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
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- 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
-
- 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)
- Medicinal Chemistry (AREA)
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- Veterinary Medicine (AREA)
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- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Zoology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Dispersion Chemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Physical Education & Sports Medicine (AREA)
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- Cell Biology (AREA)
- Psychology (AREA)
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- Dermatology (AREA)
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- Biotechnology (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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|---|---|---|---|---|
| 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 |
| US7258690B2 (en) | 2003-03-28 | 2007-08-21 | Relievant Medsystems, Inc. | Windowed thermal ablation probe |
| CA2604622A1 (en) | 2005-04-15 | 2006-10-26 | 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 |
| US10028753B2 (en) | 2008-09-26 | 2018-07-24 | Relievant Medsystems, Inc. | Spine treatment kits |
| JP5688022B2 (ja) | 2008-09-26 | 2015-03-25 | リリーバント メドシステムズ、インコーポレイテッド | 骨の内部を通って器具を誘導するためのシステムおよび方法 |
| AR080219A1 (es) | 2010-02-18 | 2012-03-21 | Osiris Therapeutics Inc | Productos de membranas corionicas inmunocompatibles |
| RU2588658C2 (ru) * | 2010-04-27 | 2016-07-10 | ЭсСиАйЭл Текнолоджи ГмбХ | Стабильные водные композиции белка mia/cd-rap |
| 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 |
| HRP20230655T1 (hr) * | 2012-07-05 | 2023-10-13 | Taiwan Liposome Company, Ltd. | Metode liječenja artritisa |
| US10588691B2 (en) | 2012-09-12 | 2020-03-17 | Relievant Medsystems, Inc. | Radiofrequency ablation of tissue within a vertebral body |
| AU2013337680B2 (en) | 2012-11-05 | 2019-04-18 | Relievant Medsystems, Inc. | Systems and methods for creating curved paths through bone and modulating nerves within the bone |
| US9724151B2 (en) | 2013-08-08 | 2017-08-08 | Relievant Medsystems, Inc. | Modulating nerves within bone using bone fasteners |
| 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 |
| US8986732B2 (en) | 2013-08-12 | 2015-03-24 | Helix Biopharma Corporation | Biphasic lipid-vesicle compositions and methods for treating cervical dysplasia by intravaginal delivery |
| DK3233136T3 (da) * | 2014-12-18 | 2019-05-20 | Bracco Suisse Sa | Formulering med målrettede gasfyldte mikrovesikler |
| MX381655B (es) | 2015-05-04 | 2025-03-13 | Versantis AG | Metodo para preparar vesiculas con gradiente de ph de transmembrana. |
| US10660852B2 (en) | 2015-09-18 | 2020-05-26 | Bionet Pharma Gmbh | Expression and folding in the manufacturing process of CD-RAP by using a CD-RAP precursor protein |
| EP3439691A4 (en) * | 2016-04-04 | 2020-05-13 | GU Ventures AB | METHODS AND COMPOSITIONS FOR TREATING INTERVERTEBRAL DISC HERNIA |
| AU2018258070A1 (en) * | 2017-04-25 | 2019-10-24 | Adjuvance Technologies, Inc. | Triterpene saponin analogues |
| MX393126B (es) * | 2017-08-28 | 2025-03-24 | Tlc Biopharmaceuticals Inc | Composiciones anestesicas de liberacion sostenida, y metodos de preparacion de las mismas |
| CN111356448A (zh) * | 2017-09-18 | 2020-06-30 | 北卡罗莱纳州立大学 | 人工β细胞及其使用方法 |
| KR102649069B1 (ko) | 2018-05-31 | 2024-03-19 | 주식회사 엑소코바이오 | 줄기세포 유래의 엑소좀을 유효성분으로 포함하는 안면 홍조 개선용 조성물 |
