Oligofluorinated cross-linked polymers and uses thereof

Abstract

The invention features oligofluorinated cross-linked polymers and their use in the manufacture of articles and coating surfaces.

1 . A monomer comprising:
 i. two or more cross-linking domains, and   ii. an oligomeric segment having a first end covalently tethered to a first cross-linking domain and a second end covalently tethered to a second cross-linking domain,   wherein at least one of said cross-linking domains is an oligofluorinated cross-linking domain.   
     
     
         2 . The monomer of  claim 1 , further described by formula (I):
   (D)-[(oligo)-(D)] n    (I)
   wherein oligo is an oligomeric segment;   each D is a cross-linking domain; and   n is an integer from 1 to 20,   wherein at least one D is an oligofluorinated cross-linking domain.   
     
     
         3 . The monomer of  claim 1 , further described by formula (II):
   (D)-[(oligo)-(LinkA-F T )] m -[(oligo)-(D)] n    (II)
   wherein oligo is an oligomeric segment;   each D is a cross-linking domain;   F T  is an oligofluoro group;   each LinkA-F T  is an organic moiety covalently bound to a first oligo, a second oligo, and F T ;   n is an integer from 1 to 20; and   m is an integer from 1 to 20,   wherein at least one D is an oligofluorinated cross-linking domain.   
     
     
         4 . The monomer of  claim 1 , wherein said cross-linking domains include a reactive moiety selected from vinyls, epoxides, aziridines, and oxazolines. 
     
     
         5 . The monomer of any of  claims 1 - 4 , wherein said oligofluorinated cross-linking domain is selected from 
       
         
           
           
               
               
           
         
       
     
     
         6 . The monomer of  claim 1 , further described by formula (III):
   (oligo) n (vinyl) m (F T ) o    (III)
   wherein oligo is an oligomeric segment;   vinyl is a cross-linking domain comprising an unsaturated moiety capable of undergoing radical initiated polymerization;   F T  is an oligofluoro group covalently tethered to said vinyl and/or said oligo; and   each of n, m, and o is, independently, an integer from 1 to 5   wherein said monomer comprises at least one oligofluorinated cross-linking domain.   
     
     
         7 . The monomer of  claim 6 , further described by formula (IV): 
       
         
           
           
               
               
           
         
         wherein oligo is an oligomeric segment; 
         vinyl is a cross-linking domain comprising an unsaturated moiety capable of undergoing radical initiated polymerization; 
         F T  is an oligofluoro group; 
         each LinkA is, independently, an organic moiety covalently bound to oligo, F T , and vinyl; and 
         a, b, and c are integers greater than 0. 
       
     
     
         8 . The monomer of any of  claims 3  to  7 , wherein F T  has the formula:
   CF 3 (CF 2 ) p X, (CF 3 ) 2 CF(CF 2 ) p X, or (CF 3 ) 3 C(CF 2 ) p X, 
 wherein X is selected from CH 2 CH 2 —, (CH 2 CH 2 O) n , CH 2 CH(OD)CH 2 O—, CH 2 CH(CH 2 OD)O—, or D-; 
 D is a moiety capable of chain growth polymerization; 
 p is an integer between 2 and 20; and 
 n is an integer between 1 and 10. 
 
     
     
         9 . The monomer of any of  claims 4 - 8 , wherein said vinyl group is selected from methylacrylate, acrylate, allyl, vinylpyrrolidone, and styrene derivatives. 
     
     
         10 . The monomer of any of  claims 4 - 8 , wherein said oligo is selected from polyurethane, polyurea, polyamides, polyaklylene oxide, polycarbonate, polyester, polylactone, polysilicone, polyethersulfone, polypeptide, polysaccharide, polysiloxane, polydimethylsiloxane, polypropylene oxide, polyethylene oxide, polytetramethyleneoxide, and combinations thereof. 
     
     
         11 . The monomer of any of  claims 1 - 10 , further comprising one or more biologically active agents covalently tethered to said monomer. 
     
     
         12 . The monomer of  claim 11 , wherein said biologically active agent is selected from proteins, peptides, carbohydrates, antibiotics, antiproliferative agents, rapamycin macrolides, analgesics, anesthetics, antiangiogenic agents, antithrombotic agents, vasoactive agents, anticoagulants, immunomodulators, cytotoxic agents, antiviral agents, antibodies, neurotransmitters, psychoactive drugs, oligonucleotides, proteins, vitamins, lipids, and prodrugs thereof. 
     
