UA78696C2 - Novel compounds of sapogenin derivatives, use thereof and composition - Google Patents
Novel compounds of sapogenin derivatives, use thereof and composition Download PDFInfo
- Publication number
- UA78696C2 UA78696C2 UA2003108904A UA2003108904A UA78696C2 UA 78696 C2 UA78696 C2 UA 78696C2 UA 2003108904 A UA2003108904 A UA 2003108904A UA 2003108904 A UA2003108904 A UA 2003108904A UA 78696 C2 UA78696 C2 UA 78696C2
- Authority
- UA
- Ukraine
- Prior art keywords
- group
- compounds
- епісарсасапогеніну
- episarsasapogenin
- pharmaceutically acceptable
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 108
- 239000000203 mixture Substances 0.000 title claims abstract description 41
- WQLVFSAGQJTQCK-UHFFFAOYSA-N diosgenin Natural products CC1C(C2(CCC3C4(C)CCC(O)CC4=CCC3C2C2)C)C2OC11CCC(C)CO1 WQLVFSAGQJTQCK-UHFFFAOYSA-N 0.000 title description 7
- NWMIYTWHUDFRPL-UHFFFAOYSA-N sapogenin Natural products COC(=O)C1(CO)C(O)CCC2(C)C1CCC3(C)C2CC=C4C5C(C)(O)C(C)CCC5(CCC34C)C(=O)O NWMIYTWHUDFRPL-UHFFFAOYSA-N 0.000 title description 3
- 150000003839 salts Chemical class 0.000 claims abstract description 81
- -1 isovaleryl Chemical group 0.000 claims abstract description 43
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 27
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 12
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims abstract description 11
- 125000003118 aryl group Chemical group 0.000 claims abstract description 11
- 150000001732 carboxylic acid derivatives Chemical group 0.000 claims abstract description 10
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims abstract description 10
- 125000004080 3-carboxypropanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C(O[H])=O 0.000 claims abstract description 9
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims abstract description 7
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims abstract description 5
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims abstract description 4
- 229940114081 cinnamate Drugs 0.000 claims abstract description 4
- DYUMLJSJISTVPV-UHFFFAOYSA-N phenyl propanoate Chemical group CCC(=O)OC1=CC=CC=C1 DYUMLJSJISTVPV-UHFFFAOYSA-N 0.000 claims abstract description 4
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- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
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- 108020004017 nuclear receptors Proteins 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
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- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
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- MTCFGRXMJLQNBG-UHFFFAOYSA-M serinate Chemical compound OCC(N)C([O-])=O MTCFGRXMJLQNBG-UHFFFAOYSA-M 0.000 description 1
- 230000006403 short-term memory Effects 0.000 description 1
- LVRAKYNQYKVPIK-BSPYNPCNSA-N smilagenin acetate Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)CC[C@@H](C[C@H]4CC[C@H]3[C@@H]2C1)OC(C)=O)C)[C@@H]1C)[C@]11CC[C@@H](C)CO1 LVRAKYNQYKVPIK-BSPYNPCNSA-N 0.000 description 1
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- 229940014800 succinic anhydride Drugs 0.000 description 1
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- TUNFSRHWOTWDNC-UHFFFAOYSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
- A61K31/585—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin containing lactone rings, e.g. oxandrolone, bufalin
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
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- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
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- A—HUMAN NECESSITIES
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- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/08—Antiepileptics; Anticonvulsants
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
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- A—HUMAN NECESSITIES
