムを含む、項目47に記載のカプセル。
(項目49)
前記カプセル充填物が、約20mgまたは約50mgの[(4−ヒドロキシ−1−メチル−7−フェノキシ−イソキノリン−3−カルボニル)−アミノ]−酢酸を含む、項目47または48に記載のカプセル。
(項目50)
前記カプセルシェルが、約2%w/wから約3.5%w/wの光安定化剤(該カプセルシェルの重量に対して)を含む、項目47に記載のカプセル。
(項目51)
前記カプセル充填物が、約20mgまたは約50mgの[(4−ヒドロキシ−1−メチル−7−フェノキシ−イソキノリン−3−カルボニル)−アミノ]−酢酸と、ラクトース一水和物、微結晶質セルロース、ポビドン、クロスカルメロースナトリウム、およびステアリン酸マグネシウムを含む薬学的に許容される添加剤とを含み、前記カプセルシェルが、約2%w/wの酸化鉄赤および約0.9%w/wの二酸化チタン(該カプセルシェルの重量に対して)を含むゼラチンシェルである、項目47に記載のカプセル。
(項目52)
前記カプセル充填物が、約20mgまたは約50mgの[(4−ヒドロキシ−1−メチル−7−フェノキシ−イソキノリン−3−カルボニル)−アミノ]−酢酸と、ラクトース一水和物、微結晶質セルロース、ポビドン、クロスカルメロースナトリウム、およびステアリン酸マグネシウムを含む薬学的に許容される添加剤とを含み、前記カプセルシェルが、約0.3%w/wのAllura Red AC、約1%w/wの酸化鉄黄、および約1%w/wの二酸化チタン(該カプセルシェルの重量に対して)を含むゼラチンシェルである、項目47に記載のカプセル。
(項目53)
前記カプセル充填物が、約20mgまたは約50mgの[(4−ヒドロキシ−1−メチル−7−フェノキシ−イソキノリン−3−カルボニル)−アミノ]−酢酸と、ラクトース一水和物、微結晶質セルロース、ポビドン、クロスカルメロースナトリウム、およびステアリン酸マグネシウムを含む薬学的に許容される添加剤とを含み、前記カプセルシェルが、約0.7%w/wの酸化鉄赤、約0.3%w/wのAllura Red AC、約1%w/wの酸化鉄黄、および約1%w/wの二酸化チタン(該カプセルシェルの重量に対して)を含むゼラチンシェルである、項目47に記載のカプセル。
(項目54)
前記カプセル充填物が、約20mgまたは約50mgの[(4−ヒドロキシ−1−メチル−7−フェノキシ−イソキノリン−3−カルボニル)−アミノ]−酢酸と、ラクトース一水和物、微結晶質セルロース、ポビドン、クロスカルメロースナトリウム、およびステアリン酸マグネシウムを含む薬学的に許容される添加剤とを含み、前記カプセルシェルが、約1%w/wの酸化鉄赤、約1%w/wの酸化鉄黄、および約1%w/wの二酸化チタン(該カプセルシェルの重量に対して)を含むゼラチンシェルである、項目47に記載のカプセル。
(項目55)
前記カプセル充填物が、約20mgまたは約50mgの[(4−ヒドロキシ−1−メチル−7−フェノキシ−イソキノリン−3−カルボニル)−アミノ]−酢酸と、ラクトース一水和物、微結晶質セルロース、ポビドン、クロスカルメロースナトリウム、およびステアリン酸マグネシウムを含む薬学的に許容される添加剤とを含み、前記カプセルシェルが、約1%w/wのAllura Red AC、約1%w/wの酸化鉄黄、および約1%w/wの二酸化チタン(該カプセルシェルの重量に対して)を含むゼラチンシェルである、項目47に記載のカプセル。
(項目56)
前記カプセル充填物が、約20mgまたは約50mgの[(4−ヒドロキシ−1−メチル−7−フェノキシ−イソキノリン−3−カルボニル)−アミノ]−酢酸と、ラクトース一水和物、微結晶質セルロース、ポビドン、クロスカルメロースナトリウム、およびステアリン酸マグネシウムを含む薬学的に許容される添加剤とを含み、前記カプセルシェルが、約2%w/wの酸化鉄赤および約1%w/wの二酸化チタン(該カプセルシェルの重量に対して)を含むゼラチンシェルである、項目47に記載のカプセル。
(項目57)
前記カプセル充填物が、約20mgまたは約50mgの[(4−ヒドロキシ−1−メチル−7−フェノキシ−イソキノリン−3−カルボニル)−アミノ]−酢酸と、ラクトース一水和物、微結晶質セルロース、ポビドン、クロスカルメロースナトリウム、およびステアリン酸マグネシウムを含む薬学的に許容される添加剤とを含み、前記カプセルシェルが、約2%w/wの酸化鉄黄および約1%w/wの二酸化チタン(該カプセルシェルの重量に対して)を含むゼラチンシェルである、項目47に記載のカプセル。
(項目58)
[(4−ヒドロキシ−1−メチル−7−フェノキシ−イソキノリン−3−カルボニル)−アミノ]−酢酸の光分解を阻害する方法であって、[(4−ヒドロキシ−1−メチル−7−フェノキシ−イソキノリン−3−カルボニル)−アミノ]−酢酸を有効量の光安定化剤と共に製剤化するステップを含む方法。
(項目59)
前記光安定化剤が、二酸化チタンおよび少なくとも1種の追加の色素を含む、項目58に記載の方法。
(項目60)
少なくとも部分的に低酸素誘導因子(HIF)により媒介される状態を処置するか、前処置するか、または該状態の発症または進行を遅延させるための方法であって、それを必要とする患者に、項目1から15のいずれか一項に記載の医薬製剤、項目19から35のいずれか一項に記載の錠剤、または項目36から57のいずれか一項に記載のカプセルを投与するステップを含む方法。
(項目61)
貧血を処置するか、前処置するか、または貧血の発症または進行を遅延させるための方法であって、それを必要とする患者に、項目1から15のいずれか一項に記載の医薬製剤、項目19から35のいずれか一項に記載の錠剤、または項目36から57のいずれか一項に記載のカプセルを投与するステップを含む方法。
