JP7384812B2 - アリピプラゾール投与戦略 - Google Patents
アリピプラゾール投与戦略 Download PDFInfo
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- JP7384812B2 JP7384812B2 JP2020546984A JP2020546984A JP7384812B2 JP 7384812 B2 JP7384812 B2 JP 7384812B2 JP 2020546984 A JP2020546984 A JP 2020546984A JP 2020546984 A JP2020546984 A JP 2020546984A JP 7384812 B2 JP7384812 B2 JP 7384812B2
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- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
Description
本出願は、2018年3月5日に出願された米国仮特許出願第62/638,587号に基づく優先権を主張する。本出願の内容全体が、参照により本明細書に組み込まれる。
約5~50mgのアリピプラゾールを含む第1の成分と;
約629~695mgのALNCDを含む第2の成分と;
治療有効量のアリピプラゾールラウロキシルを含む第3の成分と
を任意の順序で対象に投与する工程を含む方法が本明細書で提供される。
アリピプラゾールを含む第1の成分と;
ALNCDを含む第2の成分と;
アリピプラゾールラウロキシルを含む第3の成分と
を対象に投与する工程を含み、
第1、第2及び第3の成分を合わせた投与量は、対象におけるアリピプラゾールの治療有効平均血漿レベルを維持するのに十分である、
方法が本明細書で提供される。図8は本方法を使用して得られる平均血漿レベルを示す。
アリピプラゾールを含む第1の成分と;
ALNCDを含む第2の成分と;
アリピプラゾールラウロキシルを含む第3の成分と
を含み、
投与についての指示を更に含み、指示は、第1の成分の経口投与、第2の成分の筋肉内投与及び第3の成分の筋肉内投与を指定する、キットが本明細書で提供される。
本明細書で使用される種々の用語の定義を以下に列挙する。個別に又はより大きな群の一部として、具体的な例に限定されない限り、これらの定義を、本明細書及び特許請求の範囲を通して使用される用語に適用する。
それを必要とする対象の統合失調症を治療する方法及び投与レジメンであって、アリピプラゾールを含む第1の成分を対象に投与する工程を含む方法が本明細書で開示される。米国特許第4,734,416号及び同第5,006,528号は、統合失調症、双極性疾患、抑うつ及び他のCNS障害の治療に有用な非定型抗精神病薬としてのアリピプラゾール、7-{4-[4-(2,3-ジクロロフェニル)-1-ピペラジニル]ブトキシ}-3,4-ジヒドロ-2(1H)-キノリノン又は7-{4-[4-(2,3-ジクロロフェニル)-1-ピペラジニル]ブトキシ}-3,4-ジヒドロカルボスチリルを開示している。これらの文献は、全体が参照により本明細書に組み込まれる。アリピプラゾールは、以下の化学構造を有する:
本明細書で提供される方法及び投与レジメンは、それを必要とする対象の種々の障害の治療に使用することができる。例えば、本明細書に記載される医薬組成物を使用して、抑うつ、統合失調症及び双極性障害を有する対象を治療することができる。
アリピプラゾールを含む第1の成分と;
ALNCDを含む第2の成分と;
治療有効量のアリピプラゾールラウロキシルを含む第3の成分と
を対象に投与する工程を含む方法が本明細書で提供される。
約5~50mgのアリピプラゾールを含む第1の成分と;
約629~695mgのALNCDを含む第2の成分と;
治療有効量のアリピプラゾールラウロキシルを含む第3の成分と
を対象に投与する工程を含む方法が本明細書で提供される。
アリピプラゾールを含む第1の成分と;
ALNCDを含む第2の成分と;
アリピプラゾールラウロキシルを含む第3の成分と
を対象に投与する工程を含み、
第1、第2及び第3の成分を合わせた投与量は、対象におけるアリピプラゾールの治療有効平均血漿レベルを維持するのに十分である、
方法が本明細書で提供される。
アリピプラゾールを含む第1の成分と;
ALNCDを含む第2の成分と;
アリピプラゾールラウロキシルを含む第3の成分と
を含み、
投与についての指示を更に含み、指示は、第1の成分の経口投与、第2の成分の筋肉内投与及び第3の成分の筋肉内投与を指定する、キットが本明細書で提供される。
本明細書で提供される方法及び投与レジメンの成分の実際の投与量レベルは、患者にとって毒性になることなく、特定の患者についての所望の治療応答、組成及び投与様式を達成するのに有効な有効成分の量を得るように変化させることができる。
試験設計及び処置レジメン
ヘルシンキ宣言、及び1997年の医薬品規制調和国際会議によって合意された良き臨床上の基準ガイドラインに従って、試験を行った。試験プロトコル、修正及びインフォームドコンセント形態は、各現場の独立倫理員会/治験審査委員会によって承認された。全ての患者が、試験に入る前に書面によるインフォームドコンセントを提供した。
試験集団
適格患者は、精神障害の診断と統計マニュアル、第5版(DSM-5)に基づいて慢性統合失調症又は統合失調感情障害の診断を受け、アリピプラゾールに対する忍容性の文書化された実績がある又はスクリーニング中に試験用量に対する忍容性を実証した、18~65歳の成人とした。この試験では、患者に、スクリーニング前3カ月以内に急性精神医学的憎悪のための入院がなく、スクリーニング及び試験開始時に3以下の臨床全般印象・重症度(CGI-S)スコアを有するものとして定義されるように、臨床的に安定であることを要求した。患者は、スクリーニングと無作為化との間にいかなる投薬変化もなく、スクリーニング前2カ月以上の間、安定な経口抗精神病薬投薬レジメン(アリピプラゾール及びクロザピンを除く)にあった。
試験評価
液体クロマトグラフィー-タンデム質量分析用の血液試料を、アリピプラゾール血漿濃度を分析するために収集した。試料は、1日目には、投与前1時間並びに投与後1、2、3、4、5、6及び8時間(±15分)以内に収集した。開始後2~20日目には、経口アリピプラゾール(又経口プラセボ)投与前に、単一試料を収集した。1日目のように、21日目の投与前試料の収集後に、投与後1、2、3、4、5、6及び8時間(±15分)に追加の試料を収集した。23~85日目には、1日目の経口投与時間の±2時間以内、又は可能な限りその時間枠に近い時間に単一試料を収集した。113日目及び141日目には、単一PK試料を収集した。
統計分析
試験集団は、安全性集団(試験薬物を受けた全ての患者)及びPK集団(試験薬物を受け、アリピプラゾールの1つ以上の測定可能な濃度を有した全ての患者)からなっていた。
患者性質及びベースライン特性
合計で、161人の患者を登録し、開始レジメンのうちの1つを受けさせ、PK及び安全性集団に含めた(Table 1(表1))。患者を、441又は882mgのAL開始用量と共に、1日開始レジメン(n=80)又は21日開始レジメン(n=81)を受けるように無作為化した。合計で、39人の患者をAL441mg/1日開始群に登録し、41人の患者をAL881mg/1日開始群に登録した。21日開始レジメン群に登録した患者のうち、40人の患者をAL441mg/21日開始群に割り当て、41人の患者をAl882mg/21日開始群に割り当てた。
薬物動態結果
1日開始レジメン群からの結果は、21日開始レジメン群に匹敵する、最初の月内の平均血漿アリピプラゾール濃度及び曝露を示した(図2)。開始後最初の24時間では、1日開始レジメンで1日目に投与されるアリピプラゾールの用量が高いために(15mgに対して30mg)、21日開始レジメン群と比較して高いアリピプラゾール濃度が1日開始レジメン群で観察された。1日開始レジメンは、最初のAL投与後4日以内に治療アリピプラゾール濃度を達成することにおいて21日開始レジメンを再現するように設計されたので、開始後4日目の血漿濃度に特に関心が持たれた。図2に示されるように、1日レジメンは、4日以内で、21日開始レジメンと類似のアリピプラゾールの治療レベルの達成をもたらす。
有害事象
試験期間を通して、全ての時点の各開始レジメン群で、CGI-Sスコアのベースライン(スコア3.0;軽度)からの小さな類似の平均変化(≦0.1)が見られ、疾患重症度の変化がないことを示した。全ての患者が、試験を通してC-SSRSについてスコア0(自殺行為も観念化もなし)を有した。
集団薬物動態(PK)モデル
そのうちの3つが製剤開発及びALのための開始レジメン(Hardら CNS Drugs、提出;Wehrら 準備中)としてALNCDを使用することの実現可能性にとって重要である、4つのフェーズ1試験からのデータを使用して、アリピプラゾールについてのPopPKモデルを開発した。これらの試験(ALK9072-1、ALK9072-B102及びALK9072-B103)を、ここではそれぞれ試験1、試験2及び試験3と呼ぶ。第4の試験は、ALを単独で投与するフェーズ1前試験であった(ALKS9072-A105、試験4と呼ぶ)。全ての試験が、第一選択抗精神病薬投薬(アリピプラゾールを除く)で安定している統合失調症又は統合失調感情障害を有する成人患者を登録した;投与、実際のサンプリング時間及びアリピプラゾール濃度データについての十分なデータがある全ての患者をPopPK分析に含めた。
