JP2019507783A - 乱用防止医薬製剤 - Google Patents
乱用防止医薬製剤 Download PDFInfo
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- JP2019507783A JP2019507783A JP2018547372A JP2018547372A JP2019507783A JP 2019507783 A JP2019507783 A JP 2019507783A JP 2018547372 A JP2018547372 A JP 2018547372A JP 2018547372 A JP2018547372 A JP 2018547372A JP 2019507783 A JP2019507783 A JP 2019507783A
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- Prior art keywords
- poloxamer
- weight
- opioid
- gum
- formulation
- Prior art date
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Landscapes
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Abstract
Description
本出願は、2016年3月9日に出願された米国特許出願第62/305,937号の優先権を主張するものであり、その全容が参照により本明細書に組み込まれる。
メタドン、メトポン、モルヒネ、ミロフィン(ミロフィネ)、ナルセイン、ニコモルヒネ、ノルレボルファノール、ノルメタドン、ナロルフィン、ナルブフェン、ノルモルヒネ、ノルピパノン、アヘン、オキシコドン、オキシモルホン、パパベレタム、ペンタゾシン、フェナドキソン、フェノモルファン、フェナゾシン、フェノペリジン、ピミノジン、ピリトラミド、プロフェプタジン、プロメドール、プロペリジン、プロポキシフェン、スフェンタニル、タペンタドール、チリジン、トラマドール、又はこれらのいずれかの薬学的に許容される塩、若しくはこれらのいずれかの薬学的に許容されるプロドラッグが挙げられる。
HO−[−CH2−CH2−O−]a−[−CH(CH3)−CH2−O−]b−[−CH2−CH2−O−]a−H
[式中、a=2〜130であり、b=15〜67である。]を有する。例示的なのポロキサマーとしては、ポロキサマー101、ポロキサマー105、ポロキサマー108、ポロキサマー122、ポロキサマー123、ポロキサマー124、ポロキサマー181、ポロキサマー182、ポロキサマー183、ポロキサマー184、ポロキサマー185、ポロキサマー188、ポロキサマー212、ポロキサマー215、ポロキサマー217、ポロキサマー231、ポロキサマー234、ポロキサマー235、ポロキサマー237、ポロキサマー238、ポロキサマー282、ポロキサマー284、ポロキサマー288、ポロキサマー331、ポロキサマー333、ポロキサマー334、ポロキサマー335、ポロキサマー338、ポロキサマー401、ポロキサマー402、ポロキサマー403、ポロキサマー407、又はこれらの2つ以上の組み合わせが挙げられる。一実施形態において、ポロキサマーは、ポロキサマー122、ポロキサマー123、ポロキサマー124、ポロキサマー181、ポロキサマー182、ポロキサマー183、ポロキサマー184、ポロキサマー185、ポロキサマー188、又はこれらの2つ以上の組み合わせである。一実施形態において、ポロキサマーは、ポロキサマー122、ポロキサマー123、ポロキサマー124、又はこれらの2つ以上の組み合わせである。一実施形態において、このポロキサマーは、ポロキサマー124である。用語「ポロキサマー」の後ろの数については、上2ケタ×100が中央のポリオキシプロピレンポリマーの分子質量を示し、下1ケタ×10はポリオキシエチレンポリマー含有量の百分率を示す。例えば、ポロキサマー407は、ポリオキシプロピレンの分子質量が4,000g/モルであり、ポリオキシエチレン含有量が70%のポロキサマーである。ポロキサマーは、商品名PLURONICS(登録商標)(BASF Corporation)、SYNPERONICS(登録商標)(Croda International)、及びKOLLIPHOR(登録商標)(BASF SE)で、入手可能である。
Claims (50)
- (a)約0.01重量%〜約10重量%のオピオイド、
(b)ポリオキシプロピレンとポリオキシエチレンとのコポリマー、及びポリオキシプロピレンとポリオキシエチレンとのブロックコポリマーからなる群から選択される約10重量%〜約80重量%のポリマー、並びに
(c)約25重量%〜約70重量%のガム、
を含む、医薬製剤。 - (a)約0.01重量%〜約5重量%のオピオイド、
