JP2013528194A - 転用防止微粒剤および微小錠剤 - Google Patents
転用防止微粒剤および微小錠剤 Download PDFInfo
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- JP2013528194A JP2013528194A JP2013513668A JP2013513668A JP2013528194A JP 2013528194 A JP2013528194 A JP 2013528194A JP 2013513668 A JP2013513668 A JP 2013513668A JP 2013513668 A JP2013513668 A JP 2013513668A JP 2013528194 A JP2013528194 A JP 2013528194A
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Classifications
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- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
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- A—HUMAN NECESSITIES
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- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
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- A—HUMAN NECESSITIES
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Abstract
Description
投薬形態
「経口投薬形態」は、活性成分を含んでなる微粒剤および/または微小錠剤から調製することができる任意の経口投薬形態、詳細には懸濁液、シロップ、錠剤、カプセルを意味するのに用いられる。
「中性支持体」または「中性コア」または更に一層簡単に「中性物質」とは、大きさが50μm〜3mm、優先的には100〜1000μmの不活性な球状または擬似球状支持体であって、例えば、微粒剤を構築するための活性成分の基剤支持体として医薬産業で一般に用いられているものを意味するものと解釈される。
本発明の微粒剤は、中性支持体の中心に構成され少なくとも1種類の層で被覆された球状投薬単位に関する。
本発明の微小錠剤は、粉末または顆粒の圧縮によって生じる投薬単位に関し、大きさが10(質量/質量)未満である。
本出願において、持続放出という用語は、活性成分が欧州薬局方によって定義された即時放出系においてのみ有した放出プロフィール(45分間で放出される活性成分の量が少なくとも75%に等しい、欧州薬局方(Ph. Eur.),第6版2.9.3.)と比較して変更されている活性成分の放出プロフィールを表すのに用いられる。
本出願において、「ゲル化活性剤」という用語は、所定のゲル化剤のゲル化力を増加させることができる化合物を表すのに用いられる。例えば、下記のゲル化活性剤を用いることができる:固定部位または架橋部位と呼ばれる高分子鎖の一定の正確な部位に結びつくことによって前記鎖間にブリッジを形成する多価カチオン、一般的にはカルシウムイオンまたはアルミニウムイオンのような二または三価のイオン性剤。これによって形成したゲルは、「向イオン性ゲル」として知られていることがある。これらのゲルの中では、アルギン酸塩、ペクチン、カラギーナン、カルボキシメチルセルロースおよびキトサンを挙げることができる。
カーボポール(Carbopol)(商標)型のポリアクリル酸およびその誘導体(カルボマー(Carbomer)またはカルボキシポリメチレンとして知られている)、
ポリオキシエチレン(POE)、および/または
ポリビニルアルコール(PVA)、
ポリビニルピロリドン(PVP)、および/または
ゼラチン、および/または
セルロース誘導体(例えば、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、ヒドロキシエチルセルロース、カルボキシメチルセルロース)、および/または
多糖類、好ましくは、アルギン酸塩、詳細にはアルギン酸ナトリウム、ペクチン、グアー、キサンタン、カラギーナン、ジェランを含んでなるサブグループのもの、および
それらの混合物。
カルボキシポリメチレン(カーボポール(商標))/重炭酸ナトリウム、
アルギン酸塩/Ca2+イオン、
アルギン酸塩/粘土誘導体、例えば、ビーガム(商標)(ケイ酸マグネシウムアルミニウム)、
キサンタンガム/粘土誘導体、例えば、ビーガム(商標)(ケイ酸マグネシウムアルミニウム)、
ポリビニルアルコール/Cu2+イオン、
ペクチン/Ca2+イオン、
カルボキシメチルセルロース/Al2+、
ジェランガム/Ca2+、
K−カラギーナン/K+、
l−カラギーナン/Ca2+。
本発明による微粒剤の活性層の構成は、任意の性質のものでよい少なくとも1種類の医薬活性成分を含んでなる。
