Hydrophilic latex particles and use thereof

• US 4,415,700 A
• Filed: 12/16/1981
• Issued: 11/15/1983
• Est. Priority Date: 12/23/1980
• Status: Expired due to Term

• Current Assignee: Boehringer Mannheim GmbH (Roche Holding AG), Tschechoslowakische Akademie Der Wisenscaften
• Original Assignee: Boehringer Mannheim GmbH (Roche Holding AG), Tschechoslowakische Academie Der Wissenschaften
• Inventors: Svec, Frantisek, Batz, Hans-Georg, Baier, Manfred, Kalal, Jaroslav, Tanswell, Paul, Bouchal, Karel, Zurkova, Eva
• Primary Examiner(s): GRIFFIN, RONALD
• Application Number:
  US06/331,114
• Time in Patent Office: 699 Days
• Field of Search: 424/3, 424/12, 524/548, 524/801, 524/811, 523/335, 523/410
• US Class Current: 524/548
• CPC Class Codes: A61K 39/44 Antibodies bound to carriers
• CPC Class Codes: C08F 2/22 Emulsion polymerisation
• CPC Class Codes: C12N 11/087 Acrylic polymers
• CPC Class Codes: G01N 33/54313 the carrier being characterised by its particulate form
• CPC Class Codes: G01N 33/74 involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors

Abstract

Hydrophilic latex particles consisting of a homo- or co-polymer of monomers which are sparingly soluble in water, which hydrophilic latex particles can be prepared by emulsion polymerization in the presence of a water-soluble, radical-forming initiator but without an addition of an emulsifier, stabilizer or wetting agent. A process for the preparation of these hydrophilic latex particles, wherein a monomer which is sparingly soluble in water or several monomers which are sparingly soluble in water are dispersed in water and, with the exclusion of oxygen, for example in an inert atmosphere, are homo- or co-polymerized by emulsion polymerization in the presence of a water-soluble, radical-forming initiator but without any addition of an emulsifier, stabilizer or wetting agent.

A diagnostic agent containing these hydrophilic latex particles as carrier and biologically and/or immunologically active substances covalently bound to this carrier either directly or via a coupling agent as a bridge.

Claims

1. Hydrophilic latex particles which are sparingly soluble in water consisting of a homo- or co-polymer of monomers containing at least one epoxy group and at least one polymerizable carbon-carbon double bond in the molecule.

2. Hydrophilic latex particles as claimed in claim 1, prepared by emulsion polymerization in the presence of a water soluble, radical-forming initiator and in the absence of an emulsifier, stabilizer or wetting agent.

3. Hydrophilic latex particles as claimed in claim 2, wherein the particles consist of a homo-polymer comprising at least 10% epoxide in the molecule.

4. Hydrophilic latex particles as claimed in claim 2, wherein the particles consist of a co-polymer wherein one of the monomers comprising at least 10% of the co-polymer, is an epoxide containing at least one polymerizable carbon-carbon double bond in the molecule.

5. Hydrophilic latex particles as claimed in claim 2, wherein at least one of the monomers is an epoxyalkylene compound.

6. Hydrophilic latex particles as claimed in claim 2, wherein at least one of the monomers is a glycidyl ester or glycidyl ether.

7. Hydrophilic latex particles as claimed in claim 6, wherein said ester is glycidyl acrylate or glycidyl methacrylate.

8. Hydrophilic latex particles as claimed in claim 2, wherein the homo- or co-polymer is cross-linked with a di- or polyunsaturated cross-linking agent.

9. Hydrophilic latex particles as claimed in claim 2, wherein the particles are monodisperse spheroids, all having substantially the same diameter in the range of from 0.15 to 1.5 μ

m.

10. Hydrophilic latex particles as claimed in claim 2, wherein the homo- or co-polymer has terminal hydroxyl, primary or secondary amino, thiol, aldehyde or carboxyl groups.

11. Hydrophilic latex particles as claimed in claim 2, also containing co-polymerized dyestuffs or fluorescing compounds.

12. Hydrophobic latex particles as claimed in claim 1 comprising 15% to 100% of said monomers containing epoxy groups.

13. Process for the preparation of hydrophilic latex particles as claimed in claim 1, which process comprises dispersing at least one monomer which is sparingly water soluble in water and, under the exclusion of oxygen, polymerizing same by emulsion polymerization in the presence of a water soluble radical forming initiator and in the absence of an emulsifier, stabilizer, or wetting agent.

14. Process as claimed in claim 13, wherein the polymerization is carried out in an inert atmosphere.

15. Process as claimed in claim 13, wherein an epoxide containing at least one (co)polymerizable carbon-carbon double bond in the molecule is dispersed in water alone or in admixture with other co-polymerizable monomers, and is homo- or co-polymerized by emulsion polymerization without the addition of an emulsifier.

16. Process as claimed in claim 15, wherein an epoxyalkylene compound or a glycidyl ester or glycidyl ether is used as the epoxide.

17. Process as claimed in claim 15, wherein glycidyl acrylate or glycidyl methacrylate is used as the epoxide.

18. Process as claimed in claim 13, wherein the emulsion polymerization is carried out with the addition of a di- or poly-unsaturated cross-linking agent.

19. Process as claimed in claim 13, wherein the emulsion polymerization is carried out with a bath ratio (water:

monomer phase) of 8;

1 to 16;

1, referred to the volumes.

20. Process as claimed in claim 13, wherein the initiator concentration in the aqueous phase is 0.5 to 1.5 g./liter.

21. Process as claimed in claim 13, wherein the concentration of epoxide in the monomer phase is 1 to 100% by weight.

22. Process as claimed in claim 13, wherein the emulsion polymerization is carried out at a temperature of from 0°

to 80°

C.

23. Process as claimed in claim 13, wherein a latex containing terminal epoxide groups is, during or after the emulsion polymerization, subjected to hydrolysis, ammonolysis, aminolysis or thiolysis with aqueous alkali metal hydroxide solution, aqueous ammonia solution, with a primary amine, a hydrazine or a sulfide, terminal hydroxyl, amino groups, mono- or disubstituted amino groups or thiol groups thereby being formed.

24. The process of claim 23 further comprising subsequently reacting said groups, enzymatically, with periodate, or with periodic acid, to convert them into aldehyde groups.

25. Diagnostic agent containing hydrophilic latex particles as claimed in claim 1 as a carrier and also comprising biologically or immunologically active substance covalently bound to said particles.

26. Diagnostic agent as claimed in claim 25, wherein said covalent bonding to the carrier is via a coupling agent.

27. Diagnostic agent as claimed in claim 25, wherein said covalent bonding to the carrier is via direct coupling.

28. Diagnostic agent as claimed in claim 25, wherein the biologically and/or immunologically active substances are selected from peptides, proteins, enzymes, hormones, vitamins, antigens, antibodies and micro-organisms.

29. Diagnostic agents as claimed in claim 25 for the determination of thyroxine, containing a thyroxine antibody as said biologically or immunologically active substance.

30. Diagnostic agent as claimed in claim 25 for the determination of human thyreotropin, containing a human thyreotropin antibody as the biologically and/or immunologically active substance.