(b)ポリオキシプロピレンとポリオキシエチレンとのコポリマー、及びポリオキシプロピレンとポリオキシエチレンとのブロックコポリマーからなる群から選択される約35重量%〜約65重量%のポリマー、並びに
(c)約40重量%〜約60重量%のガム、
を含む、医薬製剤。 - (a)約0.05重量%〜約2.5重量%のオピオイド、
(b)ポリオキシプロピレンとポリオキシエチレンとのコポリマー、及びポリオキシプロピレンとポリオキシエチレンとのブロックコポリマーからなる群から選択される約45重量%〜約55重量%のポリマー、並びに
(c)約45重量%〜約55重量%のガム、
を含む、医薬製剤。 - (a)約0.1重量%〜約1.2重量%のオピオイド、
(b)ポリオキシプロピレンとポリオキシエチレンとのコポリマー、及びポリオキシプロピレンとポリオキシエチレンとのブロックコポリマーからなる群から選択される約48重量%〜約52重量%のポリマー、並びに
(c)約48重量%〜約52重量%のガム、
を含む、医薬製剤。 - (a)約0.01重量%〜約10重量%のオピオイド、
(b)ポリオキシプロピレンとポリオキシエチレンとのコポリマー、及びポリオキシプロピレンとポリオキシエチレンとのブロックコポリマーからなる群から選択される約30重量%〜約80重量%のポリマー、
(c)約20重量%〜約50重量%のガム、並びに
(d)約0.1重量%〜約20重量%のセルロース化合物、
を含む、医薬製剤。 - (a)約0.01重量%〜約5重量%のオピオイド、
(b)ポリオキシプロピレンとポリオキシエチレンとのコポリマー、及びポリオキシプロピレンとポリオキシエチレンとのブロックコポリマーからなる群から選択される約40重量%〜約75重量%のポリマー、
(c)約20重量%〜約40重量%のガム、並びに
(d)約0.1重量%〜約20重量%のセルロース化合物、
を含む、医薬製剤。 - (a)約0.05重量%〜約2.0重量%のオピオイド、
(b)ポリオキシプロピレンとポリオキシエチレンとのコポリマー、及びポリオキシプロピレンとポリオキシエチレンとのブロックコポリマーからなる群から選択される約50重量%〜約70重量%のポリマー、
(c)約25重量%〜約35重量%のガム、並びに
(d)約1重量%〜約15重量%のセルロース化合物、
を含む、医薬製剤。 - (a)約0.1重量%〜約1.2重量%のオピオイド、
(b)ポリオキシプロピレンとポリオキシエチレンとのコポリマー、及びポリオキシプロピレンとポリオキシエチレンとのブロックコポリマーからなる群から選択される約60重量%〜約65重量%のポリマー、
(c)約28重量%〜約32重量%のガム、並びに
(d)約5重量%〜約10重量%のセルロース化合物、
を含む、医薬製剤。 - 前記オピオイドが、オピオイド作動薬である、請求項1〜8のいずれか一項に記載の医薬製剤。
- 前記オピオイドが、ブプレノルフィン、アズルミン、アルフェンタニル、アロクリプトピン、アリルプロジン、アルファプロジン、アニレリジン、アポルフィン、ベンジルモルフィン、ベルベリン、ビククリン、ビクシン、ベジトラミド、ブルボカプニン(bulbocaprine)、ブトルファノール、クロニタゼン、コデイン、デソモルヒネ、デキストロモラミド、デゾシン、ジアンプロミド、ジアモルフォン、ジヒドロコデイン、ジヒドロモルヒネ、ジメノキサドール、ジメフェプタノール、ジメチルチアンブテン、ジオキサフェチルブチレート、ジピパノン、エプタゾシン、エトヘプタジン、エチルメチルチアンブテン、エチルモルヒネ、エトニタゼン、フェンタニル、ヘロイン、ヒドロコドン、ヒドロモルホン、ヒドロキシペチジン、イソメタドン、ケトベミドン、レボルファノール、レボフェナシルモルファン、ロフェンタニル、メペリジン、メプタジノール、メタゾシン、
メタドン、メトポン、モルヒネ、ミロフィン(ミロフィネ)、ナルセイン、ニコモルヒネ、ノルレボルファノール、ノルメタドン、ナロルフィン、ナルブフェン、ノルモルヒネ、ノルピパノン、アヘン、オキシコドン、オキシモルホン、パパベレタム、ペンタゾシン、フェナドキソン、フェノモルファン、フェナゾシン、フェノペリジン、ピミノジン、ピリトラミド、プロフェプタジン、プロメドール、プロペリジン、プロポキシフェン、スフェンタニル、タペンタドール、チリジン、トラマドール、又はこれらのいずれかの薬学的に許容される塩である、請求項1〜8のいずれか一項に記載の医薬製剤。 - 前記オピオイドが、ブプレノルフィン、モルヒネ、ヒドロコドン、オキシコドン、メタドン、メペリジン、ヒドロモルホン、オキシモルホン、フェンタニル、又はこれらのいずれかの薬学的に許容される塩である、請求項1〜8のいずれか一項に記載の医薬製剤。
- 前記オピオイドが、ブプレノルフィン遊離塩基、又はブプレノルフィンの薬学的に許容される塩である、請求項1〜8のいずれか一項に記載の医薬製剤。
- 前記オピオイドが、式(I)の化合物若しくはその薬学的に許容される塩、式(II)の化合物若しくはその薬学的に許容される塩、式(III)の化合物若しくはその薬学的に許容される塩、式(IV)の化合物若しくはその薬学的に許容される塩、又は式(V)の化合物若しくはその薬学的に許容される塩である、請求項1〜8のいずれか一項に記載の医薬製剤。
