AU2012326976B2 - Sustained-release preparation - Google Patents
Sustained-release preparation Download PDFInfo
- Publication number
- AU2012326976B2 AU2012326976B2 AU2012326976A AU2012326976A AU2012326976B2 AU 2012326976 B2 AU2012326976 B2 AU 2012326976B2 AU 2012326976 A AU2012326976 A AU 2012326976A AU 2012326976 A AU2012326976 A AU 2012326976A AU 2012326976 B2 AU2012326976 B2 AU 2012326976B2
- Authority
- AU
- Australia
- Prior art keywords
- pioglitazone
- polyethylene oxide
- sustained
- gel forming
- release preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
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- 239000003405 delayed action preparation Substances 0.000 title claims abstract description 138
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Classifications
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- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
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- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
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- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- Biophysics (AREA)
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- Organic Chemistry (AREA)
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- Neurology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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| JP2011232302 | 2011-10-21 | ||
| JP2011-232302 | 2011-10-21 | ||
| PCT/JP2012/077662 WO2013058409A1 (en) | 2011-10-21 | 2012-10-19 | Sustained-release preparation |
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| BR112014008744A2 (pt) | 2011-10-21 | 2017-04-18 | Takeda Pharmaceuticals Co | preparação de libertação prolongada, e, métodos para produzir uma preparação de liberação prolongada, e para prevenir e/ou retardar o início ou suprimir a progressão da doença de alzheimer |
| SG11201401189WA (en) | 2012-04-20 | 2014-09-26 | Gilead Sciences Inc | Benzothiazol- 6 -yl acetic acid derivatives and their use for treating an hiv infection |
| US20150141517A1 (en) * | 2013-11-15 | 2015-05-21 | Shin-Etsu Chemical Co., Ltd. | Granulated composite, rapid release tablet and method for producing same |
| KR102485766B1 (ko) | 2019-12-11 | 2023-01-09 | 한국유나이티드제약 주식회사 | 생체이용률이 향상된 피오글리타존 함유 약학조성물 |
| UY39094A (es) * | 2020-02-27 | 2021-07-30 | Hk Inno N Corp | Composición farmacéutica que comprende compuesto derivado de bencimidazol |
| JP2023066053A (ja) * | 2021-10-28 | 2023-05-15 | 東和薬品株式会社 | 放出制御医薬組成物 |
| WO2025064867A1 (en) * | 2023-09-21 | 2025-03-27 | Yuva Biosciences, Inc. | Delivery system for mitochondrial health enhancers |
Citations (3)
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|---|---|---|---|---|
| CN101269040A (zh) * | 2008-05-16 | 2008-09-24 | 北京正大绿洲医药科技有限公司 | 盐酸吡格列酮缓释滴丸及其制备方法 |
| EP2172200A1 (en) * | 2007-07-12 | 2010-04-07 | Takeda Pharmaceutical Company Limited | Coated preparation |
| US20120184584A1 (en) * | 2011-01-10 | 2012-07-19 | Zinfandel Pharmaceuticals, Inc. | Methods and drug products for treating alzheimer's disease |
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| US4810502A (en) | 1987-02-27 | 1989-03-07 | Alza Corporation | Pseudoephedrine brompheniramine therapy |
| US4820522A (en) | 1987-07-27 | 1989-04-11 | Mcneilab, Inc. | Oral sustained release acetaminophen formulation and process |
| JPH0624991A (ja) | 1991-06-20 | 1994-02-01 | Tokyo Tanabe Co Ltd | ウルソデスオキシコール酸持続性製剤 |
| JPH0624959A (ja) | 1991-10-04 | 1994-02-01 | Bayer Yakuhin Kk | 胃内浮遊型薬物徐放性固形製剤 |
| DK0661045T3 (da) | 1992-09-18 | 2002-10-28 | Yamanouchi Pharma Co Ltd | Hydrogelpræparat med forsinket frigivelse |
| JPH06316517A (ja) | 1993-02-22 | 1994-11-15 | Grelan Pharmaceut Co Ltd | 放出制御製剤 |
| AU8532798A (en) | 1997-06-13 | 1998-12-30 | Roland Bodmeier | Compounds which delay the release of active substances |
| US6191154B1 (en) * | 1998-11-27 | 2001-02-20 | Case Western Reserve University | Compositions and methods for the treatment of Alzheimer's disease, central nervous system injury, and inflammatory diseases |
| WO2003013609A1 (fr) | 2001-08-03 | 2003-02-20 | Takeda Chemical Industries, Ltd. | Medicaments a liberation continue |
| US9060941B2 (en) | 2002-09-20 | 2015-06-23 | Actavis, Inc. | Pharmaceutical formulation containing a biguanide and a thiazolidinedione derivative |
