CA3006303C - Shape changing drug delivery devices and methods - Google Patents
Shape changing drug delivery devices and methods Download PDFInfo
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- CA3006303C CA3006303C CA3006303A CA3006303A CA3006303C CA 3006303 C CA3006303 C CA 3006303C CA 3006303 A CA3006303 A CA 3006303A CA 3006303 A CA3006303 A CA 3006303A CA 3006303 C CA3006303 C CA 3006303C
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- hydrogel
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- MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 description 1
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
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- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
- A61K9/0051—Ocular inserts, ocular implants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- 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
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Ophthalmology & Optometry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Preparation (AREA)
- Materials For Medical Uses (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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| US201662319033P | 2016-04-06 | 2016-04-06 | |
| US62/319,033 | 2016-04-06 | ||
| PCT/US2016/063633 WO2017091749A1 (en) | 2015-11-25 | 2016-11-23 | Shape changing drug delivery devices and methods |
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| CA3006303A1 CA3006303A1 (en) | 2017-06-01 |
| CA3006303C true CA3006303C (en) | 2023-11-14 |
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| CA3006303A Active CA3006303C (en) | 2015-11-25 | 2016-11-23 | Shape changing drug delivery devices and methods |
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| CA (1) | CA3006303C (enExample) |
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Families Citing this family (23)
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| CN107278151A (zh) | 2014-12-15 | 2017-10-20 | 约翰霍普金斯大学 | 舒尼替尼制剂及其在治疗青光眼中的使用方法 |
| US9855317B2 (en) | 2015-04-27 | 2018-01-02 | Reflex Medical, Inc. | Systems and methods for sympathetic cardiopulmonary neuromodulation |
| US11458041B2 (en) | 2015-10-08 | 2022-10-04 | Ocular Therapeutix, Inc. | Punctal plug and bioadhesives |
| BR112018009644A2 (pt) | 2015-11-12 | 2018-11-06 | Graybug Vision Inc | micropartículas agregantes sólidas modificadas na superfície, material injetável, processo para preparação de micropartículas agregantes sólidas modificadas na superfície, método para tratamento de um distúrbio ocular, e, uso de micropartículas agregantes sólidas modificadas na superfície |
| CN108601725B (zh) | 2015-11-25 | 2024-03-08 | 因赛普特有限责任公司 | 形状改变的药物递送装置和方法 |
| WO2017139487A1 (en) | 2016-02-09 | 2017-08-17 | Northwind Medical, Inc. | Methods, agents, and devices for local neuromodulation of autonomic nerves |
| WO2018005848A1 (en) | 2016-06-29 | 2018-01-04 | Bright, Corinne | Treatment of sepsis and related inflammatory conditions by local neuromodulation of the autonomic nervous system |
| KR102814241B1 (ko) | 2016-09-23 | 2025-05-29 | 인셉트, 엘엘씨 | 전안방내 약물 전달 데포 |
| CA3057875A1 (en) | 2017-05-10 | 2018-11-15 | Graybug Vision, Inc. | Extended release microparticles and suspensions thereof for medical therapy |