本発明の微粒剤は、中性の球状支持体を流動床リアクションチャンバーに導入し、前記中性の球状支持体に、少なくとも1種類の活性成分を少なくとも1種類の水溶性または非水溶性ポリマーを加えた有機および/または水性溶媒に溶解または懸濁したものを噴霧し、少なくとも1種類の疎水性ポリマーを含んでなるコーティング懸濁液を前段階で得られたコーティングした粒子に噴霧し、必要に応じてこうして得られた医薬微粒剤を乾燥する段階を含んでなる方法によって調製することができる。
本発明による活性層のマウンティングとして知られる段階によって活性成分含量が正確かつ均一である微粒剤を得ることができる。
活性成分は、流動床または孔あきタービンなどにおいて噴霧することによって通常の方法で微粒子に塗布される。一般に、この方法は、マウンティング溶液に溶解または分散している活性成分および必要に応じて結合剤をノズルを通して同時噴霧することに基づいており、これにより、この方法のこの段階が内容物を完全に均質にすることができる。
ゲル化活性剤は、流動床または孔あきタービンなどで噴霧することによって通常の方法で中性物質(微粒子)に適用される。
コーティングポリマーは、噴霧、流動床または孔あきタービンなどによる通常の方法によって前記微粒剤に塗布される。一般に、この方法は、コーティングポリマーおよび必要に応じて適当な溶媒に溶解または分散している可塑剤および/または界面活性剤および/または不活性充填剤を、ノズル通して同時噴霧することに基づいている。
a) 活性成分とゲル化剤とを含む集団1の調製
用いた活性成分は、硫酸モルヒネである。
用いた中性コアは、砂糖球(ニュートラルス(Neutrals)#30、NPPHARM)である。
下記の比に準じてカプセル化する前に、それぞれのプロトタイプA、BおよびCの集団1および2をそれぞれ混合する。
用いた活性成分は、硫酸モルヒネである。
用いた中性コアは、砂糖球(ニュートラルス#30、NPPHARM)である。前記支持体の大きさは、約400〜600μmである。
下記の比に準じてカプセル化する前に、それぞれのプロトタイプA、BおよびCの集団1および2をそれぞれ混合する。
a) 活性成分およびゲル化剤を含む集団1の調製
用いた活性成分は、硫酸モルヒネである。
用いた中性コアは、砂糖球(ニュートラルス#30、NPPHARM)である。前記支持体の大きさは、約400〜600μmである。
a) 集団1の調製
活性成分およびゲル化剤を含む集団1
ゲル化活性剤を含む集団2。ミキサーに、微晶質セルロース(アビセル PH102)および塩化カルシウムを入れる。均質混合物が、調製される。
用いた方法は、下記の通りである。すなわち、最終投薬形態の微小錠剤を乳鉢中で乳棒を用いて2分間摩砕し、それらを微細な粉末に粉砕する。次いで、前記粉末をマグネティックバーが入っている20mlビーカーに移し、様々な溶媒10mlを加え、正確に5分間撹拌する。次いで、試料を、ガラス管において濾紙上で正確に1時間濾過する。濾液が全く通過しなかったときには、試料を1μm(GF/B)のガラス繊維フィルターを備えたシリンジを用いて濾過する。得られた濾液を、0.1N HClで1/10倍に希釈する。濾液が得られない場合には、0%の活性成分を抽出することができたと結論される。最後に、抽出された活性成分の百分率を決定する目的で、試料をHPLCを通過させる。
様々な種類の放出プロフィールが考えられることを示すために、溶解試験を例4の様々な処方について粉砕されていない微小錠剤で行った。
Claims (15)
- 微粒剤または微小錠剤の2つの集団であって、依存性を生じる可能性がある少なくとも1種類の活性成分とゲル化剤とを含んでなる第一の集団と、活性成分とゲル化剤を含まず少なくとも1種類のゲル化活性剤を含んでなる第二の集団とを含んでなる、微粒剤および/または微小錠剤を基剤とする経口投薬形態。
- 微粒剤または微小錠剤から構成される、請求項1に記載の投薬形態。
- 微粒剤の第一の集団が、中性支持体と、少なくとも1種類の活性成分および必要に応じて薬学上許容可能な結合剤を含んでなる少なくとも1種類のマウンティング層と、マウンティング層または別個の層に含まれているゲル化剤とを含んでなり、微粒剤の第二の集団が、中性支持体と、少なくとも1種類のゲル化活性剤を含んでなる少なくとも1種類のマウンティング層とを含んでなる、請求項2に記載の投薬形態。
- ゲル化剤が、ポリアクリル酸およびその誘導体、ポリオキシエチレン、ポリビニルアルコール、ポリビニルピロリドン(PVP)、ゼラチン、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、ヒドロキシエチルセルロース、カルボキシメチルセルロースのようなセルロース誘導体、多糖類、好ましくは、アルギン酸ナトリウム、ペクチン、グアー、キサンタン、カラギーナン、ジェラン、およびそれらの混合物を含んでなるサブグループのものから選択される、請求項1〜3のいずれか一項に記載の投薬形態。
- ゲル化剤と共同するゲル化活性剤により、ゲル化剤のポリマー鎖の所定部位にブリッジを形成することができ、および/またはゲル化剤のポリマー性ネットワークを強化することができる、請求項1〜4のいずれか一項に記載の投薬形態。
- ゲル化剤/ゲル化活性剤の対が、カルボキシポリメチレン/重炭酸ナトリウム、アルギン酸塩/Ca2+イオン、アルギン酸塩/ケイ酸マグネシウムアルミニウムおよびキサンタンガム/ケイ酸マグネシウムアルミニウムから選択される、請求項1〜5のいずれか一項に記載の投薬形態。