- 前記オピオイドが、ブプレノルフィンヘミアジペート、又はその薬学的に許容される塩である、請求項1〜8のいずれか一項に記載の医薬製剤。
- 前記ポリマーが、ポリオキシプロピレンとポリオキシエチレンとの少なくとも1種のブロックコポリマーからなる、請求項1〜14のいずれか一項に記載の医薬製剤。
- 前記ポリマーが、ポロキサマーである、請求項1〜15のいずれか一項に記載の医薬製剤。
- 前記ポロキサマーが、ポロキサマー101、ポロキサマー105、ポロキサマー108、ポロキサマー122、ポロキサマー123、ポロキサマー124、ポロキサマー181、ポロキサマー182、ポロキサマー183、ポロキサマー184、ポロキサマー185、ポロキサマー188、ポロキサマー212、ポロキサマー215、ポロキサマー217、ポロキサマー231、ポロキサマー234、ポロキサマー235、ポロキサマー237、ポロキサマー238、ポロキサマー282、ポロキサマー284、ポロキサマー288、ポロキサマー331、ポロキサマー333、ポロキサマー334、ポロキサマー335、ポロキサマー338、ポロキサマー401、ポロキサマー402、ポロキサマー403、ポロキサマー407、又はこれらの2つ以上の組み合わせである、請求項16に記載の医薬製剤。
- 前記ポロキサマーが、ポロキサマー122、ポロキサマー123、ポロキサマー124、ポロキサマー181、ポロキサマー182、ポロキサマー183、ポロキサマー184、ポロキサマー185、ポロキサマー188、又はこれらの2つ以上の組み合わせである、請求項16に記載の医薬製剤。
- 前記ポロキサマーが、ポロキサマー122、ポロキサマー123、ポロキサマー124、又はこれらの2つ以上の組み合わせである、請求項16に記載の医薬製剤。
- 前記ポロキサマーが、ポロキサマー124である、請求項16に記載の医薬製剤。
- 前記ガムが、グアーガム、ローカストビーンガム、タラガム、デキストラン、カラギーナン、キサンタンガム、ジェランガム、キタン(chitan)、キトサン、アカシアガム、アラビアガム、トラガントガム、カラヤガム、メスキートガム、ペクチン、ガムレバン、キシラン、プルラン、マンナン、マンノグルカン、カロブビーンガム、又はこれらの2つ以上の組み合わせである、請求項1〜20のいずれか一項に記載の医薬製剤。
- 前記ガムが、カラギーナン、デキストラン、アラビアガム、トラガントガム、ペクチン、カラヤガム、キサンタンガム、グアーガム、又はこれらの2つ以上の組み合わせである、請求項21に記載の医薬製剤。
- 前記ガムが、キサンタンガム、グアーガム、又はこれらの組み合わせである、請求項21に記載の医薬製剤。
- 前記ガムが、グアーガムである、請求項21に記載の医薬製剤。
- 前記セルロース化合物が、アルキルセルロース、ヒドロキシアルキルセルロース、カルボキシアルキルセルロース、又はこれらの2つ以上の組み合わせである、請求項5〜20のいずれか一項に記載の医薬製剤。
- 前記セルロース化合物が、メチルセルロース、エチルセルロース、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース、エチルメチルセルロース、カルボキシメチルセルロース、エチルヒドロキシエチルセルロース、又はこれらの2つ以上の組み合わせである、請求項25に記載の医薬製剤。
- 前記セルロース化合物が、ヒドロキシプロピルメチルセルロース、カルボキシメチルセルロース、又はこれらの組み合わせである、請求項25に記載の医薬製剤。
- オピオイド依存症の治療を必要とするヒトにおける治療のための方法であって、請求項1〜27のいずれか一項に記載の治療有効量の医薬製剤を前記ヒトに投与することで、オピオイド依存症を治療すること、を含む、方法。
- 疼痛の治療を必要とするヒトにおける治療のための方法であって、請求項1〜27のいずれか一項に記載の治療有効量の医薬製剤を前記ヒトに投与することで、前記疼痛を治療すること、を含む、方法。
- 請求項1〜27のいずれか一項に記載の治療有効量の医薬製剤を含む、経口投与カプセル。
- オピオイド依存症の治療を必要とするヒトにおける治療のための方法であって、請求項30に記載のカプセルを前記ヒトに経口投与することで、前記オピオイド依存症を治療すること、を含む、方法。
- 疼痛の治療を必要とするヒトにおける治療のための方法であって、請求項30に記載のカプセルを前記ヒトに経口投与することで、前記疼痛を治療すること、を含む、方法。
- (a)非オピオイド鎮痛薬、非ステロイド抗炎症薬、ベンゾジアゼピン、バルビツレート、刺激薬、及びこれらの混合物からなる群から選択される、乱用されやすい活性、
(b)ポリオキシエチレンの2つの親水性鎖が隣接している平均分子量が2000〜2400ダルトンの中央のポリオキシプロピレンの疎水性鎖を、含むノニオン性トリブロックコポリマー、並びに
