CA2664637C - Dried reconstituted vesicle formation for pharmaceutical application - Google Patents
Dried reconstituted vesicle formation for pharmaceutical application Download PDFInfo
- Publication number
- CA2664637C CA2664637C CA2664637A CA2664637A CA2664637C CA 2664637 C CA2664637 C CA 2664637C CA 2664637 A CA2664637 A CA 2664637A CA 2664637 A CA2664637 A CA 2664637A CA 2664637 C CA2664637 C CA 2664637C
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- Prior art keywords
- dried
- lipid
- liposomes
- active agent
- composition
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- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
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- Pharmacology & Pharmacy (AREA)
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- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Biomedical Technology (AREA)
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- Dispersion Chemistry (AREA)
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- Virology (AREA)
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- Developmental Biology & Embryology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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| EP06021093.7 | 2006-10-06 | ||
| PCT/EP2007/008659 WO2008040556A1 (en) | 2006-10-06 | 2007-10-05 | Dried reconstituted vesicle formation for pharmaceutical application |
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| TW (1) | TWI455731B (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7258690B2 (en) | 2003-03-28 | 2007-08-21 | Relievant Medsystems, Inc. | Windowed thermal ablation probe |
| US6907884B2 (en) | 2002-09-30 | 2005-06-21 | Depay Acromed, Inc. | Method of straddling an intraosseous nerve |
| US8361067B2 (en) | 2002-09-30 | 2013-01-29 | Relievant Medsystems, Inc. | Methods of therapeutically heating a vertebral body to treat back pain |
| EP1868539A2 (en) | 2005-04-15 | 2007-12-26 | Musculoskeletal Transplant Foundation | Vertebral disc repair |
| US7959683B2 (en) | 2006-07-25 | 2011-06-14 | Musculoskeletal Transplant Foundation | Packed demineralized cancellous tissue forms for disc nucleus augmentation, restoration, or replacement and methods of implantation |
| CA2737374C (en) | 2008-09-26 | 2017-03-28 | Relievant Medsystems, Inc. | Systems and methods for navigating an instrument through bone |
| US10028753B2 (en) | 2008-09-26 | 2018-07-24 | Relievant Medsystems, Inc. | Spine treatment kits |
| WO2011103462A1 (en) | 2010-02-18 | 2011-08-25 | Osiris Therapeutics, Inc. | Methods of manufacture of immunocompatible amniotic membrane products |
| WO2011134979A2 (en) * | 2010-04-27 | 2011-11-03 | Scil Technology Gmbh | Stable mia/cd-rap formulation |
| US10390877B2 (en) | 2011-12-30 | 2019-08-27 | Relievant Medsystems, Inc. | Systems and methods for treating back pain |
| US20130202682A1 (en) * | 2012-01-24 | 2013-08-08 | The Trustees Of Columbia University In The City Of New York | Synthetic matrix vesicles for biomimetic mineralization |
| BR112015000174A2 (pt) * | 2012-07-05 | 2017-06-27 | Taiwan Liposome Co Ltd | método para o tratamento da artrite |
| US10588691B2 (en) | 2012-09-12 | 2020-03-17 | Relievant Medsystems, Inc. | Radiofrequency ablation of tissue within a vertebral body |
| IL238516B (en) | 2012-11-05 | 2022-08-01 | Relievant Medsystems Inc | System and methods for creating curved pathways through bone and regulating the nerves within the bone |
| US9724151B2 (en) | 2013-08-08 | 2017-08-08 | Relievant Medsystems, Inc. | Modulating nerves within bone using bone fasteners |
| US8986732B2 (en) | 2013-08-12 | 2015-03-24 | Helix Biopharma Corporation | Biphasic lipid-vesicle compositions and methods for treating cervical dysplasia by intravaginal delivery |