- ゲル化剤が、1〜100mg、更に優先的には1〜50mg、更に一層優先的には1〜30mgの割合で投薬単位に含まれている、請求項1〜6のいずれか一項に記載の投薬形態。
- ゲル化活性剤が、1〜100mg、更に優先的には1〜50mg、更に一層優先的には1〜30mgの割合で投薬単位に含まれている、請求項1〜7のいずれか一項に記載の投薬形態。
- 微粒剤および/または微小錠剤が、活性成分の即時放出を防止するための少なくとも1種類の疎水性ポリマーを基剤とするコーティングを含んでなる、請求項1〜8のいずれか一項に記載の投薬形態。
- 疎水性ポリマーが、エチルセルロース、酪酸酢酸セルロース、酢酸セルロース、ポリ(アクリル酸エチル、メタクリル酸メチル、メタクリル酸トリメチルアンモニオエチル)、ポリ酢酸ビニル、およびそれらの混合物のファミリーのユードラジット(商標)、詳細にはユードラジット(商標)RS 30D、ユードラジットNE 30D、ユードラジット(商標)RL 30D、ユードラジット(商標)RS POおよびユードラジット(商標)RL POという商品名で販売されているA型およびB型のアンモニオ−メタクリレートコポリマーから選択される、請求項9に記載の投薬形態。
- コーティングが、少なくとも1種類の可塑剤を含んでなる、請求項10に記載の投薬形態。
- 活性成分が、鎮痛剤、詳細には非オピエート、低オピエート鎮痛剤、混合オピオイド、モルヒネ製剤または痙攣剤、詳細にはヒドロコドン、ヒドロモルフォン、モルヒネ、オキシコドン、オキシモルフォン、トラマドールおよびその誘導体から選択される、請求項1〜11のいずれか一項に記載の投薬形態。
- 微粒剤または微小錠剤を、カプセル形態で調整する、請求項1に記載の投薬形態。
- 微粒剤または微小錠剤を、多微粒子状錠剤形態で調整する、請求項1に記載の投薬形態。
- 微粒剤または微小錠剤を、単回用量包装で調整する、請求項1に記載の投薬形態。
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Families Citing this family (38)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7776314B2 (en) | 2002-06-17 | 2010-08-17 | Grunenthal Gmbh | Abuse-proofed dosage system |
DE102005005446A1 (de) | 2005-02-04 | 2006-08-10 | Grünenthal GmbH | Bruchfeste Darreichungsformen mit retardierter Freisetzung |
DE10336400A1 (de) | 2003-08-06 | 2005-03-24 | Grünenthal GmbH | Gegen Missbrauch gesicherte Darreichungsform |
DE10361596A1 (de) | 2003-12-24 | 2005-09-29 | Grünenthal GmbH | Verfahren zur Herstellung einer gegen Missbrauch gesicherten Darreichungsform |
US20070048228A1 (en) | 2003-08-06 | 2007-03-01 | Elisabeth Arkenau-Maric | Abuse-proofed dosage form |
DE102004032049A1 (de) | 2004-07-01 | 2006-01-19 | Grünenthal GmbH | Gegen Missbrauch gesicherte, orale Darreichungsform |
DE102005005449A1 (de) | 2005-02-04 | 2006-08-10 | Grünenthal GmbH | Verfahren zur Herstellung einer gegen Missbrauch gesicherten Darreichungsform |
BRPI0906467C1 (pt) | 2008-01-25 | 2021-05-25 | Gruenenthal Gmbh | forma de dosagem farmacêutica com formato exterior modificado resistente à ruptura e com liberação controlada |
NZ594207A (en) | 2009-02-06 | 2013-03-28 | Egalet Ltd | Immediate release composition resistant to abuse by intake of alcohol |
AU2010265213B2 (en) | 2009-06-24 | 2012-08-23 | Egalet Ltd. | Controlled release formulations |
AU2010275754B2 (en) | 2009-07-22 | 2014-05-15 | Grünenthal GmbH | Tamper-resistant dosage form for oxidation-sensitive opioids |
EP2456427B1 (en) | 2009-07-22 | 2015-03-04 | Grünenthal GmbH | Hot-melt extruded controlled release dosage form |