・ALを数日後に投与する場合と比較して、1日開始レジメンを同じ日にALと同時投与する場合のアリピプラゾール濃度に対する影響を評価するため。同じ日に1日開始レジメン(単回投与のALNCDと単回30mg用量の経口アリピプラゾール)の投与で、全部で5つの承認されたAL投与量強度及び投与間隔(441、662及び882mg q4w、882mg q6w、及び1064mg q8w)についてシミュレーションを行った。更に、AL(全て承認された用量)を1日開始レジメンの1、3、7、10又は14日後に投与するシミュレーションも行った。最初の投与時点から所定の投与間隔で、AL処置を続けた。
・ALの逃した投与後に治療アリピプラゾール血漿濃度を再確立するための毎日の経口アリピプラゾール補充の現在の推奨に対する代替としてのALNCDの使用を評価するため。「再確立」レジメン(ALNCD又は1日開始レジメン)を後の投与と同時に開始した。ALNCDの補充を用いて及び用いないで、後のAL投与による、蓋然性が高い影響を決定するための複数回投与シナリオに従って、シミュレーションを行って蓋然性が高いアリピプラゾール濃度-時間プロファイルを予測した。定常状態で5つの投与レジメンをシミュレートした(441、662及び882mg q4wk、882mg q6wk、及び1064mg q8wk)。一定用量のALを、単独で、又は7日間の経口アリピプラゾール若しくはALNCDを補充して、1、2、3、4又は6週間後に投与した。
Claims (15)
- 統合失調症を治療する方法で使用するためのキットであって、治療有効量の
約5~50mgのアリピプラゾールを含む第1の成分と;
約629~695mgのALNCDを含む第2の成分と;
アリピプラゾールラウロキシルを含む第3の成分と
を含み、
前記方法が、第1の成分の経口投与、第2の成分の筋肉内投与及び第3の成分の筋肉内投与を含み、方法の全ての成分が実質的に同時に投与される、キット。 - 第1の成分の治療有効量が約30mgである、請求項1に記載のキット。
- 第1の成分の治療有効量が約15mgである、請求項1に記載のキット。
- 第2の成分の治療有効量が約675mgである、請求項1に記載のキット。
- 第3の成分の治療有効量が約300~1500mgである、請求項1から4のいずれか一項に記載のキット。
- 第3の成分の治療有効量が441、662、882又は1064mgである、請求項1から5のいずれか一項に記載のキット。
- ALNCDが、ポリソルベート20、クエン酸ナトリウム、塩化ナトリウム、水性緩衝液及びアリピプラゾールラウロキシルの粒子の集団を含む、請求項1から6のいずれか一項に記載のキット。
- アリピプラゾールラウロキシルの粒子の集団が約175nm~約350nmの間の、体積に基づく粒子分布径(Dv50)を有する、請求項7に記載のキット。
- ALNCDが17:1の粒子のポリソルベート20に対する比を有する、請求項1から8のいずれか一項に記載のキット。
- 方法が、第1、第2及び第3の成分が実質的に同時に投与され、第1の成分が初回投与の21日以内に再び投与されないレジメンを含む、請求項1から9のいずれか一項に記載のキット。
- 方法が、第1、第2及び第3の成分が実質的に同時に投与され、成分の第2の投与が初回治療の21日後以降に行われるレジメンを含む、請求項1から10のいずれか一項に記載のキット。
- 方法が、第1、第2及び第3の成分が実質的に同時に投与され、これに第3の成分のみを投与することを含む第2の治療が続くレジメンを含む、請求項1から11のいずれか一項に記載のキット。
- 第2の治療が、初回治療の21日後以降に行われる、請求項12に記載のキット。
- 第1の成分が治療期間中に1回のみ投与される、請求項1から13のいずれか一項に記載のキット。
- 第1の成分が初回治療後21日以内に再び投与されない、請求項1から14のいずれか一項に記載のキット。
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Family Cites Families (196)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2418499A (en) | 1944-06-20 | 1947-04-08 | Du Pont | 2-alkoxymethylmercapto-thiazoles and thiazolines and a process for preparing the same |
DE1070760B (de) | 1955-11-19 | 1959-12-10 | Badische Anilin- S- Soda-Fabrik Aktiengesellschaft, Ludwigshafen / Rhein | Verfahren zur Herstellung von Azofarbstoffen |
GB849541A (en) | 1956-02-23 | 1960-09-28 | Rohm & Haas | Preparation of unsaturated cyclic urea derivatives |
DE1273533B (de) | 1962-09-08 | 1968-07-25 | Hoechst Ag | Verfahren zur Herstellung von N-(ª‡-Alkoxy-alkyl)-carbonsaeureamiden |
NL128370C (ja) | 1964-08-28 | |||
US3452034A (en) | 1967-03-09 | 1969-06-24 | American Cyanamid Co | Substituted 2-(1,3,4-thiadiazol-2-yl)-4(5)-nitroimidazoles |
US3573308A (en) | 1969-04-03 | 1971-03-30 | Hoffmann La Roche | 3-lower alkoxy methyl-3,4-dihydro-4-hydroxy-4-aryl quinazolin-2(1h) ones and related compounds |
US3957808A (en) | 1969-09-03 | 1976-05-18 | Rohm And Haas Company | 3-alkoxyisothiazoles |
US3798219A (en) | 1971-10-18 | 1974-03-19 | Warner Lambert Co | 3-(methylsulfinyl)cinnolinones and their derivatives |
US4727151A (en) | 1974-06-24 | 1988-02-23 | Interx Research Corporation | Labile quaternary ammonium salts as prodrugs |
US3998815A (en) | 1974-06-24 | 1976-12-21 | Interx Research Corporation | 1-hydrocarbonoyloxymethyl-3-carbamoyl or 3-carboethoxy-pyridinium salts |
US4204065A (en) | 1975-09-22 | 1980-05-20 | Interx Research Corporation | Soft quaternary surface active agents and method of using same |
JPS5331676A (en) | 1976-09-06 | 1978-03-25 | Mitsui Toatsu Chem Inc | Uracil derivatives and their preparation |
US4260769A (en) | 1977-04-22 | 1981-04-07 | Interx Research Corporation | 5,5-Diphenylhydantoins |
JPS54130587A (en) | 1978-03-30 | 1979-10-09 | Otsuka Pharmaceut Co Ltd | Carbostyryl derivative |
DE2960178D1 (en) | 1978-06-06 | 1981-04-09 | Hoechst Ag | New substituted phenylpiperazine derivatives, pharmaceutical compositions containing them and process for their preparation |
GB2050355A (en) | 1979-04-27 | 1981-01-07 | Sumitomo Chemical Co | 3,5-dioxo-1,2,4-triazine derivatives and their use and production |