| US10159646B2 (en) * | 2013-08-12 | 2018-12-25 | Altum-Avro Pharma Partnership | Biphasic lipid-vesicle compositions and methods for treating cervical dysplasia by intravaginal delivery |
| ES2726924T3 (es) * | 2014-12-18 | 2019-10-10 | Bracco Suisse Sa | Formulación de microvesículas dirigidas rellenas de gas |
| AU2016256979B2 (en) | 2015-05-04 | 2021-01-28 | Genfit | Method for preparing transmembrane pH-gradient vesicles |
| WO2017046314A2 (en) * | 2015-09-18 | 2017-03-23 | Sanofi | Improvement of expression and folding in the manufacturing process of cd-rap by using a cd-rap precursor protein |
| WO2017176196A1 (en) * | 2016-04-04 | 2017-10-12 | Chalmers Ventures Ab | Methods and compositions for the treatment of intervertebral disc herniation |
| CN110582282A (zh) * | 2017-04-25 | 2019-12-17 | 佐剂技术公司 | 三萜皂苷类似物 |
| TWI806894B (zh) * | 2017-08-28 | 2023-07-01 | 台灣微脂體股份有限公司 | 緩釋麻醉劑組成物及其製備方法 |
| US11389405B2 (en) | 2017-09-18 | 2022-07-19 | North Carolina State University | Artificial beta cells and methods of use thereof |
| KR102649069B1 (ko) | 2018-05-31 | 2024-03-19 | 주식회사 엑소코바이오 | 줄기세포 유래의 엑소좀을 유효성분으로 포함하는 안면 홍조 개선용 조성물 |
| CN112261871B (zh) | 2018-07-28 | 2022-05-17 | 韩国外泌体生技有限公司 | 用于使外排体冻干的方法 |
| KR102163806B1 (ko) * | 2018-07-30 | 2020-10-07 | 주식회사 엑소코바이오 | 줄기세포 유래의 엑소좀을 유효성분으로 포함하는 피지분비 감소용 조성물 |
| DK3864163T3 (da) * | 2018-10-09 | 2024-05-06 | Univ British Columbia | Sammensætninger og systemer omfattende transfektionskompetente vesikler fri for organiske opløsningsmidler og rengøringsmidler og fremgangsmåder forbundet dermed |
| AU2020346827B2 (en) | 2019-09-12 | 2026-03-12 | Relievant Medsystems, Inc. | Systems and methods for tissue modulation |
| AU2021306313B2 (en) | 2020-07-10 | 2026-07-09 | Relievant Medsystems, Inc. | Vertebral denervation in conjunction with vertebral fusion |
| US12082876B1 (en) | 2020-09-28 | 2024-09-10 | Relievant Medsystems, Inc. | Introducer drill |
| AU2021409967A1 (en) | 2020-12-22 | 2023-08-03 | Relievant Medsystems, Inc. | Prediction of candidates for spinal neuromodulation |
| US12433668B1 (en) | 2021-11-08 | 2025-10-07 | Relievant Medsystems, Inc. | Impedance stoppage mitigation during radiofrequency tissue ablation procedures |
| CN113995852B (zh) * | 2021-11-08 | 2024-01-30 | 河北大学 | Arg-脂质体微囊、微囊包封的鱼精蛋白-siRNA复合体及其制备方法和应用 |
| CN221431621U (zh) * | 2023-07-10 | 2024-07-30 | 常州富谦生物科技有限公司 | 一种多层膜结构 |
Family Cites Families (25)
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| CH621479A5 (enExample) * | 1977-08-05 | 1981-02-13 | Battelle Memorial Institute | |
| FR2416008A1 (fr) * | 1978-02-02 | 1979-08-31 | Oreal | Lyophilisats de liposomes |
| IL79114A (en) * | 1985-08-07 | 1990-09-17 | Allergan Pharma | Method and composition for making liposomes |
| FR2591105B1 (fr) * | 1985-12-11 | 1989-03-24 | Moet Hennessy Rech | Composition pharmaceutique, notamment dermatologique, ou cosmetique, a base de phases lamellaires lipidiques hydratees ou de liposomes contenant un retinoide ou un analogue structural dudit retinoide tel qu'un carotenoide. |
| US4897353A (en) * | 1986-03-13 | 1990-01-30 | University Of Southwestern Louisiana | Cryogenic protection of phosphofructokinase using amino acids and zinc ions |
| US5709879A (en) * | 1990-06-29 | 1998-01-20 | Chiron Corporation | Vaccine compositions containing liposomes |
| AU8329391A (en) * | 1990-08-08 | 1992-03-02 | Liposome Technology, Inc. | Stable doxorubicin/liposome composition |
| CA2120197A1 (en) * | 1993-04-02 | 1994-10-03 | Kenji Endo | Stable aqueous dispersions containing liposomes |
| GB9320668D0 (en) | 1993-10-07 | 1993-11-24 | Secr Defence | Liposomes containing particulare materials |
| US6066331A (en) * | 1994-07-08 | 2000-05-23 | Barenholz; Yechezkel | Method for preparation of vesicles loaded with biological structures, biopolymers and/or oligomers |