定義
本明細書で使用されるとき、下記の用語は、下記の意味を有する。
a. ICHオプション1:
可視および紫外(UV)出力を組み合わせる人工昼光色蛍光ランプ、キセノン、またはメタルハライドランプなど、D65/ID65放出規格に類似した出力を生成するように設計された、任意の光源。D65は、ISO 10977(1993年)で定義された、屋外昼光に関して国際的に認められた規格である。ID65は同等の屋内間接昼光基準である。320ナノメートル(nm)よりも下の大量の放射線を放出する光源の場合、そのような放射線を排除するのに適切なフィルタ(複数可)を装着させてもよい。
b. ICHオプション2:
ISO 10977(1993年)で指定されたものに類似した、出力を生成するように設計された白色蛍光ランプと;
最大エネルギー放出が350nmから370nmの間である、320nmから400nmのスペクトル分布を有する近UV蛍光ランプ;UVのかなりの割合は、320から360nmおよび360から400nmの両方の帯域にあるべきである。
医薬製剤
AC、酸化鉄黄、および二酸化チタンを含む。一実施形態では、光安定化剤は、酸化鉄赤、酸化鉄黄、および二酸化チタンを含む。一実施形態では、光安定化剤は、酸化鉄黄および二酸化チタンを含む。
FCF、Brilliant Blue FCF、インジゴチン、インジゴチンアルミニウムレーキ、ならびにこれらの組合せからなる群から選択される色素を含む。
錠剤
少なくとも約0.1mg/cm2のAllura Red AC;
少なくとも約0.1mg/cm2の、アルミニウムレーキ状Allura Red AC;
少なくとも約0.004mg/cm2の酸化鉄赤;
少なくとも約0.009mg/cm2の酸化鉄黄;
少なくとも約0.01mg/cm2のSunset Yellow FCF;および
少なくとも約0.01mg/cm2の、アルミニウムレーキ状Sunset Yellow FCF
からなる群から選択される少なくとも1種の追加の色素とを含み、ここで光安定化剤の量は、錠剤コアの表面積に対するものである。
約0.1から約0.4mg/cm2のAllura Red AC;
約0.1から約0.4mg/cm2の、アルミニウムレーキ状Allura Red AC;
約0.004から約0.4mg/cm2の酸化鉄赤;
約0.009から約0.2mg/cm2の酸化鉄黄;
約0.01から0.03mg/cm2のSunset Yellow FCF;および
約0.01から0.03mg/cm2の、アルミニウムレーキ状Sunset Yellow FCF
からなる群から選択される少なくとも1種の追加の色素とを含み、ここで光安定化剤の量は、錠剤コアの表面積に対するものである。
カプセル
AC、酸化鉄黄、および二酸化チタンを含む。さらに別の実施形態では、光安定化剤は、酸化鉄赤、酸化鉄黄、および二酸化チタンを含む。さらになお別の実施形態では、光安定化剤は、Allura Red AC、酸化鉄黄、および二酸化チタンを含む。さらになお別の実施形態では、光安定化剤は、酸化鉄黄および二酸化チタンを含む。
投与経路
vitroデータから推定することができる。局所投与または選択的摂取の場合、薬物の有効局所濃度は、血漿中濃度に関連しなくてもよい。あるいは、所望のパラメータの調製、例えば内因性エリスロポエチンの刺激は、1)負荷用量の投与およびその後の維持用量の投与、2)目標範囲内で、所望のパラメータ、例えばエリスロポエチンレベルを素早く達成するための、誘導用量の投与と、その後の、所望の目標範囲内に、例えばヘマトクリットを維持するための、より低い維持用量の投与、または3)断続的な投薬の繰り返しによって達成されてもよい。
方法
化合物Aの固体状態の日光曝露
化合物A乾燥粉末約500mgを、1ガロンのポリエチレンバッグに入れ、連続して2カ月間、日中に日光に曝露した。粉末を、非常に薄い層にし、バッグを頻繁に振盪させて、最上層だけでなく全ての粉末が日光に確実に曝露されるようにした。化合物A粉末の対照試料を、比較の目的で、同じ時間にわたり、暗所で琥珀色のバイアル内に貯蔵した。2カ月後、2つの試料の目視検査は、黄色であった対照試料に比べ、露光試料はオフホワイトになったことを示した。露光試料および対照試料を、HPLCにより分析して、それらの組成の相違を評価した。HPLC法では、逆相Zorbax Eclipse XDB−C8、3.5μm、4.6×150mmカラムを使用した。移動相は、トリフルオロ酢酸で酸性化させた水とアセトニトリルとの混合物から構成した。アセトニトリルを増加させることによるグラジエント溶離で、230nmでのUV検出により、化合物Aの対照試料(図1、露光前)および化合物Aの露光試料(図1、露光後)のクロマトグラムを提供した。露光試料のHPLCは、図1中に「光分解生成物」と示す、新しいピークの出現を示す。
錠剤の光安定化コーティング
[(4−ヒドロキシ−1−メチル−7−フェノキシ−イソキノリン−3−カルボニル)−アミノ]−酢酸を含む錠剤は、光に曝露されると光分解することが見出された。錠剤中の化合物Aの光分解を低減させるため、様々なコーティングを、それらの光安定化特性に関して試験した。
配合物1:酸化鉄赤、酸化鉄黄、および二酸化チタン(「ピンク/ピーチ#1」);
配合物2:Sunset Yellow FCF、酸化鉄赤、および二酸化チタン(「ピンク/ピーチ#2」);または
配合物3:酸化鉄赤、酸化鉄黄、および二酸化チタン(「ピンク/ピーチ#3」)
を含むコーティングを含んだ。
