JP5021318B2 - β−シクロデキストリンを液体投薬形態に用いて多用量製剤を達成するための抗菌性防腐剤 - Google Patents
β−シクロデキストリンを液体投薬形態に用いて多用量製剤を達成するための抗菌性防腐剤 Download PDFInfo
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- JP5021318B2 JP5021318B2 JP2006550330A JP2006550330A JP5021318B2 JP 5021318 B2 JP5021318 B2 JP 5021318B2 JP 2006550330 A JP2006550330 A JP 2006550330A JP 2006550330 A JP2006550330 A JP 2006550330A JP 5021318 B2 JP5021318 B2 JP 5021318B2
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- cyclodextrin
- formula
- compound
- cresol
- meta
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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
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| PCT/IB2005/000100 WO2005082416A2 (en) | 2004-01-30 | 2005-01-17 | Antimicrobial preservatives to achieve multi-dose formulation using beta-cyclodextrins for liquid dosage forms |
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| CA2852716C (en) * | 2011-11-29 | 2015-11-17 | Jurox Pty Ltd | Methods of preserving injectable pharmaceutical compositions comprising a cyclodextrin and a hydrophobic drug |
| HRP20251029T1 (hr) | 2013-07-19 | 2025-10-24 | Boehringer Ingelheim Vetmedica Gmbh | Konzervirani eterificirani derivati ciklodekstrina koji sadrže tekući vodeni farmaceutski pripravak |
| PL3106150T3 (pl) | 2013-12-04 | 2022-01-03 | Boehringer Ingelheim Vetmedica Gmbh | Ulepszone kompozycje farmaceutyczne pimobendanu |
| NL2015865B1 (en) | 2015-11-27 | 2017-06-13 | Le Vet B V | Maropitant Formulation. |
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| EP3645120B1 (en) | 2017-06-30 | 2024-12-11 | Chase Therapeutics Corporation | Nk-1 antagonist compositions and methods for use in treating depression |
| CA3129648A1 (en) * | 2019-02-15 | 2020-08-20 | Saol International Limited | Injectable formulations comprising phenol and cyclodextrin and uses thereof________________________________ |
| EP3725298A1 (en) | 2019-04-16 | 2020-10-21 | Faes Farma, S.A. | Stable and preserved pharmaceutical compositions of bilastine |
| CN112370451A (zh) * | 2020-12-08 | 2021-02-19 | 河北科技大学 | 一种枸橼酸马罗匹坦包合物、注射液及制备方法 |
| AT527172A1 (de) * | 2023-04-25 | 2024-11-15 | Vetviva Richter Gmbh | Maropitantformulierung |
Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5910510A (ja) * | 1982-07-08 | 1984-01-20 | Nippon Zenyaku Kogyo Kk | 低刺激性チアムリン注射剤 |
| JPS59152320A (ja) * | 1983-02-17 | 1984-08-31 | Takeda Chem Ind Ltd | 水性製剤 |
| JPS6419737A (en) * | 1987-07-15 | 1989-01-23 | Hitachi Ltd | Multilayer interconnection tape carrier |
| JPH039848A (ja) * | 1989-06-06 | 1991-01-17 | Canon Inc | 液体噴射記録装置 |
| WO1992021677A1 (en) | 1991-05-31 | 1992-12-10 | Pfizer Inc. | bibNUCLIDINE DERIVATIVES |
| US5602112A (en) * | 1992-06-19 | 1997-02-11 | Supergen, Inc. | Pharmaceutical formulation |
| KR950704311A (ko) | 1992-11-12 | 1995-11-17 | 알렌 제이. 스피겔 | 물질 p 길항체로서의 퀴누클리딘 유도체(quinuclidine derivative as substance p antagonist) |
| US5393762A (en) | 1993-06-04 | 1995-02-28 | Pfizer Inc. | Pharmaceutical agents for treatment of emesis |
| WO2000012137A1 (en) | 1998-09-02 | 2000-03-09 | Allergan Sales, Inc. | Preserved cyclodextrin-containing compositions |
| US6255320B1 (en) | 1999-06-01 | 2001-07-03 | Pfizer Inc. | Polymorphs of a crystalline azo-bicyclo (2,2,2) octan-3-amine citrate and their pharmaceutical compositions |
| AU5975700A (en) * | 1999-07-02 | 2001-01-22 | Janssen Pharmaceutica N.V. | Nasal formulation of an antifungal |
| US7163681B2 (en) * | 2000-08-07 | 2007-01-16 | Centocor, Inc. | Anti-integrin antibodies, compositions, methods and uses |
| US7034013B2 (en) * | 2001-03-20 | 2006-04-25 | Cydex, Inc. | Formulations containing propofol and a sulfoalkyl ether cyclodextrin |
| EP1383445A4 (en) * | 2001-03-20 | 2005-04-13 | Cydex Inc | FORMULATIONS WITH PROPOFOL AND A SULFOALKYL ETHER CYCLODEXTRIN |
| KR20040029375A (ko) * | 2001-07-20 | 2004-04-06 | 화이자 프로덕츠 인코포레이티드 | 개, 고양이 및 말에서 결함있는 행태를 변화시키기 위한ｎｋ-1 수용체 길항제의 용도 |
| WO2003072141A1 (en) | 2002-02-22 | 2003-09-04 | Pharmacia Corporation | Ophthalmic antibiotic drug formulations containing a cyclodextrin compound and cetyl pyridinium chloride |
| US6869939B2 (en) | 2002-05-04 | 2005-03-22 | Cydex, Inc. | Formulations containing amiodarone and sulfoalkyl ether cyclodextrin |
| DE10228049A1 (de) | 2002-06-24 | 2004-01-15 | Merck Patent Gmbh | Flüssige Zubereitung enthaltend Oligopeptide |
| US6861526B2 (en) | 2002-10-16 | 2005-03-01 | Pfizer Inc. | Process for the preparation of (S,S)-cis-2-benzhydryl-3-benzylaminoquinuclidine |
| MXPA06008648A (es) | 2004-01-30 | 2006-09-04 | Pfizer Prod Inc | Composiciones farmaceuticas de antagonistas del receptor de neuroquinina y ciclodextrina y metodos para una tolerancia mejorada en el sitio de inyeccion. |
| WO2005082366A1 (en) | 2004-01-30 | 2005-09-09 | Pfizer Products Inc. | Nk-1 receptor antagonists anesthesia recovery |
| ES2296131T3 (es) | 2004-02-02 | 2008-04-16 | Pfizer Products Incorporated | Procedimiento para la preparacion de 1-(2s,3s)-2-bencidril-n-(5-terc-butil-2-metoxibencil)quinuclidin-3-amina. |
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