(c)ガム、を含む乱用防止医薬製剤であって、
前記活性薬剤が、前記製剤の0.1〜20重量%を構成し、前記ノニオン性トリブロックコポリマーが、前記製剤の45〜70重量%を構成し、前記ガムが、前記製剤の30〜50重量%を構成する、乱用防止医薬製剤。 - 前記ノニオン性トリブロックコポリマーが、前記製剤の45〜65重量%を構成し、前記グアーガムが、前記製剤の30〜50重量%を構成する、請求項33に記載の乱用防止製剤。
- 前記ガムが、グアーガムである、請求項33に記載の乱用防止製剤。
- ヒドロキシプロピルメチルセルロース、クロスカルメロースナトリウム、又はこれら2つの混合物から選択される賦形剤を更に含む、請求項33に記載の乱用防止製剤。
- 水、湯、及びエタノールと水との混合物から選択される溶媒中に抽出した場合、濾過することの困難なゲルが形成される、請求項33に記載の乱用防止製剤。
- 前記製剤が、カプセル内に充填されている、請求項33〜37のいずれか一項に記載の乱用防止製剤。
- 前記カプセルにより、以下の条件下で、すなわち、USPの溶出装置3により、往復シリンダーを備え付け、毎分30のストローク速度で、pH2のホスフェート緩衝液中で操作し、緩衝溶液に投与した場合、30分以内に前記活性の少なくとも50重量%が放出される、請求項38に記載の乱用防止製剤。
- 粘度が、5000cpより高い、請求項38に記載の乱用防止製剤。
- 前記カプセルにより、以下の条件下で、すなわち、USPの溶出装置3により、往復シリンダーを備え付け、毎分30のストローク速度で、pH2のホスフェート緩衝液中で操作し、緩衝溶液に投与した場合、60分以内に前記活性の少なくとも85重量%が放出される、請求項33に記載の乱用防止製剤。
- USPの装置III溶出試験において10分以内に前記オピオイドの少なくとも75%が放出される、請求項1〜27のいずれか一項に記載の医薬製剤。
- USPの装置III溶出試験において10分以内に前記オピオイドの少なくとも80%が放出される、請求項1〜27のいずれか一項に記載の医薬製剤。
- USPの装置III溶出試験において10分以内に前記オピオイドの少なくとも85%が放出される、請求項1〜27のいずれか一項に記載の医薬製剤。
- USPの装置III溶出試験において10分以内に前記オピオイドの少なくとも90%が放出される、請求項1〜27のいずれか一項に記載の医薬製剤。
- USPの装置III溶出試験において10分以内に前記オピオイドの少なくとも95%が放出される、請求項1〜27のいずれか一項に記載の医薬製剤。
- USPの装置III溶出試験において10分以内に前記オピオイドの少なくとも75%が放出される、請求項30に記載のカプセル。
- USPの装置III溶出試験において10分以内に前記オピオイドの少なくとも80%が放出される、請求項30に記載のカプセル。
- USPの装置III溶出試験において10分以内に前記オピオイドの少なくとも85%が放出される、請求項30に記載のカプセル。
- USPの装置III溶出試験において10分以内に前記オピオイドの少なくとも90%が放出される、請求項30に記載のカプセル。
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PCT/IB2017/051362 WO2017153933A1 (en) | 2016-03-09 | 2017-03-08 | Abuse-resistant pharmaceutical formulations |
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JP2019507783A true JP2019507783A (ja) | 2019-03-22 |
JP2019507783A5 JP2019507783A5 (ja) | 2020-03-12 |
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JP2018547372A Pending JP2019507783A (ja) | 2016-03-09 | 2017-03-08 | 乱用防止医薬製剤 |
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EP (1) | EP3426234A1 (ja) |
JP (1) | JP2019507783A (ja) |
CA (1) | CA3016510A1 (ja) |
WO (1) | WO2017153933A1 (ja) |
Cited By (1)
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---|---|---|---|---|