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
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- A—HUMAN NECESSITIES
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P27/02—Ophthalmic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Epidemiology (AREA)
- Pulmonology (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pain & Pain Management (AREA)
- Ophthalmology & Optometry (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Nutrition Science (AREA)
- Psychiatry (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Plant Substances (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0107822.9A GB0107822D0 (en) | 2001-03-28 | 2001-03-28 | Sapogenin derivatives their synthesis and use methods based upon their use |
| PCT/GB2002/001578 WO2002079221A2 (en) | 2001-03-28 | 2002-03-28 | Sapogenin derivatives, their synthesis and use |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| UA78696C2 true UA78696C2 (en) | 2007-04-25 |
Family
ID=9911795
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| UA2003108904A UA78696C2 (en) | 2001-03-28 | 2002-03-28 | Novel compounds of sapogenin derivatives, use thereof and composition |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US20040147495A1 (ru) |
| EP (1) | EP1383787B1 (ru) |
| JP (1) | JP2004525945A (ru) |
| KR (1) | KR20040007479A (ru) |
| CN (1) | CN1678325A (ru) |
| AR (2) | AR033079A1 (ru) |
| AT (1) | ATE416185T1 (ru) |
| AU (1) | AU2002242894B2 (ru) |
| BR (1) | BR0208533A (ru) |
| CA (1) | CA2442150A1 (ru) |
| CZ (1) | CZ20032620A3 (ru) |
| GB (1) | GB0107822D0 (ru) |
| HR (1) | HRP20030770A2 (ru) |
| IL (1) | IL158115A0 (ru) |
| MX (1) | MXPA03008800A (ru) |
| NO (1) | NO20034364L (ru) |
| NZ (1) | NZ529136A (ru) |
| PE (1) | PE20021042A1 (ru) |
| PL (1) | PL364825A1 (ru) |
| RU (1) | RU2311423C2 (ru) |
| TR (2) | TR200700134T1 (ru) |
| UA (1) | UA78696C2 (ru) |
| WO (1) | WO2002079221A2 (ru) |
| ZA (2) | ZA200307478B (ru) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0000228D0 (en) * | 2000-01-06 | 2000-03-01 | Phytopharm Plc | Fluoro substituted sapogenins and their use |
| NZ563183A (en) * | 2002-03-27 | 2009-03-31 | Phytopharm Plc | Therapeutic methods and uses of sapogenins and their derivatives |
| MXPA04009321A (es) * | 2002-03-27 | 2005-01-25 | Phytopharm Plc | Metodos y usos terapeuticos de sapogeninas y sus derivados. |
| PT1558627E (pt) * | 2002-10-28 | 2010-05-06 | Phytopharm Plc | Reduçao estereoespecífica de sapogen-3-onas |
| GB0409567D0 (en) | 2004-04-28 | 2004-06-02 | Phytopharm Plc | Chemical compounds |
| EP1618881A1 (en) * | 2004-07-20 | 2006-01-25 | Santhera Pharmaceuticals (Schweiz) GmbH | Use of non-glucocorticoid steroids for the treatment of muscular dystrophy |
| GB0424528D0 (en) * | 2004-11-05 | 2004-12-08 | Phytopharm Plc | Chemical compounds |
| AU2010207597A1 (en) | 2009-01-24 | 2011-08-18 | Phytopharm Plc | Treatment of neurotrophic factor mediated disorders |
| 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 |
| CA2805693A1 (en) | 2010-07-20 | 2012-01-26 | Phytopharm Plc | Treatment of l-dopa, dopamine agonist and/or dopamine enhancer induced disorders |
| TWI422378B (zh) * | 2010-11-18 | 2014-01-11 | Univ Chung Shan Medical | 使用薯蕷皂素來改善與停經期症候群有關聯的認知缺陷 |
| JP6205362B2 (ja) | 2011-09-08 | 2017-09-27 | セージ セラピューティクス， インコーポレイテッド | 神経刺激性のステロイド、組成物、およびそれらの使用 |
| CU20110244A7 (es) * | 2011-12-27 | 2013-08-29 | Ct De Investigación Y Desarrollo De Medicamentos Cidem | Sistemas espiroesteroidales con efectos neuroactivos y anti-inflamatorios |
| ES2699445T3 (es) | 2013-03-13 | 2019-02-11 | Sage Therapeutics Inc | Esteroides neuroactivos y métodos de utilización de los mismos |
| KR101480982B1 (ko) * | 2013-03-20 | 2015-02-03 | (주)셀인바이오 | 골형성 유도 화합물 및 이의 응용 |
| CN104177469A (zh) * | 2013-05-28 | 2014-12-03 | 江苏柯菲平医药有限公司 | 一种知母中菝葜皂苷元衍生物的制备方法 |
