Embolic compositions

Abstract

Embolic compositions comprising macromers having a backbone comprising a polymeric backbone comprising units with a 1,2-diol or 1,3-diol structure, such as polyvinyl alcohol, and pendant chains bearing crosslinkable groups and, optionally, other modifiers. When crosslinked, the macromers form hydrogels having many properties advantageous for use as embolic agents to block and fill lumens and spaces. The embolic compositions can be used as liquid embolic agents and crosslinked in situ or as preformed embolic articles, such as microspheres.

What is claimed is: 
     
       1. A method for embolization, comprising the steps:
 providing a composition comprising macromers having a polymeric backbone comprising units with a 1,2-diol or 1,3-diol structure and at least two pendant chains bearing crosslinkable groups and having the formula:   
       
         
           
           
               
               
           
         
         in which R is a linear or branched C 1 -C 8  alkylene or a linear or branched C 1 -C 12  alkane; R 1  is hydrogen, a C 1 -C 6  alkyl, or a cycloalkyl; R 2  is hydrogen or a C 1 -C 6  alkyl; and R 3  is an olefinically unsaturated electron attracting copolymerizable radical having up to 25 carbon atoms; 
         delivering the composition to the intended site of embolization, or upstream of the intended site; and 
         then crosslinking the macromers to form a hydrogel; 
         wherein the crosslinkable groups of the macromer are crosslinkable via free radical polymerization that is redox initiated; 
         and the composition comprises a first solution comprising a reductant and a second solution comprising an oxidant and the macromers are present in either or both solutions. 
       
     
     
       2. The method of  claim 1 , wherein the macromere further comprises pendant modifier groups. 
     
     
       3. The method of  claim 1 , further comprising administering an active agent. 
     
     
       4. The method of  claim 3 , wherein the active agent is a chemotherapeutic agent. 
     
     
       5. The method of  claim 1 , wherein the hydrogel is biodegradable. 
     
     
       6. The method of  claim 1 , wherein the composition further comprises a copolymerizable monomer. 
     
     
       7. The method of  claim 1 , wherein the method comprises using a delivery device to deliver the solutions separately and mixing the solutions to initiate crosslinking. 
     
     
       8. The method of  claim 7  wherein the solutions are delivered to the intended site using a multilumen catheter. 
     
     
       9. The method of  claim 8  wherein the solutions are mixed in the catheter. 
     
     
       10. The method of  claim 1 , wherein the embolization is used for treatment of a uterine fibroid, by delivering the embolic composition to a vessel feeding the fibroid to occlude the vessel. 
     
     
       11. The method of  claim 1 , wherein the embolization is used for treatment of a tumor, by delivering the embolic composition to a vessel feeding the tumor to occlude the vessel. 
     
     
       12. The method of  claim 1 , wherein the embolization is used for treatment of an endoleak by delivering the embolic composition to seal the endoleak. 
     
     
       13. The method of  claim 12 , wherein sealing the endoleak comprises partially or completely filling the aneurysm sac with the embolic composition. 
     
     
       14. The method of  claim 1 , wherein the embolization is used for treatment of an arteriovenous malformation by delivering the embolic composition to occlude the malformation. 
     
     
       15. A method of treating an animal, comprising:
 providing a composition comprising macromers having a polymeric backbone comprising units with a 1,2-diol or 1,3-diol structure and at least two pendant chains bearing crosslinkable groups and having the formula:   
       
         
           
           
               
               
           
         
         in which R is a linear or branched C 1 -C 8  alkylene or a linear or branched C 1 -C 12  alkane; R 1  is hydrogen, a C 1 -C 6  alkyl, or a cycloalkyl; R 2  is hydrogen or a C 1 -C 6  alkyl; and R 3  is an olefinically unsaturated electron attracting copolymerizable radical having up to 25 carbon atoms; 
         delivering the composition to the animal to partially or totally block or fill a lumen, space, or cavity; and 
         crosslinking the macromers to form a hydrogel; 
         wherein the crosslinkable groups of the macromer are crosslinkable via free radical polymerization that is redox initiated; and 
         wherein the composition comprises a first solution comprising a reductant and a second solution comprising an oxidant and the macromers are present in either or both solutions.  
       
     
     
       16. The method of claim 15 wherein the composition is delivered to block or fill a lumen.  
     
     
       17. The method of claim 15 wherein the composition is delivered to block or fill a space.  
     
     
       18. The method of claim 15 wherein the composition is delivered to block or fill a cavity.  
     
     
       19. The method of claim 15, wherein the macromer further comprises pendant modifier groups.  
     
     
       20. The method of claim 15, wherein the composition includes an active agent.  
     
     
       21. The method of claim 15, wherein the hydrogel is biodegradable.  
     
     
       22. The method of claim 15, wherein the composition further comprises a copolymerizable monomer.  
     
     
       23. The method of claim 15, wherein the method comprises using a delivery device to deliver the solutions separately and mixing the solutions to initiate crosslinking.  
     
     
       24. The method of claim 15, wherein the solutions are delivered to the intended site using a multilumen catheter.  
     
     
       25. The method of claim 15, wherein the solutions are mixed in the catheter.  
     
     
       26. The method of claim 15, wherein the solutions are delivered to the intended site using a syringe.