| IL115199A (en) | 1995-09-07 | 2005-05-17 | Opperbas Holding Bv | Composition comprising a polynucleic acid molecule in a liposome and method using said composition |
| US6287590B1 (en) * | 1997-10-02 | 2001-09-11 | Esperion Therapeutics, Inc. | Peptide/lipid complex formation by co-lyophilization |
| AU5702099A (en) * | 1998-09-01 | 2000-03-21 | Millennium Pharmaceuticals, Inc. | A novel protein related to melanoma-inhibiting protein and uses thereof |
| EP1025871A1 (en) * | 1999-01-28 | 2000-08-09 | F. Hoffmann-La Roche Ag | Use of a melanoma inhibiting activity factor (MIA) for cartilage and bone repair |
| US7435260B2 (en) * | 1999-08-13 | 2008-10-14 | Ferree Bret A | Use of morphogenetic proteins to treat human disc disease |
| DK1244388T3 (da) * | 1999-12-06 | 2007-05-14 | Warsaw Orthopedic Inc | Indretning til behandling af mellemhvirvelskiver |
| EP1432403B1 (en) * | 2001-10-03 | 2010-07-28 | Celator Pharmaceuticals, Inc. | Liposome loading with metal ions |
| CA2486967A1 (en) * | 2002-05-24 | 2003-12-04 | Neopharm, Inc. | Cardiolipin compositions their methods of preparation and use |
| US7169405B2 (en) * | 2003-08-06 | 2007-01-30 | Warsaw Orthopedic, Inc. | Methods and devices for the treatment of intervertebral discs |
| KR101153035B1 (ko) * | 2004-03-30 | 2012-06-11 | 리립사, 인크. | 이온 결합 조성물 |
| WO2005113032A2 (en) * | 2004-05-21 | 2005-12-01 | Synthes (U.S.A.) | Replacement of nucleus pulposus using a hydrogel |
| CA2567405A1 (en) * | 2004-05-25 | 2005-12-08 | Stryker Corporation | Use of morphogenic proteins for treating cartilage defects |
| EP1604693A1 (en) * | 2004-06-09 | 2005-12-14 | Scil Technology GmbH | In situ forming scaffold, its manufacturing and use |
| CA2584583A1 (en) * | 2004-10-28 | 2006-05-11 | Alza Corporation | Lyophilized liposome formulations and method |
| US20110071056A1 (en) * | 2009-09-24 | 2011-03-24 | Rajesh K Saini | Degradable Surfactants, Including Degradable Gemini Surfactants, and Associated Methods |
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2007
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- 2007-10-05 WO PCT/EP2007/008660 patent/WO2008040557A1/en not_active Ceased
- 2007-10-05 JP JP2009530810A patent/JP5404402B2/ja not_active Expired - Fee Related
- 2007-10-05 HR HRP20130328TT patent/HRP20130328T1/hr unknown
- 2007-10-05 CN CN2007800397245A patent/CN101528197B/zh not_active Expired - Fee Related
- 2007-10-05 RS RS20130131A patent/RS52706B/sr unknown
- 2007-10-05 SI SI200731193T patent/SI2081551T1/sl unknown
- 2007-10-05 CN CNA2007800422016A patent/CN101605534A/zh active Pending
- 2007-10-05 KR KR1020097009193A patent/KR101333279B1/ko not_active Expired - Fee Related
- 2007-10-05 WO PCT/EP2007/008659 patent/WO2008040556A1/en not_active Ceased
- 2007-10-05 EP EP07818735A patent/EP2081551B1/en active Active
- 2007-10-05 ES ES07818735T patent/ES2400162T3/es active Active
- 2007-10-05 RU RU2009117170/15A patent/RU2443412C2/ru not_active IP Right Cessation
- 2007-10-05 EP EP07818736.6A patent/EP2086507B1/en not_active Not-in-force
- 2007-10-05 CA CA2664637A patent/CA2664637C/en not_active Expired - Fee Related
- 2007-10-05 CN CN2012104557068A patent/CN102940878A/zh active Pending
- 2007-10-05 PT PT78187358T patent/PT2081551E/pt unknown
- 2007-10-05 DK DK07818735.8T patent/DK2081551T3/da active
- 2007-10-05 JP JP2009530811A patent/JP5484059B2/ja not_active Expired - Fee Related
- 2007-10-05 ES ES07818736T patent/ES2708851T3/es active Active
- 2007-10-05 TW TW096137658A patent/TWI455731B/zh not_active IP Right Cessation
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2009
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2013
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2016
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Legal Events
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