WO2002000137A1 - Biodegradable vehicles and delivery systems of biologically active substances - Google Patents
Biodegradable vehicles and delivery systems of biologically active substances Download PDFInfo
- Publication number
- WO2002000137A1 WO2002000137A1 PCT/US2001/006138 US0106138W WO0200137A1 WO 2002000137 A1 WO2002000137 A1 WO 2002000137A1 US 0106138 W US0106138 W US 0106138W WO 0200137 A1 WO0200137 A1 WO 0200137A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- agents
- biodegradable
- peg
- glyceryl
- poly
- Prior art date
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- 239000013543 active substance Substances 0.000 title abstract description 9
- 239000000203 mixture Substances 0.000 claims abstract description 218
- 239000004014 plasticizer Substances 0.000 claims abstract description 128
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- 238000000034 method Methods 0.000 claims abstract description 59
- 239000002904 solvent Substances 0.000 claims abstract description 43
- 229920002988 biodegradable polymer Polymers 0.000 claims abstract description 36
- 239000004621 biodegradable polymer Substances 0.000 claims abstract description 36
- 229940088623 biologically active substance Drugs 0.000 claims abstract description 25
- 241001465754 Metazoa Species 0.000 claims abstract description 11
- 229920000642 polymer Polymers 0.000 claims description 130
- 239000003981 vehicle Substances 0.000 claims description 128
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- 239000003795 chemical substances by application Substances 0.000 claims description 51
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- 239000001069 triethyl citrate Substances 0.000 claims description 38
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 claims description 38
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- 239000000622 polydioxanone Substances 0.000 claims description 8
- 102000004169 proteins and genes Human genes 0.000 claims description 8
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical class [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims description 8
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- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/602—Type of release, e.g. controlled, sustained, slow
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Surgery (AREA)
- Vascular Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Heart & Thoracic Surgery (AREA)
- Biomedical Technology (AREA)
- Dermatology (AREA)
- Molecular Biology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Inorganic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Materials For Medical Uses (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Claims
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA002413157A CA2413157A1 (en) | 2000-06-28 | 2001-02-26 | Biodegradable vehicles and delivery systems of biologically active substances |
NZ523385A NZ523385A (en) | 2000-06-28 | 2001-02-26 | Biodegradable vehicles and BAS-loaded delivery systems for use as biodegradable fillers and/or spacers, e.g. artificial skin |
JP2002504922A JP2004511431A (en) | 2000-06-28 | 2001-02-26 | Biodegradable vehicles and delivery systems containing bioactive agents |
EP01918249A EP1299048A4 (en) | 2000-06-28 | 2001-02-26 | Biodegradable vehicles and delivery systems of biologically active substances |
AU2001245346A AU2001245346A1 (en) | 2000-06-28 | 2001-02-26 | Biodegradable vehicles and delivery systems of biologically active substances |
US10/312,394 US20040018238A1 (en) | 2001-02-26 | 2001-02-26 | Biodegradable vehicles and delivery systems of biolgically active substances |
Applications Claiming Priority (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US09/605,661 US6432438B1 (en) | 1997-10-29 | 2000-06-28 | Biodegradable vehicle and filler |
US09/605,661 | 2000-06-28 | ||
