ES2939612T3 - Composición fluyente inyectable que comprende buprenorfina - Google Patents
Composición fluyente inyectable que comprende buprenorfina Download PDFInfo
- Publication number
- ES2939612T3 ES2939612T3 ES17205986T ES17205986T ES2939612T3 ES 2939612 T3 ES2939612 T3 ES 2939612T3 ES 17205986 T ES17205986 T ES 17205986T ES 17205986 T ES17205986 T ES 17205986T ES 2939612 T3 ES2939612 T3 ES 2939612T3
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- ES
- Spain
- Prior art keywords
- buprenorphine
- weight
- flowable composition
- implant
- composition
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 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
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/36—Opioid-abuse
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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]
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
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- Proteomics, Peptides & Aminoacids (AREA)
- Inorganic Chemistry (AREA)
- Emergency Medicine (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Dermatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Addiction (AREA)
- Neurology (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Rheumatology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Materials For Medical Uses (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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| GB1009549.5A GB2481018B (en) | 2010-06-08 | 2010-06-08 | Injectable flowable composition comprising buprenorphine |
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| ES2939612T3 true ES2939612T3 (es) | 2023-04-25 |
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| US8470359B2 (en) | 2000-11-13 | 2013-06-25 | Qlt Usa, Inc. | Sustained release polymer |
| GB2513267B (en) | 2010-06-08 | 2015-03-18 | Rb Pharmaceuticals Ltd | Injectable flowable composition comprising buprenorphine |
| GB2513060B (en) | 2010-06-08 | 2015-01-07 | Rb Pharmaceuticals Ltd | Microparticle buprenorphine suspension |
| US9272044B2 (en) | 2010-06-08 | 2016-03-01 | Indivior Uk Limited | Injectable flowable composition buprenorphine |
| WO2013126552A1 (en) | 2012-02-21 | 2013-08-29 | Auburn University | Buprenorphine nanoparticle composition and methods thereof |
| CH708257B1 (de) | 2012-04-17 | 2019-05-15 | Purdue Pharma Lp | Zusammensetzung zur Behandlung einer Opioid-induzierten unerwünschten pharmakodynamischen Reaktion. |
| ES2837803T3 (es) | 2012-07-26 | 2021-07-01 | Camurus Ab | Formulaciones de opioides |
| EP2877155B1 (en) * | 2012-07-26 | 2020-10-28 | Camurus AB | Opioid formulations |
| US20150320866A1 (en) * | 2012-12-13 | 2015-11-12 | Heron Therapeutics, Inc. | Pharmaceutical composition comprising antiemetic compounds and polyorthoester |
| KR102370470B1 (ko) * | 2013-03-15 | 2022-03-04 | 헤론 테라퓨틱스 인코포레이티드 | 폴리오르토에스테르 및 비프로톤성 용매의 조성물 |
| US9636308B2 (en) | 2013-03-15 | 2017-05-02 | Oakwood Laboratories LLC | High drug load buprenorphine microspheres and method of producing same |
| US9393211B2 (en) | 2013-03-15 | 2016-07-19 | Oakwood Laboratories LLC | High drug load buprenorphine microspheres and method of producing same |
| GB201404139D0 (en) * | 2014-03-10 | 2014-04-23 | Rb Pharmaceuticals Ltd | Sustained release buprenorphine solution formulations |
| HUE055973T2 (hu) | 2014-04-21 | 2022-01-28 | Heron Therapeutics Inc | Hosszanható polimerikus célba juttató rendszerek |
| US11083730B2 (en) | 2014-04-21 | 2021-08-10 | Heron Therapeutics, Inc. | Long-acting polymeric delivery systems |
| US9801945B2 (en) | 2014-04-21 | 2017-10-31 | Heron Therapeutics, Inc. | Long-acting polymeric delivery systems |
| HRP20202010T1 (hr) * | 2014-04-21 | 2021-03-05 | Heron Therapeutics, Inc. | Pripravci poliortoestera i organska kiselina kao pomoćna tvar |
| CA2945181C (en) | 2014-04-28 | 2022-10-18 | Orphomed, Inc. | Pharmaceutically active dimers linked through phenolic hydroxyl groups |
