Anionic-cationic polyion complexes comprising zwitterionic monomer component

Abstract

A polyion complex (PIC) is formed of an anionic soluble polymer formed from ethylenically unsaturated monomers including at least one anionic or monomer and a cationic soluble polymer formed from ethylenically unsaturated monomer including at least one cationic monomer, in which the monomers used to form at lest one of the polymers comprise a switterionic monomer and in which the monomers used to form at least one of the polymers include non-ionic monomer, preferably C1-24 alkyl(meth)acrylate, in which the overall ratio of anionic groups to cationic groups in the PIC is in the range 1.5:1 to 1:1.5, and in which the polymers are combined in ratios to provide a PIC in which there are units derived from zwitterionic monomer in an amount in the range 1 to 70 mole % based on total monomer derived units in the PIC and there are units derived from non-ionic monomer in an amount in the range 0 to 60 mole % based on total monomer derived units in the PIC. The PIC is preferably swollen in water and is a flowable gel The zitterionic monomer is preferably 2-(methacyloyloxyethyl)-2′-(trimethylammoniumethyl)phosphate inner salt.

1 . A polyion complex formed from a cationic polymer having an overall cationic charge and an anionic polymer having an overall anionic charge, in which the anionic polymer is obtainable by polymerising ethylenically unsaturated monomers including: 
 a) 5 to 100 mole % anionic monomer having an anionic or anionisable group;    b) 0 to 85 mole % zwitterionic monomer having a zwitterionic group; and    c) 0 to 80 mole % nonionic monomer;    and in which the cationic polymier is obtainable by polymerising ethylenically unsaturated monomers including    d) 5 to 100 cationic monomer having a cationic or cationisable group;    e) 0 to 85 mole % zwitterionic monomer having a pendant zwitterionic group; and    f) 0 to 80 mole % non ionic monomer;    in which the total units in the polyion complex derivable from nonionic monomer c and f is in the range 0 to 60 mole %, the total mole % of units in the polyion complex derivable from zwitterionic monomer is in the range 1 to 70 mole %, and the ratio of moles of excess anionic or anionisable groups in the anionic polymer to the moles of excess cationic or cationisable groups in the cationic polymer is in the range 1.5:1 to 1:1.5.    
     
     
         2 . A polyion complex formed from a cationic polymer having an overall cationic charge and an anionic polymer having an overall anionic charge, in which the anionic polymer is water soluble and is obtainable by polymerising monomers including 
 a) 5 to 100% anionic monomer having an anionic or anionisable group; and    b) 0 to 85 mole % zwitterionic monomer having pendant zwitterionic group;    c) 0 to 60 mole % non ionic monomer;    and in which the cationic polymer is water soluble and is obtainable by polymerising ethylenically unsaturated monomers including    d) 5 to 100 mole % cationic monomer having a cationic or cationisable group;    e) 0 to 85 mole % zwitterionic monomer having a zwitterionic pendant group;    f) 0 to 60 mole % nonionic monomer; and    in which the total moles of units in the polyion complex derivable from zwitterionic monomers in the range 1 to 70 mole %, and in which the ratio of total moles anionic groups in excess of cationic groups in anionic polymer to total moles cationic groups in excess of anionic groups of cationic polymer is in the range 1.5:1 to 1:1.5.    
     
     
         3 . A polyion complex according to  claim 1  or  claim 2 , in which the total of units derivable from nonionic monomer in the polyion complex is preferably at least 5 mole %.  
     
     
         4 . A polyion complex according to any preceding claim in which the anionic polymer is formed from monomers substantially free of cationic monomer and the cationic polymer is formed of monomers substantially free of anionic monomer.  
     
     
         5 . A polyion complex according to any preceding claim in which the ratio of total moles of anionic monomer used to form anionic polymer to total moles of cationic monomer used to form the cationic polymer is in the range 1.25:1 to 1:1.25, preferably in the range 1.1:1 to 1:1.1, preferably about 1:1.  
     
     
         6 . A polyion complex according to any preceding claim which is water-insoluble and water-swellable.  
     