| CN108744048B (zh) * | 2018-06-29 | 2020-11-13 | 重庆科技学院 | 一种可实现自卷曲的双层水凝胶及其制备方法 |
| US20210315587A1 (en) | 2018-07-02 | 2021-10-14 | Tulavi Therapeutics, Inc. | Methods and devices for in situ formed nerve cap with rapid release |
| CA3105343A1 (en) | 2018-07-02 | 2020-01-09 | Corinne Bright | Methods and devices for in situ formed nerve cap |
| SG11202103505YA (en) * | 2018-11-09 | 2021-05-28 | Taris Biomedical Llc | Drug delivery devices and systems for local drug delivery to the upper urinary tract |
| CN109350355B (zh) * | 2018-11-30 | 2023-09-12 | 西安市第四医院 | 一种smile手术来源角膜基质透镜泪道栓及其制备方法 |
| US11523896B2 (en) | 2019-05-02 | 2022-12-13 | Kevin L. Waltz | Ocular protection ring |
| CN111150545A (zh) * | 2020-01-02 | 2020-05-15 | 首都医科大学附属北京同仁医院 | 一种相变降温支架及其制备方法和相变降温组合支架 |
| EP4252776A3 (en) | 2020-02-06 | 2023-11-22 | Ocular Therapeutix, Inc. | Compositions and methods for treating ocular diseases |
| WO2021195163A1 (en) | 2020-03-25 | 2021-09-30 | Ocular Therapeutix, Inc. | Ocular implant containing a tyrosine kinase inhibitor |
| WO2021222117A1 (en) | 2020-04-27 | 2021-11-04 | Ocular Therapeutix, Inc. | Methods of treating allergic conjunctivitis |
| WO2022066884A1 (en) | 2020-09-24 | 2022-03-31 | Ocular Therapeutix, Inc. | Sustained release biodegradalbe intracanalicular inserts comprising a hydrogel and cyclosporine |
| US12161753B2 (en) | 2020-09-24 | 2024-12-10 | Ocular Therapeutix, Inc. | Sustained release biodegradable intracanalicular inserts comprising a hydrogel and an active agent |
| EP4590593A2 (en) * | 2022-09-25 | 2025-07-30 | Albert-Ludwigs-Universität Freiburg | Marine polysaccharide networks |
| EP4583930A1 (en) | 2023-04-11 | 2025-07-16 | Ocular Therapeutix, Inc. | Ocular implant comprising axitinib polymorph iv |
Family Cites Families (52)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US1014335A (en) | 1910-11-10 | 1912-01-09 | Union Typewriter Co | Type-writing machine. |
| US3640741A (en) | 1970-02-24 | 1972-02-08 | Hollister Inc | Composition containing gel |
| US3865108A (en) | 1971-05-17 | 1975-02-11 | Ortho Pharma Corp | Expandable drug delivery device |
| US4002173A (en) | 1974-07-23 | 1977-01-11 | International Paper Company | Diester crosslinked polyglucan hydrogels and reticulated sponges thereof |
| DE2437629C3 (de) | 1974-08-05 | 1978-09-21 | Basf Ag, 6700 Ludwigshafen | Verfahren zur Herstellung von unlöslichen in Wasser nur wenig quellbaren Polymerisaten von N-Vinyllactamen |
| US4014335A (en) | 1975-04-21 | 1977-03-29 | Alza Corporation | Ocular drug delivery device |
| US4207893A (en) | 1977-08-29 | 1980-06-17 | Alza Corporation | Device using hydrophilic polymer for delivering drug to biological environment |
| US4484922A (en) | 1981-06-25 | 1984-11-27 | Rosenwald Peter L | Occular device |
| US4741872A (en) | 1986-05-16 | 1988-05-03 | The University Of Kentucky Research Foundation | Preparation of biodegradable microspheres useful as carriers for macromolecules |
| US5160745A (en) | 1986-05-16 | 1992-11-03 | The University Of Kentucky Research Foundation | Biodegradable microspheres as a carrier for macromolecules |
| IL82834A (en) | 1987-06-09 | 1990-11-05 | Yissum Res Dev Co | Biodegradable polymeric materials based on polyether glycols,processes for the preparation thereof and surgical artiicles made therefrom |