| CN104324038B (zh) * | 2013-07-24 | 2018-11-06 | 四川京华创生物科技有限公司 | 一种薯蓣皂苷元-3-位衍生物的用途 |
| EP3157528B1 (en) | 2014-06-18 | 2023-09-13 | Sage Therapeutics, Inc. | Oxysterols and methods of use thereof |
| MA55097A (fr) | 2015-07-06 | 2022-01-05 | Sage Therapeutics Inc | Oxystérols et leurs procédés d'utilisation |
| MA42409A (fr) | 2015-07-06 | 2018-05-16 | Sage Therapeutics Inc | Oxystérols et leurs procédés d'utilisation |
| PE20180482A1 (es) | 2015-07-06 | 2018-03-07 | Sage Therapeutics Inc | Oxiesteroles y metodos de uso de los mismos |
| LT3436022T (lt) | 2016-04-01 | 2022-06-27 | Sage Therapeutics, Inc. | Oksisteroliai ir jų panaudojimo būdai |
| US10752653B2 (en) | 2016-05-06 | 2020-08-25 | Sage Therapeutics, Inc. | Oxysterols and methods of use thereof |
| RS62222B1 (sr) | 2016-07-07 | 2021-09-30 | Sage Therapeutics Inc | 24-hidroksisteroli supstituisani na poziciji 11 za upotrebu u lečenju stanja povezanih sa nmda |
| MA46351A (fr) | 2016-09-30 | 2021-06-02 | Sage Therapeutics Inc | Oxystérols substitués en c7 et procédés en tant que modulateurs nmda |
| EP3529256B1 (en) | 2016-10-18 | 2023-08-09 | Sage Therapeutics, Inc. | Oxysterols and methods of use thereof |
| ES2952106T3 (es) | 2016-10-18 | 2023-10-27 | Sage Therapeutics Inc | Oxisteroles y procedimientos de utilización de los mismos |
| CN109053854B (zh) * | 2018-09-29 | 2021-05-14 | 深圳清博汇能医药科技有限公司 | 基于知母菝契皂苷元结构的衍生物、药物组合物及其应用 |
Family Cites Families (45)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| 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 |
| 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 |
| JP3168542B2 (ja) * | 1990-01-18 | 2001-05-21 | キュラー ノミニーズ プロプライエタリー リミテッド | グリコアルカロイド |
| 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 |
| BR9306619A (pt) * | 1992-06-26 | 1998-12-08 | Pfizer | Glicosídeos esteroidais para o tratamento da hipercolesterolemia |
| DE4303214A1 (de) * | 1993-02-04 | 1994-08-11 | Wolfgang Marks | Behandlung von Erkrankungen viraler, viroidaler oder onkogener Genese durch Steroid-Saponine oder deren Aglykone |
| EP0696292A1 (en) * | 1993-04-28 | 1996-02-14 | Pfizer Inc. | Spirostanyl glycosidal crystalline monohydrate |
| US5589182A (en) * | 1993-12-06 | 1996-12-31 | Tashiro; Renki | Compositions and method of treating cardio-, cerebro-vascular and alzheimer's diseases and depression |
| EP0737203A1 (en) * | 1993-12-28 | 1996-10-16 | Pfizer Inc. | Steroidal glycosides |
| AU7948394A (en) * | 1993-12-28 | 1995-07-17 | Pfizer Inc. | Hypocholesterolemic agents |
| 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 |
| US5840936A (en) * | 1995-06-07 | 1998-11-24 | Magainin Pharmaceuticals Inc. | Aminosterol compounds useful as inhibitors of the sodium/proton exchanger (NHE) |
| US5847172A (en) * | 1995-06-07 | 1998-12-08 | Magainin Pharmaceuticals Inc. | Certain aminosterol compounds and pharmaceutical compositions including these compounds |
| US6143738A (en) * | 1995-06-07 | 2000-11-07 | Magainin Pharmaceuticals, Inc. | Therapeutic uses for an aminosterol compound |
| US5763430A (en) * | 1995-06-07 | 1998-06-09 | Magainin Pharmaceuticals Inc. | Method of treating a viral infection by administering a steroid compound |
| 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 |
| EP0863141B1 (en) * | 1995-10-13 | 2001-09-12 | Banyu Pharmaceutical Co., Ltd. | Substituted heteroaromatic derivatives |
| US6178679B1 (en) * | 1996-02-13 | 2001-01-30 | David M. Dundorf | Weather-proof readerboard signage system |
| US5726179A (en) * | 1996-04-01 | 1998-03-10 | The University Of Toledo | Muscarinic agonists |
| CN1245982C (zh) * | 1996-05-09 | 2006-03-22 | 阿姆瑞德手术有限公司 | 哮喘和气道疾病的治疗 |
| US5804239A (en) * | 1996-07-26 | 1998-09-08 | Nouveau Technologies, Inc. | Method and composition for food flavoring |
| 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 |
| GB9923076D0 (en) * | 1999-09-29 | 1999-12-01 | Phytopharm Plc | Sapogenin derivatives and their use |