配合物4:Allura Red ACおよびインジゴチンアルミニウムレーキ、および二酸化チタン(「Allura Red AC/インジゴチン」);
配合物5:Allura Red ACアルミニウムレーキおよび二酸化チタン(「Allura Red AC」);または
配合物6:酸化鉄赤および二酸化チタン(「赤色酸化鉄」)
を含むコーティングを含んだ。
光安定化ゼラチンカプセル
ゼラチンカプセル中の化合物Aも、露光による光分解を示す。様々な色素の組合せを含有するゼラチンフィルムコーティングを、それらの光安定化特性に関して試験をした。
Claims (1)
- 本明細書に記載の発明。
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Families Citing this family (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
PT1644336E (pt) | 2003-06-06 | 2011-04-21 | Fibrogen Inc | Compostos de heteroarilo que contêm azoto e sua utilização no aumento da eritropoetina endógena |
AU2009314155B2 (en) | 2008-11-14 | 2015-10-08 | Fibrogen, Inc. | Thiochromene derivatives as HIF hydroxylase inhibitors |
MY171483A (en) | 2012-07-16 | 2019-10-15 | Fibrogen Inc | Process for making isoquinoline compounds |
ES2905898T3 (es) | 2012-07-16 | 2022-04-12 | Fibrogen Inc | Formas cristalinas de un inhibidor de prolil hidroxilasa |
US8883823B2 (en) | 2012-07-16 | 2014-11-11 | Fibrogen, Inc. | Crystalline forms of a prolyl hydroxylase inhibitor |
KR102291860B1 (ko) | 2013-06-06 | 2021-08-20 | 피브로겐, 인크. | Hif 하이드록실라제 억제자의 약학적 제형 |
IL292262B2 (en) * | 2015-04-01 | 2024-02-01 | Akebia Therapeutics Inc | Formulation of an oral administration form of {[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid |
WO2019042485A1 (en) | 2017-08-30 | 2019-03-07 | Zentiva, K.S. | FORMS IN THE STRONG STATE OF ROXADUSTAT |
PL3679017T3 (pl) * | 2017-09-04 | 2022-01-17 | Sandoz Ag | Kokryształ doustnie dostępnego inhibitora hydroksylazy prolilowej hif |
CN110664814A (zh) * | 2019-10-24 | 2020-01-10 | 上海长海医院 | Fg-4592在制备治疗炎性肠病药物中的用途 |
CN110934833B (zh) * | 2019-12-17 | 2022-08-19 | 河北长天药业有限公司 | 一种复方氨酚那敏颗粒 |
EP4121009A4 (en) * | 2020-03-17 | 2024-04-17 | Zydus Lifesciences Limited | FORMULATION COMPRISING HIF PROLYL HYDROXYLASE INHIBITORS |
WO2022192097A1 (en) * | 2021-03-06 | 2022-09-15 | Mind Medicine, Inc. | Formulations of psilocin that have enhanced stability |
CN114796280B (zh) * | 2022-06-15 | 2024-06-25 | 河北长天药业有限公司 | 一种复方氨酚那敏颗粒及其制备工艺 |
EP4321155A1 (en) * | 2022-08-08 | 2024-02-14 | Sanovel Ilac Sanayi Ve Ticaret A.S. | An oral pharmaceutical composition comprising roxadustat |
Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005087237A1 (ja) * | 2004-03-16 | 2005-09-22 | Asahi Kasei Pharma Corporation | ファスジル含有製剤及びその安定性を改善する方法 |
JP2006514113A (ja) * | 2002-12-06 | 2006-04-27 | ファイブローゲン、インコーポレーテッド | 脂肪調節 |
