NO328243B1 - 2-metyl-tieno-benzodiazepinpamoatsalt eller solvat derav - Google Patents
2-metyl-tieno-benzodiazepinpamoatsalt eller solvat derav Download PDFInfo
- Publication number
- NO328243B1 NO328243B1 NO20011583A NO20011583A NO328243B1 NO 328243 B1 NO328243 B1 NO 328243B1 NO 20011583 A NO20011583 A NO 20011583A NO 20011583 A NO20011583 A NO 20011583A NO 328243 B1 NO328243 B1 NO 328243B1
- Authority
- NO
- Norway
- Prior art keywords
- olanzapine
- pamoate
- solvate
- added
- stirred
- Prior art date
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- WBHHMMIMDMUBKC-XLNAKTSKSA-N ricinelaidic acid Chemical class CCCCCC[C@@H](O)C\C=C\CCCCCCCC(O)=O WBHHMMIMDMUBKC-XLNAKTSKSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- 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
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- 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
- A61P25/22—Anxiolytics
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Psychiatry (AREA)
- Anesthesiology (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US16376898A | 1998-09-30 | 1998-09-30 | |
| US09/163,769 US6169084B1 (en) | 1997-09-30 | 1998-09-30 | 2-methyl-thieno-benzodiazepine formulation |
| PCT/US1999/006417 WO2000018408A1 (en) | 1998-09-30 | 1999-03-24 | 2-methyl-thieno-benzodiazepine formulation |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO20011583D0 NO20011583D0 (no) | 2001-03-28 |
| NO20011583L NO20011583L (no) | 2001-03-28 |
| NO328243B1 true NO328243B1 (no) | 2010-01-11 |
Family
ID=26859927
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20011583A NO328243B1 (no) | 1998-09-30 | 2001-03-28 | 2-metyl-tieno-benzodiazepinpamoatsalt eller solvat derav |
Country Status (28)
| Country | Link |
|---|---|
| EP (1) | EP1119359B1 (sk) |
| JP (1) | JP4551988B2 (sk) |
| CN (1) | CN1146422C (sk) |
| AT (2) | ATE267602T1 (sk) |
| AU (1) | AU759751B2 (sk) |
| BR (1) | BR9914156A (sk) |
| CA (1) | CA2344873A1 (sk) |
| CZ (1) | CZ302367B6 (sk) |
| DE (2) | DE69935873T2 (sk) |
| DK (2) | DK1119359T3 (sk) |
| EA (1) | EA002580B1 (sk) |
| ES (2) | ES2221376T3 (sk) |
| GE (1) | GEP20094818B (sk) |
| HK (1) | HK1041199B (sk) |
| HR (1) | HRP20010238B1 (sk) |
| HU (1) | HU227400B1 (sk) |
| ID (1) | ID29574A (sk) |
| IL (2) | IL141766A0 (sk) |
| MY (1) | MY126476A (sk) |
| NO (1) | NO328243B1 (sk) |
| NZ (1) | NZ510208A (sk) |
| PL (1) | PL196821B1 (sk) |
| PT (2) | PT1468689E (sk) |
| SK (1) | SK285944B6 (sk) |
| TR (1) | TR200100885T2 (sk) |
| TW (1) | TW577890B (sk) |
| UA (1) | UA66872C2 (sk) |
| WO (1) | WO2000018408A1 (sk) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK1246827T3 (da) * | 1999-12-28 | 2005-05-23 | Cipla Ltd | Nye polymorfe former af olanzapin |
| US7022698B2 (en) | 1999-12-28 | 2006-04-04 | U & I Pharmaceuticals, Ltd. | Pharmaceutical compositions containing new polymorphic forms of olanzapine and uses thereof |
| PL196814B1 (pl) * | 2002-05-17 | 2008-02-29 | Inst Farmaceutyczny | Sposób wytwarzania odmiany polimorficznej I olanzapiny i jej solwaty |
