RU2014149164A - Аналог оксистерола oxy133 индуцирует остеогенез и сигнальный путь hedgehog и ингибирует липогенез - Google Patents
Аналог оксистерола oxy133 индуцирует остеогенез и сигнальный путь hedgehog и ингибирует липогенез Download PDFInfo
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Abstract
1. Соединение, Оху133, имеющее формулу I,или его фармацевтически приемлемая соль или сольват.2. Биоактивная композиция, содержащая соединение Оху133 и фармацевтически приемлемый носитель.3. Биоактивная композиция по п. 2, дополнительно содержащая, по меньшей мере, одно дополнительное средство, выбранное из группы, состоящей из паратиреоидного гормона, фторида натрия, инсулиноподобного фактора роста I (ILGF-I), инсулиноподобного фактора роста II (ILGF-II), трансформирующего ростового фактора бета (TGF-β), ингибитора цитохрома Р450, остеогенного простаноида, BMP 2, BMP 4, BMP 7 и BMP 14.4. Способ лечения субъекта, имеющего заболевание кости, остеопороз или перелом кости, включающий введение субъекту эффективного количества биоактивной композиции по п. 2.5. Способ по п. 4, включающий введение субъекту биоактивной композиции в терапевтически эффективной дозе в эффективной лекарственной форме с подобранным интервалом с целью увеличения костной массы.6. Способ по п. 4, включающий введение субъекту биоактивной композиции в терапевтически эффективной дозе в эффективной лекарственной форме с подобранным интервалом с целью улучшения симптомов остеопороза.7. Способ лечения субъекта, нуждающегося в увеличении остеоморфогенеза и/или остеопролиферации, включающий введение субъекту эффективного количества композиции по п. 2.8. Способ лечения субъекта, предназначенный для стимулирования костеобразования, включающий введение композиции по п. 2 в эффективной лекарственной форме с подобранным интервалом с целью увеличения костной массы.9. Способ индукции остеобластической дифференцировки и/или ингибирования дифференцировки адипоцитов мезенхимальных стволовых клеток млекопитающих, включающий к
Claims (26)
1. Соединение, Оху133, имеющее формулу I,
или его фармацевтически приемлемая соль или сольват.
2. Биоактивная композиция, содержащая соединение Оху133 и фармацевтически приемлемый носитель.
3. Биоактивная композиция по п. 2, дополнительно содержащая, по меньшей мере, одно дополнительное средство, выбранное из группы, состоящей из паратиреоидного гормона, фторида натрия, инсулиноподобного фактора роста I (ILGF-I), инсулиноподобного фактора роста II (ILGF-II), трансформирующего ростового фактора бета (TGF-β), ингибитора цитохрома Р450, остеогенного простаноида, BMP 2, BMP 4, BMP 7 и BMP 14.
4. Способ лечения субъекта, имеющего заболевание кости, остеопороз или перелом кости, включающий введение субъекту эффективного количества биоактивной композиции по п. 2.
5. Способ по п. 4, включающий введение субъекту биоактивной композиции в терапевтически эффективной дозе в эффективной лекарственной форме с подобранным интервалом с целью увеличения костной массы.
6. Способ по п. 4, включающий введение субъекту биоактивной композиции в терапевтически эффективной дозе в эффективной лекарственной форме с подобранным интервалом с целью улучшения симптомов остеопороза.
7. Способ лечения субъекта, нуждающегося в увеличении остеоморфогенеза и/или остеопролиферации, включающий введение субъекту эффективного количества композиции по п. 2.
8. Способ лечения субъекта, предназначенный для стимулирования костеобразования, включающий введение композиции по п. 2 в эффективной лекарственной форме с подобранным интервалом с целью увеличения костной массы.
9. Способ индукции остеобластической дифференцировки и/или ингибирования дифференцировки адипоцитов мезенхимальных стволовых клеток млекопитающих, включающий контактирование клетки с эффективным количеством композиции по п. 2, согласно которому мезенхимальная стволовая клетка млекопитающего является клеткой костномозговой стромы у субъекта.
10. Способ лечения субъекта, у которого наблюдается образование ксантом, локализованное скопление жировых «подушек» и ожирение, включающий введение субъекту эффективного количества биоактивной композиции по п. 2.
11. Способ стимулирования ответа, опосредованного путем hedgehog (Hh), в клетке или ткани, включающий контактирование клетки или ткани с эффективным количеством биоактивной композиции по п. 2.
12. Способ по п. 11, в котором ответ, опосредованный путем hedgehog (Hh), является стимулированием остеобластической дифференцировки, остеоморфогенеза, остеопролиферации и/или ингибированием дифференцировки адипоцитов, морфогенеза адипоцитов и/или пролиферации адипоцитов.
