RU2325396C2 - Производные 5бета-сапогенина и псевдосапогенина и их применение при лечении деменции - Google Patents
Производные 5бета-сапогенина и псевдосапогенина и их применение при лечении деменции Download PDFInfo
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- RU2325396C2 RU2325396C2 RU2002111355/04A RU2002111355A RU2325396C2 RU 2325396 C2 RU2325396 C2 RU 2325396C2 RU 2002111355/04 A RU2002111355/04 A RU 2002111355/04A RU 2002111355 A RU2002111355 A RU 2002111355A RU 2325396 C2 RU2325396 C2 RU 2325396C2
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- smilagenin
- sarsasapogenin
- neurons
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| PL213697B1 (pl) * | 2002-03-27 | 2013-04-30 | Phytopharm Plc | Substancje czynne do stosowania w leczeniu chorób, zwlaszcza chorób neurodegeneracyjnych |
| NZ535093A (en) * | 2002-03-27 | 2006-09-29 | Phytopharm Plc | Therapeutic methods and uses of sapogenins and their derivatives |
| KR20080031062A (ko) * | 2002-03-27 | 2008-04-07 | 파이토팜 피엘씨 | 사포게닌 및 그 유도체의 치료 방법 및 용도 |
| US7718792B2 (en) | 2002-10-28 | 2010-05-18 | Phytopharm Plc | Stereospecific reduction of sapogen-3-ones |
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| CN101768202B (zh) * | 2009-02-18 | 2013-10-30 | 沈阳药科大学 | 知母中菝葜皂苷元及其衍生物的制备方法及其医药新用途 |
| AU2011281336B2 (en) | 2010-07-20 | 2015-03-05 | Junaxo, Inc. | Treatment of L-DOPA, dopamine agonist and/or dopamine enhancer induced disorders |
| CU20110244A7 (es) * | 2011-12-27 | 2013-08-29 | Ct De Investigación Y Desarrollo De Medicamentos Cidem | Sistemas espiroesteroidales con efectos neuroactivos y anti-inflamatorios |
| US11319338B2 (en) | 2012-04-03 | 2022-05-03 | Goldporp Pharma Limited | Timosaponin compounds |
| CN102924559B (zh) * | 2012-11-16 | 2015-10-28 | 沈阳药科大学 | 菝葜皂苷元衍生物及其制备和应用 |
| CN103232520A (zh) * | 2013-05-13 | 2013-08-07 | 中国药科大学 | 一种螺甾类化合物、其制备方法及医药用途 |
| CN106905407B (zh) * | 2015-01-27 | 2019-08-13 | 华东理工大学 | 知母皂苷元结构修饰的衍生物、其药物组合物及其应用 |
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Family Cites Families (77)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB852847A (en) | 1958-03-04 | 1960-11-02 | British Drug Houses Ltd | Improvements in or relating to 6-methyl steroid compounds |
| US3575810A (en) * | 1967-07-19 | 1971-04-20 | Takashi Matsushima | Method for removal of side chain of sapogenins |
| BE794362A (fr) | 1972-01-22 | 1973-07-23 | Merck Patent Gmbh | Sulfates hydrosolubles de sterine |
| US3929769A (en) | 1972-05-19 | 1975-12-30 | Ciba Geigy Corp | Process for the manufacture of steroid epoxides |
| CA985172A (en) | 1972-10-06 | 1976-03-09 | Dushan M. Dvornik | Compositions and methods for reducing blood cholesterol |
| DE2416978A1 (de) | 1974-04-08 | 1975-10-09 | Degussa | Arzneimittel mit dem hauptsapogenin der helleborus-arten als wirkstoff |
| LU81256A1 (fr) | 1979-05-15 | 1980-12-16 | Oreal | Composition cosmetique capillaire notamment pour le lavage et/ou le demelage des cheveux,a base d'un extrait de plantes contenant des saponosides |
| IT1144136B (it) | 1980-03-05 | 1986-10-29 | Zenyaku Kogyo Kk | Glucosidi di condurango agenti antitumorali che li comprendono e procedimento per la loro preparazione |