JPS568318A (en) | 1979-06-28 | 1981-01-28 | Janssen Pharmaceutica Nv | Non oral long acting composition of haloperidol and bromperidol derivative |
DE3149010A1 (de) | 1981-12-10 | 1983-07-07 | A. Nattermann & Cie GmbH, 5000 Köln | (+)-2-(1-(2,6-dichlorphenoxy)-ethyl)-1,3- diazacyclopent-2-en, dessen herstellung und seine verwendung in pharamazeutischen praeparaten |
US4428935A (en) | 1982-05-24 | 1984-01-31 | Pfizer Inc. | Penicillanic acid dioxide prodrug |
US4448906A (en) | 1982-06-16 | 1984-05-15 | Nuodex Inc. | Surface-coating compositions |
IT1212743B (it) | 1983-05-17 | 1989-11-30 | Dompe Farmaceutici Spa | Sali quaternari di derivati di benzo[ 1,4 ]diazepinonici,pirido [1,4]benzodiazepinonici,prido [1,5]benzodiazepinonici e loro atti vita' farmacologica |
JPS602331A (ja) | 1983-06-20 | 1985-01-08 | Yoshino Kogyosho Co Ltd | 飽和ポリエステル樹脂製壜の成形方法 |
US4760057A (en) | 1983-06-23 | 1988-07-26 | Merck & Co., Inc. | (Acyloxyalkoxy)carbonyl derivatives as bioreversible prodrug moieties for primary and secondary amine functions in drugs |
DK302883D0 (da) | 1983-06-30 | 1983-06-30 | Hans Bundgaard | Allopurinol prodrugs |
US4500708A (en) | 1984-04-23 | 1985-02-19 | G. D. Serle & Co. | Benzothiazine derivatives |
JPS61171467A (ja) | 1985-01-23 | 1986-08-02 | Mitsubishi Chem Ind Ltd | N−(α−アルコキシエチル)ピロリドンの製造方法 |
DE3544134A1 (de) | 1984-12-15 | 1986-06-19 | Mitsubishi Chemical Industries Ltd., Tokio/Tokyo | Verfahren zur herstellung von n-((alpha)-alkoxyethyl) pyrrolidon |
AR240698A1 (es) | 1985-01-19 | 1990-09-28 | Takeda Chemical Industries Ltd | Procedimiento para preparar compuestos de 5-(4-(2-(5-etil-2-piridil)-etoxi)benzil)-2,4-tiazolidindiona y sus sales |
DK173350B1 (da) | 1985-02-26 | 2000-08-07 | Sankyo Co | Thiazolidinderivater, deres fremstilling og farmaceutisk paæparat indeholdende dem |
GB8513754D0 (en) | 1985-05-31 | 1985-07-03 | Jones T R | Anti-cancer quinazoline derivatives |
FR2587029B1 (fr) | 1985-09-11 | 1987-10-30 | Synthelabo | Derives de benzimidazole, leur preparation et leur application en therapeutique |
DK588486A (da) | 1985-12-09 | 1987-06-10 | Otsuka Pharma Co Ltd | Anvendelse af en forbindelse til behandling af hypoxi |
GB8607683D0 (en) | 1986-03-27 | 1986-04-30 | Ici Plc | Anti-tumor agents |
MX173362B (es) | 1987-03-02 | 1994-02-23 | Pfizer | Compuestos de piperazinil heterociclicos y procedimiento para su preparacion |
JPS63284165A (ja) | 1987-05-14 | 1988-11-21 | Sankyo Co Ltd | 5−フルオロウラシル誘導体 |
US4925860A (en) | 1987-08-05 | 1990-05-15 | E. I. Du Pont De Nemours And Company | Stable pharmaceutical composition of 3-(hydroxymethyl)-5,5-diphenylhydantoin disodium phosphate ester |
US4831031A (en) | 1988-01-22 | 1989-05-16 | Pfizer Inc. | Aryl piperazinyl-(C2 or C4) alkylene heterocyclic compounds having neuroleptic activity |
GB8809978D0 (en) | 1988-04-27 | 1988-06-02 | Ici Plc | Anti-tumour agents |
US5006528A (en) | 1988-10-31 | 1991-04-09 | Otsuka Pharmaceutical Co., Ltd. | Carbostyril derivatives |
JP2608788B2 (ja) | 1988-10-31 | 1997-05-14 | 大塚製薬 株式会社 | 精神分裂病治療剤 |
DK24089D0 (da) | 1989-01-20 | 1989-01-20 | Hans Bundgaard | Novel prodrug derivatives of biologically active agents containing hydroxyl groups or nh-acidic groups |
US5350747A (en) | 1989-07-07 | 1994-09-27 | Pfizer Inc | Heteroaryl piperazine antipsychotic agents |
WO1991000863A1 (en) | 1989-07-07 | 1991-01-24 | Pfizer Inc. | Heteroaryl piperazine antipsychotic agents |
GB9007569D0 (en) | 1990-04-04 | 1990-05-30 | Nycomed As | Carbo-nucleoside derivatives |
US5229382A (en) | 1990-04-25 | 1993-07-20 | Lilly Industries Limited | 2-methyl-thieno-benzodiazepine |
JP2800953B2 (ja) | 1990-07-06 | 1998-09-21 | 住友製薬株式会社 | 新規なイミド誘導体 |
DK238190D0 (da) | 1990-10-03 | 1990-10-03 | Lundbeck & Co As H | Depotderivater |
US5206386A (en) | 1991-03-20 | 1993-04-27 | Isp Investments Inc. | Controlled release N-substituted pyrrolidone esters and process for the use thereof |
MX9201991A (es) | 1991-05-02 | 1992-11-01 | Jonh Wyeth & Brother Limited | Derivados de piperazina y procedimiento para su preparacion. |
