KR102679979B1 - 장기 작용 제형 - Google Patents
장기 작용 제형 Download PDFInfo
- Publication number
- KR102679979B1 KR102679979B1 KR1020207003364A KR20207003364A KR102679979B1 KR 102679979 B1 KR102679979 B1 KR 102679979B1 KR 1020207003364 A KR1020207003364 A KR 1020207003364A KR 20207003364 A KR20207003364 A KR 20207003364A KR 102679979 B1 KR102679979 B1 KR 102679979B1
- Authority
- KR
- South Korea
- Prior art keywords
- months
- bedaquiline
- pharmaceutical composition
- administration
- administered
- 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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Classifications
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- 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
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- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
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- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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- 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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- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- A—HUMAN NECESSITIES
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- A61P31/04—Antibacterial agents
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- A61P31/04—Antibacterial agents
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- B—PERFORMING OPERATIONS; TRANSPORTING
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- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
Landscapes
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- Chemical & Material Sciences (AREA)
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- Biomedical Technology (AREA)
- Physics & Mathematics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Inorganic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020247021329A KR20240108542A (ko) | 2017-07-14 | 2018-07-13 | 장기 작용 제형 |
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| EP17181354 | 2017-07-14 | ||
| EP17181354.6 | 2017-07-14 | ||
| EP18167463.1 | 2018-04-16 | ||
| EP18167463 | 2018-04-16 | ||
| PCT/EP2018/069066 WO2019012100A1 (en) | 2017-07-14 | 2018-07-13 | EXTENDED ACTION FORMULATIONS |
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| KR1020247021329A Division KR20240108542A (ko) | 2017-07-14 | 2018-07-13 | 장기 작용 제형 |
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| KR20200028964A KR20200028964A (ko) | 2020-03-17 |
| KR102679979B1 true KR102679979B1 (ko) | 2024-06-28 |
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| KR1020207003364A Active KR102679979B1 (ko) | 2017-07-14 | 2018-07-13 | 장기 작용 제형 |
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| KR1020247021329A Pending KR20240108542A (ko) | 2017-07-14 | 2018-07-13 | 장기 작용 제형 |
Country Status (29)
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| JP7654544B2 (ja) * | 2018-12-13 | 2025-04-01 | マンカインド コーポレイション | ベダキリンの組成物、それらを含む組み合わせ、それらを調製するための方法、それらを含む使用及び治療方法 |
| CA3182854A1 (en) * | 2020-07-09 | 2022-01-13 | Rene Holm | Long-acting formulations |
| US20240277614A1 (en) * | 2020-07-09 | 2024-08-22 | Janssen Pharmaceutica Nv | Long-acting formulations |
| MX2023000439A (es) | 2020-07-09 | 2023-02-09 | Janssen Pharmaceutica Nv | Formulaciones a largo plazo. |
| KR20230107275A (ko) * | 2020-11-12 | 2023-07-14 | 얀센 파마슈티카 엔.브이. | 비결핵성 마이코박테리아 질환의 치료에서 베다퀼린, 에탐부톨 및 마크롤라이드의 조합물 |
| US11793808B2 (en) | 2021-02-22 | 2023-10-24 | Mannkind Corp. | Compositions of clofazimine, combinations comprising them, processes for their preparation, uses and methods comprising them |
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| WO2024068693A1 (en) | 2022-09-28 | 2024-04-04 | Janssen Pharmaceutica Nv | Long-acting formulations |
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Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5145684A (en) | 1991-01-25 | 1992-09-08 | Sterling Drug Inc. | Surface modified drug nanoparticles |
| US5346702A (en) | 1992-12-04 | 1994-09-13 | Sterling Winthrop Inc. | Use of non-ionic cloud point modifiers to minimize nanoparticle aggregation during sterilization |
| US5352459A (en) | 1992-12-16 | 1994-10-04 | Sterling Winthrop Inc. | Use of purified surface modifiers to prevent particle aggregation during sterilization |
| US6495534B2 (en) | 2000-05-15 | 2002-12-17 | Pharmacia & Upjohn Spa | Stabilized aqueous suspensions for parenteral use |
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| EE05394B1 (et) | 2004-12-24 | 2011-04-15 | Janssen Pharmaceutica N.V. | Kinoliinihendid kasutamiseks latentse tuberkuloosi ravis |
| PT1888604E (pt) | 2005-05-25 | 2012-05-28 | Janssen Pharmaceutica Nv | Processo para preparar (alfa s, beta r)-6-bromo-alfa-[2- (dimetilamino)etil]-2-metoxi-alfa-1-naftalenil-beta-fenil- 3-quinolinoetanol |
| HUE068406T2 (hu) | 2006-06-23 | 2024-12-28 | Janssen Sciences Ireland Unlimited Co | A TMC278 vizes szuszpenziója |
| UA97813C2 (uk) | 2006-12-05 | 2012-03-26 | Янссен Фармацевтика Н.В. | Фумаратна сіль (альфа s, бета r)-6-бром-альфа-[2-(диметиламіно)етил]-2-метоксі-альфа-1-нафталеніл-бета-феніл-3-хінолінетанолу |
| TW201023912A (en) | 2008-12-05 | 2010-07-01 | Alcon Res Ltd | Pharmaceutical suspension |
| US9421194B2 (en) | 2010-04-05 | 2016-08-23 | Rutgers, The State University Of New Jersey | Lung targeting dual drug delivery system |
| TWI577377B (zh) | 2010-09-16 | 2017-04-11 | Ｖｉｉｖ醫療保健公司 | 醫藥組合物 |
| CA2832410C (en) | 2011-04-15 | 2019-07-23 | Janssen Pharmaceutica Nv | Freeze dried drug nanosuspensions |
| EP3177366A4 (en) | 2014-08-08 | 2018-04-04 | Pharmacyclics LLC | Bruton's tyrosine kinase inhibitor combinations and uses thereof |
| US10653679B2 (en) * | 2015-05-04 | 2020-05-19 | Board Of Trustees Of Michigan State University | Compositions and methods for inhibiting bacterial growth |
| HK1254620A1 (zh) | 2015-10-14 | 2019-07-26 | 结核病药物开发全球联盟公司 | 联合抗菌组合物以及短疗程抗菌方案 |
| RU2018111482A (ru) * | 2015-10-20 | 2019-11-21 | Чжэцзян Хисунь Фармасьютикал Ко., Лтд. | Кристаллические формы бедаквилин фумарата и способы их получения |
| WO2018226512A1 (en) | 2017-06-06 | 2018-12-13 | Merck Sharp & Dohme Corp. | Long-action implant for treatment of infectious diseases |
| SI3943070T1 (sl) | 2017-07-14 | 2024-03-29 | Janssen Pharmaceutica Nv, | Dolgo delujoče formulacije bedakilina |
| MX2023000439A (es) | 2020-07-09 | 2023-02-09 | Janssen Pharmaceutica Nv | Formulaciones a largo plazo. |
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| CA3182854A1 (en) | 2020-07-09 | 2022-01-13 | Rene Holm | Long-acting formulations |
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