     
         13 . A method for coating an article said method comprising the steps of (a) contacting said article with a monomer of any of  claims 1 - 12  and (b) polymerizing said monomer to form a cross-linked coating. 
     
     
         14 . A method for making a shaped article said method comprising the steps of (a) polymerizing a monomer of any of  claims 1 - 12  to form a base polymer and (b) shaping said base polymer to form a shaped article. 
     
     
         15 . The method of  claim 13  or  14 , wherein said shaped article is an implantable medical device. 
     
     
         16 . The method of  claim 15 , wherein said implantable medical device is selected from cardiac-assist devices, catheters, stents, prosthetic implants, artificial sphincters, and drug delivery devices. 
     
     
         17 . The implantable medical device of  claim 16 , wherein said implantable medical device is a stent. 
     
     
         18 . The method of  claim 13  or  14 , wherein said shaped article is a nonimplantable medical device. 
     
     
         19 . The method of any of  claims 13 - 18 , wherein said polymerizing is initiated by heat, UV radiation, a photoinitiator, or a free-radical initiator. 
     
     
         20 . The method of  claim 19 , wherein said polymerizing is initiated by heat. 
     
     
         21 . The method of any of  claims 13 - 18 , wherein said polymerizing further comprises mixing said monomer with a second compound containing a vinyl group. 
     
     
         22 . The method of  claim 21 , wherein said second compound is a monomer of any of  claims 1 - 12 . 
     
     
         23 . The method of  claim 22 , wherein said second vinyl monomer is selected from acrylic acid, methyl acrylate, ethyl acrylate, n-butyl acrylate, 2-hydroxyethyl acrylate, n-butyl acrylate, glycidyl acrylate, vinyl acrylate, allyl acrylate, 2-hydroxyethyl acrylate, 2-hydroxy ethyl methacrylate (HEMA), 2-amino ethyl methacrylate, glycerol monomethacrylate, acrylamide, methacrylamide, N-(3-aminopropyl)methacrylamide, crotonamide, allyl alcohol, and 1,1,1-trimethylpropane monoallyl ether. 
     
     
         24 . A method for encapsulating a biologically active agent in a polymer, said method comprising (a) contacting a biologically active agent with a monomer of any of  claims 1 - 12  and (b) polymerizing said monomer to form an oligofluorinated cross-linked polymer. 
     
     
         25 . The method of  claim 24 , wherein said biologically active agent is selected from proteins, peptides, carbohydrates, antibiotics, antiproliferative agents, rapamycin macrolides, analgesics, anesthetics, antiangiogenic agents, antithrombotic agents, vasoactive agents, anticoagulants, immunomodulators, cytotoxic agents, antiviral agents, antibodies, neurotransmitters, psychoactive drugs, oligonucleotides, vitamins, lipids, and prodrugs thereof. 
     
     
         26 . A composition comprising: (i) a first component having a core substituted with m nucleophilic groups, where m≧2; and a second component having a core substituted with n electrophilic groups, where n≧12 and m+n>4; wherein the composistion comprises at least one oligofluorinated nucleophilic group or one oligofluorinated electrophilic group, and wherein the first component and the second component react to form oligofluorinated cross-linked polymer. 
     
     
         27 . The composition of  claim 26 , wherein said first component comprises an oligomeric segment having a first end covalently tethered to a first nucleophilic group and a second end covalently tethered to a second nucleophilic group,
 wherein said first nucleophilic group or said second nucleophilic group is an oligofluorinated nucleophilic group.   
     
     
         28 . The composition of  claim 26 , wherein said second component comprises an oligomeric segment having a first end covalently tethered to a first electrophilic group and a second end covalently tethered to a second electrophilic group,
 wherein said first electrophilic group or said second electrophilic group is an oligofluorinated nucleophilic group.   
     
     
         29 . The composition of  claim 26 , wherein said first component or said second component is further described by formula (V):
   (G)-[(oligo)-(G)] n    (V)
   wherein oligo is an oligomeric segment;   G is either a nucleophilic group or an electrophilic group; and   n is an integer from 1 to 5,   wherein at least one G is an oligofluorinated nucleophilic group or oligofluorinated electroophilic group.   
     
