CA2289196C - Sustained-release delayed gels - Google Patents
Sustained-release delayed gels Download PDFInfo
- Publication number
- CA2289196C CA2289196C CA002289196A CA2289196A CA2289196C CA 2289196 C CA2289196 C CA 2289196C CA 002289196 A CA002289196 A CA 002289196A CA 2289196 A CA2289196 A CA 2289196A CA 2289196 C CA2289196 C CA 2289196C
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- pharmaceutical formulation
- sustained
- biologically active
- release
- active agent
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Classifications
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- 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
- 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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- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
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- A—HUMAN NECESSITIES
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A61P3/04—Anorexiants; Antiobesity agents
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P3/06—Antihyperlipidemics
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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
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
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- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- Epidemiology (AREA)
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- Hematology (AREA)
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- Endocrinology (AREA)
- Pain & Pain Management (AREA)
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- Child & Adolescent Psychology (AREA)
- Toxicology (AREA)
- Vascular Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US85797397A | 1997-05-16 | 1997-05-16 | |
| US08/857,973 | 1997-05-16 | ||
| US91290297A | 1997-08-15 | 1997-08-15 | |
| US08/912,902 | 1997-08-15 | ||
| PCT/US1998/010013 WO1998051348A2 (en) | 1997-05-16 | 1998-05-18 | Sustained-release delayed gels |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2289196A1 CA2289196A1 (en) | 1998-11-19 |
| CA2289196C true CA2289196C (en) | 2007-08-07 |
Family
ID=27127437
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002289196A Expired - Fee Related CA2289196C (en) | 1997-05-16 | 1998-05-18 | Sustained-release delayed gels |
Country Status (18)
| Country | Link |
|---|---|
| EP (1) | EP0981374B1 (enExample) |
| JP (1) | JP2001525826A (enExample) |
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Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2003200609B2 (en) * | 1998-05-18 | 2006-02-23 | Amgen Inc. | Biodegradable sustained-release alginate gels |
| US6432449B1 (en) * | 1998-05-18 | 2002-08-13 | Amgen Inc. | Biodegradable sustained-release alginate gels |
| JP2000256216A (ja) * | 1999-03-04 | 2000-09-19 | Meiji Milk Prod Co Ltd | ゲル組成物 |
| US7582311B1 (en) | 1999-10-15 | 2009-09-01 | Genentech, Inc. | Injection vehicle for polymer-based formulations |
| US7651703B2 (en) | 1999-10-15 | 2010-01-26 | Genentech, Inc. | Injection vehicle for polymer-based formulations |
| EP1233751A1 (en) * | 1999-11-29 | 2002-08-28 | ADVANCED RESEARCH AND TECHNOLOGY INSTITUTE, Inc. | Sustained percutaneous delivery of a biologically active substance |
| FR2823119B1 (fr) * | 2001-04-05 | 2004-02-20 | Seppic Sa | Adjuvant d'immunite contenant un cation metallique complexe et vaccin le contenant |
| MXPA05004299A (es) * | 2002-10-25 | 2005-08-03 | Pfizer Prod Inc | Formulacion de liberacion prolongada de agentes activos arilheterociclicos en forma de suspension. |
| CN101309688B (zh) * | 2005-05-23 | 2016-06-22 | 自然选择国际公司 | 持续释放β-丙氨酸的组合物和方法 |
| US20070202186A1 (en) * | 2006-02-22 | 2007-08-30 | Iscience Interventional Corporation | Apparatus and formulations for suprachoroidal drug delivery |
| JP5107585B2 (ja) * | 2007-01-29 | 2012-12-26 | 株式会社 メドレックス | 低温充填ゼリー組成物とその製造方法 |
| EP1985286A1 (en) * | 2007-04-24 | 2008-10-29 | Biocompatibles UK Limited | Microspheres for treatment of brain tumours |
| CN106214321B (zh) | 2010-10-15 | 2018-08-28 | 科尼尔赛德生物医学公司 | 用于进入眼睛的装置 |
| EA034963B1 (ru) | 2012-11-08 | 2020-04-13 | Клиасайд Байомедикал, Инк. | Способ лечения расстройства заднего сегмента глаза |
| CN105246529B (zh) | 2013-05-03 | 2019-06-14 | 科尼尔赛德生物医学公司 | 用于眼部注射的设备和方法 |
| US10010447B2 (en) | 2013-12-18 | 2018-07-03 | Novartis Ag | Systems and methods for subretinal delivery of therapeutic agents |
| EP3157598A4 (en) | 2014-06-20 | 2018-05-16 | Clearside Biomedical, Inc. | Variable diameter cannula and methods for controlling insertion depth for medicament delivery |
| US10390901B2 (en) | 2016-02-10 | 2019-08-27 | Clearside Biomedical, Inc. | Ocular injection kit, packaging, and methods of use |