| GB2097672A (en) | 1981-05-01 | 1982-11-10 | Pattni Ramesh Damji Devji | Process for extraction of crude sapogenins from Agave Leaves |
| JPS5855500A (ja) | 1981-09-25 | 1983-04-01 | Tokiwa Yakuhin Kogyo Kk | 16−デヒドロプレグネノロンの製造法 |
| US4602003A (en) | 1982-05-17 | 1986-07-22 | Medical Research Foundation Of Oregon | Synthetic compounds to inhibit intestinal absorption of cholesterol in the treatment of hypercholesterolemia |
| US4602005A (en) | 1982-05-17 | 1986-07-22 | Medical Research Foundation Of Oregon | Tigogenin cellobioside for treating hypercholesterolemia and atherosclerosis |
| US4562250A (en) | 1982-09-13 | 1985-12-31 | Regents Of The University Of Minnesota | Steroidal glycosides produced by Yucca tissue culture |
| US4546097A (en) | 1983-11-04 | 1985-10-08 | The United States Of America As Represented By The Department Of Health And Human Services | Saponin-based polyether polyols, pharmaceutical compositions and a method of using same |
| US4680289A (en) | 1985-06-05 | 1987-07-14 | Progenics, Inc. | Treatment of obesity and diabetes using sapogenins |
| JPS62234025A (ja) | 1986-04-03 | 1987-10-14 | Asahi Chem Ind Co Ltd | 老人性痴呆者用食品 |
| US5017562A (en) | 1987-02-11 | 1991-05-21 | Regents Of The University Of Minnesota | Crystalline saponin-containing complex |
| DE3838716A1 (de) | 1988-11-15 | 1990-05-17 | Kanoldt Arzneimittel Gmbh | Arzneimittelzubereitung aus esterderivaten des hecogenins und dessen verwendung zur behandlung von benigner prostatahyperplasie |
| JPH02188528A (ja) | 1989-01-13 | 1990-07-24 | Tsurataka Tashiro | 痴呆症治療薬 |
| ATE188036T1 (de) | 1990-01-18 | 2000-01-15 | Cura Nominees Pty Ltd | Glykoalkaloide |
| SE9100342D0 (sv) | 1991-02-04 | 1991-02-04 | Astra Ab | Novel steroid esters |
| US5252729A (en) | 1991-10-23 | 1993-10-12 | Schering Corporation | Extraction of compounds from plant materials using supercritical fluids |
| US5244887A (en) | 1992-02-14 | 1993-09-14 | Straub Carl D | Stanols to reduce cholesterol absorption from foods and methods of preparation and use thereof |
| JPH05246866A (ja) * | 1992-03-06 | 1993-09-24 | Ruibosuteii Japan:Kk | 脳代謝促進・脳機能改善剤 |
| JPH07504921A (ja) | 1992-06-26 | 1995-06-01 | フアイザー・インコーポレイテツド | 高コレステロール血症を治療するためのステロイドグリコシド |
| DE4303214A1 (de) * | 1993-02-04 | 1994-08-11 | Wolfgang Marks | Behandlung von Erkrankungen viraler, viroidaler oder onkogener Genese durch Steroid-Saponine oder deren Aglykone |
| WO1994018994A1 (en) | 1993-02-23 | 1994-09-01 | Pharmakon Usa, Inc. | Therapeutic herbal composition |
| CN1052636C (zh) | 1993-03-29 | 2000-05-24 | 中国科学院沈阳应用生态研究所 | 文冠果子的醇提取物在制备治疗智力低下的药物中的应用 |
| CN1092992A (zh) | 1993-03-29 | 1994-10-05 | 中国科学院沈阳应用生态研究所 | 提高脑功能的药物及其制备方法 |
| JPH06305952A (ja) | 1993-04-27 | 1994-11-01 | Sumitomo Pharmaceut Co Ltd | スレオ−3−(3,4−ジヒドロキシフェニル)セリン経鼻投与製剤 |
| EP0696292A1 (en) | 1993-04-28 | 1996-02-14 | Pfizer Inc. | Spirostanyl glycosidal crystalline monohydrate |
| CN1033754C (zh) * | 1993-05-31 | 1997-01-08 | 上海第二医科大学 | 知母皂甙元作为制备β肾上腺素和M胆碱受体双向调节药的用途及其制法 |
| CN1102186A (zh) | 1993-10-29 | 1995-05-03 | 沈阳医学院 | 中药薤白新成分的鉴定及用途 |
