FI116620B - Farmaseuttisesti aktiiviset sfingolipidiyhdisteet ja liposomit sekä niitä sisältävät farmaseuttiset koostumukset - Google Patents
Farmaseuttisesti aktiiviset sfingolipidiyhdisteet ja liposomit sekä niitä sisältävät farmaseuttiset koostumukset Download PDFInfo
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- FI116620B FI116620B FI963045A FI963045A FI116620B FI 116620 B FI116620 B FI 116620B FI 963045 A FI963045 A FI 963045A FI 963045 A FI963045 A FI 963045A FI 116620 B FI116620 B FI 116620B
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
- A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/29—Coated or structually defined flake, particle, cell, strand, strand portion, rod, filament, macroscopic fiber or mass thereof
- Y10T428/2982—Particulate matter [e.g., sphere, flake, etc.]
- Y10T428/2984—Microcapsule with fluid core [includes liposome]
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Dispersion Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Steroid Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US19029594A | 1994-02-02 | 1994-02-02 | |
| US19029594 | 1994-02-02 | ||
| US9501490 | 1995-02-02 | ||
| PCT/US1995/001490 WO1995021175A1 (en) | 1994-02-02 | 1995-02-02 | Pharmaceutically active compounds and liposomes, and methods of use therof |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI963045A0 FI963045A0 (fi) | 1996-08-01 |
| FI963045A FI963045A (fi) | 1996-08-01 |
| FI116620B true FI116620B (fi) | 2006-01-13 |
Family
ID=22700754
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI963045A FI116620B (fi) | 1994-02-02 | 1996-08-01 | Farmaseuttisesti aktiiviset sfingolipidiyhdisteet ja liposomit sekä niitä sisältävät farmaseuttiset koostumukset |
Country Status (14)
| Country | Link |
|---|---|
| US (3) | US5631394A (de) |
| EP (2) | EP0742789B1 (de) |
| JP (1) | JPH09508900A (de) |
| AT (1) | ATE195944T1 (de) |
| AU (1) | AU691886B2 (de) |
| CA (1) | CA2182485A1 (de) |
| DE (1) | DE69518627T2 (de) |
| DK (1) | DK0742789T3 (de) |
| ES (1) | ES2149350T3 (de) |
| FI (1) | FI116620B (de) |
| GR (1) | GR3034521T3 (de) |
| NO (1) | NO314405B1 (de) |
| PT (1) | PT742789E (de) |
| WO (1) | WO1995021175A1 (de) |
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| US6255336B1 (en) | 1995-09-20 | 2001-07-03 | The Regents Of The University Of Michigan | Amino ceramide-like compounds and therapeutic methods of use |
| WO1997010817A1 (en) * | 1995-09-20 | 1997-03-27 | The Regents Of The University Of Michigan | Amino ceramide-like compounds and therapeutic methods of use |
| EP0892638B1 (de) * | 1996-04-04 | 2002-11-13 | Cilag AG | Topische vitamin d zusammensetzung auf liposomenbasis |
| US6274309B1 (en) * | 1996-07-26 | 2001-08-14 | Richard Kolesnick | Method for the modulation of acid-sphingomyelinase-related apoptosis |
| CN1055640C (zh) * | 1996-11-29 | 2000-08-23 | 沃维汉 | 人降钙素基因相关肽脂质体组合物及其制法 |
| US6982142B2 (en) | 1997-12-01 | 2006-01-03 | John Wayne Cancer Institute | Methods for screening therapeutically effective agents |
| AU3740000A (en) * | 1999-03-25 | 2000-10-16 | Center For Molecular Medicine And Immunology | Sphingomyelin containing preparation for the enhancement of tumor therapy |
