Temperature-responsive polymer compound and process for producing the same

Abstract

A temperature-responsive polymer and polymer material which has ester bond(s) and/or acid amide bond(s) respectively at one or more sites in the side chain and can be arbitrarily controlled by varying the side chain is provided. The process for production thereof and the use thereof are also provided.

1 - 18 . (canceled)  
   
   
       19 . A polymer compound comprising the following formula:  
     
       
         
         
             
             
         
       
       wherein R represents a linear or branched divalent aliphatic hydrocarbon group having 1 to 8 carbon atoms, a divalent alicyclic hydrocarbon group having 3 to 8 carbon atoms, or a divalent aromatic hydrocarbon group having 6 to 14 carbon atoms;  
       R′ represents a linear or branched aliphatic hydrocarbon group having 1 to 8 carbon atoms, a linear or branched aliphatic hydrocarbon group having one or more hydroxyl groups and 1 to 8 carbon atoms, a linear or branched aliphatic hydrocarbon group having one or more acid amide bonds and/or ester bonds and 2 to 9 carbon atoms, or a linear or branched aliphatic hydrocarbon group having one or more acid amide bonds and/or ester bonds, one or more hydroxyl groups and 3 to 9 carbon atoms; and n is an integer of 2 or above; provided that when R represents an methylene group (—CH 2 —), R′ represents a hydroxymethyl group (—CH 2 —OH) or a hyroxyethyl group (—CH 2 CH 2 —OH).  
     
   
   
       20 . The polymer compound of  claim 19  which has a functional group at the polymer chain terminal.  
   
   
       21 . The polymer compound of  claim 20 , wherein said functional group is selected from the group consisting of carboxyl, amino and hydroxyl groups.  
   
   
       22 . The polymer compound of  claim 19  which has acid amide bonds at two or more sites in the polymer side chain.  
   
   
       23 . A heat-responsive polymer material which contains a polymer compound represented by the following formula and shows a cloud point due to a temperature change in an aqueous solution:  
     
       
         
         
             
             
         
       
       wherein R represents a linear or branched divalent aliphatic hydrocarbon group having 1 to 8 carbon atoms, a divalent alicyclic hydrocarbon group having 3 to 8 carbon atoms, or a divalent aromatic hydrocarbon group having 6 to 14 carbon atoms;  
       R′ represents a linear or branched aliphatic hydrocarbon group having 1 to 8 carbon atoms, a linear or branched aliphatic hydrocarbon group having one or more hydroxyl groups and 1 to 8 carbon atoms, a linear or branched aliphatic hydrocarbon group having one or more acid amide bonds and/or ester bonds and 2 to 9 carbon atoms, or a linear or branched aliphatic hydrocarbon group having one or more acid amide bonds and/or ester bonds, one or more hydroxyl groups and 3 to 9 carbon atoms; and n is an integer of 2 or above; provided that when R represents an methylene group (—CH 2 —), R′ represents a hydroxymethyl group (—CH 2 —OH) or a hyroxyethyl group (—CH 2 CH 2 —OH).  
     
   
   
       24 . The heat-responsive polymer material of  claim 23 , wherein said polymer compound has acid amide bonds at two or more sites in the polymer side chain.  
   
   
       25 . The heat-responsive polymer material of  claim 23 , wherein the polarity of the hydrophilic nature/hydrophobic nature varies at its cloud point and the polarity of which can be controlled depending on the pH value, salt concentration or the size of R and R′.  
   
   
       26 . A Chromatographic packing which contains a polymer compound represented by the following formula and shows a cloud point due to a temperature change in an aqueous solution:  
     
       
         
         
             
             
         
       
       wherein R represents a linear or branched divalent aliphatic hydrocarbon group having 1 to 8 carbon atoms, a divalent alicyclic hydrocarbon group having 3 to 8 carbon atoms, or a divalent aromatic hydrocarbon group having 6 to 14 carbon atoms;  
       R′ represents a linear or branched aliphatic hydrocarbon group having 1 to 8 carbon atoms, a linear or branched aliphatic hydrocarbon group having one or more hydroxyl groups and 1 to 8 carbon atoms, a linear or branched aliphatic hydrocarbon group having one or more acid amide bonds and/or ester bonds and 2 to 9 carbon atoms, or a linear or branched aliphatic hydrocarbon group having one or more acid amide bonds and/or ester bonds, one or more hydroxyl groups and 3 to 9 carbon atoms; and n is an integer of 2 or above; provided that when R represents an methylene group (—CH 2 —), R′ represents a hydroxymethyl group (—CH 2 —OH) or a hyroxyethyl group (—CH 2 CH 2 —OH).  
     
   
   
       27 . The chromatographic packing of  claim 26 , wherein said polymer compound has acid amide bonds at two or more sites in the polymer side chain.  
   
   
       28 . A method for separating substances comprising holding a substance on a stationary phase comprising the chromatographic packing of  claim 25 , then changing the hydrophilic/hydrophobic balance of the surface of the stationary phase by a temperature gradient method wherein the external temperature is changed stepwise, and then passing through a single mobile phase, thus effecting separation.  
   