| US4938763B1 (en) | 1988-10-03 | 1995-07-04 | Atrix Lab Inc | Biodegradable in-situ forming implants and method of producing the same |
| US5304595A (en) | 1988-11-21 | 1994-04-19 | Collagen Corporation | Collagen-polymer conjugates |
| US5162430A (en) | 1988-11-21 | 1992-11-10 | Collagen Corporation | Collagen-polymer conjugates |
| IL90193A (en) | 1989-05-04 | 1993-02-21 | Biomedical Polymers Int | Polurethane-based polymeric materials and biomedical articles and pharmaceutical compositions utilizing the same |
| US5410016A (en) | 1990-10-15 | 1995-04-25 | Board Of Regents, The University Of Texas System | Photopolymerizable biodegradable hydrogels as tissue contacting materials and controlled-release carriers |
| JP3165734B2 (ja) | 1992-05-19 | 2001-05-14 | テルモ株式会社 | 新規な高吸水形状記憶材料 |
| US5304959A (en) | 1992-10-16 | 1994-04-19 | Spectrian, Inc. | Planar microstrip balun |
| US6371975B2 (en) | 1998-11-06 | 2002-04-16 | Neomend, Inc. | Compositions, systems, and methods for creating in situ, chemically cross-linked, mechanical barriers |
| WO1999021512A1 (en) | 1997-10-27 | 1999-05-06 | The Regents Of The University Of California | Methods and pharmaceutical compositions for the closure of retinal breaks |
| US6605294B2 (en) | 1998-08-14 | 2003-08-12 | Incept Llc | Methods of using in situ hydration of hydrogel articles for sealing or augmentation of tissue or vessels |
| US6632457B1 (en) | 1998-08-14 | 2003-10-14 | Incept Llc | Composite hydrogel drug delivery systems |
| US6514534B1 (en) | 1998-08-14 | 2003-02-04 | Incept Llc | Methods for forming regional tissue adherent barriers and drug delivery systems |
| US6152943A (en) | 1998-08-14 | 2000-11-28 | Incept Llc | Methods and apparatus for intraluminal deposition of hydrogels |
| WO2000033764A1 (en) | 1998-12-04 | 2000-06-15 | Pathak Chandrashekhar P | Biocompatible crosslinked polymers |
| US6958212B1 (en) | 1999-02-01 | 2005-10-25 | Eidgenossische Technische Hochschule Zurich | Conjugate addition reactions for the controlled delivery of pharmaceutically active compounds |
| DE60135352D1 (de) | 2000-08-30 | 2008-09-25 | Univ Johns Hopkins | Vorrichtung zur intraokularen wirkstoffverabreichung |
| CA2438193A1 (en) | 2001-02-26 | 2002-09-06 | Duke University | Novel dendritic polymers and their biomedical uses |
| US20040131582A1 (en) | 2002-02-26 | 2004-07-08 | Grinstaff Mark W. | Novel dendritic polymers and their biomedical uses |
| US7129210B2 (en) | 2003-07-23 | 2006-10-31 | Covalent Medical, Inc. | Tissue adhesive sealant |
| CN1882338A (zh) * | 2003-09-18 | 2006-12-20 | 马库赛特公司 | 经巩膜递送 |
| WO2006031358A2 (en) | 2004-08-13 | 2006-03-23 | Hyperbranch Medical Technology, Inc. | Dendritic polymers, crosslinked gels, and their uses as ophthalmic sealants and lenses |
| WO2006031388A2 (en) | 2004-08-20 | 2006-03-23 | Hyperbranch Medical Technology, Inc. | Dentritic polymers, crosslinked gels, and their uses in orthopedic applications |
| WO2007001926A2 (en) | 2005-06-24 | 2007-01-04 | Hyperbranch Medical Technology, Inc. | Low-swelling hydrogel sealants for wound repair |
| WO2007005249A2 (en) | 2005-06-29 | 2007-01-11 | Hyperbranch Medical Technology, Inc. | Nanoparticles and dendritic-polymer-based hydrogels comprising them |
