TWI405581B - 蛋白質或胜肽持續釋放給藥之組合物 - Google Patents
蛋白質或胜肽持續釋放給藥之組合物 Download PDFInfo
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- TWI405581B TWI405581B TW098103813A TW98103813A TWI405581B TW I405581 B TWI405581 B TW I405581B TW 098103813 A TW098103813 A TW 098103813A TW 98103813 A TW98103813 A TW 98103813A TW I405581 B TWI405581 B TW I405581B
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- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
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- A61K47/60—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
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- 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
- A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
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- A—HUMAN NECESSITIES
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- 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
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- Epidemiology (AREA)
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- Proteomics, Peptides & Aminoacids (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hematology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Obesity (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
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| TW (1) | TWI405581B (enExample) |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| TWI816381B (zh) * | 2022-04-28 | 2023-09-21 | 樸心有限公司 | 使用生長因子來治療肺纖維化 |
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US7731947B2 (en) | 2003-11-17 | 2010-06-08 | Intarcia Therapeutics, Inc. | Composition and dosage form comprising an interferon particle formulation and suspending vehicle |
| WO2006083761A2 (en) | 2005-02-03 | 2006-08-10 | Alza Corporation | Solvent/polymer solutions as suspension vehicles |
| US11246913B2 (en) | 2005-02-03 | 2022-02-15 | Intarcia Therapeutics, Inc. | Suspension formulation comprising an insulinotropic peptide |
| US8852638B2 (en) | 2005-09-30 | 2014-10-07 | Durect Corporation | Sustained release small molecule drug formulation |
| MX2008014870A (es) | 2006-05-30 | 2009-02-12 | Intarcia Therapeutics Inc | Modulador de flujo para sistema de suministro osmotico con canal interno de dos piezas. |
| MX2009001114A (es) | 2006-08-09 | 2009-02-10 | Intarcia Therapeutics Inc | Sistemas de suministro osmotico y ensambles de piston. |
| CN104000779A (zh) | 2007-04-23 | 2014-08-27 | 精达制药公司 | 促胰岛素释放肽的混悬制剂及其应用 |
| CA2687979C (en) | 2007-05-25 | 2017-07-04 | Tolmar Therapeutics, Inc. | Sustained delivery formulations of risperidone compounds |
| CA2726861C (en) | 2008-02-13 | 2014-05-27 | Intarcia Therapeutics, Inc. | Devices, formulations, and methods for delivery of multiple beneficial agents |
| DK2462246T3 (da) | 2009-09-28 | 2017-11-06 | Intarcia Therapeutics Inc | Hurtig etablering og/eller afslutning af væsentlig steady-state-lægemiddelafgivelse |
| US9272044B2 (en) | 2010-06-08 | 2016-03-01 | Indivior Uk Limited | Injectable flowable composition buprenorphine |
| GB2481017B (en) | 2010-06-08 | 2015-01-07 | Rb Pharmaceuticals Ltd | Microparticle buprenorphine suspension |
| US20120208755A1 (en) | 2011-02-16 | 2012-08-16 | Intarcia Therapeutics, Inc. | Compositions, Devices and Methods of Use Thereof for the Treatment of Cancers |
| UA113626C2 (xx) | 2011-06-02 | 2017-02-27 | Композиція для лікування діабету, що містить кон'югат інсуліну тривалої дії та кон'югат інсулінотропного пептиду тривалої дії | |
| GB201404139D0 (en) | 2014-03-10 | 2014-04-23 | Rb Pharmaceuticals Ltd | Sustained release buprenorphine solution formulations |
| WO2015183984A2 (en) * | 2014-05-28 | 2015-12-03 | Stealth Peptides International, Inc. | Therapeutic compositions including tocopherol and uses thereof |
| US9889085B1 (en) | 2014-09-30 | 2018-02-13 | Intarcia Therapeutics, Inc. | Therapeutic methods for the treatment of diabetes and related conditions for patients with high baseline HbA1c |
| US10925639B2 (en) | 2015-06-03 | 2021-02-23 | Intarcia Therapeutics, Inc. | Implant placement and removal systems |
| MA53353A (fr) | 2016-05-16 | 2021-06-09 | Intarcia Therapeutics Inc | Polypeptides sélectifs pour le récepteur du glucagon et méthodes pour leur utilisation |