IN694/MUM/2000 | 2000-07-25 | ||
IN694MU2000 IN189074B (en) | 2000-07-25 | 2000-07-25 | |
CN00120871.3 | 2000-08-03 | ||
CN 00120871 CN1206001C (en) | 2000-06-28 | 2000-08-03 | Biodegradable carrier and biodegradable transfer system |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2002000137A1 true WO2002000137A1 (en) | 2002-01-03 |
Family
ID=27178759
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2001/006138 WO2002000137A1 (en) | 2000-06-28 | 2001-02-26 | Biodegradable vehicles and delivery systems of biologically active substances |
Country Status (7)
Country | Link |
---|---|
EP (1) | EP1299048A4 (en) |
JP (1) | JP2004511431A (en) |
CN (1) | CN1283215C (en) |
AU (1) | AU2001245346A1 (en) |
CA (1) | CA2413157A1 (en) |
NZ (1) | NZ523385A (en) |
WO (1) | WO2002000137A1 (en) |
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---|---|---|---|---|
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WO2004000269A1 (en) | 2002-06-25 | 2003-12-31 | Alza Corporation | Short duration depot formulations |
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WO2004108180A1 (en) * | 2003-06-04 | 2004-12-16 | Inion Ltd | Biodegradable implant and method for manufacturing one |
WO2005002625A2 (en) * | 2003-06-26 | 2005-01-13 | Control Delivery Systems, Inc. | In-situ gelling drug delivery system |
JP2005537309A (en) * | 2002-08-22 | 2005-12-08 | プリヴァ−ラケマ,エー.エス. | Biodegradable compositions with long-term release of bioactive compounds and their preparation |
JP2005538107A (en) * | 2002-07-31 | 2005-12-15 | アルザ・コーポレーション | Injectable multimodal polymer depot composition and use thereof |
JP2006511582A (en) * | 2002-12-20 | 2006-04-06 | ジェネリファーム インコーポレイテッド | Intradermal injection method |
EP1731178A2 (en) * | 2005-05-10 | 2006-12-13 | University Of Zurich | Resorbable polymer composition, implant and method of making implant |
WO2007020430A2 (en) * | 2005-08-18 | 2007-02-22 | Smith & Nephew, Plc | Multimodal high strength devices and composites |
JP2007515196A (en) * | 2003-09-23 | 2007-06-14 | オーソ・セラピューティクス・リミテッド・ライアビリティ・カンパニー | Resorbable implants and their use in the treatment of hemostasis and bone defects |
JP2007517902A (en) * | 2004-01-12 | 2007-07-05 | ザ・トラスティーズ・オブ・ザ・ユニバーシティ・オブ・ペンシルバニア | Long-term delivery formulations and methods of use |
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US7824700B2 (en) | 2001-02-23 | 2010-11-02 | Genentech, Inc. | Erodible polymers for injection |
US8221778B2 (en) | 2005-01-12 | 2012-07-17 | The Trustees Of The University Of Pennsylvania | Drug-containing implants and methods of use thereof |
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US9649364B2 (en) | 2015-09-25 | 2017-05-16 | Xeris Pharmaceuticals, Inc. | Methods for producing stable therapeutic formulations in aprotic polar solvents |
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US11400019B2 (en) | 2020-01-13 | 2022-08-02 | Durect Corporation | Sustained release drug delivery systems with reduced impurities and related methods |
US11590205B2 (en) | 2015-09-25 | 2023-02-28 | Xeris Pharmaceuticals, Inc. | Methods for producing stable therapeutic glucagon formulations in aprotic polar solvents |
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Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4343787A (en) * | 1975-07-29 | 1982-08-10 | Merck & Co., Inc. | Shaped ophthalmic inserts for treating dry eye syndrome |
US5324519A (en) * | 1989-07-24 | 1994-06-28 | Atrix Laboratories, Inc. | Biodegradable polymer composition |
US5324520A (en) * | 1988-12-19 | 1994-06-28 | Vipont Pharmaceutical, Inc. | Intragingival delivery systems for treatment of periodontal disease |
US5340849A (en) * | 1988-10-03 | 1994-08-23 | Atrix Laboratories, Inc. | Biodegradable in-situ forming implants and methods for producing the same |
US5487897A (en) * | 1989-07-24 | 1996-01-30 | Atrix Laboratories, Inc. | Biodegradable implant precursor |
