RU2744878C2 - Ингибиторы дипептидилпептидазы-4 для местного офтальмологического лечения нейродегенеративных заболеваний сетчатки - Google Patents
Ингибиторы дипептидилпептидазы-4 для местного офтальмологического лечения нейродегенеративных заболеваний сетчатки Download PDFInfo
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- RU2744878C2 RU2744878C2 RU2018140127A RU2018140127A RU2744878C2 RU 2744878 C2 RU2744878 C2 RU 2744878C2 RU 2018140127 A RU2018140127 A RU 2018140127A RU 2018140127 A RU2018140127 A RU 2018140127A RU 2744878 C2 RU2744878 C2 RU 2744878C2
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- retinal
- inhibitor
- topical
- veterinary
- saxagliptin
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| RU2727898C1 (ru) * | 2020-02-25 | 2020-07-24 | Общество с ограниченной ответственностью «Необиотек» | Фармацевтическая композиция на основе действующего вещества, ингибитора дипептидилпептидазы-4, для предупреждения развития и лечения сахарного диабета 2 типа |
| CN111166870A (zh) * | 2020-03-18 | 2020-05-19 | 复旦大学附属眼耳鼻喉科医院 | 艾塞那肽在制备滴眼治疗眼部缺血疾病、改善眼部血液循环的药物中的应用 |
| GB202014740D0 (en) * | 2020-09-18 | 2020-11-04 | Invex Therapeutics Ltd | Method of reducing intraocular pressure |
| WO2026078034A1 (en) | 2024-10-09 | 2026-04-16 | Fundació Hospital Universitari Vall D'hebron - Institut De Recerca | Sitagliptin for use in retinal diseases with neovascularization |
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| RU2189233C2 (ru) * | 1996-04-25 | 2002-09-20 | Пробиодруг Гезелльшафт Фюр Арцнаймиттельфоршунг Мбх | Применение снижающих активность эффекторов дипептидил пептидазы (dp iv) и соответственно энзима dp iv с аналогичной активностью для снижения уровня сахара в крови |
| US20080221200A1 (en) * | 2005-09-30 | 2008-09-11 | Malcolm Allison | Combination of Organic Compounds |
| EP2444094A1 (en) * | 2009-06-16 | 2012-04-25 | Hainan Deze Drug Research Co., Ltd. | Mangiferin-berberine salt, manufacturing method and use thereof |
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| US7560597B2 (en) * | 2007-03-08 | 2009-07-14 | The University Court Of The University Of Aberdeen | 2′,4′-dichloro-biphenyl-4-yl-hydroxy-ketones and related compounds and their use as therapeutic agents |
| WO2009084024A2 (en) * | 2007-11-02 | 2009-07-09 | Glenmark Generics Limited | A process for the preparation of r-sit agliptin and its pharmaceutically acceptable salts thereof |
| US20100330177A1 (en) * | 2008-02-05 | 2010-12-30 | Merck Sharp & Dohme Corp. | Pharmaceutical compositions of a combination of metformin and a dipeptidyl peptidase-iv inhibitor |
| EP2251028A1 (en) * | 2009-05-12 | 2010-11-17 | Biocompatibles Uk Ltd. | Treatment of eye diseases using encapsulated cells encoding and secreting an anti-angiogenic factor and/or a neuroprotective factor |
| TWI469785B (zh) * | 2012-04-25 | 2015-01-21 | Inovobiologic Inc | 用於治療代謝性疾病之膳食纖維組成物 |
| JP6368722B2 (ja) * | 2013-03-01 | 2018-08-01 | フンダシオ オスピタル ウニベルシタリ バル デブロン−インスティテュート デ レセルカ | 網膜神経変性疾患の、特に、初期の糖尿病性網膜症及び神経変性が本質的な役割を果たす他の網膜疾患における局所治療における使用のためのペプチド |
| CA2914791A1 (en) * | 2013-06-14 | 2014-12-18 | Boehringer Ingelheim International Gmbh | Dpp-4 inhibitors for treating diabetes and its complications |
| JP7068706B2 (ja) * | 2016-04-29 | 2022-05-17 | フンダシオ オスピタル ウニベルシタリ バル デブロン－インスティテュート デ レセルカ | 網膜神経変性疾患の眼局所治療のためのジペプチジルペプチダーゼ－４阻害剤 |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2189233C2 (ru) * | 1996-04-25 | 2002-09-20 | Пробиодруг Гезелльшафт Фюр Арцнаймиттельфоршунг Мбх | Применение снижающих активность эффекторов дипептидил пептидазы (dp iv) и соответственно энзима dp iv с аналогичной активностью для снижения уровня сахара в крови |
| US20080221200A1 (en) * | 2005-09-30 | 2008-09-11 | Malcolm Allison | Combination of Organic Compounds |
| EP2444094A1 (en) * | 2009-06-16 | 2012-04-25 | Hainan Deze Drug Research Co., Ltd. | Mangiferin-berberine salt, manufacturing method and use thereof |
Non-Patent Citations (4)
| Title |
|---|
| Rahul S Pandit et al: "Retinal and lens protective effect of sitagliptin in streptozotocin induced type-I diabetic wistar rats", Biomedicine & Aging Pathology, 01.04.2013, v.3, n.2, р. 65-73, , параграф 2,5. * |
| Rahul S Pandit et al: "Retinal and lens protective effect of sitagliptin in streptozotocin induced type-I diabetic wistar rats", Biomedicine & Aging Pathology, 01.04.2013, v.3, n.2, р. 65-73, реферат, параграф 2,5. * |
| Yuya Nakamura et al: "Diabetes therapies in hemodialysis patients: Dipeptidase-4 inhibitors", World Journal of Diabetes, 01.01.2015, v.6, n. 6, стр. 845, табл.4, . * |
| Yuya Nakamura et al: "Diabetes therapies in hemodialysis patients: Dipeptidase-4 inhibitors", World Journal of Diabetes, 01.01.2015, v.6, n. 6, стр. 845, табл.4, реферат. * |
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| CN109152776A (zh) | 2019-01-04 |
| JP7068706B2 (ja) | 2022-05-17 |
| RU2018140127A3 (https=) | 2020-07-02 |
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| US11918577B2 (en) | 2024-03-05 |
| EP3448388B1 (en) | 2020-11-18 |
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| BR112018072127A2 (pt) | 2019-03-19 |
| IL262526B (en) | 2022-05-01 |
| KR102411574B1 (ko) | 2022-06-21 |
| CA3022152A1 (en) | 2017-11-02 |
| EP3448388A1 (en) | 2019-03-06 |
| AU2017256803B2 (en) | 2022-12-01 |
| RU2018140127A (ru) | 2020-05-29 |
| US11013738B2 (en) | 2021-05-25 |
| JP2019519479A (ja) | 2019-07-11 |
| CA3022152C (en) | 2024-10-29 |
| ES2863701T3 (es) | 2021-10-11 |
| KR20190003575A (ko) | 2019-01-09 |
| DK3448388T3 (da) | 2021-02-08 |
| US20210315890A1 (en) | 2021-10-14 |
| CN109152776B (zh) | 2022-04-29 |
| IL262526A (en) | 2018-12-31 |
| US20190134030A1 (en) | 2019-05-09 |
| AU2017256803A1 (en) | 2018-12-06 |
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