TW226016B (ja) | 1991-12-30 | 1994-07-01 | Sterling Winthrop Inc | |
JPH05194517A (ja) | 1992-01-16 | 1993-08-03 | Tanabe Seiyaku Co Ltd | 6−メルカプトプリン誘導体及びその製法 |
US5462934A (en) | 1992-03-09 | 1995-10-31 | Takeda Chemical Industries | Condensed heterocyclic ketone derivatives and their use |
WO1993025197A1 (en) | 1992-06-12 | 1993-12-23 | Affymax Technologies N.V. | Compositions and methods for enhanced drug delivery |
DK0590793T3 (da) | 1992-08-31 | 2000-01-31 | Sankyo Co | Oxazolidin-derivater med anti-diabetiske og anti-obesitas-egenskaber, fremstilling deraf samt deres terapeutiske anvendelse |
US5719303A (en) | 1993-03-08 | 1998-02-17 | Eisai Co., Ltd. | Phosphonic acid derivatives |
TW376319B (en) | 1993-04-28 | 1999-12-11 | Janssen Pharmaceutica Nv | Pharmaceutical composition containing risperidone pamoate and having a long acting activity for treating psychoses induced by the release of dopamine |
DE4439493A1 (de) | 1994-10-25 | 1996-05-02 | Schering Ag | Neue Chinoxalindionderivate, deren Herstellung und Verwendung in Arzneimitteln |
US5510118A (en) | 1995-02-14 | 1996-04-23 | Nanosystems Llc | Process for preparing therapeutic compositions containing nanoparticles |
EP0812318B1 (en) | 1995-02-28 | 2006-02-08 | H. Lundbeck A/S | 4-aminotetrahydrobenzisoxazole or -isothiazole compounds |
JP3571795B2 (ja) | 1995-04-18 | 2004-09-29 | 株式会社日本触媒 | N−(1−アルキルオキシアルキル)カルバメート類の気相分子内脱アルコール反応用触媒およびn−ビニルカルバメート類の製造方法 |
US7833543B2 (en) | 1995-06-07 | 2010-11-16 | Durect Corporation | High viscosity liquid controlled delivery system and medical or surgical device |
NZ332039A (en) | 1996-03-25 | 2000-06-23 | Lilly Co Eli | Method for treating pain using olanzapine and NSAIDs |
HU227454B1 (en) | 1996-03-29 | 2011-06-28 | Duphar Int Res | Piperazine and piperidine compounds, process for their preparation and pharmaceutical compositions containing the same |
PT900227E (pt) | 1996-04-30 | 2002-05-31 | Warner Lambert Co | Processo melhorado para a sintese de diesteres de ester 2,5-dioxo-4,4-difenil-imidazolidin-1-ilmetilico do acido fosforicoo |
DE19619819A1 (de) | 1996-05-16 | 1997-11-20 | Boehringer Mannheim Gmbh | Neue Thiazolidindione, Verfahren zu ihrer Herstellung und diese enthaltenden Arzneimittel |
KR100542816B1 (ko) | 1996-08-22 | 2006-01-11 | 알티피 파마 코포레이션 | 수불용성 물질의 미립자를 포함하는 조성물 및 이것의 제조 방법 |
CA2288140C (en) | 1997-04-25 | 2007-04-03 | Janssen Pharmaceutica N.V. | Farnesyltransferase inhibiting quinazolinones |
ATE253941T1 (de) | 1997-06-13 | 2003-11-15 | Cydex Inc | Zusammensetzung mit erhöhter lagerstabilität enthaltend cyclodextrin und wirkstoffe oder wirkstoff-vorstufen, die in wasserunlösliche komponenten zersetzt werden |
HUP0004534A3 (en) | 1997-09-30 | 2002-10-28 | Lilly Co Eli | Pharmaceutical formulation containing olanzapine |
UA72189C2 (uk) | 1997-11-17 | 2005-02-15 | Янссен Фармацевтика Н.В. | Фармацевтична композиція, що містить водну суспензію субмікронних ефірів 9-гідроксирисперидон жирних кислот |
US6180095B1 (en) | 1997-12-17 | 2001-01-30 | Enzon, Inc. | Polymeric prodrugs of amino- and hydroxyl-containing bioactive agents |
KR20010033811A (ko) | 1997-12-31 | 2001-04-25 | 토마스 안 빅토리아 | 2차 및 3차 아민을 함유하는 약제의 물에 용해가능한프로드럭 및 그것의 제조방법 |
US6150366A (en) | 1998-06-15 | 2000-11-21 | Pfizer Inc. | Ziprasidone formulations |
EP1114028B1 (en) | 1998-08-26 | 2006-11-29 | Aventis Pharma Limited | Aza-bicycles which modulate the inhibition of cell adhesion |
FR2783519B1 (fr) | 1998-09-23 | 2003-01-24 | Sod Conseils Rech Applic | Nouveaux derives d'amidines, leur preparation, leur application a titre de medicaments et les compositions pharmaceutiques les contenant |
GB9904275D0 (en) | 1999-02-24 | 1999-04-21 | Cancer Res Campaign Tech | Anti-cancer compounds |
US7374779B2 (en) | 1999-02-26 | 2008-05-20 | Lipocine, Inc. | Pharmaceutical formulations and systems for improved absorption and multistage release of active agents |
US6509334B1 (en) | 1999-05-04 | 2003-01-21 | American Home Products Corporation | Cyclocarbamate derivatives as progesterone receptor modulators |