| US7683044B2 (en) * | 1999-03-25 | 2010-03-23 | Center For Molecular Medicine And Immunology | Sphingomyelin therapy of autoimmune disease |
| US7820718B1 (en) * | 1999-04-07 | 2010-10-26 | Roger Williams Hospital | Combinations of ceramide and chemotherapeutic agents for inducing cell death and uses thereof in treating cancer |
| TW502133B (en) | 1999-06-10 | 2002-09-11 | Wako Pure Chem Ind Ltd | Resist composition, agent and method for reducing substrate dependence thereof |
| US6682545B1 (en) * | 1999-10-06 | 2004-01-27 | The Penn State Research Foundation | System and device for preventing restenosis in body vessels |
| WO2001038295A1 (fr) * | 1999-11-24 | 2001-05-31 | Taisho Pharmaceutical Co.,Ltd. | Derives de sphingosine |
| US6410597B1 (en) * | 2000-02-25 | 2002-06-25 | Virginia Commonwealth University | Hydroxyalkyl amide analogs of ceramide |
| US6858383B2 (en) * | 2000-12-22 | 2005-02-22 | Medlyte, Inc. | Compositions and methods for the treatment and prevention of cardiovascular diseases and disorders, and for identifying agents therapeutic therefor |
| CA2453978C (en) | 2001-07-16 | 2011-10-11 | Genzyme Corporation | Synthesis of udp-glucose: n-acylsphingosine glucosyltransferase inhibitors |
| EP1287815A1 (de) * | 2001-08-31 | 2003-03-05 | Cosmoferm B.V. | Verwendung einer Sphingoidbase zur Inhibierung von Ceramidase-Aktivität |
| US6916802B2 (en) * | 2002-04-29 | 2005-07-12 | Genzyme Corporation | Amino ceramide-like compounds and therapeutic methods of use |
| US20060217560A1 (en) * | 2002-04-29 | 2006-09-28 | Shayman James A | Amino ceramide-like compounds and therapeutic methods of use |
| US20070031480A1 (en) * | 2003-03-07 | 2007-02-08 | Lawrence Mayer | Enhanced delivery of sphingolipids |
| WO2004087097A2 (en) * | 2003-03-31 | 2004-10-14 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Stable liposomes or micelles comprising a sphinolipid and a peg-lipopolymer |
| BRPI0409663A (pt) | 2003-04-25 | 2006-04-18 | Penn State Res Found | método e sistema para o envio sistêmico de compostos bioativos derivados de lipìdeo de detenção de crescimento |
| US7906122B2 (en) | 2003-06-18 | 2011-03-15 | Yissum Research Development Company Of The Hebrew University Of Jersusalem | Sphingoid polyalkylamine conjugates for Hepatitis B virus vaccination |
| WO2004110496A1 (en) * | 2003-06-18 | 2004-12-23 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Sphingoid polyalkylamine conjugates for vaccination |
| US7794713B2 (en) | 2004-04-07 | 2010-09-14 | Lpath, Inc. | Compositions and methods for the treatment and prevention of hyperproliferative diseases |
| CA2586761A1 (en) | 2004-11-10 | 2006-05-18 | Genzyme Corporation | Methods of treating diabetes mellitus |
| JP2008520560A (ja) * | 2004-11-15 | 2008-06-19 | イッスム・リサーチ・ディベロップメント・カンパニー・オブ・ザ・ヘブルー・ユニバーシティ・オブ・エルサレム | 組合せ治療 |
| JP4791082B2 (ja) * | 2005-05-30 | 2011-10-12 | 株式会社クラレ | リポソームおよびそれを含む皮膚外用剤 |
| WO2007044748A2 (en) * | 2005-10-11 | 2007-04-19 | University Of Pittsburgh | Sphingomyelin liposomes for the treatment of hyperactive bladder disorders |
| ES2546181T3 (es) | 2006-05-09 | 2015-09-21 | Genzyme Corporation | Métodos de tratar la enfermedad del hígado graso mediante inhibición de la síntesis de glucoesfingolípidos |
| US9217749B2 (en) | 2006-05-31 | 2015-12-22 | Lpath, Inc. | Immune-derived moieties reactive against lysophosphatidic acid |