| JP2019514581A (ja) | 2016-05-02 | 2019-06-06 | クリアサイド バイオメディカル，インコーポレイテッド | 眼の薬物送達のためのシステムおよび方法 |
| CN110177527B (zh) | 2016-08-12 | 2022-02-01 | 科尼尔赛德生物医学公司 | 用于调节药剂递送用针的插入深度的装置和方法 |
| US12090294B2 (en) | 2017-05-02 | 2024-09-17 | Georgia Tech Research Corporation | Targeted drug delivery methods using a microneedle |
| WO2019234010A1 (en) * | 2018-06-04 | 2019-12-12 | Spermvital As | Functionalized kit for preparing hydrogels |
| EP3878476B1 (en) * | 2018-11-06 | 2025-10-01 | National Cancer Center | Alginic acid-based injectable hydrogel system |
| JP2022550457A (ja) * | 2019-10-01 | 2022-12-01 | ブリリアン・ファーマ・インコーポレイテッド | 肥満の処置又は防止及び体重管理の方法 |
| EP4130235A4 (en) * | 2020-03-26 | 2024-07-10 | Osaka University | SUPPORT BATH FOR THREE-DIMENSIONAL (3D) TISSUE CULTURE |
| CN114533653B (zh) * | 2020-11-26 | 2023-12-22 | 上海凯茂生物医药有限公司 | 一种人促红素杂合Fc融合蛋白相变型制剂及其制备方法 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5416979B2 (enExample) * | 1972-01-08 | 1979-06-26 | ||
| US4241099A (en) * | 1979-02-26 | 1980-12-23 | Tiemstra Peter J | Pectin formulations, products and methods having delayed-action acidulants |
| US4690682A (en) * | 1983-04-15 | 1987-09-01 | Damon Biotech, Inc. | Sustained release |
| US4789516A (en) * | 1983-04-15 | 1988-12-06 | Damon Biotech, Inc | Production of sustained released system |
| US4744933A (en) * | 1984-02-15 | 1988-05-17 | Massachusetts Institute Of Technology | Process for encapsulation and encapsulated active material system |
| CA1215922A (en) * | 1984-05-25 | 1986-12-30 | Connaught Laboratories Limited | Microencapsulation of living tissue and cells |
| JPS645460A (en) * | 1987-06-29 | 1989-01-10 | Sanei Kagaku Kogyo Kk | Production of delaying gelatinous material |
| JPH0794583B2 (ja) * | 1989-12-15 | 1995-10-11 | 株式会社大塚製薬工場 | 高含水高分子ゲル |
| IT1245383B (it) * | 1991-03-28 | 1994-09-20 | Eniricerche Spa | Composizione acquosa gelificabile avente tempo di gelificazione ritardato |
| US5711968A (en) * | 1994-07-25 | 1998-01-27 | Alkermes Controlled Therapeutics, Inc. | Composition and method for the controlled release of metal cation-stabilized interferon |
| KR960006730B1 (ko) * | 1993-02-11 | 1996-05-23 | 재단법인한국화학연구소 | 에멀젼 네트웍(emulsion network)을 이용한 약물의 피부 전달체계 |
| GB9708773D0 (en) * | 1997-04-30 | 1997-06-25 | Reckitt & Colmann Prod Ltd | Organic compositions |
-
1998
- 1998-05-18 ES ES98922348T patent/ES2294814T3/es not_active Expired - Lifetime
- 1998-05-18 SK SK1543-99A patent/SK286437B6/sk not_active IP Right Cessation
- 1998-05-18 CZ CZ0396399A patent/CZ299180B6/cs not_active IP Right Cessation
- 1998-05-18 PL PL336887A patent/PL199565B1/pl unknown
- 1998-05-18 IL IL13281498A patent/IL132814A0/xx unknown
- 1998-05-18 HU HU0003393A patent/HUP0003393A3/hu unknown
- 1998-05-18 EP EP98922348A patent/EP0981374B1/en not_active Expired - Lifetime
- 1998-05-18 KR KR1019997010326A patent/KR20010012374A/ko not_active Ceased
- 1998-05-18 CA CA002289196A patent/CA2289196C/en not_active Expired - Fee Related
- 1998-05-18 YU YU58599A patent/YU58599A/sh unknown
- 1998-05-18 EA EA199901013A patent/EA199901013A1/ru unknown
- 1998-05-18 JP JP54960298A patent/JP2001525826A/ja not_active Ceased
- 1998-05-18 AU AU74918/98A patent/AU7491898A/en not_active Abandoned
- 1998-05-18 WO PCT/US1998/010013 patent/WO1998051348A2/en not_active Ceased
- 1998-05-18 BR BR9809117-4A patent/BR9809117A/pt not_active Application Discontinuation
- 1998-05-18 DE DE69838750T patent/DE69838750T2/de not_active Expired - Fee Related
-
1999
- 1999-11-15 NO NO995591A patent/NO995591D0/no not_active Application Discontinuation
- 1999-11-23 BG BG103914A patent/BG64860B1/bg unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JP2001525826A (ja) | 2001-12-11 |
| HUP0003393A2 (hu) | 2001-02-28 |
| ES2294814T3 (es) | 2008-04-01 |
| SK286437B6 (sk) | 2008-10-07 |
| EP0981374B1 (en) | 2007-11-21 |
| BG103914A (en) | 2000-07-31 |
| DE69838750D1 (de) | 2008-01-03 |
| IL132814A0 (en) | 2001-03-19 |
| DE69838750T2 (de) | 2008-10-30 |
| EP0981374A2 (en) | 2000-03-01 |
| AU7491898A (en) | 1998-12-08 |
| WO1998051348A3 (en) | 1999-02-18 |
| NO995591L (no) | 1999-11-15 |
| BG64860B1 (bg) | 2006-07-31 |
| NO995591D0 (no) | 1999-11-15 |
| CZ396399A3 (cs) | 2000-04-12 |
| PL336887A1 (en) | 2000-07-17 |
| SK154399A3 (en) | 2000-07-11 |
| WO1998051348A2 (en) | 1998-11-19 |
| BR9809117A (pt) | 2000-08-01 |
| PL199565B1 (pl) | 2008-10-31 |
| HUP0003393A3 (en) | 2001-03-28 |
| KR20010012374A (ko) | 2001-02-15 |
| EA199901013A1 (ru) | 2000-06-26 |
| YU58599A (sh) | 2000-12-28 |
| CA2289196A1 (en) | 1998-11-19 |
| CZ299180B6 (cs) | 2008-05-14 |
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| EEER | Examination request | ||
| MKLA | Lapsed |