| USD860451S1 (en) | 2016-06-02 | 2019-09-17 | Intarcia Therapeutics, Inc. | Implant removal tool |
| USD840030S1 (en) | 2016-06-02 | 2019-02-05 | Intarcia Therapeutics, Inc. | Implant placement guide |
| KR20190104039A (ko) | 2017-01-03 | 2019-09-05 | 인타르시아 세라퓨틱스 인코포레이티드 | Glp-1 수용체 효능제의 연속적인 투여 및 약물의 동시-투여를 포함하는 방법 |
| EP3620494A1 (en) | 2018-09-06 | 2020-03-11 | Holland Novochem Technical Coatings B.V. | Rheology modifier and compatibilizer |
| CN112679580B (zh) * | 2021-01-14 | 2022-12-16 | 南方海洋科学与工程广东省实验室(湛江) | 促骨发育的方格星虫低聚肽及其制备方法和应用 |
| CN112661811B (zh) * | 2021-01-21 | 2022-10-21 | 南方海洋科学与工程广东省实验室(湛江) | 一种降压肽、长效降压肽及其制备方法 |
| KR20250077606A (ko) * | 2022-07-12 | 2025-05-30 | 레인 테라퓨틱스, 인크. | 변형된 카베올린-1 펩타이드 제형 그리고 이의 제조 방법 및 용도 |
| WO2025108545A1 (en) * | 2023-11-22 | 2025-05-30 | Danmarks Tekniske Universitet | Delivery of nucleotides from injectable biomaterial |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5747058A (en) * | 1995-06-07 | 1998-05-05 | Southern Biosystems, Inc. | High viscosity liquid controlled delivery system |
| US20080020016A1 (en) * | 2006-07-11 | 2008-01-24 | Quest Pharmaceutical Services, Llc | Pharmaceutical compositions for sustained release delivery of peptides |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK1006935T3 (da) * | 1995-06-07 | 2005-06-06 | Durect Corp | Styret afgivelsessystem med en væske med höj viskositet |
| US6413536B1 (en) * | 1995-06-07 | 2002-07-02 | Southern Biosystems, Inc. | High viscosity liquid controlled delivery system and medical or surgical device |
| US5968542A (en) | 1995-06-07 | 1999-10-19 | Southern Biosystems, Inc. | High viscosity liquid controlled delivery system as a device |
| IL118003A0 (en) * | 1996-04-23 | 1996-08-04 | Yeda Res & Dev | Novel vip fragments and pharmaceutical compositions comprising them |
| US5792477A (en) * | 1996-05-07 | 1998-08-11 | Alkermes Controlled Therapeutics, Inc. Ii | Preparation of extended shelf-life biodegradable, biocompatible microparticles containing a biologically active agent |
| US6051558A (en) | 1997-05-28 | 2000-04-18 | Southern Biosystems, Inc. | Compositions suitable for controlled release of the hormone GnRH and its analogs |
| US20060025328A1 (en) * | 1997-05-28 | 2006-02-02 | Burns Patrick J | Compositions suitable for controlled release of the hormone GnRH and its analogs |
| AU5911101A (en) | 2000-04-19 | 2001-10-30 | Genentech Inc | Sustained release formulations |
| IL159048A0 (en) * | 2001-06-21 | 2004-05-12 | Genentech Inc | Sustained release formulation |
| MXPA06012980A (es) * | 2004-05-10 | 2007-06-12 | Nastech Pharm Co | Composiciones y metodos para el suministro mucosal mejorado de la hormona paratiroidea. |
| CA2567405A1 (en) * | 2004-05-25 | 2005-12-08 | Stryker Corporation | Use of morphogenic proteins for treating cartilage defects |
| ITBO20040485A1 (it) * | 2004-07-30 | 2004-10-30 | Magneti Marelli Holding S P A | Pompa carburante ad attuazione idraulica per un motore a combustione interna |
| WO2009100222A1 (en) * | 2008-02-08 | 2009-08-13 | Qps Llc | Non-polymeric compositions for controlled drug delivery |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5747058A (en) * | 1995-06-07 | 1998-05-05 | Southern Biosystems, Inc. | High viscosity liquid controlled delivery system |
| US20080020016A1 (en) * | 2006-07-11 | 2008-01-24 | Quest Pharmaceutical Services, Llc | Pharmaceutical compositions for sustained release delivery of peptides |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI816381B (zh) * | 2022-04-28 | 2023-09-21 | 樸心有限公司 | 使用生長因子來治療肺纖維化 |
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| CN102231981A (zh) | 2011-11-02 |
| CA2714506A1 (en) | 2009-08-13 |
| TW200936168A (en) | 2009-09-01 |
| JP2011511087A (ja) | 2011-04-07 |
| AU2009212367A1 (en) | 2009-08-13 |
| WO2009100216A1 (en) | 2009-08-13 |
| JP5718058B2 (ja) | 2015-05-13 |
| AU2009212367B2 (en) | 2013-08-01 |
| US20090202481A1 (en) | 2009-08-13 |
| CA2714506C (en) | 2016-06-07 |
| EP2254559A1 (en) | 2010-12-01 |
| EP2254559B1 (en) | 2018-10-10 |
| EP2254559A4 (en) | 2013-01-09 |
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