13. Способ по п. 11, в котором ответ, опосредованный путем hedgehog (Hh), является стимулированием роста волос.
14. Способ по п. 11, в котором ответ, опосредованный путем hedgehog (Hh), является стимулированием ангиогенеза.
15. Способ по п. 14, который представляет собой способ лечения сердечнососудистого заболевания, артериосклероза, инфаркта миокарда, болезни периферических сосудов и/или инсульта.
16. Способ по п. 11, в котором ответ, опосредованный путем hedgehog (Hh), представляет собой стимуляцию костеобразования.
17. Способ по п. 16, который представляет собой способ лечения остеоартрита.
18. Способ лечения субъекта, предназначенный для индукции костеобразования, включающий:
сбор мезенхимальных стволовых клеток млекопитающего;
обработку мезенхимальных клеток млекопитающего биоактивной композицией по п. 2, чтобы вызвать остеобластическую дифференцировку; и
введение дифференцированных клеток субъекту.
19. Способ по любому из пп. 4-17, согласно которому биоактивная композиция вводится локально в клетку, ткань или орган у субъекта.
20. Способ стимулирования клетки млекопитающего с целью получения уровня экспрессии биологического маркера остеобластической дифференцировки, превышающего уровень биологического маркера в необработанной клетке, включающий воздействие на клетку млекопитающего эффективного количества соединения по п. 1.
21. Способ по п. 20, в котором биологическим маркером является активность щелочной фосфатазы, включение кальция, минерализация и/или экспрессия мРНК остеокальцина.
22. Способ по п. 20, в котором клетка млекопитающих является мезенхимальной стволовой клеткой, остеопрогениторной клеткой или клеткой в органной культуре кости свода черепа.
23. Способ по п. 20, в котором клетка или ткань находится в культуре (in vitro).
24. Способ по п. 20, в котором клетка или ткань находится in vivo (в организме).
25. Имплантат для применения в организме человека или животного, содержащий субстрат, имеющий поверхность, при этом поверхность или внутреннее пространство имплантата содержит биоактивную композицию по п. 2 в количестве, достаточном для индукции костеобразования в окружающей костной ткани.
26. Имплантат по п. 25, в котором субстрат изготовлен в форме стержня, шурупа, пластинки или протезного сочленения.
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| CN101951915A (zh) | 2007-12-03 | 2011-01-19 | 加利福尼亚大学董事会 | 用于刺猬蛋白信号、骨诱导、抗脂肪形成和wnt信号的激活的氧固醇 |
| EP2847206A4 (en) | 2012-05-07 | 2016-01-20 | Univ California | OXYSTEROL ANALOGUE OXY133 FOR INDUCTION OF OSTEOGENESIS AND HEDGEHOG SIGNALING AND ADIPOGENESIS INHIBITION |
| CN105263500A (zh) * | 2013-05-02 | 2016-01-20 | 加利福尼亚大学董事会 | 骨选择性成骨性氧固醇-骨靶向剂 |
| CA2945404A1 (en) * | 2014-05-02 | 2015-11-05 | The Regents Of The University Of California | Bone-selective osteogenic oxysterol bisphosphonate analogs |
| CN107427526B (zh) | 2014-12-09 | 2021-08-03 | 华沙整形外科股份有限公司 | 涉及甾醇的化合物和方法 |
| EP3310372A4 (en) * | 2015-05-19 | 2019-03-06 | Mayo Foundation For Medical Education And Research | METHOD AND MATERIALS FOR PROMOTING BONE TRAINING |
| US10632230B2 (en) | 2015-07-10 | 2020-04-28 | Warsaw Orthopedic, Inc. | Implants having a high drug load of an oxysterol and methods of use |
| US9878070B2 (en) * | 2015-06-17 | 2018-01-30 | Warsaw Orthopedic, Inc. | Malleable implants including an oxysterol and methods of use |
| CA2986753A1 (en) * | 2015-06-17 | 2016-12-22 | Warsaw Orthopedic, Inc. | Implants including an oxysterol and methods of use |
| US9877836B2 (en) | 2015-07-10 | 2018-01-30 | Warsaw Orthopedic, Inc. | Compression resistant implants including an oxysterol and methods of use |
| US9987289B2 (en) | 2015-07-10 | 2018-06-05 | Warsaw Orthopedic, Inc. | Slow release oxysterols and methods of use |
| US9637514B1 (en) * | 2015-10-26 | 2017-05-02 | MAX BioPharma, Inc. | Oxysterols and hedgehog signaling |