| HU226410B1 (en) * | 2003-04-22 | 2008-11-28 | Egis Gyogyszergyar Nyilvanosan | Novel polymorphous forms of olanzapine hydrochlorides, process for producing them, use thereof and pharmaceutical compositions containing them |
| US6987111B2 (en) * | 2003-08-06 | 2006-01-17 | Alkermes Controlled Therapeutics, Ii | Aripiprazole, olanzapine and haloperidol pamoate salts |
| ES2289974T1 (es) * | 2004-07-14 | 2008-02-16 | Shasun Chemicals And Drugs Limited | Metodo mejorado para producir la forma i de la olanzapina. |
| ES2253091B1 (es) * | 2004-07-27 | 2007-02-01 | Inke, S.A. | Solvato mixto de olanzapina, procedimiento para su obtencion y procedimiento de obtencion de la forma i de olanzapina a partir del mismo. |
| KR20130030305A (ko) * | 2004-11-16 | 2013-03-26 | 엘란 파마 인터내셔널 리미티드 | 주사가능한 나노입자형 올란자핀 제형 |
| US20090155331A1 (en) * | 2005-11-16 | 2009-06-18 | Elan Pharma International Limited | Injectable nanoparticulate olanzapine formulations |
| US7932249B2 (en) * | 2005-01-05 | 2011-04-26 | Eli Lilly And Company | Olanzapine pamoate dihydrate |
| CZ299218B6 (cs) * | 2006-11-07 | 2008-05-21 | Zentiva, A. S. | Kompozice depotních olanzapinových injekcních systému |
| FR2927965B1 (fr) * | 2008-02-22 | 2010-06-04 | Valeo Materiaux De Friction Sa | Procede de fabrication d'un materiau de friction et notamment d'une couronne de friction d'embrayage. |
| WO2011060352A1 (en) * | 2009-11-16 | 2011-05-19 | Ipsen Pharma S.A.S. | Pharmaceutical compositions of melanocortin receptor ligands |
| WO2011091142A2 (en) * | 2010-01-20 | 2011-07-28 | Teva Pharmaceutical Industries Ltd. | Crystalline and amorphous forms of olanzapine pamoate |
| JP5893616B2 (ja) | 2010-10-18 | 2016-03-23 | 大日本住友製薬株式会社 | 注射用徐放性製剤 |
| EP2956456B1 (en) | 2013-02-13 | 2017-07-12 | Neuland Laboratories Ltd | A process for preparation of olanzapine pamoate |
| CN105044231B (zh) * | 2015-06-27 | 2022-09-13 | 万特制药(海南)有限公司 | 一种分离测定奥氮平双羟萘酸盐一水合物有关物质的方法 |
| CA3057438A1 (en) * | 2017-03-20 | 2018-09-27 | Teva Pharmaceuticals International Gmbh | Sustained release olanzapine formulaitons |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2095499A1 (en) * | 1992-05-08 | 1993-11-09 | Petrus J. M. Van Den Oetelaar | Depot preparation |
| DK0669128T3 (da) * | 1992-11-17 | 2000-06-19 | Yoshitomi Pharmaceutical | Sustained-release mikrosfære indeholdende antipsykotikum og fremgangsmåde til at fremstille samme |
| 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 |
| EG23659A (en) * | 1995-03-24 | 2007-03-26 | Lilly Co Eli | Process and crystal forms of methyl-thieno-benzodiazepine |
| US5891461A (en) * | 1995-09-14 | 1999-04-06 | Cygnus, Inc. | Transdermal administration of olanzapine |
| BR9711541A (pt) * | 1996-09-23 | 1999-08-24 | Lilly Co Eli | Dihidrato d de olanzapina |
| UA73715C2 (en) * | 1997-09-30 | 2005-09-15 | Lilly Co Eli | Pharmaceutically acceptable formulation of olanzapine pamoate and its use for treatment |
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