US6444668B1 (en) | 1999-05-04 | 2002-09-03 | Wyeth | Combination regimens using progesterone receptor modulators |
US20060034937A1 (en) | 1999-11-23 | 2006-02-16 | Mahesh Patel | Solid carriers for improved delivery of active ingredients in pharmaceutical compositions |
AU3275301A (en) | 2000-01-28 | 2001-08-07 | Rohm And Haas Company | Enhanced propertied pharmaceuticals |
CA2311734C (en) | 2000-04-12 | 2011-03-08 | Bristol-Myers Squibb Company | Flash-melt oral dosage formulation |
TWI270545B (en) | 2000-05-24 | 2007-01-11 | Sugen Inc | Mannich base prodrugs of 3-(pyrrol-2-ylmethylidene)-2-indolinone derivatives |
US6656505B2 (en) | 2000-07-21 | 2003-12-02 | Alpharma Uspd Inc. | Method for forming an aqueous flocculated suspension |
US20030049320A1 (en) | 2000-12-18 | 2003-03-13 | Wockhardt Limited | Novel in-situ forming controlled release microcarrier delivery system |
US7053092B2 (en) | 2001-01-29 | 2006-05-30 | Otsuka Pharmaceutical Co., Ltd. | 5-HT1a receptor subtype agonist |
JP2004518726A (ja) | 2001-02-14 | 2004-06-24 | ワーナー−ランバート・カンパニー、リミテッド、ライアビリティ、カンパニー | ベンゾチアジアジンマトリックスメタロプロテイナーゼ阻害剤 |
JP2005511477A (ja) | 2001-03-19 | 2005-04-28 | プラエシス ファーマシューティカルズ インコーポレーテッド | 持続放出のための医薬調合物 |
US20060293217A1 (en) | 2001-03-19 | 2006-12-28 | Praecis Pharmaceuticals, Inc. | Pharmaceutical formulations for sustained release |
WO2002096351A2 (en) | 2001-04-03 | 2002-12-05 | Aryx Therapeutics | Ultrashort-acting opioids for transdermal application |
MY129350A (en) | 2001-04-25 | 2007-03-30 | Bristol Myers Squibb Co | Aripiprazole oral solution |
WO2002100861A1 (en) | 2001-06-13 | 2002-12-19 | Akzo Nobel N.V. | 1-(3-phenyloxypropyl)piperidine derivatives |
AR033485A1 (es) | 2001-09-25 | 2003-12-26 | Otsuka Pharma Co Ltd | Sustancia medicinal de aripiprazol de baja higroscopicidad y proceso para la preparacion de la misma |
DE60325025D1 (de) | 2002-02-15 | 2009-01-15 | Glaxo Group Ltd | Modulatoren des vanilloidrezeptors |
US6930100B2 (en) | 2002-03-20 | 2005-08-16 | Bristol-Myers Squibb Company | Phosphate prodrugs of fluoroxindoles |
EP1493448A4 (en) | 2002-04-05 | 2007-12-05 | Sankyo Co | MEDICAL COMPOSITION WITH ACAT HEMMER AND AGENT TO IMPROVE INSULIN RESISTANCE |
JP4667867B2 (ja) | 2002-08-02 | 2011-04-13 | メルク・シャープ・エンド・ドーム・コーポレイション | 置換フロ[2,3−b]ピリジン誘導体 |
EP1542668B1 (en) | 2002-08-20 | 2009-04-15 | Bristol-Myers Squibb Company | Aripiprazole complex formulation and method |
BR0314393A (pt) | 2002-09-17 | 2005-07-19 | Warner Lambert Co | Piperazinas heterocìclicas substituìdas para o tratamento de esquizofrenia |
US7148211B2 (en) | 2002-09-18 | 2006-12-12 | Genzyme Corporation | Formulation for lipophilic agents |
WO2004029054A1 (ja) | 2002-09-27 | 2004-04-08 | Sumitomo Pharmaceuticals Company, Limited | 新規アデニン化合物及びその用途 |
MXPA05002734A (es) | 2002-10-24 | 2005-05-23 | Pfizer Prod Inc | Derivados de acilo de 5- (2-(4 -(1, 2-bencisotiazol -3-il) -1-piperazinil) etil)- 6-cloro -1, 3-dihidro -2h- indol -2-ona que presentan actividad neuroleptica. |
US20040156931A1 (en) | 2002-12-18 | 2004-08-12 | Algorx | Administration of capsaicinoids |
CA2510181C (en) | 2002-12-18 | 2011-03-08 | Algorx Pharmaceuticals, Inc. | Administration of capsaicinoids |
DE10303669A1 (de) | 2003-01-28 | 2004-07-29 | Hans-Knöll-Institut für Naturstoff-Forschung e.V. | Tetraalkylammoniumsalze vom Kohlensäureestertyp, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende pharmazeutische Zusammensetzungen |
SG160211A1 (en) | 2003-04-03 | 2010-04-29 | Semafore Pharmaceuticals Inc | Pi-3 kinase inhibitor prodrugs |
CN102166359A (zh) | 2003-05-23 | 2011-08-31 | 大塚制药株式会社 | 用于治疗情感障碍的喹诺酮衍生物和情绪稳定剂 |
DE602004013331T2 (de) | 2003-07-24 | 2009-07-16 | Merial Ltd. | Vakzin-formulierungen mit einer öl-in-wasser-emulsion |
US20050032811A1 (en) | 2003-08-06 | 2005-02-10 | Josiah Brown | Methods for administering aripiprazole |
US6987111B2 (en) | 2003-08-06 | 2006-01-17 | Alkermes Controlled Therapeutics, Ii | Aripiprazole, olanzapine and haloperidol pamoate salts |
US7160888B2 (en) | 2003-08-22 | 2007-01-09 | Warner Lambert Company Llc | [1,8]naphthyridin-2-ones and related compounds for the treatment of schizophrenia |