WO2012028319A1 (en) | 2010-09-02 | 2012-03-08 | Grünenthal GmbH | Tamper resistant dosage form comprising inorganic salt |
MX2013002293A (es) | 2010-09-02 | 2013-05-09 | Gruenenthal Gmbh | Forma de dosificacion resistente a alteracion que comprende un polimero anionico. |
LT2736497T (lt) | 2011-07-29 | 2017-11-10 | Grünenthal GmbH | Sugadinimui atspari tabletė, pasižyminti greitu vaisto atpalaidavimu |
BR112014002022A2 (pt) | 2011-07-29 | 2017-02-21 | Gruenenthal Gmbh | comprimido resistente à violação proporcionando liberação de fármaco imediata |
US20130225697A1 (en) | 2012-02-28 | 2013-08-29 | Grunenthal Gmbh | Tamper-resistant dosage form comprising pharmacologically active compound and anionic polymer |
AU2013248351B2 (en) | 2012-04-18 | 2018-04-26 | Grunenthal Gmbh | Tamper resistant and dose-dumping resistant pharmaceutical dosage form |
US10064945B2 (en) | 2012-05-11 | 2018-09-04 | Gruenenthal Gmbh | Thermoformed, tamper-resistant pharmaceutical dosage form containing zinc |
MX362838B (es) | 2012-07-12 | 2019-02-19 | SpecGx LLC | Composiciones farmacéuticas de liberación prolongada para disuadir el abuso de opioides que comprenden un plastómero, un elastómero y un plastificante delicuescente. |
MX2015010041A (es) | 2013-02-05 | 2015-10-30 | Purdue Pharma Lp | Formulacion farmaceuticas resistentes a la alteracion. |
US10751287B2 (en) * | 2013-03-15 | 2020-08-25 | Purdue Pharma L.P. | Tamper resistant pharmaceutical formulations |
JP6466417B2 (ja) | 2013-05-29 | 2019-02-06 | グリュネンタール・ゲゼルシャフト・ミト・ベシュレンクテル・ハフツング | 二峰性放出プロファイルを有する改変防止(tamper−resistant)剤形 |
CA2907950A1 (en) | 2013-05-29 | 2014-12-04 | Grunenthal Gmbh | Tamper-resistant dosage form containing one or more particles |
EA032465B1 (ru) | 2013-07-12 | 2019-05-31 | Грюненталь Гмбх | Защищенная от применения не по назначению пероральная фармацевтическая лекарственная форма, содержащая этиленвинилацетатный полимер, и способ ее изготовления |
WO2015023675A2 (en) | 2013-08-12 | 2015-02-19 | Pharmaceutical Manufacturing Research Services, Inc. | Extruded immediate release abuse deterrent pill |
US9770514B2 (en) | 2013-09-03 | 2017-09-26 | ExxPharma Therapeutics LLC | Tamper-resistant pharmaceutical dosage forms |
AU2014356581C1 (en) | 2013-11-26 | 2020-05-28 | Grunenthal Gmbh | Preparation of a powdery pharmaceutical composition by means of cryo-milling |