     
         7 . A polyion complex according to any preceding claim in which the zwitterionic monomer preferably has the formula VI  
       YBX   VI  
       wherein 
 B is a straight or branched alkanediyl or alkanediyloxaalkanediyl or alkanediyloligo(oxaalkanediyl) chain optionally containing one or more fluorine atoms up to and including perfluorinated chains or, if X or Y contains a terminal carbon atom bonded to B, a valence bond;  
 X is the zwitterionic group; and  
 Y is an ethylenically unsaturated polymerisable group selected from  
                     
 CH 2 ═C(R)—CH 2 —O—, CH 2 ═C(R)—CH 2 OC(O)—, CH 2 ═C(R)OC(O)—, CH 2 ═C(R)—O—, CH 2 ═C(R)CH 2 OC(O)N(R 11 )—, R 12 OCCR═CRC(O)—O—, RCH═CHC(O)O—, RCH═C(COOR 12 )CH 2 —C(O)—O—,  
                     
 wherein:  
 R is hydrogen or a C 1-4  alkyl group;  
 R 11  is hydrogen or a C 1-4  alkyl group or R 11  is —B—X where B and X are as defined above; and  
 R 12  is hydrogen or a C 1-4  alkyl group or BX where B and X are as defined above;  
 A is —O— or —NR 11 —;  
 K is a group —(CH 2 ) p OC(O)—, —(CH 2 ) p C(O)O —, —(CH 2 ) p OC(O)O—, —(CH 2 ) p NR 13 —, —(CH) p NR 13 C(O)—, —(CH) p C(O)NR 13 —, —(CH 2 ) p NR 13 C(O)O—, —(CH 2 ) p OC(O)NR 13 —, —(CH) p NR 13 C(O)NR 13 — (in which the groups R 13  are the sarne or different), —(CH) p O—, —(CH) p SO 3 —, or, optionally in combination with B, a valence bond and p is from 1 to 12 and R 13  is hydrogen or a C 1-4  alkyl group.  
 
     
     
         8 . A polyion complex according to  claim 7  in which the zwitterion has the formula IV  
       
         
           
           
               
               
           
         
       
       in which the moieties X 4  and X 5 , which are the same or different, are —O—, —S—, —NH— or a valence bond, preferably —O—, and 
 W +  is a group comprising an ammonium, phosphonium or sulphonium cationic group and a group linking the anionic and cationic moieties which is preferably a C 1-12 -alkanediyl group.  
 
     
     
         9 . A polyion complex according to  claim 8  in which W +  is a group of fonnula —W 1 —N + R 8   3 , —W 1 —P + R 9   3 , —W 1 —S + R 9   2  or —W 1 —Het +  in which: 
 W 1  is alkanediyl of 1 or more, preferably 2-6 carbon atoms optionally containing one or more ethylenically unsaturated double or triple bonds, disubstituted-aryl, alkylene aryl, aryl alkylene, or alkylene aryl alkylene, disubstituted cycloalkyl, alkylene cycloalkyl, cycloalkyl alkylene or alkylene cycloalkyl alkylene, which group W 1  optionally contains one or more fluorine substituents and/or one or more functional groups; and  
 either the groups R 8  are the same or different and each is hydrogen or alkyl of 1 to 4 carbon atoms, preferably methyl, or aryl, such as phenyl or two of the groups R 8  together with the nitrogen atom to which they are attached form a heterocyclic ring containing from 5 to 7 atoms or the three groups R 8  together with the nitrogen atom to which they are attached form a fused ring structure containing from 5 to 7 atoms in each ring, and optionally one or more of the groups R 8  is substituted by a hydrophilic functional group, and  
 the groups R 9  are the same or different and each is R 8  or a group OR 8 , where R 8  is as defined above; or  
 Het is an aromatic nitrogen-, phosphorus- or sulphur-, preferably nitrogen-, containing ring, for example pyridine.  
 
     
     
         10 . A polyion complex according to  claim 8  or  claim 9  in which the zwitterion is a group of formula V:  
       
         
           
           
               
               
           
         
       
       where the groups R 10  are the same or different and each is hydrogen or C 1-4  alkyl, and m is from 1 to 4, preferably in which all groups R 10  are methyl.  
     
