Polyglutaraldehyde synthesis and protein bonding substrates

• US 4,267,234 A
• Filed: 03/19/1979
• Issued: 05/12/1981
• Est. Priority Date: 03/17/1978
• Status: Expired due to Term

• Current Assignee: California Institute of Technology
• Original Assignee: California Institute of Technology
• Inventors: Rembaum, Alan
• Primary Examiner(s): Lesmes, George F.
• Assistant Examiner(s): Buffalow, E. Rollins
• Application Number:
  US06/021,989
• Time in Patent Office: 785 Days
• Field of Search: 528/270, 528/263, 428/406, 428/407, 428/524, 428/403, 252/62.54, 427/127, 424/32, 424/12
• US Class Current: 428/403
• CPC Class Codes: A61K 39/44 Antibodies bound to carriers
• CPC Class Codes: A61K 9/50 Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals A61K9/2081 takes precedence; particles with a single coating comprising drug A61K9/167
• CPC Class Codes: C07K 14/805 Haemoglobins; Myoglobins
• CPC Class Codes: C08G 6/00 Condensation polymers of aldehydes or ketones only
• CPC Class Codes: C12N 11/089 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: G01N 2446/20 the magnetic material being present in the particle core
• CPC Class Codes: G01N 2446/30 the magnetic material being dispersed in the polymer composition before their conversion into particulate form
• CPC Class Codes: G01N 2446/40 the magnetic material being dispersed in the monomer composition prior to polymerisation
• CPC Class Codes: G01N 2446/60 the magnetic material being dispersed in a medium other than the main solvent prior to incorporation into the polymer particle
• CPC Class Codes: G01N 33/531 Production of immunochemical test materials
• CPC Class Codes: G01N 33/5434 using magnetic particle immunoreagent carriers which constitute new materials per se
• CPC Class Codes: G01N 33/582 with fluorescent label
• CPC Class Codes: G01N 33/585 with a particulate label, e.g. coloured latex
• CPC Class Codes: Y10S 428/90 Magnetic feature
• CPC Class Codes: Y10S 428/913 Material designed to be responsive to temperature, light, moisture
• CPC Class Codes: Y10S 436/80 Fluorescent dyes, e.g. rhodamine
• CPC Class Codes: Y10T 428/2991 Coated
• CPC Class Codes: Y10T 428/2996 Glass particles or spheres
• CPC Class Codes: Y10T 428/2998 including synthetic resin or polymer
• CPC Class Codes: Y10T 428/31942 Of aldehyde or ketone condensation product

Abstract

Polyglutaraldehyde (PGL) is polymerized in aqueous base or in aqueous highly polar solvent basic media to prepare powders, castable films or coatings for substrates such as amine substituted microbeads. PGL microspheres can be prepared by suspension polymerization in presence of a surfactant or by precipitating PGL from solution containing surfactant. Magnetic PGL microspheres are formed by suspension polymerization in the presence of magnetic particles such as iron oxide. Polyglutaraldehyde can be converted to a fluorescent polymer by reaction with m-aminophenol or other reagent. Proteins can be readily covalently bound to the polyglutaraldehyde.

Claims

1. Microspheres having a diameter from 200 A to 10μ

consisting essentially of polylutaraldehyde having a repeating conjugated aldehyde containing structural unit of the formula;

##STR4##

2. Micropheres according to claim 1 in which the diameter is from 500 A to 1.5μ

.

3. Microspheres according to claim 1 containing 0.5 to 40% of metal containing particles having a diameter below 1000 A.

4. Micropheres according to claim 3 in which the metal particles have a diameter from 25 A to 500 A and represent in an amount from 1% to 10% by weight.

5. Microspheres according to claim 3 in which the metal has an atomic number above 50.

6. Microspheres according to claim 5 in which the particles are magnetically attractable.

7. Microspheres according to claim 6 in which the particles comprise Fe₃ O₄.

8. Microspheres according to claim 1 in which the fluorogen groups are the reaction products of acrolein groups and a compound that forms a fluorogen on reaction with said groups.

9. Microspheres according to claim 1 containing fluorogen groups.

10. Microspheres according to claim 9 in which the fluorogen is the reaction product of aldehyde groups with an aldehyde reactive fluorochrome.

11. Microspheres according to claim 10 in which the fluorochrome is selected from aminofluorescein, 9-amino acridine, propidium bromide, or fluorescein isothiocyanate.

12. Microspheres according to claim 9 bound to protein.

13. Microspheres according to claim 12 in which the protein is selected from antibodies, antigens, immunoglobulins, lymphocytes or hemoglobin.

14. Microspheres according to claim 13 in which the protein is an antibody.

15. Microspheres according to claim 14 further comprising the fluorescent condensation product of polyglutaraldehyde and a non-fluorescent reagent.

16. Microspheres according to claim 15 in which the reagent is selected from anthrone, m-aminophenol and aminofluorescein.