US10632201B2 (en) | 2017-10-19 | 2020-04-28 | Capsugel Belgium Nv | Immediate release abuse deterrent formulations |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20090123386A1 (en) * | 2005-04-06 | 2009-05-14 | Victor Morrison Young | Abuse Resistant Capsules |
WO2014152296A1 (en) * | 2013-03-15 | 2014-09-25 | Mallinckrodt Llc | Abuse deterrent solid dosage form for immediate release with functional score |
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US20030068375A1 (en) * | 2001-08-06 | 2003-04-10 | Curtis Wright | Pharmaceutical formulation containing gelling agent |
EP2301526B1 (en) * | 2003-03-26 | 2016-03-23 | Egalet Ltd. | Morphine controlled release system |
US20070202177A1 (en) * | 2006-02-28 | 2007-08-30 | Becton, Dickinson And Company | Antimicrobial Compositions and Methods for Locking Catheters |
GB0606124D0 (en) | 2006-03-28 | 2006-05-03 | Reckitt Benckiser Healthcare | Buprenorphine derivatives and uses thereof |
WO2010083843A1 (en) * | 2009-01-26 | 2010-07-29 | Egalet A/S | Controlled release formulations with continuous efficacy |
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2017
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- 2017-03-08 EP EP17712836.0A patent/EP3426234A1/en not_active Withdrawn
- 2017-03-08 WO PCT/IB2017/051362 patent/WO2017153933A1/en active Application Filing
- 2017-03-08 US US16/083,364 patent/US20190029966A1/en not_active Abandoned
- 2017-03-08 JP JP2018547372A patent/JP2019507783A/ja active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20090123386A1 (en) * | 2005-04-06 | 2009-05-14 | Victor Morrison Young | Abuse Resistant Capsules |
WO2014152296A1 (en) * | 2013-03-15 | 2014-09-25 | Mallinckrodt Llc | Abuse deterrent solid dosage form for immediate release with functional score |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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US10632201B2 (en) | 2017-10-19 | 2020-04-28 | Capsugel Belgium Nv | Immediate release abuse deterrent formulations |
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WO2017153933A1 (en) | 2017-09-14 |
CA3016510A1 (en) | 2017-09-14 |
US20190029966A1 (en) | 2019-01-31 |
EP3426234A1 (en) | 2019-01-16 |
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