RU2197967C2 - Способ повышения биологической доступности фексофенадина и его производных - Google Patents
Способ повышения биологической доступности фексофенадина и его производных Download PDFInfo
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- RU2197967C2 RU2197967C2 RU2000106042/14A RU2000106042A RU2197967C2 RU 2197967 C2 RU2197967 C2 RU 2197967C2 RU 2000106042/14 A RU2000106042/14 A RU 2000106042/14A RU 2000106042 A RU2000106042 A RU 2000106042A RU 2197967 C2 RU2197967 C2 RU 2197967C2
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- Prior art keywords
- peg
- glycoprotein
- antihistamine
- inhibitor
- glycoprotein inhibitor
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Cited By (4)
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| RU2352561C2 (ru) * | 2003-08-26 | 2009-04-20 | Сипла Лимитед | Полиморфы фексофенадина и способы их получения |
| RU2404758C2 (ru) * | 2004-08-03 | 2010-11-27 | Новартис Аг | Способы повышения биологической доступности ингибитора ренина |
| RU2453315C2 (ru) * | 2010-08-17 | 2012-06-20 | Открытое акционерное общество "Химико-фармацевтический комбинат "АКРИХИН" (ОАО "АКРИХИН") | Фармацевтическая композиция для лечения аллергических заболеваний |
| RU2504018C1 (ru) * | 2012-05-28 | 2014-01-10 | Государственное бюджетное образовательное учреждение высшего профессионального образования "Рязанский государственный медицинский университет имени академика И.П. Павлова" Министерства здравоохранения и социального развития Российской Федерации | Способ моделирования состояния индукции функциональной активности гликопротеина-р финастеридом в эксперименте |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE69624559T2 (de) | 1995-02-28 | 2003-07-10 | Aventis Pharmaceuticals Inc., Bridgewater | Arzneizubereitungen für piperidinalkanolderivate |
| EP0998272B1 (en) * | 1997-08-26 | 2003-05-02 | Aventis Pharmaceuticals Inc. | Pharmaceutical composition for combination of piperidinoalkanol-decongestant |
| GB9822170D0 (en) * | 1998-10-13 | 1998-12-02 | Danbioyst Uk Ltd | Novel formulations of fexofenadine |
| WO2003101437A2 (en) * | 2002-05-29 | 2003-12-11 | Aventis Pharmaceuticals Holdings Inc. | Method of treating asthma using fexofenadine |
| JP2008120684A (ja) * | 2005-03-07 | 2008-05-29 | Kumamoto Univ | 抗アレルギー薬 |
| KR101106374B1 (ko) | 2009-06-05 | 2012-01-19 | 민병욱 | 고체연료에 의한 가연성 가스 발생 장치 |
| KR101117014B1 (ko) * | 2009-09-09 | 2012-06-14 | 민병욱 | 부패성 폐기물의 바이오매스 처리에 의한 폐자원 재활용 방법 및 장치 |
| CN101843616B (zh) * | 2010-06-04 | 2011-07-27 | 西安万隆制药有限责任公司 | 一种盐酸非索非那定与微晶纤维素组合物及其制备方法 |
| EA201391742A1 (ru) | 2011-05-20 | 2014-04-30 | Авентис Фармасьютикалз Инк. | Фармацевтическая композиция, включающая фексофенадин |
| RU2553362C1 (ru) * | 2014-01-09 | 2015-06-10 | Государственное бюджетное образовательное учреждение высшего профессионального образования "Рязанский государственный медицинский университет имени академика И.П. Павлова" Министерства здравоохранения Российской Федерации | Способ моделирования состояния ингибирования функциональной активности гликопротеина-р линестренолом в эксперименте |
| CN104188998A (zh) * | 2014-09-18 | 2014-12-10 | 中山大学 | 一种柚皮苷与盐酸非索非那丁药物组合物及其制剂 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4254129A (en) * | 1979-04-10 | 1981-03-03 | Richardson-Merrell Inc. | Piperidine derivatives |
| US5567592A (en) * | 1994-02-02 | 1996-10-22 | Regents Of The University Of California | Screening method for the identification of bioenhancers through the inhibition of P-glycoprotein transport in the gut of a mammal |
| RU2079301C1 (ru) * | 1989-01-31 | 1997-05-20 | Др.Цозер Б.Салама | Способ регулируемого выделения активного вещества из состава |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2224227A1 (en) * | 1995-06-07 | 1996-12-19 | Avmax, Inc. | Use of essential oils to increase bioavailability of oral pharmaceutical compounds |
| AU5893796A (en) * | 1995-06-07 | 1996-12-30 | Novo Nordisk A/S | Modification of polypeptides |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4254129A (en) * | 1979-04-10 | 1981-03-03 | Richardson-Merrell Inc. | Piperidine derivatives |
| RU2079301C1 (ru) * | 1989-01-31 | 1997-05-20 | Др.Цозер Б.Салама | Способ регулируемого выделения активного вещества из состава |
| US5567592A (en) * | 1994-02-02 | 1996-10-22 | Regents Of The University Of California | Screening method for the identification of bioenhancers through the inhibition of P-glycoprotein transport in the gut of a mammal |
Non-Patent Citations (1)
| Title |
|---|
| FLOREN LC et al, Tacrolimus oral bioavailability doubles with coadministration of ketoconazole. Clin. Pharmacol. Ther. 1997, Jul. 62(1):41-9. * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2352561C2 (ru) * | 2003-08-26 | 2009-04-20 | Сипла Лимитед | Полиморфы фексофенадина и способы их получения |
| RU2404758C2 (ru) * | 2004-08-03 | 2010-11-27 | Новартис Аг | Способы повышения биологической доступности ингибитора ренина |
| RU2453315C2 (ru) * | 2010-08-17 | 2012-06-20 | Открытое акционерное общество "Химико-фармацевтический комбинат "АКРИХИН" (ОАО "АКРИХИН") | Фармацевтическая композиция для лечения аллергических заболеваний |
| RU2504018C1 (ru) * | 2012-05-28 | 2014-01-10 | Государственное бюджетное образовательное учреждение высшего профессионального образования "Рязанский государственный медицинский университет имени академика И.П. Павлова" Министерства здравоохранения и социального развития Российской Федерации | Способ моделирования состояния индукции функциональной активности гликопротеина-р финастеридом в эксперименте |
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