     
         30 . The composition of  claim 26 , wherein said first component or said second component is further described by formula (VI): 
       
         
           
           
               
               
           
         
         wherein oligo is an oligomeric segment; 
         G is either a nucleophilic group or an electrophilic group; 
         F T  is an oligofluoro group; 
         each LinkA is, independently, an organic moiety covalently bound to oligo, F T , and G; and 
         a, b, and c are integers greater than 0. 
       
     
     
         31 . The composition of  claim 30 , wherein F T  has the formula:
   CF 3 (CF 2 ) p X, (CF 3 ) 2 CF(CF 2 ) p X, or (CF 3 ) 3 C(CF 2 ) p X,   wherein X is selected from CH 2 CH 2 —, (CH 2 CH 2 O) n , CH 2 CH(OD)CH 2 O—, CH 2 CH(CH 2 OD)O—, or D-;   D is a moiety capable of chain growth polymerization;   p is an integer between 2 and 20; and   n is an integer between 1 and 10.   
     
     
         32 . The composition of any of  claims 26  to  31 , wherein said nucleophilic groups and said electrophilic groups undergo a nucleophilic substitution reaction, a nucleophilic addition reaction, or both. 
     
     
         33 . The composition of  claim 32 , wherein the nucleophilic groups are selected from primary amines, secondary amines, thiols, alcohols, and phenols. 
     
     
         34 . The composition of  claim 32 , wherein the electrophilic groups are selected from carboxylic acid esters, acid chloride groups, anhydrides, isocyanato, thioisocyanato, epoxides, activated hydroxyl groups, succinimidyl ester, sulfosuccinimidyl ester, maleimido, and ethenesulfonyl. 
     
     
         35 . The composition of  claim 26 , wherein the number of nucleophilic groups in the mixture is approximately equal to the number of electrophilic groups in the mixture. 
     
     
         36 . The composition of  claim 35 , wherein the ratio of moles of nucleophilic groups to moles of electrophilic groups is about 2:1 to 1:2. 
     
     
         37 . The composition of  claim 36 , wherein the ratio is 1:1. 
     
     
         38 . A method for coating an article said method comprising the steps of (a) contacting said article with a composition of any of  claims 26 - 37 ; and (b) polymerizing said composition on said article to form a cross-linked coating. 
     
     
         39 . A method for making a shaped article said method comprising the steps of (a) polymerizing a composition of any of  claims 26 - 37  to form a base polymer and (b) shaping said base polymer to form a shaped article. 
     
     
         40 . The method of  claim 38  or  39 , wherein said article is an implantable medical device. 
     
     
         41 . The method of  claim 40 , wherein said implantable medical device is selected from cardiac-assist devices, catheters, stents, prosthetic implants, artificial sphincters, and drug delivery devices. 
     
     
         42 . The method of  claim 41 , wherein said implantable medical device is a stent. 
     
     
         43 . The method of  claim 38  or  39 , wherein said article is a nonimplantable medical device. 
     
     
         44 . A method for coating a stent comprising initiating a polymerization reaction on the surface of said stent to form a polymerized coating. 
     
     
         45 . The method of  claim 44 , wherein said polymerized coating is a cross-linked polymer coating. 
     
     
         46 . The method of  claim 45 , wherein said polymerized coating is an oligofluorinated cross-linked polymer coating. 
     
     
         47 . The method of  claim 44 , wherein said polymerization reaction is a chain growth polymerization reaction. 
     
     
         48 . The method of  claim 44 , wherein said polymerization reaction is a nucleophilic substitution reaction and/or a nucleophilic addition reaction. 
     
     
         49 . The method of any of  claims 44 - 48 , comprising the steps of (a) contacting said stent with a monomer of any of  claims 1 - 12  or a composition of any of  claims 26 - 36 ; and (b) polymerizing said monomer or polymerizing said composition to form a cross-linked coating. 
     
     
         50 . The method of  claim 13  or  38 , wherein an uncoated implantable medical device is coated to produce a coated implantable medical device, said coated implantable medical device having, upon implantation into an animal, reduced protein deposition, reduced fibrinogene deposition, reduced platelet deposition, or reduced inflammatory cell adhesion in comparison to said uncoated implantable medical device.