| US5589182A (en) | 1993-12-06 | 1996-12-31 | Tashiro; Renki | Compositions and method of treating cardio-, cerebro-vascular and alzheimer's diseases and depression |
| WO1995018144A1 (en) | 1993-12-28 | 1995-07-06 | Pfizer Inc. | Steroidal glycosides |
| CA2180148A1 (en) | 1993-12-28 | 1995-07-06 | Michael Paul Deninno | Hypocholesterolemic agents |
| IL109614A (en) | 1994-05-10 | 1998-06-15 | Yissum Res Dev Co | Comestible products containing saponins |
| US5563131A (en) | 1994-08-04 | 1996-10-08 | Pherin Corporation | Pregnane steroids as neurochemical initiators of change in human hypothalamic function and related pharmaceutical compositions and methods |
| US5840740A (en) | 1995-06-07 | 1998-11-24 | Magainin Pharmaceuticals Inc. | Aminosterol compounds and a method of treating infection using the aminosterol compounds |
| US5856535A (en) | 1994-08-18 | 1999-01-05 | Magainin Pharmaceuticals, Inc. | Aminosterol ester compounds |
| CA2198097A1 (en) | 1994-08-30 | 1996-03-07 | Douglas J. Allen | Spirostanyl glycosidal crystals |
| AU2453295A (en) | 1994-09-20 | 1996-04-19 | Pfizer Inc. | Combination of a cholesterol absorption inhibitor and a cholesterol synthesis inhibitor |
| WO1996038466A1 (en) | 1995-05-29 | 1996-12-05 | Pfizer Inc. | Steroidal glycosides |
| US5847172A (en) | 1995-06-07 | 1998-12-08 | Magainin Pharmaceuticals Inc. | Certain aminosterol compounds and pharmaceutical compositions including these compounds |
| US5763430A (en) | 1995-06-07 | 1998-06-09 | Magainin Pharmaceuticals Inc. | Method of treating a viral infection by administering a steroid compound |
| US5840936A (en) | 1995-06-07 | 1998-11-24 | Magainin Pharmaceuticals Inc. | Aminosterol compounds useful as inhibitors of the sodium/proton exchanger (NHE) |
| US5792635A (en) | 1995-06-07 | 1998-08-11 | Magainin Pharmaceuticals, Inc. | Method of inhibiting the sodium/proton exchanger NHE3 and method of inhibiting growth by administering squalamine |
| US5795885A (en) | 1995-06-07 | 1998-08-18 | Magainin Pharmaceuticals Inc. | Method of inhibiting profileration of cells by administering an aminosterol compound |
| US6143738A (en) | 1995-06-07 | 2000-11-07 | Magainin Pharmaceuticals, Inc. | Therapeutic uses for an aminosterol compound |
| JPH09100295A (ja) | 1995-06-13 | 1997-04-15 | Toray Ind Inc | 新規トリテルペノイドサポニン類およびそれを有効成分とする神経突起伸展作用を有する治療剤 |
| CU22860A1 (es) | 1995-10-12 | 2003-05-26 | Univ La Habana | Espirostanonas con funciones oxigenadas en el anillo a. como reguladores del crecimiento vegetal y su procedimiento de obtención |
| EP0863141B1 (en) | 1995-10-13 | 2001-09-12 | Banyu Pharmaceutical Co., Ltd. | Substituted heteroaromatic derivatives |
| FR2743561B1 (fr) | 1996-01-15 | 1998-02-20 | Fournier Sca Lab | Derives de steroides, procede de preparation et utilisation en therapeutique |
| KR0169536B1 (ko) | 1996-02-27 | 1999-01-15 | 손경식 | 신규한 인삼 사포닌, 그의 제조방법 및 이를 유효성분으로 하는 항종양제 |
| US5726179A (en) | 1996-04-01 | 1998-03-10 | The University Of Toledo | Muscarinic agonists |
| EP0923376B1 (en) | 1996-05-09 | 2004-11-03 | Amrad Operations Pty.,Ltd. | Use of steroids for treatment of asthma and airway diseases |
| CA2632790A1 (en) | 1996-07-22 | 1998-01-29 | Renovo Limited | Use of sex steroid function modulators to treat wounds and fibrotic disorders |
