Hydrophilic crosslinked polymer

Abstract

The present invention relates to a hydrophilic crosslinked polymer, preferably in the form of porous particles, and to the preparation and use thereof. The polymer according to the invention is produced by polymerisation from chain-forming hydrophilic vinyl ethers and crosslinking, preferably heterocyclic divinyl ethers.

1 - 20 . (canceled) 
     
     
         21 . A polymer based on a copolymer, which is in the form of polymeric particles, comprising
 a) at least one hydrophilically substituted alkyl vinyl ether of formula I   
       
         
           
           
               
               
           
         
       
       where
 R1, R2, R3, independently of one another, is H or C1 to C6 alkyl, and 
 R4 is a radical which carries at least one hydroxyl group,
 and 
 
 b) at least one crosslinking agent of formula II and/or III and/or IV 
 
       
         
           
           
               
               
           
         
       
       where
 X is a divalent alkyl radical having 2 to 5 C atoms in which one or more methylene groups which are not adjacent and are not located in the direct vicinity of N may be replaced by O, C═O, S, S═O, SO 2 , NH, NOH or N and one or more H atoms of the methylene groups may be substituted, independently of one another, by hydroxyl, C1-C6-alkyl, halogen, NH 2 , C5-C10-aryl, NH—(C1-C8)-alkyl, N—(C1-C8)-alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH, 
 
       
         
           
           
               
               
           
         
       
       where
 Y1 and Y2 in formula III and IV
 are, independently of one another, C1 to C10 alkyl or cycloalkyl, where one or more non-adjacent methylene groups or methylene groups which are not located in the direct vicinity of N may be replaced by O, C═O, S, S═O, SO 2 , NH, NOH or N and one or more H atoms of the methylene groups may be substituted, independently of one another, by hydroxyl, C1-C6-alkyl, halogen, NH 2 , C5-C10-aryl, NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH, or 
 C6 to C18 aryl, where one or more H atoms in the aryl system may be substituted, independently of one another, by hydroxyl, C1-C6-alkyl, halogen, NH 2 , NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH, and 
 
 A is a divalent alkyl radical having 2 to 5 C atoms in which one or more non-adjacent methylene groups or methylene groups which are not located in the direct vicinity of N may be replaced by O, C═O, S, S═O, SO 2 , NH, NOH or N and one or more H of the methylene groups may be substituted, independently of one another, by hydroxyl groups, C1-C6-alkyl, halogen, NH 2 , C5-C10-aryl, NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH, 
 wherein a) and b) have been copolymerized and the resultant polymer is in the form of polymeric particles. 
 
     
     
         22 . A polymer according to  claim 21 , wherein R4 in formula I is a straight-chain or branched C1 to C10 alkyl radical, in which one or more non-adjacent methylene groups may be replaced by O, C═O, S, S═O, SO 2 , NH, NOH, or N and/or in which one or more H atoms may be substituted, independently of one another, by C1-C6-alkyl, C5-C10-aryl, halogen, NH 2 , NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH and in which at least one OH group is present either on the C1 to C10 alkyl radical or on a substituent, or
 a cycloaliphatic radical, in which one or more non-adjacent methylene groups may be replaced by O, C═O, S, S═O, SO 2 , NH, NOH, or N and/or in which one or more H atoms of the cycloaliphatic radical may be substituted, independently of one another, by C1-C6-alkyl, C5-C10-aryl, halogen, NH 2 , NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH, where at least one OH group is present either on the cycloaliphatic ring or on a side chain or substituent, or 
 a C6 to C18 aryl radical, where one or more H atoms in the aryl radical may be substituted, independently of one another, by hydroxyl, C1-C6-alkyl, C5-C10-aryl, halogen, NH 2 , NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH, where at least one OH group is present either on the aryl radical or on a side chain or substituent, or 
 a C5 to C18 heteroaryl radical, where one or more H atoms in the heteroaryl radical may be substituted, independently of one another, by hydroxyl, C1-C6-alkyl, C5-C10-aryl, halogen, NH 2 , NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH, where at least one OH group is present either on the heteroaryl radical or on a side chain or substituent. 
 
     
     
         23 . A polymer according to  claim 21 , wherein the hydrophilically substituted alkyl vinyl ether is a compound of formula I in which R4 is a radical which carries a hydroxyl group. 
     
     
         24 . A polymer according to  claim 21 , wherein the hydrophilically substituted alkyl vinyl ether is 1,2-ethanediol monovinyl ether, 1,3-propanediol monovinyl ether, 1,4-butanediol monovinyl ether, 1,5-pentanediol monovinyl ether, 1,6-hexanediol monovinyl ether, diethylene glycol monovinyl ether or cyclohexanedimethanol monovinyl ether. 
     
     
         25 . A polymer according to  claim 21 , wherein the crosslinking agent is divinylethyleneurea (1,3-divinylimidazolin-2-one) or divinylpropyleneurea (1,3-divinyltetrahydropyrimidin-2-one). 
     
     
         26 . A polymer according to  claim 21 , wherein the hydrophilically substituted alkyl vinyl ether is 1,2-ethanediol monovinyl ether, 1,3-propanediol monovinyl ether, 1,4-butanediol monovinyl ether, 1,5-pentanediol monovinyl ether, 1,6-hexanediol monovinyl ether, diethylene glycol monovinyl ether or cyclohexanedimethanol monovinyl ether, and the crosslinking agent is divinylethyleneurea (1,3-divinylimidazolin-2-one) or divinylpropyleneurea (1,3-divinyltetrahydropyrimidin-2-one). 
     