| ID26989A (id) * | 1998-03-26 | 2001-02-22 | Phytopharm Plc | Smilagenin dan anzurogenin-d untuk pengobatan penyakit alzheimer |
| GB9905275D0 (en) * | 1999-03-08 | 1999-04-28 | Phytopharm Ltd | Treatment of conditions associated with membrane-bound receptors and their function |
| GB2347676A (en) * | 1999-03-08 | 2000-09-13 | Phytopharm Plc | Screening method |
| US6544566B1 (en) * | 1999-04-23 | 2003-04-08 | Protein Technologies International, Inc. | Composition containing plant sterol, soy protein and isoflavone for reducing LDL cholesterol |
| US20050130948A1 (en) * | 2002-03-27 | 2005-06-16 | Daryl Rees | Therapeutic methods and uses of sapogenins and their derivatives |
-
2001
- 2001-03-28 GB GBGB0107822.9A patent/GB0107822D0/en not_active Ceased
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2002
- 2002-03-27 AR ARP020101170A patent/AR033079A1/es unknown
- 2002-03-27 PE PE2002000253A patent/PE20021042A1/es not_active Application Discontinuation
- 2002-03-28 JP JP2002577845A patent/JP2004525945A/ja active Pending
- 2002-03-28 PL PL02364825A patent/PL364825A1/xx unknown
- 2002-03-28 US US10/472,892 patent/US20040147495A1/en not_active Abandoned
- 2002-03-28 TR TR2007/00134T patent/TR200700134T1/xx unknown
- 2002-03-28 NZ NZ529136A patent/NZ529136A/en unknown
- 2002-03-28 WO PCT/GB2002/001578 patent/WO2002079221A2/en active Application Filing
- 2002-03-28 CA CA002442150A patent/CA2442150A1/en not_active Abandoned
- 2002-03-28 TR TR2003/01613T patent/TR200301613T2/xx unknown
- 2002-03-28 AT AT02708534T patent/ATE416185T1/de not_active IP Right Cessation
- 2002-03-28 KR KR10-2003-7012755A patent/KR20040007479A/ko not_active Application Discontinuation
- 2002-03-28 RU RU2003131883/04A patent/RU2311423C2/ru not_active IP Right Cessation
- 2002-03-28 CN CNA028074270A patent/CN1678325A/zh active Pending
- 2002-03-28 MX MXPA03008800A patent/MXPA03008800A/es unknown
- 2002-03-28 UA UA2003108904A patent/UA78696C2/uk unknown
- 2002-03-28 CZ CZ20032620A patent/CZ20032620A3/cs unknown
- 2002-03-28 IL IL15811502A patent/IL158115A0/xx unknown
- 2002-03-28 BR BR0208533-0A patent/BR0208533A/pt not_active IP Right Cessation
- 2002-03-28 EP EP02708534A patent/EP1383787B1/en not_active Expired - Lifetime
- 2002-03-28 AU AU2002242894A patent/AU2002242894B2/en not_active Ceased
-
2003
- 2003-03-27 AR AR20030101078A patent/AR040402A1/es unknown
- 2003-09-24 HR HR20030770A patent/HRP20030770A2/hr not_active Application Discontinuation
- 2003-09-25 ZA ZA200307478A patent/ZA200307478B/xx unknown
- 2003-09-29 NO NO20034364A patent/NO20034364L/no not_active Application Discontinuation
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2004
- 2004-09-16 ZA ZA200407460A patent/ZA200407460B/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ZA200407460B (en) | 2009-09-30 |
| PL364825A1 (en) | 2004-12-27 |
| PE20021042A1 (es) | 2002-11-19 |
| HRP20030770A2 (en) | 2005-08-31 |
| MXPA03008800A (es) | 2004-10-15 |
| AR040402A1 (es) | 2005-04-06 |
| CN1678325A (zh) | 2005-10-05 |
| BR0208533A (pt) | 2004-04-20 |
| AR033079A1 (es) | 2003-12-03 |
| EP1383787B1 (en) | 2008-12-03 |
| RU2003131883A (ru) | 2005-05-10 |
| CA2442150A1 (en) | 2002-10-10 |
| TR200301613T2 (tr) | 2004-08-23 |
| KR20040007479A (ko) | 2004-01-24 |
| AU2002242894B2 (en) | 2008-08-21 |
| US20040147495A1 (en) | 2004-07-29 |
| CZ20032620A3 (cs) | 2004-04-14 |
| ZA200307478B (en) | 2009-04-29 |
| EP1383787A2 (en) | 2004-01-28 |
| RU2311423C2 (ru) | 2007-11-27 |
| TR200700134T1 (tr) | 2007-02-21 |
| GB0107822D0 (en) | 2001-05-23 |
| NO20034364D0 (no) | 2003-09-29 |
| ATE416185T1 (de) | 2008-12-15 |
| NZ529136A (en) | 2005-12-23 |
| JP2004525945A (ja) | 2004-08-26 |
| WO2002079221A3 (en) | 2003-04-17 |
| NO20034364L (no) | 2003-11-28 |
| IL158115A0 (en) | 2004-03-28 |
| WO2002079221A2 (en) | 2002-10-10 |
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