| WO2020027466A1 (ko) | 2018-07-28 | 2020-02-06 | 주식회사 엑소코바이오 | 엑소좀의 동결건조 방법 |
| KR102163806B1 (ko) * | 2018-07-30 | 2020-10-07 | 주식회사 엑소코바이오 | 줄기세포 유래의 엑소좀을 유효성분으로 포함하는 피지분비 감소용 조성물 |
| CN113166783B (zh) * | 2018-10-09 | 2024-10-11 | 不列颠哥伦比亚大学 | 包含无有机溶剂和去污剂的转染活性囊泡的组合物和系统以及与之相关的方法 |
| WO2021050767A1 (en) | 2019-09-12 | 2021-03-18 | Relievant Medsystems, Inc. | Systems and methods for tissue modulation |
| AU2021306313A1 (en) | 2020-07-10 | 2023-03-02 | Relievant Medsystems, Inc. | Vertebral denervation in conjunction with vertebral fusion |
| US12082876B1 (en) | 2020-09-28 | 2024-09-10 | Relievant Medsystems, Inc. | Introducer drill |
| EP4268150A4 (en) | 2020-12-22 | 2024-12-18 | Relievant Medsystems, Inc. | PREDICTION OF CANDIDATES FOR SPINAL CORD NEUROMODULATION |
| 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 |
| US12433668B1 (en) | 2021-11-08 | 2025-10-07 | Relievant Medsystems, Inc. | Impedance stoppage mitigation during radiofrequency tissue ablation procedures |
| 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)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CA2088975A1 (en) | 1990-08-08 | 1992-02-09 | Anthony H. Huang | 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 |
| WO2000012762A1 (en) * | 1998-09-01 | 2000-03-09 | 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 |
| JP4672947B2 (ja) * | 1999-12-06 | 2011-04-20 | ウォーソー・オーソペディック・インコーポレーテッド | 椎間板の治療装置及び方法 |
| JP4822666B2 (ja) * | 2001-10-03 | 2011-11-24 | セレーター ファーマシューティカルズ インコーポレイテッド | 金属イオンをローディングするリポソーム |
| EP1513853A2 (en) * | 2002-05-24 | 2005-03-16 | Neopharm, Inc. | Cardiolipin compositions, 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 |
| CA2557999C (en) * | 2004-03-30 | 2013-11-12 | Ilypsa, Inc. | Methods and compositions for treatment of ion imbalances |
| AU2005245017A1 (en) * | 2004-05-21 | 2005-12-01 | Synthes Gmbh | Replacement of nucleus pulposus using a hydrogel |
| ES2369629T3 (es) * | 2004-05-25 | 2011-12-02 | Stryker Corporation | Uso de op-1 para tratar defectos del cartílago. |
| EP1604693A1 (en) * | 2004-06-09 | 2005-12-14 | Scil Technology GmbH | In situ forming scaffold, its manufacturing and use |
| EP1809254A2 (en) * | 2004-10-28 | 2007-07-25 | 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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- 2007-10-05 JP JP2009530810A patent/JP5404402B2/ja not_active Expired - Fee Related
- 2007-10-05 TW TW096137658A patent/TWI455731B/zh not_active IP Right Cessation
- 2007-10-05 DK DK07818735.8T patent/DK2081551T3/da active
- 2007-10-05 HR HRP20130328TT patent/HRP20130328T1/hr unknown
- 2007-10-05 CA CA2664637A patent/CA2664637C/en not_active Expired - Fee Related
- 2007-10-05 SI SI200731193T patent/SI2081551T1/sl unknown
- 2007-10-05 CN CNA2007800422016A patent/CN101605534A/zh active Pending
- 2007-10-05 JP JP2009530811A patent/JP5484059B2/ja not_active Expired - Fee Related
- 2007-10-05 RU RU2009117170/15A patent/RU2443412C2/ru not_active IP Right Cessation
- 2007-10-05 PT PT78187358T patent/PT2081551E/pt unknown
- 2007-10-05 CN CN2007800397245A patent/CN101528197B/zh not_active Expired - Fee Related
- 2007-10-05 ES ES07818735T patent/ES2400162T3/es active Active
- 2007-10-05 WO PCT/EP2007/008659 patent/WO2008040556A1/en not_active Ceased
- 2007-10-05 PL PL07818735T patent/PL2081551T3/pl unknown
- 2007-10-05 CN CN2012104557068A patent/CN102940878A/zh active Pending
- 2007-10-05 WO PCT/EP2007/008660 patent/WO2008040557A1/en not_active Ceased
- 2007-10-05 ES ES07818736T patent/ES2708851T3/es active Active
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2009
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