Polyacrolein microspheres

• US 4,678,814 A
• Filed: 07/01/1985
• Issued: 07/07/1987
• Est. Priority Date: 03/30/1981
• Status: Expired due to Fees

• Current Assignee: California Institute of Technology
• Original Assignee: California Institute of Technology
• Inventors: Rembaum, Alan
• Primary Examiner(s): Foelak, Morton
• Application Number:
  US06/750,028
• Time in Patent Office: 736 Days
• Field of Search: 522/175, 522/174, 522/79, 522/81
• US Class Current: 522/175
• CPC Class Codes: A61K 47/58 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
• CPC Class Codes: A61K 9/5138 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: C08F 16/34 by an aldehydo radical
• CPC Class Codes: G01N 33/54313 the carrier being characterised by its particulate form

Abstract

Microspheres of acrolein homopolymers and copolymer with hydrophillic comonomers such as methacrylic acid and/or hydroxyethylmethacrylate are prepared by cobalt gamma irradiation of dilute aqueous solutions of the monomers in presence of suspending agents, especially alkyl sulfates such as sodium dodecyl sulfate. Amine or hydroxyl modification is achieved by forming adducts with diamines or alkanol amines. Carboxyl modification is effected by oxidation with peroxides. Pharmaceuticals or other aldehyde reactive materials can be coupled to the microspheres. The microspheres directly form antibody adducts without agglomeration.

Claims

1. A method of preparing small polymeric microspheres comprising the steps of:

forming a solution of less than 5% by weight of a monomer mixture containing at least 10% by weight of an unsaturated aldehyde selected from the group consisting of acrolein and C₁ to C₈ aryl, alkyl and cycloalkyl derivatives thereof and at least 20% by weight of at least one addition copolymerizable monomer having a hydrophilic substituent selected from hydroxyl amino or carboxyl and 0.1 to 20% of a polyunsaturated crosslinking agent;

irradiating the solution with radiation capable of initiating polymerization; and

recovering said microspheres.

2. A method according to claim 1 in which the aldehyde is present in the mixture in an amount from 20% to 90% by weight.

3. A method according to claim 1 in which the aldehyde is acrolein.

4. A method according to claim 2 in which the comonomer is present in an amount from 10 to 50% of the mixture and comprises a mono-unsaturated, freely water-soluble acrylic monomer substituted with amino, carboxyl or hydroxyl.

5. A method according to claim 4 in which the comonomer is selected from acrylamide, methacrylamide, acrylic acid, methacrylic acid, dimethylaminomethacrylate or compounds of the formula:

##STR3## where R¹ is hydrogen or lower alkyl of 1-8 carbon atoms R² is alkylene of 1-12 carbon atoms and Z is --OH or R³ -N-R⁴ where R³ or R⁴ are individually selected from H, lower alkyl or lower alkoxy of 1-8 carbon atoms.

6. A method according to claim 5 in which the comonomer comprises hydroxyethyl methacrylate.

7. A method according to claim 4 in which the comonomer imparts a negative charge to the microsphere.

8. A method according to claim 7 in which said comonomer is methacrylic acid.

9. A method according to claim 1 in which the cross-linking agent further includes functional groups.

10. A method according to claim 9 in which the cross-linking agent is bis-acrylamide.

11. A method according to claim 2 further including 0.05 to 5% by weight of a copolymerizable fluorescent chromophore monomer.

12. A method according to claim 11 in which the fluorescent monomer contains functional groups reactive with aldehyde.

13. A method according to claim 12 in which the fluorescent monomer contains addition polymerizable unsaturated groups.

14. A method according to claim 2 in which said solution contain a dispersion of metal particles.

15. A method according to claim 14 in which the metals are magnetizable.

16. A method according to claim 1 in which the solution contains a suspending agent.

17. A method according to claim 16 in which the suspending agent is selected from polyalkylene oxide liquid polymers and an alkali metal alkyl sulfate containing 8 to 20 carbon atoms.

18. A method according to claim 17 in which the agent is selected from sodium lauryl sulfate and sodium dodecyl sulfate.

19. A method according to claim 1 further including the step of oxidizing the recovered microspheres to convert the aldehyde groups to carboxyl groups.

20. A method according to claim 1 further including the step of reacting the recovered microspheres with a compound of the formula:

##STR4## where R^l is hydrogen or a hydrocarbon group, R Z is hydroxyl or R is selected from aliphatic or aromatic and Z is amine, hydroxyl or carboxyl to form an adduct.

21. A method according to claim 1 further including the step of further reacting the adduct with a material reactive with Z to form a further adduct.