CN1423564A - 癌症的aplidine治疗 - Google Patents
癌症的aplidine治疗 Download PDFInfo
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- CN1423564A CN1423564A CN00818404A CN00818404A CN1423564A CN 1423564 A CN1423564 A CN 1423564A CN 00818404 A CN00818404 A CN 00818404A CN 00818404 A CN00818404 A CN 00818404A CN 1423564 A CN1423564 A CN 1423564A
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Applications Claiming Priority (10)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9927006.8 | 1999-11-15 | ||
| GBGB9927006.8A GB9927006D0 (en) | 1999-11-15 | 1999-11-15 | Aplidine treatment of cancers |
| GB0005701A GB0005701D0 (en) | 2000-03-09 | 2000-03-09 | Antitumor utility of aplidine |
| GB0005701.8 | 2000-03-09 | ||
| GB0007639.8 | 2000-03-29 | ||
| GB0007639A GB0007639D0 (en) | 2000-03-29 | 2000-03-29 | Antitumour and anti-angiogenic compound |
| GB0015496A GB0015496D0 (en) | 2000-06-23 | 2000-06-23 | Antitumour and anti-angiogenic compound |
| GB0015496.3 | 2000-06-23 | ||
| GB0025209.8 | 2000-10-13 | ||
| GB0025209A GB0025209D0 (en) | 2000-10-13 | 2000-10-13 | Treatment of cancers |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103463020A (zh) * | 2013-09-23 | 2013-12-25 | 南京广康协生物医药技术有限公司 | Lycojaponicumin A在治疗肾癌药物中的应用 |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030148933A1 (en) | 1990-10-01 | 2003-08-07 | Pharma Mar S.A. | Derivatives of dehydrodidemnin B |
| GB9803448D0 (en) | 1998-02-18 | 1998-04-15 | Pharma Mar Sa | Pharmaceutical formulation |
| UA76718C2 (uk) | 2000-06-30 | 2006-09-15 | Фарма Мар, С.А. | Протипухлинні похідні аплідину |
| NZ525196A (en) | 2000-10-12 | 2004-09-24 | Pharma Mar S | Treatment of cancers by aplidine in conjunction with a myoprotector |
| KR20050038578A (ko) * | 2001-10-19 | 2005-04-27 | 파르마 마르, 에스.에이. | 항종양성 화합물의 암치료에 있어서의 향상된 용도 |
| DE60229414D1 (de) * | 2001-10-19 | 2008-11-27 | Pharma Mar Sa | Verwendung von aplidine in der behandlung von pankreaskrebs |
| KR20060002778A (ko) | 2003-03-12 | 2006-01-09 | 파르마 마르, 에스.에이. | 개선된 항종양 치료 |
| DK1603584T3 (da) | 2003-03-12 | 2009-01-05 | Dana Farber Cancer Inst Inc | Aplidine til behandling af multipelt myelom |
| DK2029155T3 (en) * | 2006-02-28 | 2016-08-01 | Pharma Mar Sa | IMPROVED treatment of multiple myeloma |
| ATE479432T1 (de) * | 2006-11-03 | 2010-09-15 | Nerviano Medical Sciences Srl | Verfahren zur verabreichung einer antitumoralen verbindung |
| RU2360712C1 (ru) * | 2007-10-02 | 2009-07-10 | Федеральное государственное учреждение "Ростовский научно-исследовательский онкологический институт Росмедтехнологий" | Способ лечения местно-распространенного неоперабельного рака прямой кишки |
| CA2703024A1 (en) * | 2007-10-19 | 2009-04-23 | Giuseppe Longo Sorbello | Improved antitumoral treatments |
| MX2010009697A (es) * | 2008-03-07 | 2010-09-30 | Pharm Mar S A | Tratamientos anticancerigenos mejorados. |
| JOP20190254A1 (ar) | 2017-04-27 | 2019-10-27 | Pharma Mar Sa | مركبات مضادة للأورام |
Family Cites Families (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4342744A (en) * | 1979-07-19 | 1982-08-03 | Lever Brothers Company | Hair treatment products |
| EP0048149B1 (en) * | 1980-09-12 | 1983-11-30 | University of Illinois Foundation | Novel antibiotics, derivatives thereof, processes for their extraction, and compositions containing them |
| US4493796A (en) * | 1980-09-12 | 1985-01-15 | Board Of Trustees, Univ. Of Ill. | Didemnins A, B, C, and derivatives thereof, as antiviral agents |
| US4950649A (en) * | 1980-09-12 | 1990-08-21 | University Of Illinois | Didemnins and nordidemnins |
| IT1153974B (it) * | 1982-09-23 | 1987-01-21 | Erba Farmitalia | Composizioni farmacologiche a base di cisplatino e metodo per il loro ottenimento |
| DE3684868D1 (de) * | 1985-09-20 | 1992-05-21 | Cernitin Sa | Verwendung von pflanzenpollenextrakten zur herstellung von das wachstum von tumorzellen hemmenden pharmazeutischen praeparaten und verfahren zu ihrer herstellung. |
| US20030148933A1 (en) * | 1990-10-01 | 2003-08-07 | Pharma Mar S.A. | Derivatives of dehydrodidemnin B |
| GB8922026D0 (en) * | 1989-09-29 | 1989-11-15 | Pharma Mar Sa | Novel anti-viral and cytotoxic agent |
