US2015283171A1PendingUtilityA1

Polymers for reversing heparin-based anticoagulation

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Assignee: UNIV BRITISH COLUMBIAPriority: Jun 1, 2011Filed: Jun 18, 2015Published: Oct 8, 2015
Est. expiryJun 1, 2031(~4.8 yrs left)· nominal 20-yr term from priority
Inventors:Jayachandran N. KizhakkedathuRajesh A. ShenoiCedric J. CarterDonald E. Brooks
A61K 9/06C08G 2340/00A61K 31/795A61K 31/765C08L 71/02B01D 15/36A61K 9/0014A61M 2202/0021A61K 31/785A61M 2202/0478A61M 2202/0413C08G 73/024A61K 47/34A61M 1/3675A61M 1/3679
62
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Claims

Abstract

Embodiments presented herein relate to various polymers. Some of the polymer embodiments are heparin binding polymers. Some embodiments of the heparin binding polymers can be employed to bind to heparin for methods such as separating, purifying, removing, and/or isolating heparin and heparin like molecules.

Claims

exact text as granted — not AI-modified
1 - 111 . (canceled) 
     
     
         112 . A heparin binding polymer, the polymer comprising:
 a first dendritic polyol; and   one or more cationic moieties attached to the first dendritic polyol,   wherein the polymer comprises either:   a) the structure of Formula (I):   
       
         
           
           
               
               
           
         
         wherein L 1  is the first dendritic polyol, L 2  is a second dendritic polyol, L 3  is a third dendritic polyol, L 4  is a fourth dendritic polyol, and L 5  is a fifth dendritic polyol, or 
         b) the structure of Formula (II): 
       
       
         
           
           
               
               
           
         
         wherein L 1  is the first dendritic polyol and L 2  is a second dendritic polyol, and wherein L 3  is a third dendritic polyol, and L 4  is a fourth dendritic polyol. 
       
     
     
         113 . The heparin binding polymer of  claim 112 , wherein the polymer comprises the structure of Formula (I): 
       
         
           
           
               
               
           
         
       
     
     
         114 . The heparin binding polymer of  claim 113 , wherein at least the first dendritic polyol comprises a polyether polyol, and wherein the polymer is immobilized on a support. 
     
     
         115 . The heparin binding polymer of  claim 113 , wherein the cationic moiety comprises Formula (VI): 
       
         
           
           
               
               
           
         
         and wherein the heparin binding polymer comprises an average of 4 to 100 cationic moieties. 
       
     
     
         116 . The heparin binding polymer of  claim 113 , further comprising a protective moiety covalently attached to the first dendritic polyol. 
     
     
         117 . The heparin binding polymer of  claim 116 , wherein the protective moiety comprises polyethylene glycol. 
     
     
         118 . The heparin binding polymer of  claim 117 , wherein the polymer has a polyethelene glycol content of about 75% by weight. 
     
     
         119 . The heparin binding polymer of  claim 113 , wherein the one or more cationic moieties comprises an amine group. 
     
     
         120 . The heparin binding polymer of  claim 119 , wherein the amine group is a tetra-amine group, hexa-amine group, or a deca-amine group. 
     
     
         121 . The heparin binding polymer of  claim 119 , wherein the amine group comprises a methylated amine. 
     
     
         122 . The heparin binding polymer of  claim 119 , wherein the amine group comprises a methylated tetra-amine group, a methylated hexa-amine group, or a methylated deca-amine group. 
     
     
         123 . The heparin binding polymer of  claim 113 , wherein the first dendritic polyol comprises a polyether polyol. 
     
     
         124 . The heparin binding polymer of  claim 123 , wherein the polyether polyol is hyperbranched. 
     
     
         125 . The heparin binding polymer of  claim 123 , wherein the polyether polyol has a degree of branching in the range of 0.05 to 0.95. 
     
     
         126 . The heparin binding polymer of  claim 125 , wherein the degree of branching in the range of 0.40-0.65. 
     
     
         127 . The heparin binding polymer of  claim 112 , wherein the polymer comprises the structure of Formula (II): 
       
         
           
           
               
               
           
         
         wherein L 1  is the first dendritic polyol and L 2  is a second dendritic polyol, and wherein L 3  is a third dendritic polyol, and L 4  is a fourth dendritic polyol. 
       
     
     
         128 . The heparin binding polymer of  claim 127 , wherein at least the first dendritic polyol comprises a polyether polyol, and wherein the polymer is immobilized on a support. 
     
     
         129 . The heparin binding polymer of  claim 127 , wherein the cationic moiety comprises Formula (VI): 
       
         
           
           
               
               
           
         
         and wherein the heparin binding polymer comprises an average of 4 to 100 cationic moieties. 
       
     
     
         130 . The heparin binding polymer of  claim 127 , further comprising a protective moiety covalently attached to the first dendritic polyol. 
     
     
         131 . The heparin binding polymer of  claim 130 , wherein the protective moiety comprises polyethylene glycol. 
     
     
         132 . The heparin binding polymer of  claim 131 , wherein the polymer has a polyethelene glycol content of about 75% by weight. 
     