TW200510721A (en) | 2003-08-29 | 2005-03-16 | Toshiba Kk | Color reagent, concentration measuring kit, concentration measuring method and sensor chip for use therein |
CN1870980B (zh) | 2003-10-23 | 2010-06-23 | 大冢制药株式会社 | 控释无菌阿立哌唑注射剂和方法 |
BRPI0418255A (pt) | 2003-12-31 | 2007-04-17 | Warner Lambert Co | derivados de piperazina e piperidina n-substituìdos |
PE20051096A1 (es) | 2004-02-04 | 2006-01-23 | Novartis Ag | Formas de sal de 4-(4-metilpiperazin-1-ilmetil)-n-[4-metil-3-(4-piridin-3-il)pirimidin-2-ilamino)fenil]-benzamida |
CA2556160A1 (en) | 2004-02-13 | 2005-09-01 | Pfizer Products Inc. | Therapeutic combinations of atypical antipsychotics with corticotropin releasing factor antagonists |
US7169803B2 (en) | 2004-03-15 | 2007-01-30 | Bristol-Myers Squibb Company | N-substituted prodrugs of fluorooxindoles |
CN101429200B (zh) | 2004-03-23 | 2012-05-30 | 日产化学工业株式会社 | 用作抗心律失常剂的三环苯并吡喃化合物 |
US7119214B2 (en) | 2004-04-13 | 2006-10-10 | Cephalon France | Thio-substituted tricyclic and bicyclic aromatic methanesulfinyl derivatives |
GB2413795A (en) | 2004-05-05 | 2005-11-09 | Cipla Ltd | Process for the preparation of rosiglitazone |
US20070293517A1 (en) | 2004-06-09 | 2007-12-20 | Ramot At Tel Aviv University Ltd. | Derivatives Of Chemotherapeutic Agents With A Formaldehyde Releasing Moiety |
US7405216B2 (en) | 2004-08-18 | 2008-07-29 | Solvay Pharmaceuticals, B.V. | Stable crystalline form of bifeprunox mesylate (7-[4-([1,1′-biphenyl]-3-ylmethyl)-1-piperazinyl]-2(3H)-benzoxazolone monomethanesulfonate) |
WO2006037090A2 (en) | 2004-09-28 | 2006-04-06 | Purdue Research Foundation | Drug-phosphate conjugates as prodrugs |
JP5324098B2 (ja) | 2004-11-16 | 2013-10-23 | アルケルメス ファーマ アイルランド リミテッド | 注射可能なナノ粒子のオランザピン製剤 |
WO2006082588A2 (en) | 2005-02-07 | 2006-08-10 | Pharmalight Inc. | Method and device for ophthalmic administration of active pharmaceutical ingredients |
GB0502573D0 (en) | 2005-02-08 | 2005-03-16 | Topotarget As | Therapeutic compounds |
WO2006090273A2 (en) | 2005-02-22 | 2006-08-31 | Warner-Lambert Company Llc | [1,8]naphthyridin-2-ones and related compounds with keto or hydroxyl linkers for the treatment of schizophrenia |
WO2006134864A1 (ja) | 2005-06-13 | 2006-12-21 | Dainippon Sumitomo Pharma Co., Ltd. | 可溶化型製剤 |
US20070148100A1 (en) | 2005-09-15 | 2007-06-28 | Elan Pharma International, Limited | Nanoparticulate aripiprazole formulations |
EP1777222A1 (en) | 2005-09-22 | 2007-04-25 | Galantos Pharma GmbH | Cholinergic enhancers with improved blood-brain barrier permeability for the treatment of diseases accompanied by cognitive impairment |
WO2007052104A2 (en) | 2005-10-31 | 2007-05-10 | Pfizer Products Inc. | Crystalline salts of 7-[4-(4-naphthalen-1-yl-piperazin-1-yl)-but oxy]-3,4-dihydro-1h-[1,8]naphthyridin-2-one |
WO2007059111A2 (en) | 2005-11-14 | 2007-05-24 | Entremed, Inc. | Anti-angiogenic activity of 2-methoxyestradiol in combination with anti-cancer agents |
MY149143A (en) | 2006-01-18 | 2013-07-15 | Amgen Inc | Thiazole compounds as protien kinase b (pkb) inhibitors |
TW200804359A (en) | 2006-01-19 | 2008-01-16 | Speedel Experimenta Ag | Substituted 4-phenylpiperidines |
MX2008011136A (es) | 2006-03-07 | 2008-09-08 | Squibb Bristol Myers Co | Compuestos de profamarco de pirrolotriazina anilina utiles como inhibidores de cinasa. |
BRPI0715445A2 (pt) | 2006-08-31 | 2014-05-13 | Solvay Pharm Bv | Uso de um composto de bifeprunox, e, kit de titulação |
US20090068290A1 (en) | 2006-08-31 | 2009-03-12 | Michel Bourin | Bifeprunox doses for treating schizophrenia |
US20080085888A1 (en) | 2006-09-15 | 2008-04-10 | Breining Scott R | Therapeutic Combinations |
US20090291134A1 (en) | 2006-11-21 | 2009-11-26 | Jina Pharmaceuticals, Inc. | Endoxifen methods and compositions in the treatment of psychiatric and neurodegenerative diseases |
AU2007328007A1 (en) | 2006-12-05 | 2008-06-12 | Neurogesx, Inc. | Prodrugs and methods of making and using the same |