| US8795709B2 (en) | 2006-03-29 | 2014-08-05 | Incept Llc | Superabsorbent, freeze dried hydrogels for medical applications |
| US20080220047A1 (en) * | 2007-03-05 | 2008-09-11 | Sawhney Amarpreet S | Low-swelling biocompatible hydrogels |
| US20080287633A1 (en) | 2007-05-18 | 2008-11-20 | Drumheller Paul D | Hydrogel Materials |
| US9125807B2 (en) | 2007-07-09 | 2015-09-08 | Incept Llc | Adhesive hydrogels for ophthalmic drug delivery |
| EP2396070B1 (en) * | 2009-02-12 | 2024-12-04 | Incept Llc | Drug delivery through hydrogel plugs |
| CN102844054B (zh) | 2009-12-15 | 2016-04-20 | 因赛普特有限责任公司 | 植入物和能生物降解的基准标记物 |
| US8961501B2 (en) | 2010-09-17 | 2015-02-24 | Incept, Llc | Method for applying flowable hydrogels to a cornea |
| EP2699317B1 (en) | 2011-04-21 | 2016-08-10 | Mapi Pharma Limited | Random pentapolymer for treatment of autoimmune diseases |
| WO2012150265A1 (en) * | 2011-05-02 | 2012-11-08 | Dsm Ip Assets B.V. | Fiber comprising a biodegradable polymer |
| EP4094734A1 (en) | 2011-09-14 | 2022-11-30 | Forsight Vision5, Inc. | Ocular insert apparatus |
| US10226417B2 (en) | 2011-09-16 | 2019-03-12 | Peter Jarrett | Drug delivery systems and applications |
| KR102039468B1 (ko) | 2011-12-05 | 2019-11-01 | 인셉트, 엘엘씨 | 의료용 유기젤 방법 및 조성물 |
| SI2911623T1 (sl) | 2012-10-26 | 2019-12-31 | Forsight Vision5, Inc. | Oftalmični sistem za podaljšano sproščanje zdravila v oko |
| CN120501693A (zh) | 2014-12-10 | 2025-08-19 | 因赛普特有限责任公司 | 水凝胶药物递送植入物 |
| WO2016183296A1 (en) | 2015-05-12 | 2016-11-17 | Incept, Llc | Drug delivery from hydrogels |
| CA2993182A1 (en) | 2015-07-22 | 2017-01-26 | Incept, Llc | Coated punctal plug |
| CN108601725B (zh) * | 2015-11-25 | 2024-03-08 | 因赛普特有限责任公司 | 形状改变的药物递送装置和方法 |
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2016
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- 2016-11-23 JP JP2018526903A patent/JP2018536484A/ja active Pending
- 2016-11-23 EP EP16816493.7A patent/EP3380077A1/en active Pending
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- 2016-11-23 BR BR112018010671A patent/BR112018010671A8/pt not_active Application Discontinuation
- 2016-11-23 WO PCT/US2016/063633 patent/WO2017091749A1/en not_active Ceased
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- 2016-11-23 KR KR1020187017686A patent/KR20180086468A/ko not_active Abandoned
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2020
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| EP3380077A1 (en) | 2018-10-03 |
| AU2016361579A1 (en) | 2018-06-21 |
| WO2017091749A8 (en) | 2017-07-06 |
| US20210128478A1 (en) | 2021-05-06 |
| US20220339108A1 (en) | 2022-10-27 |
| US11413250B2 (en) | 2022-08-16 |
| BR112018010671A8 (pt) | 2019-02-26 |
| AU2016361579B2 (en) | 2022-08-04 |
| CN108601725A (zh) | 2018-09-28 |
| IL259530A (en) | 2018-07-31 |
| JP2018536484A (ja) | 2018-12-13 |
| KR20180086468A (ko) | 2018-07-31 |
| CN108601725B (zh) | 2024-03-08 |
| US10786462B2 (en) | 2020-09-29 |
| US20200030241A1 (en) | 2020-01-30 |
| WO2017091749A1 (en) | 2017-06-01 |
| CA3006303A1 (en) | 2017-06-01 |
| US20170143636A1 (en) | 2017-05-25 |
| US10420724B2 (en) | 2019-09-24 |
| BR112018010671A2 (pt) | 2018-11-13 |
| US11938223B2 (en) | 2024-03-26 |
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|
| EEER | Examination request |
Effective date: 20211122 |