CN111454207B - 用于治疗精神分裂症的缓释制剂中阿立哌唑衍生物的结晶方法 - Google Patents
用于治疗精神分裂症的缓释制剂中阿立哌唑衍生物的结晶方法 Download PDFInfo
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- CN111454207B CN111454207B CN202010375290.3A CN202010375290A CN111454207B CN 111454207 B CN111454207 B CN 111454207B CN 202010375290 A CN202010375290 A CN 202010375290A CN 111454207 B CN111454207 B CN 111454207B
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- aripiprazole
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Psychiatry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Quinoline Compounds (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010375290.3A CN111454207B (zh) | 2014-08-25 | 2015-08-24 | 用于治疗精神分裂症的缓释制剂中阿立哌唑衍生物的结晶方法 |
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462041341P | 2014-08-25 | 2014-08-25 | |
| US62/041,341 | 2014-08-25 | ||
| PCT/US2015/046525 WO2016032950A1 (en) | 2014-08-25 | 2015-08-24 | Crystallization process of aripiprazole derivatives in extended release formulations for treatment of schizophrenia |
| CN202010375290.3A CN111454207B (zh) | 2014-08-25 | 2015-08-24 | 用于治疗精神分裂症的缓释制剂中阿立哌唑衍生物的结晶方法 |
| CN201580057857.XA CN107106556B (zh) | 2014-08-25 | 2015-08-24 | 用于治疗精神分裂症的缓释制剂中阿立哌唑衍生物的结晶方法 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201580057857.XA Division CN107106556B (zh) | 2014-08-25 | 2015-08-24 | 用于治疗精神分裂症的缓释制剂中阿立哌唑衍生物的结晶方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111454207A CN111454207A (zh) | 2020-07-28 |
| CN111454207B true CN111454207B (zh) | 2024-10-18 |
Family
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Family Applications (2)
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| CN202010375290.3A Active CN111454207B (zh) | 2014-08-25 | 2015-08-24 | 用于治疗精神分裂症的缓释制剂中阿立哌唑衍生物的结晶方法 |
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| CA2885196C (en) | 2012-09-19 | 2021-06-22 | Alkermes Pharma Ireland Limited | Pharmaceutical compositions having improved storage stability |
| US10016415B2 (en) | 2014-08-18 | 2018-07-10 | Alkermes Pharma Ireland Limited | Aripiprazole prodrug compositions |
| MA55917A (fr) * | 2014-08-25 | 2022-03-16 | Alkermes Pharma Ireland Ltd | Procédé de cristallisation de dérivés d'aripiprazole dans des formulations à libération prolongée pour le traitement de la schizophrénie |
| WO2016181406A1 (en) * | 2015-05-08 | 2016-11-17 | Davuluri Ramamohan Rao | Improved process for the preparation of aripiprazole with reduced particle size |
| WO2018104953A1 (en) * | 2016-12-07 | 2018-06-14 | Msn Laboratories Private Limited, R&D Center | Improved process for the preparation of 7-{4-[4-(2,3-dichlorophenyl)-piperazin-1-yl]butoxy}-2oxo-3,4-dihydro-2h-quinolin-1-yl)methyl dodecanoate |
| JP7246364B2 (ja) | 2017-07-28 | 2023-03-27 | インテルキム、ソシエダッド アノニマ | アリピプラゾールラウロキシルの調製方法 |
| CN110218209B (zh) * | 2018-03-02 | 2022-09-30 | 上海现代药物制剂工程研究中心有限公司 | 一种依匹哌唑月桂酸酯的晶型a、其制备方法及应用 |
| US11273158B2 (en) | 2018-03-05 | 2022-03-15 | Alkermes Pharma Ireland Limited | Aripiprazole dosing strategy |
| CN113105389B (zh) * | 2021-04-16 | 2022-04-08 | 江苏海洋大学 | 一种阿立哌唑药物共晶及其制备方法 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5510118A (en) * | 1995-02-14 | 1996-04-23 | Nanosystems Llc | Process for preparing therapeutic compositions containing nanoparticles |
| CN103561746A (zh) * | 2011-03-18 | 2014-02-05 | 奥克梅斯制药爱尔兰有限公司 | 包含脱水山梨糖醇酯的药物组合物 |
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| 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 |
| US20050032811A1 (en) | 2003-08-06 | 2005-02-10 | Josiah Brown | Methods for administering aripiprazole |
| AU2004285448C1 (en) * | 2003-10-23 | 2021-08-19 | Otsuka Pharmaceutical Co., Ltd. | Controlled release sterile injectable aripiprazole formulation and method |
| TWI371274B (en) * | 2003-10-23 | 2012-09-01 | Bristol Myers Squibb Co | Process for making sterile aripiprazole of desired mean particle size |
| SI2234617T2 (sl) | 2007-12-19 | 2025-05-30 | Janssen Pharmaceutica Nv | Režim odmerjanja v zvezi z dolgodelujočimi paliperidonijevimi estri za injiciranje |
| 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 |
| EP2445502B2 (en) * | 2009-06-25 | 2022-09-28 | Alkermes Pharma Ireland Limited | Heterocyclic compounds for the treatment of neurological and psychological disorders |
| WO2012077134A1 (en) * | 2010-12-07 | 2012-06-14 | Ind-Swift Laboratories Limted | Process for preparing aripiprazole polymorphs |
| CA2824045C (en) * | 2011-01-07 | 2019-04-09 | Neodyne Biosciences, Inc. | Wound or skin treatment devices and methods |
| US10004807B2 (en) * | 2012-03-19 | 2018-06-26 | Alkermes Pharma Ireland Limited | Pharmaceutical compositions comprising fatty acid esters |
| CA2885196C (en) * | 2012-09-19 | 2021-06-22 | Alkermes Pharma Ireland Limited | Pharmaceutical compositions having improved storage stability |
| MA55917A (fr) * | 2014-08-25 | 2022-03-16 | Alkermes Pharma Ireland Ltd | Procédé de cristallisation de dérivés d'aripiprazole dans des formulations à libération prolongée pour le traitement de la schizophrénie |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5510118A (en) * | 1995-02-14 | 1996-04-23 | Nanosystems Llc | Process for preparing therapeutic compositions containing nanoparticles |
| CN103561746A (zh) * | 2011-03-18 | 2014-02-05 | 奥克梅斯制药爱尔兰有限公司 | 包含脱水山梨糖醇酯的药物组合物 |
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