ES2708851T3 - Un implante del núcleo pulposo espinal - Google Patents
Un implante del núcleo pulposo espinal Download PDFInfo
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- ES2708851T3 ES2708851T3 ES07818736T ES07818736T ES2708851T3 ES 2708851 T3 ES2708851 T3 ES 2708851T3 ES 07818736 T ES07818736 T ES 07818736T ES 07818736 T ES07818736 T ES 07818736T ES 2708851 T3 ES2708851 T3 ES 2708851T3
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- nucleus pulposus
- disc
- cells
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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
- A61K9/14—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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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8361067B2 (en) | 2002-09-30 | 2013-01-29 | Relievant Medsystems, Inc. | Methods of therapeutically heating a vertebral body to treat back pain |
| US6907884B2 (en) | 2002-09-30 | 2005-06-21 | Depay Acromed, Inc. | Method of straddling an intraosseous nerve |
| US7258690B2 (en) | 2003-03-28 | 2007-08-21 | Relievant Medsystems, Inc. | Windowed thermal ablation probe |
| EP1868539A2 (en) | 2005-04-15 | 2007-12-26 | Musculoskeletal Transplant Foundation | Vertebral disc repair |
| WO2008013763A2 (en) | 2006-07-25 | 2008-01-31 | 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 |
| AU2009296474B2 (en) | 2008-09-26 | 2015-07-02 | Relievant Medsystems, Inc. | Systems and methods for navigating an instrument through bone |
| EP3351625A1 (en) | 2010-02-18 | 2018-07-25 | Osiris Therapeutics, Inc. | Methods of manufacture of immunocompatible amniotic membrane products |
| BR112012027361A2 (pt) * | 2010-04-27 | 2021-04-27 | Scil Technology Gmbh | formulação mia/cd-rap estável. |
| WO2013101772A1 (en) | 2011-12-30 | 2013-07-04 | 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 |
| RU2677658C2 (ru) * | 2012-07-05 | 2019-01-18 | Тайвэн Липосом Ко, Лтд. | Способы лечения артрита |
| US10588691B2 (en) | 2012-09-12 | 2020-03-17 | Relievant Medsystems, Inc. | Radiofrequency ablation of tissue within a vertebral body |
| EP2914186B1 (en) | 2012-11-05 | 2019-03-13 | Relievant Medsystems, Inc. | Systems 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 |
| EP3233136B8 (en) * | 2014-12-18 | 2019-04-10 | Bracco Suisse SA | Targeted gas-filled microvesicles formulation |
| AU2016256979B2 (en) | 2015-05-04 | 2021-01-28 | Genfit | Method for preparing transmembrane pH-gradient vesicles |
| JP6976254B2 (ja) * | 2015-09-18 | 2021-12-08 | バイオネット ファーマ ゲゼルシャフト ミット ベシュレンクテル ハフツングBioNet Pharma GmbH | Ｃｄ−ｒａｐ前駆体タンパク質の使用による、ｃｄ−ｒａｐの製造方法における発現およびフォールディングの改善 |
| US20190111178A1 (en) * | 2016-04-04 | 2019-04-18 | Gu Ventures Ab | Methods and compositions for the treatment of intervertebral disc herniation |
| EP3618836A4 (en) * | 2017-04-25 | 2021-01-13 | Adjuvance Technologies, Inc. | TRITERPENSAPONINALOGA |
| MX393126B (es) * | 2017-08-28 | 2025-03-24 | Tlc Biopharmaceuticals Inc | Composiciones anestesicas de liberacion sostenida, y metodos de preparacion de las mismas |
| WO2019055901A1 (en) * | 2017-09-18 | 2019-03-21 | North Carolina State University | ARTIFICIAL β CELLS AND METHODS OF USE |
| KR102649069B1 (ko) | 2018-05-31 | 2024-03-19 | 주식회사 엑소코바이오 | 줄기세포 유래의 엑소좀을 유효성분으로 포함하는 안면 홍조 개선용 조성물 |
| JP7079984B2 (ja) | 2018-07-28 | 2022-06-03 | エクソコバイオ インコーポレイテッド | エキソソームの凍結乾燥方法 |
| 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 |
| AU2020346827B2 (en) | 2019-09-12 | 2026-03-12 | 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 |
| 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 (https=) * | 1977-08-05 | 1981-02-13 | Battelle Memorial Institute | |
| FR2416008A1 (fr) * | 1978-02-02 | 1979-08-31 | Oreal | Lyophilisats de liposomes |
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| 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 |
| EP0543871A1 (en) | 1990-08-08 | 1993-06-02 | 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 |
| AU774481B2 (en) * | 1999-12-06 | 2004-07-01 | Warsaw Orthopedic, Inc. | Intervertebral disc treatment devices and methods |
| CA2462376C (en) * | 2001-10-03 | 2010-12-14 | Celator Technologies Inc. | Liposome loading with metal ions |
| WO2003099830A2 (en) * | 2002-05-24 | 2003-12-04 | 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 |
| BRPI0509331B8 (pt) * | 2004-03-30 | 2021-05-25 | Ilypsa Inc | uso de uma composição de ligação de sódio |
| US20060100304A1 (en) * | 2004-05-21 | 2006-05-11 | Synthes Inc. | Replacement or supplementation of a 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 |
| AU2005302255A1 (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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