     
         11 . A polyion complex according to any preceding claim in which the anionic monomer and cationic monomer each have the formula VII  
       Y 1 B 1 Q   VII  
       in which Y 1  is an ethylenically unsaturated polymerisable group selected from  
       
         
           
           
               
               
           
         
       
       CH 2 ═C(R 15 )—CH 2 —O—, CH 2 ═C(R 15 )—CH 2  OC(O)—, CH 2 ═C(R 15 )OC(O)—, CH 2 ═C(R 15 —, CH 2 —(R 15 )CH 2 OC(O)N(R 15 )—, R 17 OOCCR 15 ═CR 15 C(O—O—, R 15 CH═CHC(O)O—, R 15 CH═C(COOR 17 )CH 2 —C(O)—O—,  
       
         
           
           
               
               
           
         
       
       wherein: 
 R 15  is hydrogen or a C 1-4  alkyl group;  
 is R 16  is hydrogen or a C 1-4  alkyl group or R 16  is B 1 Q where B 1  and Q are as defined below;  
 R 17  is hydrogen or a C 1-4  alkyl group or B 1 Q where B 1  and Q are as defined below;  
 A 1  is —O— or —NR 16 —;  
 K 1  is a group —(CH 2 ) r OC(O)—, —(CH 2 ) r C(O)O—, —(CH 2 ) r OC(O)O—, —(CH 2 ) r NR 18 —, —(CH 2 ) r NR 18 C(O)—, —(CH 2 ) r C(O)NR 18 —, —(CH 2 ) r NR 18 C(O)O—, —(CH 2 ) r NR 18 C(O)NR 18 —, —(CH 2 ) r NR 18 C(O)NR 18 O— (in which the groups R 18  are the same or different), —(CH 2 ) r O—, —(CH 2 ) r SO 3 —, or, optionally in combination with B 1 , a valence bond and r is from 1 to 12 and R 18  is hydrogen or a C 1-4  alkyl group;  
 B 1  is a straight or branched alkanediyl, oxaalkylene, alkanediyloxaalkanediyl, or alkanediyloligo(oxaalkanediyl) chain optionally containing one or more fluorine atoms up to and including perfluorinated chains or, if Q or Y 1  contains a terminal carbon atom bonded to B 1  a valence bond; and  
 Q is the ionic or ionisable group.  
 
     
     
         12 . A polyionic complex according to  claim 11  in which Q is a cationic group Q 1  which is a group N + R 1   3 , P + R 1   3  or S + R 1   2  
 in which the groups R 1  are the same or different and are each hydrogen, C 1-4 -alkyl or aryl (preferably phenyl) or two or three of the groups R 8  together with the heteroatom to which they are attached from a saturated or unsaturated heterocyclic ring containing from 5 to 7 atoms, preferably each R 8  being other than hydrogen, most preferably N + R 1   3  in which each R 1  is C 1-4 -alkyl, preferably methyl.  
 
     
     
         13 . A polyion complex according to claim  1 I in which Q is an anionic group Q 2  which is selected from carboxylate, carbonate, sulphonate, sulphate, phosphonate or phosphate, preferably a monovalent group, more preferably a sulphonate group.  
     
     
         14 . A polyion complex according to any of  claims 1  to  10  in which the cationic monomer is diallyl dialkyl ammonium halide, preferably diallyl dimethyl ammonium chloride.  
     
