公开(公告)号：US07034006B2

公开(公告)日：2006-04-25

申请号：US09756765

申请日：2001-01-10

申请人： Saul Yedgar ,  David Shuseyov ,  Gershon Golomb ,  Reuven Reich ,  Isaac Ginsburg ,  Abd-al-Roof Higazi ,  Moshe Ligumski ,  Miron Krimsky ,  David Ojcius ,  Benito Antonio Yard ,  Fokko Johannes van der Woude ,  Edit Schnitzer

发明人： Saul Yedgar ,  David Shuseyov ,  Gershon Golomb ,  Reuven Reich ,  Isaac Ginsburg ,  Abd-al-Roof Higazi ,  Moshe Ligumski ,  Miron Krimsky ,  David Ojcius ,  Benito Antonio Yard ,  Fokko Johannes van der Woude ,  Edit Schnitzer

IPC分类号： A61K31/70 ,  A61K31/715 ,  C08B37/08 ,  C08B37/10 ,  C07H5/06

CPC分类号： A61K47/544

摘要： The invention provides novel methods for treating disease based upon the medicinal use of lipids and phospholipids covalently bound to physiologically acceptable monomers or polymers. Phosphatidylethanolamine moieties conjugated to physiologically acceptable monomers and polymers (PE conjugates) manifest an unexpectedly wide range of pharmacological effects, including stabilizing cell membranes; limiting oxidative damage to cell and blood components; limiting cell proliferation, cell extravasation and (tumor) cell migratory behavior; suppressing immune responses; and attenuating physiological reactions to stress, as expressed in elevated chemokine levels. The surprisingly manifold pharmacological properties of the PL-conjugates allow for the invention, disclosed herein, of novel methods for the treatment of a diverse range of disease states, including obstructive respiratory disease, including asthma; colitis and Crohn's disease; central nervous system insult, including blood brain barrier compromise, ischemic stroke, and multiple sclerosis; contact dermatitis; psoriasis; cardiovascular disease, including ischemic conditions and prophylaxis for invasive vascular procedures; cellular proliferative disorders, including anti-tumor vasculogenesis, invasiveness, and metastases; anti-oxidant therapy; hemolytic syndromes; sepsis; acute respiratory distress syndrome; tissue transplant rejection syndromes; autoimmune disease; viral infection; and hypersensitivity conjunctivitis. The therapeutic methods of the invention include administration of phosphatidylethanolamine bound to carboxymethylcellulose, heparin, hyaluronic acid, polyethylene glycol, and hemaccel. Disclosed herein are also new compounds comprised of phospholipid moieties bound to low molecular weight monomers and dimers, including mono- and disaccharides, carboxylated disaccharides, mono- and dicarboxylic acids, salicylates, bile acids, and fatty acids.

公开(公告)号：US06200962B1

公开(公告)日：2001-03-13

申请号：US08849122

申请日：1997-08-07

申请人： Oren Tirosh ,  Joshua Katzhendler ,  Isaac Ginsburg ,  Yehezkel Barenholz ,  Ron Kohen

发明人： Oren Tirosh ,  Joshua Katzhendler ,  Isaac Ginsburg ,  Yehezkel Barenholz ,  Ron Kohen

IPC分类号： A61K31664

CPC分类号： A61Q17/00 ,  A61K8/55 ,  A61K31/664 ,  A61K2800/522

摘要： The invention relates to a compound of formula (I) in which X1 and X2 each independently represents an oxygen or nitrogen atom; p,m and n are each independently an integer of at least 2; R, R1 and R2 each independently represents a hydrogen atom; a halogen atom; an optionally substituted straight-chained or branched alkyl alkenyl or alkynyl radical; a group R3O in which R3 is hydrogen atom, an optionally substituted straight-chained or branched alkyl alkenyl or alkynyl radical; optionally substituted acyl or optionally substituted aryl or heteroaryl; a group R4O(O)C in which R4 is a hydrogen atom or an optionally straight-chained or branched alkyl, alkenyl or allkynyl radical; a group —SR5 is a hydrogen atom or an optionally substituted straight-chained or branched alkyl alkenyl or alkynyl radical; a group —NR6R7 in which R6 and R7 each independently represents a hydrogen atom, an optionally substituted straight-chained or branched alkyl, alkenyl or alkynyl radical; optionally substituted acyl; or an optionally substituted phosphate ester group. The invention also relates to processes., for The preparation of compounds of the formula and to pharmaceutical compositions containing the same.

摘要翻译： 本发明涉及式（I）化合物，其中X 1和X 2各自独立地表示氧或氮原子; p，m和n各自独立地为至少2的整数; R，R 1和R 2各自独立地表示氢原子; 卤素原子; 任选取代的直链或支链烷基烯基或炔基; R 3为氢原子的基团R 3 O，任选取代的直链或支链烷基烯基或炔基; 任选取代的酰基或任选取代的芳基或杂芳基; R 4是氢原子或任选的直链或支链烷基，烯基或全炔基的基团R4O（O）C; 基团-SR 5是氢原子或任选取代的直链或支链烷基烯基或炔基; R 6和R 7各自独立地表示氢原子的基团-NR 6 R 7，任选取代的直链或支链烷基，烯基或炔基; 任选取代的酰基; 或任选取代的磷酸酯基团。 本发明还涉及制备下式化合物和含有该化合物的药物组合物的方法。