| EP2604266A1 (en) | 2002-09-20 | 2013-06-19 | Andrx Labs Llc | Novel pharmaceutical formulation containing a biguanide and a thiazolidinedione derivative |
| JP4493970B2 (ja) | 2002-10-16 | 2010-06-30 | 武田薬品工業株式会社 | 持続性製剤 |
| MY148805A (en) | 2002-10-16 | 2013-05-31 | Takeda Pharmaceutical | Controlled release preparation |
| IN192749B (cg-RX-API-DMAC7.html) | 2002-11-15 | 2004-05-15 | Ranbaxy Lab Ltd | |
| US7442387B2 (en) | 2003-03-06 | 2008-10-28 | Astellas Pharma Inc. | Pharmaceutical composition for controlled release of active substances and manufacturing method thereof |
| EP1607088B1 (en) | 2003-03-17 | 2019-02-27 | Takeda Pharmaceutical Company Limited | Controlled release composition |
| JP4933033B2 (ja) | 2003-03-17 | 2012-05-16 | 武田薬品工業株式会社 | 放出制御組成物 |
| JP2005015477A (ja) | 2003-06-06 | 2005-01-20 | Takeda Chem Ind Ltd | 固形製剤 |
| CA2528164A1 (en) | 2003-06-06 | 2004-12-16 | Takeda Pharmaceutical Company Limited | Solid preparation |
| US20060003002A1 (en) | 2003-11-03 | 2006-01-05 | Lipocine, Inc. | Pharmaceutical compositions with synchronized solubilizer release |
| WO2005099760A1 (ja) | 2004-04-14 | 2005-10-27 | Takeda Pharmaceutical Company Limited | 固形製剤 |
| MX2007002375A (es) | 2004-08-31 | 2007-04-23 | Pfizer Prod Inc | Formas de dosificacion de liberacion controlada combinando liberacion inmediata y liberacion sostenida de un farmaco de baja solubilidad. |
| TW200803851A (en) | 2005-09-22 | 2008-01-16 | Sb Pharmco Inc | Pharmaceutical composition for improvement of cognitive function |
| WO2007054976A2 (en) | 2005-11-08 | 2007-05-18 | Panacea Biotec Ltd. | Lipid based controlled release pharmaceutical composition |
| AU2006328328B2 (en) | 2005-12-22 | 2012-08-30 | Takeda Pharmaceutical Company Limited | Solid preparation containing an insulin sensitizer |
| AU2007232836B2 (en) | 2006-03-30 | 2012-12-06 | Nippon Zoki Pharmaceutical Co., Ltd. | Solid pharmaceutical preparation |
| JP2009534292A (ja) | 2006-04-27 | 2009-09-24 | 武田薬品工業株式会社 | 塩酸ピオグリタゾンを有するアンジオテンシンｉｉ拮抗薬の医薬組成物 |
| DK2120878T3 (da) | 2007-02-09 | 2014-11-03 | Alphapharm Pty Ltd | Doseringsform indeholdende to aktive farmaceutiske ingredienser i forskellige fysiske former |
| US8445190B2 (en) | 2008-09-30 | 2013-05-21 | The Trustees Of The University Of Pennsylvania | Method of inhibiting biomaterial-induced procoagulant activity using complement inhibitors |
| TWI478712B (zh) | 2008-09-30 | 2015-04-01 | Astellas Pharma Inc | 釋控性醫藥組成物 |
| WO2011049309A2 (ko) | 2009-10-09 | 2011-04-28 | 영진약품공업 주식회사 | 속효성과 지속성을 동시에 갖는 약제학적 조성물 |
| JP2011232302A (ja) | 2010-04-30 | 2011-11-17 | Ricoh Elemex Corp | 画像検査方法及び画像検査装置 |
| CN101884627B (zh) * | 2010-07-07 | 2012-01-25 | 青岛黄海制药有限责任公司 | 盐酸吡格列酮胃内滞留缓释片及其制备方法 |
| BR112014008744A2 (pt) | 2011-10-21 | 2017-04-18 | Takeda Pharmaceuticals Co | preparação de libertação prolongada, e, métodos para produzir uma preparação de liberação prolongada, e para prevenir e/ou retardar o início ou suprimir a progressão da doença de alzheimer |
| KR20160056691A (ko) | 2014-11-12 | 2016-05-20 | 삼성에스디아이 주식회사 | 이차전지 |
-
2012
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- 2012-10-19 NZ NZ624275A patent/NZ624275A/en not_active IP Right Cessation
-
2014
- 2014-04-11 TN TNP2014000152A patent/TN2014000152A1/en unknown
- 2014-04-13 IL IL232114A patent/IL232114A0/en unknown
- 2014-04-15 DO DO2014000077A patent/DOP2014000077A/es unknown
- 2014-04-17 CL CL2014000992A patent/CL2014000992A1/es unknown
- 2014-04-29 EC ECSP14013328 patent/ECSP14013328A/es unknown
- 2014-04-29 ZA ZA2014/03103A patent/ZA201403103B/en unknown
- 2014-05-09 CR CR20140213A patent/CR20140213A/es unknown
- 2014-05-14 CO CO14103846A patent/CO6960544A2/es unknown
- 2014-05-15 MA MA37034A patent/MA35717B1/fr unknown
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2172200A1 (en) * | 2007-07-12 | 2010-04-07 | Takeda Pharmaceutical Company Limited | Coated preparation |
| CN101269040A (zh) * | 2008-05-16 | 2008-09-24 | 北京正大绿洲医药科技有限公司 | 盐酸吡格列酮缓释滴丸及其制备方法 |
| US20120184584A1 (en) * | 2011-01-10 | 2012-07-19 | Zinfandel Pharmaceuticals, Inc. | Methods and drug products for treating alzheimer's disease |
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