| US5804239A (en) | 1996-07-26 | 1998-09-08 | Nouveau Technologies, Inc. | Method and composition for food flavoring |
| WO1998051302A1 (en) | 1997-05-15 | 1998-11-19 | University Of Washington | Composition and methods for treating alzheimer's disease and other amyloidoses |
| AU7979998A (en) | 1997-06-20 | 1999-01-04 | University Of Utah Research Foundation | Use of plant-alkaloids to enhance innate immunity defense mechanisms |
| JP4520033B2 (ja) | 1997-08-28 | 2010-08-04 | エフエックス ライフ サイエンシズ アクチェンゲゼルシャフト | 薬草抽出物の化学的および薬理学的標準化 |
| JP3906948B2 (ja) * | 1997-09-13 | 2007-04-18 | 本田技研工業株式会社 | 電動式変速装置の変速制御装置 |
| CN1131237C (zh) * | 1997-09-26 | 2003-12-17 | 中国人民解放军军事医学科学院放射医学研究所 | 甾体皂甙防治老年性痴呆的用途及新的甾体皂甙 |
| CA2217088A1 (en) | 1997-09-30 | 1999-03-30 | Universite De Sherbrooke | New mandevilla velutina derivatives as steady-state r-type ca2+ channel blockers, method of making and use thereof |
| JP3873097B2 (ja) | 1997-11-06 | 2007-01-24 | 独立行政法人理化学研究所 | 抗肥満剤及び脂質代謝改善剤 |
| HUP0101693A3 (en) * | 1998-03-26 | 2002-08-28 | Phytopharm Plc Godmanchester | Use of steroidal sapogenins and their derivatives for producing pharmaceutical compositions for the treatment of alzheimeirs disease |
| GB9923076D0 (en) | 1999-09-29 | 1999-12-01 | Phytopharm Plc | Sapogenin derivatives and their use |
| GB9905275D0 (en) | 1999-03-08 | 1999-04-28 | Phytopharm Ltd | Treatment of conditions associated with membrane-bound receptors and their function |
| KR100292406B1 (ko) * | 1998-06-11 | 2001-07-12 | 윤종용 | 감광성중합체,용해억제제및이들을포함하는화학증폭형포토레지스트조성물 |
| GB2347676A (en) | 1999-03-08 | 2000-09-13 | Phytopharm Plc | Screening method |
| GB9923078D0 (en) | 1999-09-29 | 1999-12-01 | Phytopharm Plc | Sapogenin derivatives and their use |
| AUPP968699A0 (en) | 1999-04-09 | 1999-05-06 | Cura Nominees Pty Ltd | Therapeutic compositions and method for their preparation |
| US6544566B1 (en) | 1999-04-23 | 2003-04-08 | Protein Technologies International, Inc. | Composition containing plant sterol, soy protein and isoflavone for reducing LDL cholesterol |
| GB9923077D0 (en) | 1999-09-29 | 1999-12-01 | Phytopharm Plc | Sapogenin derivatives and their use |
| GB0000228D0 (en) | 2000-01-06 | 2000-03-01 | Phytopharm Plc | Fluoro substituted sapogenins and their use |
| BR0001794A (pt) | 2000-05-15 | 2001-12-26 | Laboratorios Biosintetica Ltda | Aplicação de fitosteróides (e seus isÈmeros), ácidofólico, cianocobalamina e piridoxina em fibrasdietéticas (alimentares) |
| US20050130948A1 (en) | 2002-03-27 | 2005-06-16 | Daryl Rees | Therapeutic methods and uses of sapogenins and their derivatives |
-
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Non-Patent Citations (1)
| Title |
|---|
| R.E.MARKER et al. J. of Amer. Chem. Soc. V.69, №9, 1947, p. 2167-2230. * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2663696C2 (ru) * | 2013-03-28 | 2018-08-08 | Класадо Инк | Галактоолигосахаридная композиция и ее применение для предотвращения или лечения когнитивной дисфункции и эмоциональных расстройств при психоневрологических заболеваниях или старении |
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