     
         133 . The heparin binding polymer of  claim 127 , wherein the one or more cationic moieties comprises an amine group. 
     
     
         134 . The heparin binding polymer of  claim 133 , wherein the amine group is a tetra-amine group, hexa-amine group, or a deca-amine group. 
     
     
         135 . The heparin binding polymer of  claim 133 , wherein the amine group comprises a methylated amine. 
     
     
         136 . The heparin binding polymer of  claim 133 , wherein the amine group comprises a methylated tetra-amine group, a methylated hexa-amine group, or a methylated deca-amine group. 
     
     
         137 . The heparin binding polymer of  claim 127 , wherein the first dendritic polyol comprises a polyether polyol. 
     
     
         138 . The heparin binding polymer of  claim 137 , wherein the polyether polyol is hyperbranched. 
     
     
         139 . The heparin binding polymer of  claim 137 , wherein the polyether polyol has a degree of branching in the range of 0.05 to 0.95. 
     
     
         140 . The heparin binding polymer of  claim 139 , wherein the degree of branching in the range of 0.40-0.65. 
     
     
         141 . The heparin binding polymer of  claim 127 , wherein the heparin binding polymer binds to heparin selected from at least one of: unfractionated heparin (UFH), low molecular weight heparin (LMWH), ultra low molecular weight heparin (ULMWH), fondaparinux, idraparinux enoxaparin, dalteparin, tinzaparin, semuloparin, or heparinoid. 
     
     
         142 . The heparin binding polymer of  claim 141 , wherein the heparin binding polymer binds to fondaparinux. 
     
     
         143 . The heparin binding polymer of  claim 127 , wherein the heparin binding polymer binds to heparin selected from at least one of: unfractionated heparin (UFH), low molecular weight heparin (LMWH), ultra low molecular weight heparin (ULMWH), fondaparinux, idraparinux enoxaparin, dalteparin, tinzaparin, semuloparin, or heparinoid. 
     
     
         144 . The heparin binding polymer of  claim 143 , wherein the heparin binding polymer binds to fondaparinux. 
     
     
         145 . A method of counteracting heparin in a subject, the method comprising administering a heparin binding polymer of  claim 112  to a subject, wherein the heparin binding polymer binds to heparin and thereby counteracts heparin in the subject. 
     
     
         146 . The method of  claim 145 , wherein the heparin binding polymer further comprises polyethylene glycol covalently attached to the heparin binding polymer. 
     
     
         147 . The method of  claim 146 , wherein the cationic moiety is an amine group. 
     
     
         148 . The method of  claim 147 , wherein the amine group is a tetra-amine group, a hexa-amine group, or a deca-amine group. 
     
     
         149 . The method of  claim 146 , further comprising identifying a subject who has received an excess amount of heparin, wherein the identifying occurs before the heparin binding polymer is administered to the subject. 
     
     
         150 . The method of  claim 146 , wherein an excess amount of heparin was administered to the subject. 
     
     
         151 . The method of  claim 150 , wherein the excess amount of heparin was administered for the maintenance of an intravenous catheter. 
     
     
         152 . The method of  claim 150 , wherein the excess amount of heparin was administered to treat one or more of the following: acute coronary syndrome, atrial fibrilllation, cardiac bypass, extracorporeal membrane oxygenation, pancreatitis, hemofiltration, or burns. 
     
     
         153 . The method of  claim 145 , further comprising identifying a subject that would benefit from reducing a level of exogenous heparin that is present in the subject's blood. 
     
     
         154 . The method of  claim 153 , wherein the subject will benefit from an accelerated removal of exogenous heparin from the subject. 
     
     
         155 . The method of  claim 146 , wherein the method is performed in vivo. 
     
     
         156 . The method of  claim 146 , wherein the method is performed ex vivo. 
     
     
         157 . The method of  claim 145 , wherein the subject is a human. 
     
     
         158 . The method of  claim 145 , wherein the subject is a dog, a cat, a horse, a cow, a pig, a mouse, a rat, a rabbit, a monkey, or a guinea pig. 
     
     
         159 . The method of  claim 145 , wherein the heparin binding polymer is administered subcutaneously. 
     
     
         160 . The method of  claim 145 , wherein the heparin binding polymer is administered intravenously. 
     
     
         161 . The method of  claim 145 , wherein the heparin binding polymer binds to heparin selected from at least one of: unfractionated heparin (UFH), low molecular weight heparin (LMWH), ultra low molecular weight heparin (ULMWH), fondaparinux, idraparinux enoxaparin, dalteparin, tinzaparin, semuloparin, or heparinoid. 
     
     
         162 . The method of  claim 161 , wherein the heparin binding polymer binds to fondaparinux. 
     
     
         163 . The method of  claim 150 , wherein the excess amount of heparin is selected from selected from at least one of: unfractionated heparin (UFH), low molecular weight heparin (LMWH), ultra low molecular weight heparin (ULMWH), fondaparinux, idraparinux enoxaparin, dalteparin, tinzaparin, semuloparin, or heparinoid. 
     
     
         164 . The method of  claim 163 , wherein the excess amount of heparin is fondaparinux.

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