EP2125841A1 (en) | 2006-12-13 | 2009-12-02 | Gilead Sciences, Inc. | Monophosphates as mutual prodrugs of anti-inflammatory signal transduction modulators (aistm's) and beta-agonists for the treatment of pulmonary inflammation and bronchoconstriction |
WO2008076447A2 (en) | 2006-12-15 | 2008-06-26 | Ordway Research Institute | Treatments of therapy-resistant diseases comprising drug combinations |
TWI325694B (en) | 2006-12-15 | 2010-06-01 | Ind Tech Res Inst | All digital delay locked loop |
EP1961412A1 (en) | 2006-12-27 | 2008-08-27 | LEK Pharmaceuticals D.D. | Self-microemulsifying drug delivery systems |
US20080186971A1 (en) | 2007-02-02 | 2008-08-07 | Tarari, Inc. | Systems and methods for processing access control lists (acls) in network switches using regular expression matching logic |
WO2008116024A2 (en) | 2007-03-19 | 2008-09-25 | Acadia Pharmaceuticals Inc. | Combinations of 5-ht2a inverse agonists and antagonists with antipsychotics |
JP5097265B2 (ja) | 2007-04-04 | 2012-12-12 | メルク・シャープ・エンド・ドーム・コーポレイション | 治療薬 |
JP5466147B2 (ja) | 2007-05-21 | 2014-04-09 | レビバ ファーマシューティカルズ,インコーポレーテッド | キノリノン系非定型抗精神病薬剤の組成物、合成、及び使用方法 |
WO2009003136A1 (en) | 2007-06-26 | 2008-12-31 | Rigel Pharmaceuticals, Inc. | Substituted pyrimidine-2, 4 -diamines for treating cell proliferative disorders |
US20100292316A1 (en) | 2007-07-18 | 2010-11-18 | Research Development Foundation | Improved therapeutic methods and compositions comprising chroman ring compounds |
SA08290475B1 (ar) | 2007-08-02 | 2013-06-22 | Targacept Inc | (2s، 3r)-n-(2-((3-بيردينيل)ميثيل)-1-آزا بيسيكلو[2، 2، 2]أوكت-3-يل)بنزو فيوران-2-كربوكساميد، وصور أملاحه الجديدة وطرق استخدامه |
TW200924748A (en) | 2007-09-07 | 2009-06-16 | Xenoport Inc | Masked carboxylate neopentyl sulfonyl ester cyclization release prodrugs of acamprosate, compositions thereof, and methods of use |
US8076334B2 (en) | 2007-09-20 | 2011-12-13 | Hoffmann-La Roche Inc. | Prodrugs of thyroid hormone analogs |
WO2009052467A1 (en) | 2007-10-19 | 2009-04-23 | Board Of Regents Of The University Of Texas System | Methods of identifying pi-3-kinase inhibitor resistance |
CL2008003305A1 (es) | 2007-11-06 | 2009-06-05 | M/S Panacea Biotec Ltd | Composicion inyectable que comprende un agente activo seleccionado de un grupo definido; al menos un polimero bioerosionable, al menos un solvente no toxico y opcionalmente uno o mas excipientes; proceso de preparacion; uso para tratar enfermedades mentales o cancer. |
BRPI0821408A2 (pt) | 2007-12-19 | 2015-06-16 | Janssen Pharmaceutica Nv | Regime de dosagem associado a ésteres de paliperidona injetáveis de longa ação |
US8642660B2 (en) | 2007-12-21 | 2014-02-04 | The University Of Rochester | Method for altering the lifespan of eukaryotic organisms |
US9161943B2 (en) | 2007-12-31 | 2015-10-20 | Industrial Technology Research Institute | Sustained release composition and manufacturing method thereof |
WO2009126931A2 (en) | 2008-04-11 | 2009-10-15 | Xvasive, Inc. | Combination therapy for bipolar disorder |
US20110003823A1 (en) | 2008-08-01 | 2011-01-06 | Alpha Synergy Development, Inc. | Compositions and methods for treatment of diseases and conditions associated with vasodilation and/or vascular leakage |
WO2010027921A1 (en) | 2008-09-03 | 2010-03-11 | Vertex Pharmaceuticals Incorporated | Co-crystals and pharmaceutical formulations comprising the same |
US8017515B2 (en) | 2008-12-10 | 2011-09-13 | Stats Chippac, Ltd. | Semiconductor device and method of forming compliant polymer layer between UBM and conformal dielectric layer/RDL for stress relief |
CN102356075B (zh) | 2009-01-23 | 2015-06-10 | 里格尔药品股份有限公司 | 抑制jak途径的组合物和方法 |
NZ594071A (en) | 2009-01-26 | 2013-01-25 | Egalet Ltd | Controlled release formulations comprising morphine sulphate for continuous treatment of pain |
TW201105667A (en) | 2009-05-08 | 2011-02-16 | Cytopathfinder Inc | Dihydronaphthyridinyl and related compounds for use in treating ophthalmological disorders |
US8190546B2 (en) | 2009-05-15 | 2012-05-29 | At&T Intellectual Property I, L.P. | Dependency between sources in truth discovery |
US8686009B2 (en) | 2009-06-25 | 2014-04-01 | Alkermes Pharma Ireland Limited | Prodrugs of NH-acidic compounds |