WO2015095391A1 (en) | 2013-12-17 | 2015-06-25 | Pharmaceutical Manufacturing Research Services, Inc. | Extruded extended release abuse deterrent pill |
US9492444B2 (en) | 2013-12-17 | 2016-11-15 | Pharmaceutical Manufacturing Research Services, Inc. | Extruded extended release abuse deterrent pill |
CN106572980A (zh) | 2014-05-12 | 2017-04-19 | 格吕伦塔尔有限公司 | 包含他喷他多的防篡改即释胶囊制剂 |
CN106456550A (zh) | 2014-05-26 | 2017-02-22 | 格吕伦塔尔有限公司 | 避免乙醇剂量倾泻的多颗粒 |
US9707184B2 (en) | 2014-07-17 | 2017-07-18 | Pharmaceutical Manufacturing Research Services, Inc. | Immediate release abuse deterrent liquid fill dosage form |
US9132096B1 (en) | 2014-09-12 | 2015-09-15 | Alkermes Pharma Ireland Limited | Abuse resistant pharmaceutical compositions |
CA2964628A1 (en) | 2014-10-20 | 2016-04-28 | Pharmaceutical Manufacturing Research Services, Inc. | Extended release abuse deterrent liquid fill dosage form |
AU2016251854A1 (en) | 2015-04-24 | 2017-10-19 | Grunenthal Gmbh | Tamper-resistant dosage form with immediate release and resistance against solvent extraction |
JP2018526414A (ja) | 2015-09-10 | 2018-09-13 | グリュネンタール・ゲゼルシャフト・ミト・ベシュレンクテル・ハフツング | 乱用抑止性の即放性製剤を用いた経口過剰摂取に対する保護 |
EP3473246A1 (en) | 2017-10-19 | 2019-04-24 | Capsugel Belgium NV | Immediate release abuse deterrent formulations |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2005523876A (ja) * | 2001-09-26 | 2005-08-11 | ペンウェスト ファーマシューティカルズ カンパニー | 乱用の可能性が低減したオピオイド製剤 |
JP2006506374A (ja) * | 2002-10-25 | 2006-02-23 | グリューネンタ−ル・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | 乱用が防止された製剤 |
JP2007504129A (ja) * | 2003-08-29 | 2007-03-01 | デルサイト バイオテクノロジーズ, インコーポレイテッド | 陰イオン性多糖類を含むインサイチュゲルでの生理学的な薬剤の送達 |
JP2009537456A (ja) * | 2005-11-10 | 2009-10-29 | フラメル・テクノロジーズ | 誤用防止微粒子経口医薬形態 |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2530563C2 (de) | 1975-07-09 | 1986-07-24 | Bayer Ag, 5090 Leverkusen | Analgetische Arzneimittel mit vermindertem Mißbrauchspotential |
US5811126A (en) * | 1995-10-02 | 1998-09-22 | Euro-Celtique, S.A. | Controlled release matrix for pharmaceuticals |
FR2796840B1 (fr) | 1999-07-26 | 2003-06-20 | Ethypharm Lab Prod Ethiques | Comprimes faiblement doses et procede de preparation |
US7842307B2 (en) * | 2001-08-06 | 2010-11-30 | Purdue Pharma L.P. | Pharmaceutical formulation containing opioid agonist, opioid antagonist and gelling agent |