JP2006527200A (ja) * | 2003-06-06 | 2006-11-30 | ファイブロゲン インコーポレイティッド | 窒素含有ヘテロアリール化合物および内因性エリトロポエチンを増加させる際のそれらの使用方法 |
JP2008044960A (ja) * | 2002-12-16 | 2008-02-28 | Kissei Pharmaceut Co Ltd | 経口固形医薬 |
JP2008273870A (ja) * | 2007-04-27 | 2008-11-13 | Nipro Corp | 経口固形製剤及びその製造方法 |
JP2009507051A (ja) * | 2005-09-08 | 2009-02-19 | ハー・ルンドベック・アクチエゼルスカベット | セルチンドールの安定な固形製剤 |
JP2010248106A (ja) * | 2009-04-14 | 2010-11-04 | Dainippon Sumitomo Pharma Co Ltd | フィルムコーティング錠 |
JP2012176899A (ja) * | 2009-05-19 | 2012-09-13 | Mitsubishi Tanabe Pharma Corp | 2−(1−ピペラジニル)−5−メチルベンゼンスルホン酸誘導体を含む注射用水溶液 |
WO2013070908A1 (en) * | 2011-11-09 | 2013-05-16 | Fibrogen, Inc. | Therapeutic method |
Family Cites Families (43)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE59401924D1 (de) | 1993-11-02 | 1997-04-10 | Hoechst Ag | Substituierte heterocyclische Carbonsäureamide, ihre Herstellung und ihre Verwendung als Arzneimittel |
DE19746287A1 (de) | 1997-10-20 | 1999-04-22 | Hoechst Marion Roussel De Gmbh | Substituierte Isochinolin-2-Carbonsäureamide, ihre Herstellung und ihre Verwendung als Arzneimittel |
US8318703B2 (en) * | 2001-12-06 | 2012-11-27 | Fibrogen, Inc. | Methods for improving kidney function |
CN100522946C (zh) | 2001-12-06 | 2009-08-05 | 法布罗根股份有限公司 | 低氧诱导因子(HIF)α的稳定化 |
DE10209692A1 (de) | 2002-03-06 | 2003-09-18 | Merck Patent Gmbh | Isochinolinderivate |
US8124582B2 (en) | 2002-12-06 | 2012-02-28 | Fibrogen, Inc. | Treatment of diabetes |
PL220457B1 (pl) | 2002-12-16 | 2015-10-30 | Kissei Pharmaceutical | Kapsułka do leczenia dysurii |
US8614204B2 (en) | 2003-06-06 | 2013-12-24 | Fibrogen, Inc. | Enhanced erythropoiesis and iron metabolism |
WO2005011696A1 (en) | 2003-08-01 | 2005-02-10 | Fibrogen, Inc. | Inhibitors of 2-oxoglutarate dioxygenase as gamma globin inducers |
WO2006094292A2 (en) | 2005-03-02 | 2006-09-08 | Fibrogen, Inc. | Thienopyridine compounds, and methods of use thereof |
EP1893186A2 (en) | 2005-06-06 | 2008-03-05 | Fibrogen, Inc. | Improved treatment for anemia using a hif-alpha stabilising agent |
WO2006138511A2 (en) | 2005-06-15 | 2006-12-28 | Fibrogen, Inc. | Use of hif 1alfa modulators for treatment of cancer |
ZA200803655B (en) | 2005-10-31 | 2009-10-28 | Kowa Co | Pharmaceutical preparation having excellent photostability |
GB0523810D0 (en) | 2005-11-23 | 2006-01-04 | Astrazeneca Ab | Pharmaceutical compositions |
JP5161793B2 (ja) | 2006-01-27 | 2013-03-13 | フィブロジェン, インコーポレイテッド | 低酸素症誘導因子(hif)を安定化するシアノイソキノリン化合物 |
