Fluorescent substance- or contrast medium-containing latex polymer particles, and a process to produce the same

Abstract

This invention provides a method to effectively incorporate inorganic fluorescent substance or inorganic contrast medium into latex polymer particles which are used for diagnostic test or the like, and also provides thus produced fluorescent substance-containing latex polymer particles which show decreased non-specific adsorption of protein or the like. Said latex polymer particles are produced by making latex-forming monomer, macromer which has at least a hydrophilic polymer segment and an inorganic fluorescent substance or an inorganic contrast medium co-existent simultaneously in an aqueous medium, and subjecting them to a polymerization reaction.

1 - 9 . (canceled) 
   
   
       10 . Hydrophobic core-hydrophilic shell type latex polymer particles which include, in their hydrophobic core domain, inorganic fluorescent substance or inorganic contrast medium, said latex polymer particles having an average particle size of 0.001 to 5 μm, and being formed by radical polymerization in an aqueous medium which comprises:
 (a) 0.5 to 99.5% by weight of one or more kinds of latex-forming monomer,   (b) 0.5 to 99.5% by weight of macromer which has, on one terminal, a polymerizable ethylenic group and has, on the other terminal, a hydrophilic polymer segment which is not linked by a hydrophobic polymer segment [this macromer includes two kinds of macromers each of which has, on said the other terminal, a poly(ethyleneglycol) segment which carries a group selected from the group consisting of hydroxyl group, carboxyl group, aldehyde group, amino group, imino group, mercapto group, active ester-type protected hydroxyl group, active ester-type protected carboxyl group, acetal-type protected aldehyde group, organic sulfonyl-protected hydroxyl group, reactivity-protected amino group and C 1 -C 4  alkoxyl group, recurring unit of said ethyleneglycol being 5 to 1200].   
   
   
       11 . Hydrophobic core-hydrophilic shell type latex polymer particles of  claim 10  wherein there exist two macromers, the first macromer having no hydrophobic polymer segment, and having, at the other terminal, a poly(ethyleneglycol) segment which carries a group selected from the group consisting of hydroxyl group and C1-C4 alkoxyl group; the second macromer having no hydrophobic polymer segment, and having, at the other terminal, a poly(ethyleneglycol) segment which carries a group selected from the group consisting of carboxyl group, aldehyde group, amino group, imino group, mercapto group, active ester-type protected hydroxyl group, active ester-type protected carboxyl group, acetal-type protected aldehyde group, reactivity-protected amino group and organic sulfonyl-protected hydroxyl group; said segment of the first macromer having a chain length which is the same as, or shorter than, the chain length of said segment of the second macromer; and the molar proportion of the first macromer to the second macromer ranging from 1:5000 to 5000:1. 
   
   
       12 . Hydrophobic core-hydrophilic shell type latex polymer particles of  claim 10  wherein the number of recurring unit of ethyleneglycol in the first macromer is an integer of 5 to 1200, the number of recurring unit of ethyleneglycol in the second macromer is an integer of 5 to 1200, and wherein the number of the recurring unit of the first macromer is the same as, or smaller than, the number of the recurring unit of the second macromer. 
   
   
       13 . Hydrophobic core-hydrophilic shell type latex polymer particles of  claim 10  wherein one or more kinds of latex-forming monomers are selected from the group consisting of styrene, α-methylstyrene, p-bromostyrene, vinyltoluene, 1-vinylnaphthalene, C1-C4 alkyl (meth)acrylate and divinyl benzene. 
   
   
       14 . Hydrophobic core-hydrophilic shell latex polymer particles of  claim 10  wherein inorganic fluorescent substance and inorganic contrast medium are a rare-earth metal which belongs to lanthanoid in periodic table of the element or a chelate compound thereof. 
   
   
       15 . Hydrophobic core-hydrophilic shell type latex polymer particles of  claim 10  wherein macromer has general formula (I) as follows: 
     
       
         
         
             
             
         
       
     
     wherein R denotes hydrogen atom or C1-C4 alkyl group; L1 denotes a linking group comprising a portion other than vinyl group of radically polymerizable monomer; B denotes a moiety of a structure selected from the following: 
     
       
         
         
             
             
         
       
     
     L2 denotes a linking group comprising oxygen atom, C 1 -C 4  alkylene, carbonyl, imino, or a combination of at least two thereof;
 X denotes hydrogen atom, C1-C4 alkyl, C1-C4 alkylenecarboxyl, C1-C4 alkylenecarboxyl ester (said ester is exemplified by acid halide, C1-C4 alkyl ester and other active ester), C1-C4 alkyleneamino, C1-C4 alkylenemercapto, C1-C4 alkyleneacetal, C1-C4 alkyleneoxycarbonylimidazol; m denotes an integer of 0 to 500, and n denotes an integer of 5 to 1200. 
 
   
   
       16 . Hydrophobic core-hydrophilic shell type latex polymer particles of  claim 11  wherein one or more kinds of latex-forming monomers are selected from the group consisting of styrene, α-methylstyrene, p-bromostyrene, vinyltoluene, 1-vinylnaphthalene, C1-C4 alkyl (meth)acrylate and divinyl benzene. 
   