ATE371442T1 (de) * | 2001-10-12 | 2007-09-15 | Elan Pharma Int Ltd | Zusammensetzungen mit einer kombination aus eigenschaften sofortiger freisetzung und kontrollierter freisetzung |
FR2878161B1 (fr) * | 2004-11-23 | 2008-10-31 | Flamel Technologies Sa | Forme medicamenteuse orale, solide et concue pour eviter le mesusage |
FR2881652B1 (fr) * | 2005-02-08 | 2007-05-25 | Flamel Technologies Sa | Forme pharmaceutique orale microparticulaire anti-mesuage |
US8652529B2 (en) * | 2005-11-10 | 2014-02-18 | Flamel Technologies | Anti-misuse microparticulate oral pharmaceutical form |
WO2008150526A1 (en) | 2007-06-04 | 2008-12-11 | Shear/Kershman Laboratories, Inc. | Tamper resistant lipid-based oral dosage form for opioid agonists |
-
2010
- 2010-06-07 FR FR1054465A patent/FR2960775A1/fr active Pending
- 2010-07-20 FR FR1055921A patent/FR2960776B1/fr active Active
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Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2005523876A (ja) * | 2001-09-26 | 2005-08-11 | ペンウェスト ファーマシューティカルズ カンパニー | 乱用の可能性が低減したオピオイド製剤 |
JP2006506374A (ja) * | 2002-10-25 | 2006-02-23 | グリューネンタ−ル・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | 乱用が防止された製剤 |
JP2007504129A (ja) * | 2003-08-29 | 2007-03-01 | デルサイト バイオテクノロジーズ, インコーポレイテッド | 陰イオン性多糖類を含むインサイチュゲルでの生理学的な薬剤の送達 |
JP2009537456A (ja) * | 2005-11-10 | 2009-10-29 | フラメル・テクノロジーズ | 誤用防止微粒子経口医薬形態 |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2020536056A (ja) * | 2017-10-02 | 2020-12-10 | パーデュー、ファーマ、リミテッド、パートナーシップ | 遅延放出ゲル化剤組成物を含む医薬組成物 |
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CA2800426A1 (fr) | 2011-12-15 |
MX345291B (es) | 2017-01-23 |
FR2960775A1 (fr) | 2011-12-09 |
CA2800426C (fr) | 2020-03-24 |
ZA201208976B (en) | 2013-07-31 |
FR2960776B1 (fr) | 2013-03-29 |
EP2575789B1 (fr) | 2019-10-23 |
US9993431B2 (en) | 2018-06-12 |
IL223191A0 (en) | 2013-02-03 |
FR2960776A1 (fr) | 2011-12-09 |
CN102970984A (zh) | 2013-03-13 |
ES2766349T3 (es) | 2020-06-12 |
IL223191A (en) | 2017-10-31 |
CN102970984B (zh) | 2015-10-14 |
EP2575789A1 (fr) | 2013-04-10 |
AU2011263780B2 (en) | 2015-04-09 |
KR101862887B1 (ko) | 2018-05-30 |
JP5937068B2 (ja) | 2016-06-22 |
US20130129825A1 (en) | 2013-05-23 |
MX2012014270A (es) | 2013-02-12 |
KR20130086200A (ko) | 2013-07-31 |
AU2011263780A1 (en) | 2013-01-10 |
WO2011154414A1 (fr) | 2011-12-15 |
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