NZ597107A (en) | 2009-06-25 | 2013-12-20 | Alkermes Pharma Ireland Ltd | Heterocyclic compounds for the treatment of neurological and psychological disorders |
SG176105A1 (en) | 2009-06-26 | 2011-12-29 | Novartis Ag | 1, 3-disubstituted imidazolidin-2-one derivatives as inhibitors of cyp 17 |
WO2011053829A1 (en) | 2009-10-30 | 2011-05-05 | Janssen Pharmaceutical Nv | Dosing regimen associated with long-acting injectable paliperidone esters |
JP6076740B2 (ja) | 2010-01-07 | 2017-02-08 | アルカーメス ファーマ アイルランド リミテッド | 第四級アンモニウム塩プロドラッグ |
WO2011084848A2 (en) | 2010-01-07 | 2011-07-14 | Alkermes, Inc. | Prodrugs of heteraromatic compounds |
US20110166156A1 (en) | 2010-01-07 | 2011-07-07 | Alkermes, Inc. | Prodrugs for the Treatment of Schizophrenia and Bipolar Disease |
US20110166194A1 (en) | 2010-01-07 | 2011-07-07 | Alkermes, Inc. | Asenapine Prodrugs |
WO2011084849A1 (en) | 2010-01-07 | 2011-07-14 | Alkermes, Inc. | Diaryldiazepine prodrugs for the treatment of neurological and psychological disorders |
EP2538202A4 (en) | 2010-02-16 | 2018-03-21 | Hamamatsu Photonics K.K. | Gas concentration calculation device and gas concentration measurement module |
ES2834973T3 (es) | 2010-05-04 | 2021-06-21 | Alkermes Pharma Ireland Ltd | Procedimiento de síntesis de compuestos de lactama oxidada |
CN102260290A (zh) | 2010-05-25 | 2011-11-30 | 苏州波锐生物医药科技有限公司 | 喹喏啉酮类化合物及其在制备精神病药物中的用途 |
US8691836B2 (en) | 2010-06-18 | 2014-04-08 | Altos Therapeutics, LLC | D2 antagonists, methods of synthesis and methods of use |
US8530413B2 (en) | 2010-06-21 | 2013-09-10 | Sanofi | Heterocyclically substituted methoxyphenyl derivatives with an oxo group, processes for preparation thereof and use thereof as medicaments |
CA2802733C (en) | 2010-06-24 | 2017-11-21 | Alkermes Pharma Ireland Limited | Prodrugs of nh-acidic compounds: ester, carbonate, carbamate and phosphonate derivatives |
EP2655314B1 (en) | 2010-12-23 | 2018-02-07 | Alkermes Pharma Ireland Limited | Multi-api loading prodrugs |
EP2685979B1 (en) | 2011-03-18 | 2016-08-24 | Alkermes Pharma Ireland Limited | Injectable pharmaceutical compositions comprising a water-insoluble anti-psychotic, sorbitan laurate and polysorbate 20 |
ES2715562T3 (es) | 2011-12-15 | 2019-06-04 | Alkermes Pharma Ireland Ltd | Profármacos de compuestos de amina secundaria |
ES2764383T3 (es) | 2012-03-19 | 2020-06-03 | Alkermes Pharma Ireland Ltd | Composiciones farmacéuticas que comprenden ésteres de glicerol |
AU2013235519C1 (en) | 2012-03-19 | 2018-04-26 | Alkermes Pharma Ireland Limited | Pharmaaceutical compositions comprising fatty acid esters |
WO2013142205A1 (en) | 2012-03-19 | 2013-09-26 | Alkermes Pharma Ireland Limited | Pharmaceutical compositions comprising benzyl alcohol |
WO2014080285A2 (en) | 2012-09-19 | 2014-05-30 | Alkermes Pharma Ireland Limited | Pharmaceutical compositions having improved storage stability |
US8669281B1 (en) | 2013-03-14 | 2014-03-11 | Alkermes Pharma Ireland Limited | Prodrugs of fumarates and their use in treating various diseases |
SG10201707547TA (en) | 2013-03-14 | 2017-10-30 | Alkermes Pharma Ireland Ltd | Prodrugs of fumarates and their use in treating various deseases |
US10525057B2 (en) * | 2013-09-24 | 2020-01-07 | Otsuka Pharmaceutical Co., Ltd. | Method of providing aripiprazole to patients having impaired CYP2D6 or CYP3A4 enzyme function |
BR112016021535A8 (pt) | 2014-03-20 | 2021-07-20 | Alkermes Pharma Ireland Ltd | kit compreendendo formulações de aripiprazol tendo velocidades de injeção aumentadas útil para o tratamento de uma desordem do sistema nervoso central e uso |
US10016415B2 (en) * | 2014-08-18 | 2018-07-10 | Alkermes Pharma Ireland Limited | Aripiprazole prodrug compositions |
AU2015306910B2 (en) | 2014-08-25 | 2020-11-19 | Alkermes Pharma Ireland Limited | Crystallization process of aripiprazole derivatives in extended release formulations for treatment of schizophrenia |
US11273158B2 (en) * | 2018-03-05 | 2022-03-15 | Alkermes Pharma Ireland Limited | Aripiprazole dosing strategy |
-
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