| US7862812B2 (en) | 2006-05-31 | 2011-01-04 | Lpath, Inc. | Methods for decreasing immune response and treating immune conditions |
| US9274130B2 (en) | 2006-05-31 | 2016-03-01 | Lpath, Inc. | Prevention and treatment of pain using antibodies to lysophosphatidic acid |
| US9274129B2 (en) | 2006-05-31 | 2016-03-01 | Lpath, Inc. | Methods and reagents for detecting bioactive lipids |
| US8796429B2 (en) | 2006-05-31 | 2014-08-05 | Lpath, Inc. | Bioactive lipid derivatives, and methods of making and using same |
| AU2007329759B2 (en) | 2006-10-27 | 2013-05-30 | Lpath, Inc. | Compositions and methods for binding sphingosine-1-phosphate |
| AU2007313822A1 (en) | 2006-10-27 | 2008-05-08 | Lpath, Inc. | Compositions and methods for treating ocular diseases and conditions |
| EP2594565B1 (de) | 2007-05-31 | 2018-10-24 | Genzyme Corporation | Glukosylceramid-Synthase-Hemmer vom 2-Acylaminpropanol-Typ |
| KR20160085917A (ko) | 2007-10-05 | 2016-07-18 | 젠자임 코포레이션 | 세라마이드 유도체로 다낭성 신장질환을 치료하는 방법 |
| WO2009132082A2 (en) * | 2008-04-22 | 2009-10-29 | Medical College Of Georgia Research Institute, Inc. | Immunogenic compositions containing ceramide and methods of use thereof |
| WO2010014554A1 (en) | 2008-07-28 | 2010-02-04 | Genzyme Corporation | Glucosylceramide synthase inhibition for the treatment of collapsing glomerulopathy and other glomerular disease |
| CN102271678B (zh) | 2008-10-03 | 2017-06-30 | 简詹姆公司 | 2‑酰胺基丙醇型葡糖神经酰胺合成酶抑制剂 |
| PL3599237T3 (pl) | 2009-11-27 | 2021-09-27 | Genzyme Corporation | Kompozycja farmaceutyczna inhibitora syntazy glukozyloceramidowej eliglustatu do leczenia choroby Gauchera obejmującego dostosowanie indywidualnej dawki terapeutycznej do metabolizmu P450 pacjenta |
| WO2013024843A1 (ja) * | 2011-08-15 | 2013-02-21 | 国立大学法人 千葉大学 | セラミド誘導体およびこれを用いたゴルジ体標識化蛍光プローブ |
| KR102423002B1 (ko) * | 2021-02-17 | 2022-07-21 | 주식회사 엘씨에스바이오텍 | 신규 세라마이드, 그의 제조방법 및 그의 용도 |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4522803A (en) * | 1983-02-04 | 1985-06-11 | The Liposome Company, Inc. | Stable plurilamellar vesicles, their preparation and use |
| US5030453A (en) * | 1983-03-24 | 1991-07-09 | The Liposome Company, Inc. | Stable plurilamellar vesicles |
| US4588578A (en) * | 1983-08-08 | 1986-05-13 | The Liposome Company, Inc. | Lipid vesicles prepared in a monophase |
| US5169637A (en) * | 1983-03-24 | 1992-12-08 | The Liposome Company, Inc. | Stable plurilamellar vesicles |
| US4721612A (en) * | 1984-04-12 | 1988-01-26 | The Liposome Company, Inc. | Steroidal liposomes |
| US5008050A (en) * | 1984-06-20 | 1991-04-16 | The Liposome Company, Inc. | Extrusion technique for producing unilamellar vesicles |
| US5077056A (en) * | 1984-08-08 | 1991-12-31 | The Liposome Company, Inc. | Encapsulation of antineoplastic agents in liposomes |
| US4975282A (en) * | 1985-06-26 | 1990-12-04 | The Liposome Company, Inc. | Multilamellar liposomes having improved trapping efficiencies |
| US5059421A (en) * | 1985-07-26 | 1991-10-22 | The Liposome Company, Inc. | Preparation of targeted liposome systems of a defined size distribution |
| JP2588729B2 (ja) * | 1987-10-05 | 1997-03-12 | 塩野義製薬株式会社 | スフィンゴシン誘導体 |