     
         27 . A polymer according to  claim 21 , wherein R4 in formula I is a straight-chain or branched C1 to C10 alkyl radical, in which one or more non-adjacent methylene groups may be replaced by O, C═O, S, S═O, SO 2 , NH, NOH, or N and/or in which one or more H atoms may be substituted, independently of one another, by C1-C6-alkyl, C5-C10-aryl, halogen, NH 2 , NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH and in which at least one OH group is present either on the C1 to C10 alkyl radical or on a substituent, or
 a cycloaliphatic radical having 5 to 10 C atoms, in which one or more non-adjacent methylene groups may be replaced by O, C═O, S, S═O, SO 2 , NH, NOH, or N and/or in which one or more H atoms of the cycloaliphatic radical may be substituted, independently of one another, by C1-C6-alkyl, C5-C10-aryl, halogen, NH 2 , NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH, where at least one OH group is present either on the cycloaliphatic ring or on a side chain or substituent, or 
 a C6 to C18 aryl radical, where one or more H atoms in the aryl radical may be substituted, independently of one another, by hydroxyl, C1-C6-alkyl, C5-C10-aryl, halogen, NH 2 , NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH, where at least one OH group is present either on the aryl radical or on a side chain or substituent, or 
 a C5 to C18 heteroaryl radical, where one or more H atoms in the heteroaryl radical may be substituted, independently of one another, by hydroxyl, C1-C6-alkyl, C5-C10-aryl, halogen, NH 2 , NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH, where at least one OH group is present either on the heteroaryl radical or on a side chain or substituent. 
 
     
     
         28 . A polymer according to  claim 21 , wherein b) is a crosslinking agent of formula III. 
     
     
         29 . A process for preparing a polymer, which is in the form of polymeric particles, comprising copolymerizing at least one hydrophilically substituted alkyl vinyl ether of the formula I and at least one crosslinking agent of formula II and/or III and/or IV to form said polymeric particles 
       
         
           
           
               
               
           
         
       
       where
 R1, R2, R3, independently of one another, are H or C1 to C6 alkyl, and 
 R4 is a radical which carries at least one hydroxyl group,
 and 
 
 
       
         
           
           
               
               
           
         
         where 
         X is a divalent alkyl radical having 2 to 5 C atoms in which one or more methylene groups which are not adjacent and are not located in the direct vicinity of N may be replaced by O, C═O, S, S═O, SO 2 , NH, NOH or N and one or more H atoms of the methylene groups may be substituted, independently of one another, by hydroxyl, C1-C6-alkyl, halogen, NH 2 , C5-C10-aryl, NH—(C1-C8)-alkyl, N—(C1-C8)-alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH, 
       
       
         
           
           
               
               
           
         
         where 
         Y1 and Y2 in formula III and IV
 are, independently of one another, C1 to C10 alkyl or cycloalkyl, where one or more non-adjacent methylene groups or methylene groups which are not located in the direct vicinity of N may be replaced by O, C═O, S, S═O, SO 2 , NH, NOH or N and one or more H of the methylene groups may be substituted, independently of one another, by hydroxyl, C1-C6-alkyl, halogen, NH 2 , C5-C10-aryl, NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH, or 
 C6 to C18 aryl, where one or more H in the aryl system may be substituted, independently of one another, by hydroxyl, C1-C6-alkyl, halogen, NH 2 , NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH, and 
 
         A is a divalent alkyl radical having 2 to 5 C atoms in which one or more non-adjacent methylene groups or methylene groups which are not located in the direct vicinity of N may be replaced by O, C═O, S, S═O, SO 2 , NH, NOH or N and one or more H of the methylene groups may be substituted, independently of one another, by hydroxyl, C1-C6-alkyl, halogen, NH 2 , C5-C10-aryl, NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH. 
       
     
     
         30 . A process according to  claim 29 , wherein in the compound of formula I, R4 is a straight-chain or branched C1 to C10 alkyl radical, in which one or more non-adjacent methylene groups may be replaced by O, C═O, S, S═O, SO 2 , NH, NOH, or N and/or in which one or more H atoms may be substituted, independently of one another, by C1-C6-alkyl, C5-C10-aryl, halogen, NH 2 , NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH and in which at least one OH group is present either on the C1 to C10 alkyl radical or on a substituent, or a cycloaliphatic radical, in which one or more non-adjacent methylene groups may be replaced by O, C═O, S, S═O, SO 2 , NH, NOH, or N and/or in which one or more H atoms of the cycloaliphatic radical may be substituted, independently of one another, by C1-C6-alkyl, C5-C10-aryl, halogen, NH 2 , NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH, where at least one OH group is present either on the cycloaliphatic ring or on a side chain or substituent, or
 a C6 to C18 aryl radical, where one or more H atoms in the aryl radical may be substituted, independently of one another, by hydroxyl, C1-C6-alkyl, C5-C10-aryl, halogen, NH 2 , NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH, where at least one OH group is present either on the aryl radical or on a side chain or substituent, or 
 a C5 to C18 heteroaryl radical, where one or more H atoms in the heteroaryl radical may be substituted, independently of one another, by hydroxyl, C1-C6-alkyl, C5-C10-aryl, halogen, NH 2 , NH(C1-C8)alkyl, N(C1-C8)alkyl 2 , C1-C6-alkoxy or C1-C6-alkyl-OH, where at least one OH group is present either on the heteroaryl radical or on a side chain or substituent. 
 
     
     
         31 . A process according to  claim 29 , wherein the temperature during the polymerisation is between 40 and 100° C. 
     
     
         32 . A process according to  claim 29 , wherein hydrophilically substituted alkyl vinyl ethers and crosslinking agents are in a weight ratio between 10:90 and 80:20. 
     
     
         33 . In a method for solid-phase synthesis of a biopolymer, such as a nucleic acid or peptide, wherein the improvement is to perform said solid-phase synthesis on a polymer according to claim  1 .