| AU2016347052B2 (en) * | 2015-10-27 | 2021-03-25 | Warsaw Orthopedic, Inc. | Implants having a drug load of an oxysterol and methods of use |
| US11090411B2 (en) | 2016-01-28 | 2021-08-17 | Warsaw Orthopedic, Inc. | Electron beam irradiated osteoinductive bone implant |
| US9987290B2 (en) | 2016-03-28 | 2018-06-05 | Warsaw Orthopedic, Inc. | Methods for the separation and detection of an oxysterol |
| US20170275330A1 (en) * | 2016-03-28 | 2017-09-28 | Warsaw Orthopedic, Inc. | Polymorphic forms of an oxysterol and methods of making them |
| CN105924493A (zh) * | 2016-04-23 | 2016-09-07 | 何华琼 | 盐酸布桂嗪的药物组合物及其在生物医药中的应用 |
| US10688222B2 (en) | 2016-11-21 | 2020-06-23 | Warsaw Orthopedic, Inc. | Lyophilized moldable implants containing an oxysterol |
| US11384114B2 (en) * | 2016-12-09 | 2022-07-12 | Warsaw Orthopedic, Inc. | Polymorphic forms of an oxysterol and methods of making them |
| US10294264B2 (en) | 2017-04-21 | 2019-05-21 | Warsaw Orthopedic, Inc. | Oxysterol-therapeutic agent derivative for bone healing |
| US10434106B2 (en) | 2017-05-19 | 2019-10-08 | Warsaw Orthopedic, Inc. | Oxysterol-statin compounds for bone growth |
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| WO2019048898A1 (en) | 2017-09-05 | 2019-03-14 | INSERM (Institut National de la Santé et de la Recherche Médicale) | PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF ENDOTHELIAL DYSFUNCTION |
| KR102283508B1 (ko) * | 2020-04-17 | 2021-07-29 | 가톨릭대학교 산학협력단 | 골형성 단백질-2를 유효성분으로 포함하는 줄기세포 스페로이드의 골분화 촉진용 조성물 |
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| KR20150013232A (ko) | 2015-02-04 |
| AU2013260059A1 (en) | 2014-11-27 |
| HK1207649A1 (en) | 2016-02-05 |
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| EP2847206A4 (en) | 2016-01-20 |
| CA2872751A1 (en) | 2013-11-14 |
| US9717742B2 (en) | 2017-08-01 |
| RU2632191C2 (ru) | 2017-10-03 |
| IN2014DN09805A (ru) | 2015-07-31 |
| EP2847206A1 (en) | 2015-03-18 |
| CN104395331A (zh) | 2015-03-04 |
| CN104395331B (zh) | 2016-11-02 |
| JP2015518493A (ja) | 2015-07-02 |
| WO2013169399A1 (en) | 2013-11-14 |
| JP6262723B2 (ja) | 2018-01-17 |
| AU2013260059B2 (en) | 2017-05-18 |
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| Liu et al. | The effect of low-intensity pulsed ultrasound on the osseointegration of titanium dental implants | |
| CA2643732A1 (en) | Oxysterol compounds and the hedgehog pathway | |
| Wallach et al. | Effects of calcitonin on animal and in vitro models of skeletal metabolism | |
| Rajamannan | Calcific aortic valve disease: cellular origins of valve calcification | |
| Chen et al. | Low-magnitude, high-frequency vibration promotes the adhesion and the osteogenic differentiation of bone marrow-derived mesenchymal stem cells cultured on a hydroxyapatite-coated surface: The direct role of Wnt/β-catenin signaling pathway activation | |
| Mackiewicz et al. | Bone as a source of organism vitality and regeneration | |
| Yan et al. | Low-intensity pulsed ultrasound: a potential non-invasive therapy for femoral head osteonecrosis | |
| Bradaschia-Correa et al. | Ecto-5′-nucleotidase (CD73) regulates bone formation and remodeling during intramembranous bone repair in aging mice | |
| Castillo et al. | Bone homeostasis and repair: forced into shape | |
| Drager et al. | Local delivery of iron chelators reduces in vivo remodeling of a calcium phosphate bone graft substitute | |
| Rubnikovich et al. | Morphological changes in the bone tissue around dental implants after low-frequency low-intensity ultrasound applications | |
| Tao et al. | Parathyroid hormone (1–34) can reverse the negative effect of valproic acid on the osseointegration of titanium rods in ovariectomized rats | |
| Zhu et al. | Lactate mediates the bone anabolic effect of high-intensity interval training by inducing osteoblast differentiation | |
| Uzan et al. | Application of low intensity mechanical vibrations for bone tissue maintenance and regeneration |