| FR2637598B1 (fr) * | 1988-10-06 | 1991-10-11 | Agronomique Inst Nat Rech | Nouveaux sphingophospholipides a inositol, leur obtention, et leur application comme inducteurs de resistance a diverses maladies cryptogamiques chez les vegetaux |
| US5100662A (en) * | 1989-08-23 | 1992-03-31 | The Liposome Company, Inc. | Steroidal liposomes exhibiting enhanced stability |
| DE4021082C2 (de) * | 1990-07-03 | 1995-08-17 | Hans Dr Lautenschlaeger | Hautbehandlungsmittel mit hohen Lipidgehalten unter Verwendung eines Bilayer enthaltenden Systems, Salzen organischer Säuren, Alkohol und Stabilisator |
| AU653363B2 (en) * | 1990-08-13 | 1994-09-29 | Duke University | Methods for inducing cell differentiation using ceramides |
| GB9022921D0 (en) * | 1990-10-22 | 1990-12-05 | Unilever Plc | Cosmetic composition |
| GB9100816D0 (en) * | 1991-01-15 | 1991-02-27 | Unilever Plc | Cosmetic composition |
| DE4201461A1 (de) * | 1992-01-21 | 1993-07-22 | Mueller Schulte Detlef Dr | Mittel fuer die selektive tumortherapie auf der basis ferromagnetischer partikel - verfahren zu ihrer herstellung und verwendung |
-
1995
- 1995-02-02 EP EP95910923A patent/EP0742789B1/de not_active Expired - Lifetime
- 1995-02-02 AU AU18712/95A patent/AU691886B2/en not_active Ceased
- 1995-02-02 JP JP7520799A patent/JPH09508900A/ja not_active Ceased
- 1995-02-02 PT PT95910923T patent/PT742789E/pt unknown
- 1995-02-02 DK DK95910923T patent/DK0742789T3/da active
- 1995-02-02 WO PCT/US1995/001490 patent/WO1995021175A1/en active IP Right Grant
- 1995-02-02 EP EP00102434A patent/EP1008342A3/de not_active Withdrawn
- 1995-02-02 AT AT95910923T patent/ATE195944T1/de not_active IP Right Cessation
- 1995-02-02 CA CA002182485A patent/CA2182485A1/en not_active Abandoned
- 1995-02-02 ES ES95910923T patent/ES2149350T3/es not_active Expired - Lifetime
- 1995-02-02 US US08/383,291 patent/US5631394A/en not_active Expired - Fee Related
- 1995-02-02 DE DE69518627T patent/DE69518627T2/de not_active Expired - Fee Related
- 1995-10-19 US US08/545,164 patent/US5681589A/en not_active Expired - Lifetime
- 1995-10-19 US US08/547,688 patent/US5677337A/en not_active Expired - Lifetime
-
1996
- 1996-08-01 FI FI963045A patent/FI116620B/fi not_active IP Right Cessation
- 1996-08-01 NO NO19963224A patent/NO314405B1/no unknown
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2000
- 2000-09-29 GR GR20000402211T patent/GR3034521T3/el not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| CA2182485A1 (en) | 1995-08-10 |
| AU1871295A (en) | 1995-08-21 |
| WO1995021175A1 (en) | 1995-08-10 |
| ATE195944T1 (de) | 2000-09-15 |
| DK0742789T3 (da) | 2000-11-13 |
| EP1008342A3 (de) | 2004-12-29 |
| NO314405B1 (no) | 2003-03-17 |
| EP0742789A1 (de) | 1996-11-20 |
| FI963045A0 (fi) | 1996-08-01 |
| FI963045A (fi) | 1996-08-01 |
| GR3034521T3 (en) | 2000-12-29 |
| EP0742789B1 (de) | 2000-08-30 |
| ES2149350T3 (es) | 2000-11-01 |
| EP1008342A2 (de) | 2000-06-14 |
| US5677337A (en) | 1997-10-14 |
| AU691886B2 (en) | 1998-05-28 |
| NO963224D0 (no) | 1996-08-01 |
| US5631394A (en) | 1997-05-20 |
| JPH09508900A (ja) | 1997-09-09 |
| US5681589A (en) | 1997-10-28 |
| DE69518627D1 (de) | 2000-10-05 |
| PT742789E (pt) | 2000-12-29 |
| DE69518627T2 (de) | 2001-01-11 |
| NO963224L (no) | 1996-09-27 |
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