| GB201419091D0 (en) | 2014-10-27 | 2014-12-10 | Camurus Ab | Formulations |
| WO2016071767A1 (en) * | 2014-11-07 | 2016-05-12 | Indivior Uk Limited | Buprenorphine dosing regimens |
| BR112018002414B1 (pt) | 2015-08-03 | 2023-11-21 | Tolmar International Limited | Composição farmacêutica de polímero líquido para administração no corpo de um animal, seu uso para tratar, prover uma terapia para curar ou prevenir uma doença, distúrbio ou outra enfermidade e sistema de distribuição para administração da dita composição |
| KR102766991B1 (ko) | 2015-11-16 | 2025-02-13 | 메딘셀 에스.에이. | 활액 조직에 약제학적으로 활성인 유효성분을 모셀라이징 및/또는 표적화하는 방법 |
| CA3033046C (en) | 2016-09-13 | 2021-09-07 | Alar Pharmaceuticals Inc. | Sustained-release buprenorphine formulations |
| US10646484B2 (en) | 2017-06-16 | 2020-05-12 | Indivior Uk Limited | Methods to treat opioid use disorder |
| EP3638240A2 (en) | 2017-06-16 | 2020-04-22 | Indivior UK Limited | Methods to treat opioid use disorder |
| AU2019209416A1 (en) | 2018-01-22 | 2020-07-30 | Foresee Pharmaceuticals Co., Ltd. | Pharmaceutical composition for sustained release delivery of buprenorphine |
| BR112020016576A2 (pt) | 2018-05-11 | 2020-12-15 | Alar Pharmaceuticals Inc. | Formulações injetáveis de ação prolongada e formas cristalinas de derivados de buprenorfina |
| AU2019357036B2 (en) | 2018-10-11 | 2024-11-14 | Indivior Uk Limited | Buprenorphine to treat respiratory depression |
| US12403291B2 (en) * | 2019-08-30 | 2025-09-02 | Intersect Ent, Inc. | Submucosal bioresorbable drug eluting platform |
| CN118831057A (zh) * | 2023-04-25 | 2024-10-25 | 深圳善康医药科技股份有限公司 | 丁丙诺啡植入剂及其制备方法 |
Family Cites Families (16)
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| US4938763B1 (en) | 1988-10-03 | 1995-07-04 | Atrix Lab Inc | Biodegradable in-situ forming implants and method of producing the same |
| US5702716A (en) | 1988-10-03 | 1997-12-30 | Atrix Laboratories, Inc. | Polymeric compositions useful as controlled release implants |
| US5324519A (en) | 1989-07-24 | 1994-06-28 | Atrix Laboratories, Inc. | Biodegradable polymer composition |
| CA2187353C (en) | 1994-04-08 | 2007-05-22 | Gerald L. Yewey | Liquid delivery compositions |
| US20030211157A1 (en) * | 1996-05-06 | 2003-11-13 | Simon David Lew | Semi-sol delivery blend for water soluble molecules |
| US6143314A (en) * | 1998-10-28 | 2000-11-07 | Atrix Laboratories, Inc. | Controlled release liquid delivery compositions with low initial drug burst |
| US6565874B1 (en) | 1998-10-28 | 2003-05-20 | Atrix Laboratories | Polymeric delivery formulations of leuprolide with improved efficacy |
| US6461631B1 (en) | 1999-11-16 | 2002-10-08 | Atrix Laboratories, Inc. | Biodegradable polymer composition |
| AU2003240493B2 (en) * | 2002-05-31 | 2008-06-12 | L. Molteni & C. Dei Fratelli Alitti Societa' Di Esercizio S.P.A. | Implantable polymeric device for sustained release of buprenorphine |
| KR20050088288A (ko) * | 2002-11-06 | 2005-09-05 | 알자 코포레이션 | 제어식 방출 데포 제형 |
| WO2004081196A2 (en) * | 2003-03-11 | 2004-09-23 | Qlt Usa Inc. | Formulations for cell- schedule dependent anticancer agents |
| EP1804751A2 (en) * | 2004-10-04 | 2007-07-11 | QLT USA, Inc. | Ocular delivery of polymeric delivery formulations |
| PT1824460E (pt) * | 2004-11-10 | 2015-01-14 | Tolmar Therapeutics Inc | Um sistema de administração polimérico estabilizado |
| PT2115029E (pt) | 2007-02-15 | 2015-10-26 | Tolmar Therapeutics Inc | Poli-(lactido/glicolido) de efeito de libertação imediata reduzido e métodos de produção de polímeros |
| US20090181068A1 (en) * | 2008-01-14 | 2009-07-16 | Dunn Richard L | Low Viscosity Liquid Polymeric Delivery System |
| GB2513267B (en) | 2010-06-08 | 2015-03-18 | Rb Pharmaceuticals Ltd | Injectable flowable composition comprising buprenorphine |
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2010
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