     
         15 . A polyion complex according to any preceding claim in which the nonionic monomer has the general formula VIII 
 Y 2  R 14  VIII    in which Y 2  is an ethylenically unsaturated polymerisable group selected from                          CH 2 ═C(R 19 -CH 2 —O—, CH 2 ═C(R 19 )—CH 2 OC(O)—, CH 2 ═C(R 19 )OC(O)—, CH 2 ═C(R 19 )—O—, CH 2 ═C(R 19 )CH 2 OC(O)N(R 20 )—, R 21 OOCCR 19 ═CR 19 C(O)—O—, R 19 CH═CHC(O)O—, R 19 CH═C(COOR 21 )CH 2 —C(O)—O—,                          wherein:    R 19  is hydrogen or a C 1-4  alkyl group;    R 20  is hydrogen or a C 1-4  alkyl group or R 20  is R1 4 ;    R 21  is hydrogen or a C 1-4  alkyl group or R 21  is R 1 4;    A 2  is —O— or NR 20 —;    K 2  is a group —(CH 2 ) 8 OC(O)—, —(CH 2 ) 8 C(O)O—, —(CH 2 ) 8 OC(O)O—, —(CH 2 ) 8 NR 22 —, —(CH 2 ) 8 NR 22 C(O)—, —(CH),C(O)NR 22 —, —(CH 2 ) 8 NR 22 C(O)O—, —(CH 2 ) 8 OC(O)NR 22 —, —(CH 2 ) 8 NR 22 C(O)NR 22 — (in which the groups R 22  are the same or different), —(CH 2 ) 8 O—, —(CH 2 ) 8 SO 3 —, or a valence bond and s is from 1 to 12 and R 22  is hydrogen or a C 1-4  alkyl group; and    R 14  is an optically substituted C 1-24 -alkyl or -alkenyl group, optional substituents being hydroxyl groups; halogen atoms; alkoxy and oligo-alkoxy groups, in which the alkoxy groups have 1-6, preferably 2 or 3 carbon atoms; aryl groups, preferably optionally substituted phenyl groups (optional substituents in a phenyl group being hydroxyl groups, halogen atoms or alkyl groups); acyl groups, especially C 1-6 -alkanoyl groups; acyloxy groups, especially C 1-6 -alkanoyloxy groups; or acylamino groups, especially C 1-6 -alkanoyl amino; in any ofwhich alkanoyl groups there maybe substituents selected from halogen atoms and hydroxyl and alkoxyl groups.    
     
     
         16 . A polyion complex according to  claim 15  in which R 14  is C 4-18 -unsubstituted alkyl.  
     
     
         17 . A polyion complex according to any preceding claim, when fully swollen in water, has viscoelastic properties (determined using a variable torque oscillation test (80 rN.m) using a TA instrument CSL-100 rheometer fitted with 6 cm 2° cone at 37° C.), G 1  (elasticity modulus) in the range I to 1000 and G″ (viscous modulus) in the range 1.5 to 1000.  
     
     
         18 . A composition comprising a polyion complex according to any preceding claim and a liquid absorbed in the polyion complex.  
     
     
         19 . A composition according to  claim 18  in which the liquid is aqueous.  
     
     
         20 . A composition according to  claim 19  in which the liquid is free of organic solvent.  
     
     
         21 . A composition according to any of  claims 18  to  20  comprising an active agent selected from pharmaceutically active agents and diagnostic agents.  
     
     
         22 . A method in which a solution of an anionic polymer having an overall anionic charge and a cationic polymer having an overall cationic charge together in a solvent system comprising a first solvent and an inorganic salt which is water-soluble and formed of monovalent metal ions and monovalent counterions, in solution, is gelled by contact with water, whereby the ions of the inorganic salts become dissociated from the polymer and extracted from the gel formed by electrostatic attraction between polymer bound cationic groups and polymer bound anionic groups, and is characterised in that at least one of the cationic and anionic polymers comprises zwitterionic groups.  
     
     
         23 . A method according to  claim 22  in which said first solvent is an organic solvent, preferably comprising a ketone or an alcohol.  
     
     
         24 . A method according to  claim 22  or  claim 23  in which said solvent system comprises first and second solvents which are miscible under the conditions of the process.  
     
     
         25 . A method according to  claim 24  in which the said second solvent is water.  
     
     
         26 . A method according to  claim 24  or  claim 25  in which the ratio of first to second solvent is in the range 2:1-1:10, preferably 1:1-1:5.  
     
     
         27 . A method according to any of  claims 22  to  26  in which the organic salt is a halide of an alkali metal, preferably a chloride or bromide of sodium or potassium, more preferably sodium chloride.  
     
     
         28 . A method according to any of  claims 22  to  27  having any of the features of  claims 1  to  16 .