US5525646A (en) * | 1991-03-04 | 1996-06-11 | Lundgren; Dan | Bioresorbable material and an article of manufacture made of such material for medical use |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2605592A (en) * | 1991-10-15 | 1993-04-22 | Atrix Laboratories, Inc. | Polymeric compositions useful as controlled release implants |
US5447725A (en) * | 1993-06-11 | 1995-09-05 | The Procter & Gamble Company | Methods for aiding periodontal tissue regeneration |
DE69705746T2 (en) * | 1996-12-20 | 2001-10-31 | Alza Corp | INJECTABLE DEPOT GEL PREPARATION AND PRODUCTION METHOD |
WO1998048859A1 (en) * | 1997-04-30 | 1998-11-05 | Guilford Pharmaceuticals Inc. | Biodegradable compositions comprising poly(cycloaliphatic phosphoester) compounds, articles, and methods for using the same |
ES2222694T3 (en) * | 1998-03-19 | 2005-02-01 | MERCK & CO., INC. | LIQUID POLYMER COMPOSITIONS FOR THE CONTROLLED RELEASE OF BIOACTIVE SUBSTANCES. |
US6143314A (en) * | 1998-10-28 | 2000-11-07 | Atrix Laboratories, Inc. | Controlled release liquid delivery compositions with low initial drug burst |
-
2001
- 2001-02-26 AU AU2001245346A patent/AU2001245346A1/en not_active Abandoned
- 2001-02-26 NZ NZ523385A patent/NZ523385A/en unknown
- 2001-02-26 JP JP2002504922A patent/JP2004511431A/en active Pending
- 2001-02-26 CA CA002413157A patent/CA2413157A1/en not_active Abandoned
- 2001-02-26 EP EP01918249A patent/EP1299048A4/en not_active Withdrawn
- 2001-02-26 WO PCT/US2001/006138 patent/WO2002000137A1/en not_active Application Discontinuation
- 2001-02-26 CN CNB018118518A patent/CN1283215C/en not_active Expired - Fee Related
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4343787A (en) * | 1975-07-29 | 1982-08-10 | Merck & Co., Inc. | Shaped ophthalmic inserts for treating dry eye syndrome |
US5340849A (en) * | 1988-10-03 | 1994-08-23 | Atrix Laboratories, Inc. | Biodegradable in-situ forming implants and methods for producing the same |
US5324520A (en) * | 1988-12-19 | 1994-06-28 | Vipont Pharmaceutical, Inc. | Intragingival delivery systems for treatment of periodontal disease |
US5324519A (en) * | 1989-07-24 | 1994-06-28 | Atrix Laboratories, Inc. | Biodegradable polymer composition |
US5487897A (en) * | 1989-07-24 | 1996-01-30 | Atrix Laboratories, Inc. | Biodegradable implant precursor |
US5525646A (en) * | 1991-03-04 | 1996-06-11 | Lundgren; Dan | Bioresorbable material and an article of manufacture made of such material for medical use |
Non-Patent Citations (1)
Title |
---|
See also references of EP1299048A4 * |
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US8790679B2 (en) | 2002-12-20 | 2014-07-29 | Xeris Pharmaceuticals, Inc. | Intracutaneous paste composition |
US9314424B2 (en) | 2002-12-20 | 2016-04-19 | Xeris Pharmaceuticals, Inc. | Pastes for injection of a therapeutic agent |
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US10300114B2 (en) | 2003-06-26 | 2019-05-28 | Eyepoint Pharmaceuticals Us, Inc. | Bioerodible sustained release drug delivery systems |
WO2005002625A2 (en) * | 2003-06-26 | 2005-01-13 | Control Delivery Systems, Inc. | In-situ gelling drug delivery system |
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US9120919B2 (en) | 2003-12-23 | 2015-09-01 | Smith & Nephew, Inc. | Tunable segmented polyacetal |
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US9138479B2 (en) | 2011-10-31 | 2015-09-22 | Xeris Pharmaceuticals, Inc. | Formulations for the treatment of diabetes |
US11446310B2 (en) | 2012-06-27 | 2022-09-20 | Xeris Pharmaceuticals, Inc. | Stable formulations for parenteral injection of small molecule drugs |
US10765683B2 (en) | 2012-06-27 | 2020-09-08 | Xeris Pharmaceuticals, Inc. | Stable formulations for parenteral injection of small molecule drugs |