   
       29 . A process for producing a polymer compound represented by the following formula:  
     
       
         
         
             
             
         
       
       wherein R represents a linear or branched divalent aliphatic hydrocarbon group having 1 to 8 carbon atoms, a divalent alicyclic hydrocarbon group having 3 to 8 carbon atoms, or a divalent aromatic hydrocarbon group having 6 to 14 carbon atoms;  
       R′ represents a linear or branched aliphatic hydrocarbon group having 1 to 8 carbon atoms, a linear or branched aliphatic hydrocarbon group having one or more hydroxyl groups and 1 to 8 carbon atoms, a linear or branched aliphatic hydrocarbon group having one or more acid amide bonds and/or ester bonds and 2 to 9 carbon atoms, or a linear or branched aliphatic hydrocarbon group having one or more acid amide bonds and/or ester bonds, one or more hydroxyl groups and 3 to 9 carbon atoms; and n is an integer of 2 or above; provided that when R represents an methylene group (—CH 2 —), R′ represents a hydroxymethyl group (—CH 2 —OH) or a hyroxyethyl group (—CH 2 CH 2 —OH);  
       characterized by using one of the following methods: 
 (1) reacting a compound selected from among aminoalkyl acrylamide, aminoalkyl methacrylamide, aminoalkyl acrylamide hydrochloride and aminoalkyl methacrylamide hydrochloride with an acid anhydride or lactone, and purifying the thus obtained product followed by polymerization in a solvent; and  
 (2) reacting an alkyl diamine with an acid anhydride, an alkyl acid chloride or di-t-butyl dicarbonate, or reacting a compound having an amino group and an amide bond in its molecule with acryloyl chloride or methacryloyl chloride, and then purifying the thus obtained product followed by polymerization in a solvent.  
 
     
   
   
       30 . A material for separating or adsorbing biological samples which is a polymer compound represented by the following formula and has acid amide bonds at two or more sites in the polymer side chain:  
     
       
         
         
             
             
         
       
       wherein R represents a linear or branched divalent aliphatic hydrocarbon group having 1 to 8 carbon atoms, a divalent alicyclic hydrocarbon group having 3 to 8 carbon atoms, or a divalent aromatic hydrocarbon group having 6 to 14 carbon atoms;  
       R′ represents a linear or branched aliphatic hydrocarbon group having 1 to 8 carbon atoms, a linear or branched aliphatic hydrocarbon group having one or more hydroxyl groups and 1 to 8 carbon atoms, a linear or branched aliphatic hydrocarbon group having one or more acid amide bonds and/or ester bonds and 2 to 9 carbon atoms, or a linear or branched aliphatic hydrocarbon group having one or more acid amide bonds and/or ester bonds, one or more hydroxyl groups and 3 to 9 carbon atoms; and n is an integer of 2 or above; provided that when R represents an methylene group (—CH 2 —), R′ represents a hydroxymethyl group (—CH 2 —OH) or a hyroxyethyl group (—CH 2 CH 2 —OH).  
     
   
   
       31 . The material for separating or adsorbing biological samples of  claim 30  which has a functional group at the polymer chain terminal.  
   
   
       32 . The material for separating or adsorbing biological samples of  claim 31 , wherein said functional group is selected from the group consisting of carboxyl, amino and hydroxyl groups.  
   
   
       33 . A method for separating substances characterized by comprising holding a biological sample on a stationary phase, then changing the hydrophilic/hydrophobic balance by changing the external temperature and thus adsorbing and separating the biological sample such as cells, wherein said stationary phase contains a polymer compound represented by the following formula and having acid amide bonds at two or more sites in the polymer side chain:  
     
       
         
         
             
             
         
       
       wherein R represents a linear or branched divalent aliphatic hydrocarbon group having 1 to 8 carbon atoms, a divalent alicyclic hydrocarbon group having 3 to 8 carbon atoms, or a divalent aromatic hydrocarbon group having 6 to 14 carbon atoms;  
       R′ represents a linear or branched aliphatic hydrocarbon group having 1 to 8 carbon atoms, a linear or branched aliphatic hydrocarbon group having one or more hydroxyl groups and 1 to 8 carbon atoms, a linear or branched aliphatic hydrocarbon group having one or more acid amide bonds and/or ester bonds and 2 to 9 carbon atoms, or a linear or branched aliphatic hydrocarbon group having one or more acid amide bonds and/or ester bonds, one or more hydroxyl groups and 3 to 9 carbon atoms; and n is an integer of 2 or above; provided that when R represents an methylene group (—CH 2 —), R′ represents a hydroxymethyl group (—CH 2 —OH) or a hyroxyethyl group (—CH 2 CH 2 —OH).  
     
   
   
       34 . The method for separating substances of  claim 33 , wherein said polymer compound has a functional group at the polymer chain terminal.  
   
   
       35 . The method for separating substances of  claim 34 , wherein said functional group is selected from the group consisting of carboxyl, amino and hydroxyl groups.  
   
   
       36 - 98 . (canceled)