| US5580871A (en) * | 1992-11-20 | 1996-12-03 | The Dupont Merck Pharmaceutical Company | 4-Heteroaryl- 1,4-dihydropyridine compounds with calcium agonist and alpha1 -antagonist activity |
| FR2698543B1 (fr) * | 1992-12-02 | 1994-12-30 | Rhone Poulenc Rorer Sa | Nouvelles compositions à base de taxoides. |
| US5462726A (en) * | 1993-12-17 | 1995-10-31 | Bristol-Myers Squibb Company | Method of inhibiting side effects of solvents containing ricinoleic acid or castor oil or derivatives thereof employing a thromboxane A2 receptor antagonist and pharmaceutical compositions containing such solvents |
| WO1995017901A1 (en) * | 1993-12-29 | 1995-07-06 | Matrix Pharmaceutical, Inc. | Methods and compositions for the treatment of a host with a cellular proliferative disease |
| US5861439A (en) * | 1994-11-14 | 1999-01-19 | Alza Corporation | Method for enhanced electrotransport agent delivery |
| US6365597B1 (en) * | 1996-02-14 | 2002-04-02 | Aventis Pharmaceuticals Inc. | 4-aza steroids |
| EP0914116B1 (en) * | 1996-05-22 | 2000-10-11 | Protarga Inc. | Compositions comprising conjugates of cis-docosahexaenoic acid and taxotere |
| US5795909A (en) * | 1996-05-22 | 1998-08-18 | Neuromedica, Inc. | DHA-pharmaceutical agent conjugates of taxanes |
| US6156724A (en) * | 1996-06-07 | 2000-12-05 | Rinehart; Kenneth L. | Uses of didemnins as immunomodulating agents |
| US6034058A (en) * | 1997-04-15 | 2000-03-07 | Rinehart; Kenneth L. | Semi-synthetic alanyl dilemnin analogs |
| EP0981352B8 (en) * | 1997-05-07 | 2009-06-17 | Pharma Mar, S.A. | Use of aplidine for the treatment of cardiovascular diseases |
| US6245759B1 (en) * | 1999-03-11 | 2001-06-12 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| US20010021380A1 (en) * | 1999-04-19 | 2001-09-13 | Pluenneke John D. | Soluble tumor necrosis factor receptor treatment of medical disorders |
| US6890904B1 (en) * | 1999-05-25 | 2005-05-10 | Point Therapeutics, Inc. | Anti-tumor agents |
| RU2323000C2 (ru) * | 2000-04-07 | 2008-04-27 | Дзе Трастиз Оф Дзе Юниверсити Оф Пенсильвания | Аналоги тамандарина и дидемнина и способы их получения и применения |
| US6509315B1 (en) * | 2000-04-07 | 2003-01-21 | The Trustees Of The University Of Pennsylvania | Didemnin analogs and fragments and methods of making and using them |
| UA76718C2 (uk) * | 2000-06-30 | 2006-09-15 | Фарма Мар, С.А. | Протипухлинні похідні аплідину |
| MXPA03002479A (es) * | 2000-10-05 | 2004-05-24 | Immunex Corp | Polipeptidos de nectina, polinucleotidos, metodos para elaborarlos y uso de los mismos. |
| NZ525196A (en) * | 2000-10-12 | 2004-09-24 | Pharma Mar S | Treatment of cancers by aplidine in conjunction with a myoprotector |
| AU2002224417A1 (en) * | 2000-10-18 | 2002-04-29 | Immunex Corporation | Methods for treating il-18 mediated disorders |
| US6610399B1 (en) * | 2000-11-17 | 2003-08-26 | Structural Technologies, Llc | Multi-layer, thermal protection and corrosion protection coating system for metallic tendons, especially for external post-tensioning systems |
| DE60229414D1 (de) * | 2001-10-19 | 2008-11-27 | Pharma Mar Sa | Verwendung von aplidine in der behandlung von pankreaskrebs |
| DK1603584T3 (da) * | 2003-03-12 | 2009-01-05 | Dana Farber Cancer Inst Inc | Aplidine til behandling af multipelt myelom |
| KR20060002778A (ko) * | 2003-03-12 | 2006-01-09 | 파르마 마르, 에스.에이. | 개선된 항종양 치료 |
| EP1613338A4 (en) * | 2003-03-21 | 2009-06-24 | Madeleine M Joullie | TAMANDARIN ANALOGUES, FRAGMENTS THEREOF AND METHODS OF MAKING AND USING THE SAME |
| CA2528669A1 (en) * | 2003-06-09 | 2005-01-20 | The Regents Of The University Of Michigan | Compositions and methods for treating and diagnosing cancer |
| DK2029155T3 (en) * | 2006-02-28 | 2016-08-01 | Pharma Mar Sa | IMPROVED treatment of multiple myeloma |
| CA2703024A1 (en) * | 2007-10-19 | 2009-04-23 | Giuseppe Longo Sorbello | Improved antitumoral treatments |
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- 2000-11-15 PL PL355335A patent/PL200922B1/pl not_active IP Right Cessation
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103463020A (zh) * | 2013-09-23 | 2013-12-25 | 南京广康协生物医药技术有限公司 | Lycojaponicumin A在治疗肾癌药物中的应用 |
| CN103463020B (zh) * | 2013-09-23 | 2015-11-25 | 李淑兰 | Lycojaponicumin A在制备治疗肾癌药物中的应用 |
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