SI1818057T1 (sl) * | 2006-02-09 | 2010-08-31 | Teva Pharma | Stabilne farmacevtske formulacije montelukast natrija |
JP2009528279A (ja) | 2006-02-16 | 2009-08-06 | ファイブローゲン、インコーポレーテッド | 脳卒中を治療するための化合物および方法 |
CN103497184A (zh) | 2006-04-04 | 2014-01-08 | 菲布罗根有限公司 | 作为hif调节剂的吡咯并吡啶和噻唑并吡啶化合物 |
WO2007141743A2 (en) * | 2006-06-06 | 2007-12-13 | Ranbaxy Laboratories Limited | A tablet dosage form comprising cetirizine and pseudoephedrine |
US20070293575A1 (en) | 2006-06-15 | 2007-12-20 | Fibrogen, Inc. | Compounds and methods for treatment of cancer-related anemia |
US7713986B2 (en) | 2006-06-15 | 2010-05-11 | Fibrogen, Inc. | Compounds and methods for treatment of chemotherapy-induced anemia |
TW200924768A (en) * | 2007-10-12 | 2009-06-16 | Astrazeneca Ab | Composition |
EP2222305A1 (en) | 2007-11-02 | 2010-09-01 | Fibrogen, Inc. | Methods for reducing blood pressure |
EP2227475B1 (en) | 2007-12-03 | 2014-02-19 | Fibrogen, Inc. | Isoxazolopyridine derivatives for use in the treatment of hif-mediated conditions |
WO2009075824A1 (en) | 2007-12-06 | 2009-06-18 | Fibrogen, Inc. | Methods for increasing endothelial progentior cells |
US20110039879A1 (en) | 2007-12-07 | 2011-02-17 | FibroGen ,Inc. | Methods for increasing white blood cells |
EP2252619B1 (en) | 2008-01-11 | 2013-10-09 | Fibrogen, Inc. | Isothiazole-pyridine derivatives as modulators of hif (hypoxia inducible factor) activity |
US8324405B2 (en) | 2008-02-05 | 2012-12-04 | Fibrogen, Inc. | Chromene derivatives and use thereof as HIF hydroxylase activity inhibitors |
WO2010022240A1 (en) | 2008-08-20 | 2010-02-25 | Fibrogen, Inc. | Pyrrolo [ 1, 2 -b] pyridazine derivatives and their use as hif modulators |
EP2341904A1 (en) | 2008-08-26 | 2011-07-13 | Fibrogen, Inc. | Methods for treatment of multiple sclerosis |
AU2009314155B2 (en) | 2008-11-14 | 2015-10-08 | Fibrogen, Inc. | Thiochromene derivatives as HIF hydroxylase inhibitors |
US20100144737A1 (en) | 2008-12-08 | 2010-06-10 | Fibrogen, Inc. | Methods for inhibiting t helper cell differentiation |
KR20110117133A (ko) | 2009-01-29 | 2011-10-26 | 다이닛본 스미토모 세이야꾸 가부시끼가이샤 | 내핵을 갖는 구강 내 붕괴 정 |
US20140171465A1 (en) * | 2011-01-13 | 2014-06-19 | Fibrogen, Inc. | Methods For Increasing Reticulocyte Hemoglobin Content |
WO2012097329A1 (en) | 2011-01-13 | 2012-07-19 | Fibrogen, Inc. | Methods for increasing mean corpuscular volume |
WO2012106472A1 (en) | 2011-02-02 | 2012-08-09 | Fibrogen, Inc. | Naphthyridine derivatives as inhibitors of hypoxia inducible factor (hif) hydroxylase |
