Novel prepolymers useful in biomedical devices

Abstract

A novel polyurethane based prepolymer useful in biomedical devices which provides high oxygen permeability and superior physical properties.

1 . A polymeric matrix for controlled release of an active pharmaceutical agent, wherein the: polymeric matrix is a polymerization product of a monomer mixture comprising a prepolymer described by the general chemical formulae  
         E(*D*A*D*G) a *D*A*D*E′ or  E(*D*G*D*A) a *D*G*D*E′ 
       where 
 A denotes a divalent polymeric radical of the formula  
                     
 wherein  
 R S  denotes an alkyl radical or a fluorinated alkyl radical with 1 to 3 carbon atoms;  
 p provides a moiety weight of 400 to 10,000;  
 D denotes an alkyl diradical, an alkyl cycloalkyl diradical, a cycloalkyl diradical, an alkylaryl diradical or an aryl diradical, with 6 to 30 carbon atoms;  
 G denotes an alkyl diradical, a cycloalkyl diradical, an alkyl cycloalkyl diradical, an aromatic diradical or an alkylaromatic diradical with 1 to 40 carbon atoms which may have ether, thio, or amine linkages in the main chain;  
 * denotes a urethane linkage; and  
 E and E′ denote polymerizable unsaturated organic radicals represented by the general chemical formula:  
                     
 wherein  
 R 1  denotes a divalent alkylene radical with 1 to 10 carbon atoms;  
 R 2  denotes a —H or —CH 3  radical;  
 R 3  denotes a —H radical or an alkyl radical with 1 to 6 carbon atoms or a —COY—R 4  radical where Y is —O—, —S— or —NH— and; and R 4  denotes an alkyl radical with 1 to 12 carbon atoms;  
 Z is —O— or —NH—;  
 X denotes —CO—, or —OCO—;  
 Ar denotes an aromatic radical with 6 to 30 carbon atoms;  
 a is at least 1;  
 w is 0 to 6;  
 x is 0 or 1;  
 y is 0 or 1; and  
 z is 0 or 1.  
 
     
     
         2 . The polymeric matrix of  claim 1 , wherein said prepolymer has the formula E(*D*A*D*G) a *D*A*D*E′.  
     
     
         3 . The polymeric matrix of  claim 2 , wherein the G radical is formed from neopentyl glycol, the D radical is formed from isophorone diisocyanate, and the E and E′ radicals are each formed from 2-hydroxyethylmethyacrylate.  
     
     
         4 . The polymeric matrix of  claim 1 , wherein said prepolymer has the formula E(*D*G*D*A) a *D*G*D*E′.  
     
     
         5 . The polymeric matrix of  claim 4 , wherein the D radical is formed from isophorone diisocyanate.  
     
     
         6 . The polymeric matrix of  claim 5 , wherein the G radical is formed from neopentyl glycol, diethylene glycol or 1,4-butanediol.  
     
     
         7 . The polymeric matrix of  claim 6 , wherein the E and E′ radicals are formed from 2-hydroxyethylmethyacrylate.  
     
     
         8 . The polymeric matrix of  claim 1 , wherein the monomer mixture further comprises a hydrophilic comonomer.  
     
     
         9 . The polymeric matrix of  claim 8 , wherein the hydrophilic comonomer is at least one member selected from the group consisting of 2-hydroxyethyl methacrylate, N-vinyl-2-pyrrolidinone, methacrylic acid, dimethylacrylamide and glycerol methacrylate.  
     
     
         10 . A composition comprising: an active pharmaceutical agent; and a polymeric matrix for controlled release of said active pharmaceutical agent, wherein the polymeric matrix is a polymerization product of a monomer mixture comprising a prepolymer described by the general chemical formulae  
         E(*D*A*D*G) a *D*A*D*E′ or  E(*D*G*D*A) a *D*G*D*E′
where 
 A denotes a divalent polymeric radical of the formula                          wherein    R S  denotes an alkyl radical or a fluorinated alkyl radical with 1 to 3 carbon atoms;    p provides a moiety weight of 400 to 10,000;    D denotes an alkyl diradical, an alkyl cycloalkyl diradical, a cycloalkyl diradical, an alkylaryl diradical or an aryl diradical, with 6 to 30 carbon atoms;    G denotes an alkyl diradical, a cycloalkyl diradical, an alkyl cycloalkyl diradical, an aromatic diradical or an alkylaromatic diradical with 1 to 40 carbon atoms which may have ether, thio, or amine linkages in the main chain;    * denotes a urethane linkage; and    E and E′ denote polymerizable unsaturated organic radicals represented by the general chemical formula:                          wherein    R 1  denotes a divalent alkylene radical with 1 to 10 carbon atoms;    R 2  denotes a —H or —CH 3  radical;    R 3  denotes a —H radical or an alkyl radical with 1 to 6 carbon atoms or a —COY—R 4  radical where Y is —O—, —S— or —NH— and; and R 4  denotes an alkyl radical with 1 to 12 carbon atoms;    Z is —O— or —NH—;    X denotes —C—, or —OCO—;    Ar denotes an aromatic radical with 6 to 30 carbon atoms;    a is at least 1;    w is 0 to 6;    x is 0 or 1;    y is 0 or 1; and    z is 0 or 1.    
     
     
         11 . A polymeric matrix for controlled release of an active pharmaceutical agent, wherein the polymeric matrix is a polymerization product of a monomer mixture comprising a prepolymer described by the general chemical formulae  
         E(*D*A*D*G) a *D*A*D*E′ or  E(*D*G*D*A) a *D*G*D*E′ 
       where 
 A denotes a divalent polymeric radical selected from the group consisting of:  
   —(CH 2 ) n′ —O—(R P O) n —CH 2 ) n″ — —(CH 2 ) m′ —O—(R F O) m —(CH 2 ) m″ — 
 wherein  
 R P  denotes a straight or branched alkyl group with 1 to 6 carbon atoms and n provides a moiety weight of the radical between 2000 and 10,000;  
 R F  denotes a fluorinated straight or branched alkyl group with 1 to 6 carbon atoms and m provides a moiety weight of the radical between 400 and 10,000;  
 D denotes an alkyl diradical, an alkyl cycloalkyl diradical, a cycloalkyl diradical, an alkylaryl diradical or an aryl diradical, with 6 to 30 carbon atoms;  
 G denotes an alkyl diradical, a cycloalkyl diradical, an alkyl cycloalkyl diradical, an aromatic diradical or an alkylaromatic diradical with 1 to 40 carbon atoms which may have ether, thio, or amine linkages in the main chain;  
 * denotes a urethane linkage; and  
 E and E′ denote polymerizable unsaturated organic radicals represented by the general chemical formula:  
                     
 wherein  
 R 1  denotes a divalent alkylene radical with 1 to 10 carbon atoms;  
 R 2  denotes a —H or —CH 3  radical;  
 R 3  denotes a —H radical or an alkyl radical with 1 to 6 carbon atoms or a —COY—R 4  radical where Y is —O—, —S— or —NH— and; and R 4  denotes an alkyl radical with 1 to 12 carbon atoms;  
 Z is —O— or —NH—;  
 X denotes —CO—, or —CO—;  
 Ar denotes an aromatic radical with 6 to 30 carbon atoms;  
 a is at least 1;  
 w is 0 to 6;  
 x is 0 or 1;  
 y is 0 or 1; and  
 z is 0 or 1.