US9125805B2 (en) | 2012-06-27 | 2015-09-08 | Xeris Pharmaceuticals, Inc. | Stable formulations for parenteral injection of small molecule drugs |
US9018162B2 (en) | 2013-02-06 | 2015-04-28 | Xeris Pharmaceuticals, Inc. | Methods for rapidly treating severe hypoglycemia |
US9642894B2 (en) | 2013-02-06 | 2017-05-09 | Xeris Pharmaceuticals, Inc. | Compositions for rapidly treating severe hypoglycemia |
US10226532B2 (en) | 2013-03-11 | 2019-03-12 | Durect Corporation | Compositions and methods involving polymer, solvent, and high viscosity liquid carrier material |
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US9737605B2 (en) | 2013-03-11 | 2017-08-22 | Durect Corporation | Injectable controlled release composition comprising high viscosity liquid carrier |
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US10028965B2 (en) | 2013-05-24 | 2018-07-24 | Icon Bioscience, Inc. | Use of sustained release dexamethasone in post-cataract surgery inflammation |
US11129940B2 (en) | 2014-08-06 | 2021-09-28 | Xeris Pharmaceuticals, Inc. | Syringes, kits, and methods for intracutaneous and/or subcutaneous injection of pastes |
WO2016054197A1 (en) * | 2014-09-30 | 2016-04-07 | University Of Tennessee Research Foundation | In situ gelling form for long-acting drug delivery |
US11590205B2 (en) | 2015-09-25 | 2023-02-28 | Xeris Pharmaceuticals, Inc. | Methods for producing stable therapeutic glucagon formulations in aprotic polar solvents |
US10485850B2 (en) | 2015-09-25 | 2019-11-26 | Xeris Pharmaceuticals, Inc. | Methods for producing stable therapeutic formulations in aprotic polar solvents |
US9649364B2 (en) | 2015-09-25 | 2017-05-16 | Xeris Pharmaceuticals, Inc. | Methods for producing stable therapeutic formulations in aprotic polar solvents |
WO2017083485A1 (en) | 2015-11-10 | 2017-05-18 | Mcjames Ii William Charles | A device and method for controlling the release of bioactive and therapeutic agents from an implantable medical device |
EP3373995A4 (en) * | 2015-11-10 | 2019-10-30 | Mcjames II, William Charles | A device and method for controlling the release of bioactive and therapeutic agents from an implantable medical device |
WO2017100863A1 (en) * | 2015-12-17 | 2017-06-22 | Verita Research Pte Ltd | Injectable composition and a method of treatment of the physical addiction |
CN110475545A (en) * | 2017-03-27 | 2019-11-19 | W.L.戈尔及同仁股份有限公司 | For controlling the injectable and biodegradable polymer preparation of release bioactive agent |
AU2021277631B2 (en) * | 2017-03-27 | 2023-03-30 | W. L. Gore & Associates, Inc. | Injectable and biodegradable polymer formulations for controlled release of bioactive agents |
US11752099B2 (en) | 2017-03-27 | 2023-09-12 | W. L. Gore & Associates, Inc. | Injectable and biodegradable polymer formulations for controlled release of bioactive agents |
CN110475545B (en) * | 2017-03-27 | 2024-01-05 | W.L.戈尔及同仁股份有限公司 | Injectable and biodegradable polymeric formulations for the controlled release of bioactive agents |
US11020403B2 (en) | 2017-06-02 | 2021-06-01 | Xeris Pharmaceuticals, Inc. | Precipitation resistant small molecule drug formulations |
US11833157B2 (en) | 2017-06-02 | 2023-12-05 | Xeris Pharmaceuticals, Inc. | Precipitation resistant small molecule drug formulations |
US11400019B2 (en) | 2020-01-13 | 2022-08-02 | Durect Corporation | Sustained release drug delivery systems with reduced impurities and related methods |
US11771624B2 (en) | 2020-01-13 | 2023-10-03 | Durect Corporation | Sustained release drug delivery systems with reduced impurities and related methods |
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EP1299048A1 (en) | 2003-04-09 |
CA2413157A1 (en) | 2002-01-03 |
EP1299048A4 (en) | 2005-09-28 |
CN1283215C (en) | 2006-11-08 |
NZ523385A (en) | 2005-09-30 |
AU2001245346A1 (en) | 2002-01-08 |
CN1438858A (en) | 2003-08-27 |
JP2004511431A (en) | 2004-04-15 |
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