KR102029951B1 (ko) | 2011-07-22 | 2019-11-08 | 베이징 베타 파머수티컬 컴퍼니 리미티드 | 프로릴 히드록실라제 억제제로서 화합물의 다형체형, 및 이의 용도 |
CN104470899B (zh) | 2012-03-09 | 2017-12-26 | 菲布罗根有限公司 | 作为hif羟化酶抑制剂的4‑羟基‑异喹啉化合物 |
MY171483A (en) | 2012-07-16 | 2019-10-15 | Fibrogen Inc | Process for making isoquinoline compounds |
ES2905898T3 (es) | 2012-07-16 | 2022-04-12 | Fibrogen Inc | Formas cristalinas de un inhibidor de prolil hidroxilasa |
US8883823B2 (en) | 2012-07-16 | 2014-11-11 | Fibrogen, Inc. | Crystalline forms of a prolyl hydroxylase inhibitor |
RU2666144C2 (ru) | 2013-01-24 | 2018-09-06 | Фиброген, Инк. | Кристаллические формы { [1-циано-5-(4-хлорофенокси)-4-гидроксиизохинолин-3-карбонил]-амино} -уксусной кислоты |
KR102291860B1 (ko) | 2013-06-06 | 2021-08-20 | 피브로겐, 인크. | Hif 하이드록실라제 억제자의 약학적 제형 |
-
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- 2014-06-05 PL PL14735770T patent/PL3003284T3/pl unknown
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- 2015-11-26 ZA ZA2015/08712A patent/ZA201508712B/en unknown
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- 2015-12-01 MX MX2020003096A patent/MX2020003096A/es unknown
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-
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- 2023-03-27 JP JP2023049709A patent/JP2023068197A/ja active Pending
Patent Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2006514113A (ja) * | 2002-12-06 | 2006-04-27 | ファイブローゲン、インコーポレーテッド | 脂肪調節 |
JP2008044960A (ja) * | 2002-12-16 | 2008-02-28 | Kissei Pharmaceut Co Ltd | 経口固形医薬 |
JP2006527200A (ja) * | 2003-06-06 | 2006-11-30 | ファイブロゲン インコーポレイティッド | 窒素含有ヘテロアリール化合物および内因性エリトロポエチンを増加させる際のそれらの使用方法 |
WO2005087237A1 (ja) * | 2004-03-16 | 2005-09-22 | Asahi Kasei Pharma Corporation | ファスジル含有製剤及びその安定性を改善する方法 |
JP2009507051A (ja) * | 2005-09-08 | 2009-02-19 | ハー・ルンドベック・アクチエゼルスカベット | セルチンドールの安定な固形製剤 |
JP2008273870A (ja) * | 2007-04-27 | 2008-11-13 | Nipro Corp | 経口固形製剤及びその製造方法 |
JP2010248106A (ja) * | 2009-04-14 | 2010-11-04 | Dainippon Sumitomo Pharma Co Ltd | フィルムコーティング錠 |
JP2012176899A (ja) * | 2009-05-19 | 2012-09-13 | Mitsubishi Tanabe Pharma Corp | 2−(1−ピペラジニル)−5−メチルベンゼンスルホン酸誘導体を含む注射用水溶液 |
WO2013070908A1 (en) * | 2011-11-09 | 2013-05-16 | Fibrogen, Inc. | Therapeutic method |
Non-Patent Citations (1)
Title |
---|
"塩酸パパべリン散10%「マイラン」", 医薬品インタビューフォーム, JPN6018009268, January 2013 (2013-01-01), ISSN: 0004257115 * |
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