   
       17 . Hydrophobic core-hydrophilic shell type latex polymer particles of  claim 12  wherein one or more kinds of latex-forming monomers are selected from the group consisting of styrene, α-methylstyrene, p-bromostyrene, vinyltoluene, 1-vinylnaphthalene, C1-C4 alkyl (meth)acrylate and divinyl benzene. 
   
   
       18 . Hydrophobic core-hydrophilic shell latex polymer particles of  claim 11  wherein inorganic fluorescent substance and inorganic contrast medium are a rare-earth metal which belongs to lanthanoid in periodic table of the element or a chelate compound thereof. 
   
   
       19 . Hydrophobic core-hydrophilic shell latex polymer particles of  claim 12  wherein inorganic fluorescent substance and inorganic contrast medium are a rare-earth metal which belongs to lanthanoid in periodic table of the element or a chelate compound thereof. 
   
   
       20 . Hydrophobic core-hydrophilic shell latex polymer particles of  claim 13  wherein inorganic fluorescent substance and inorganic contrast medium are a rare-earth metal which belongs to lanthanoid in periodic table of the element or a chelate compound thereof. 
   
   
       21 . Hydrophobic core-hydrophilic shell type latex polymer particles of  claim 11  wherein macromer has general formula (I) as follows: 
     
       
         
         
             
             
         
       
     
     wherein R denotes hydrogen atom or C1-C4 alkyl group; L1 denotes a linking group comprising a portion other than vinyl group of radically polymerizable monomer; B denotes a moiety of a structure selected from the following: 
     
       
         
         
             
             
         
       
     
     L2 denotes a linking group comprising oxygen atom, C1-C4 alkylene, carbonyl, imino, or a combination of at least two thereof;
 X denotes hydrogen atom, C1-C4 alkyl, C1-C4 alkylenecarboxyl, C1-C4 alkylenecarboxyl ester (said ester is exemplified by acid halide, C1-C4 alkyl ester and other active ester), C1-C4 alkyleneamino, C1-C4 alkylenemercapto, C1-C4 alkyleneacetal, C1-C4 alkyleneoxycarbonylimidazol; m denotes an integer of 0 to 500, and n denotes an integer of 5 to 1200. 
 
   
   
       22 . Hydrophobic core-hydrophilic shell type latex polymer particles of  claim 12  wherein macromer has general formula (I) as follows: 
     
       
         
         
             
             
         
       
     
     wherein R denotes hydrogen atom or C1-C4 alkyl group; L1 denotes a linking group comprising a portion other than vinyl group of radically polymerizable monomer; B denotes a moiety of a structure selected from the following: 
     
       
         
         
             
             
         
       
     
     L2 denotes a linking group comprising oxygen atom, C1-C4 alkylene, carbonyl, imino, or a combination of at least two thereof;
 X denotes hydrogen atom, C1-C4 alkyl, C1-C4 alkylenecarboxyl, C1-C4 alkylenecarboxyl ester (said ester is exemplified by acid halide, C1-C4 alkyl ester and other active ester), C1-C4 alkyleneamino, C1-C4 alkylenemercapto, C1-C4 alkyleneacetal, C1-C4 alkyleneoxycarbonylimidazol; m denotes an integer of 0 to 500, and n denotes an integer of 5 to 1200. 
 
   
   
       23 . Hydrophobic core-hydrophilic shell type latex polymer particles of  claim 13  wherein macromer has general formula (I) as follows: 
     
       
         
         
             
             
         
       
     
     wherein R denotes hydrogen atom or C1-C4 alkyl group; L1 denotes a linking group comprising a portion other than vinyl group of radically polymerizable monomer; B denotes a moiety of a structure selected from the following: 
     
       
         
         
             
             
         
       
     
     L2 denotes a linking group comprising oxygen atom, C1-C4 alkylene, carbonyl, imino, or a combination of at least two thereof;
 X denotes hydrogen atom, C1-C4 alkyl, C1-C4 alkylenecarboxyl, C1-C4 alkylenecarboxyl ester (said ester is exemplified by acid halide, C1-C4 alkyl ester and other active ester), C1-C4 alkyleneamino, C1-C4 alkylenemercapto, C1-C4 alkyleneacetal, C1-C4 alkyleneoxycarbonylimidazol; m denotes an integer of 0 to 500, and n denotes an integer of 5 to 1200. 
 
   
   
       24 . Hydrophobic core-hydrophilic shell type latex polymer particles of  claim 14  wherein macromer has general formula (I) as follows: 
     
       
         
         
             
             
         
       
     
     wherein R denotes hydrogen atom or C1-C4 alkyl group; L1 denotes a linking group comprising a portion other than vinyl group of radically polymerizable monomer; B denotes a moiety of a structure selected from the following: 
     
       
         
         
             
             
         
       
     
     L2 denotes a linking group comprising oxygen atom, C1-C4 alkylene, carbonyl, imino, or a combination of at least two thereof;
 X denotes hydrogen atom, C1-C4 alkyl, C1-C4 alkylenecarboxyl, C1-C4 alkylenecarboxyl ester (said ester is exemplified by acid halide, C1-C4 alkyl ester and other active ester), C1-C4 alkyleneamino, C1-C4 alkylenemercapto, C1-C4 alkyleneacetal, C1-C4 alkyleneoxycarbonylimidazol; m denotes an integer of 0 to 500, and n denotes an integer of 5 to 1200.