Polymeric particles having a biodegradable gelatin or aminodextran coating and processes for making same

• US 5,776,706 A
• Filed: 03/06/1997
• Issued: 07/07/1998
• Est. Priority Date: 10/31/1990
• Status: Expired due to Fees

• Current Assignee: Coulter International Corp. (Danaher Corporation)
• Original Assignee: Coulter Corporation (Danaher Corporation)
• Inventors: Burshteyn, Alexander, Gupta, Ravinder K., Siiman, Olavi
• Primary Examiner(s): Chin, Christopher L.
• Application Number:
  US08/813,022
• Time in Patent Office: 488 Days
• Field of Search: 427/2.11, 427/2.13, 427/2.14, 427/127-131, 427/213.35, 427/215.216, 427/337, 427/338, 428/403, 428/407, 435/5, 435/7.21, 436/518, 436/524, 436/525, 436/526, 436/529, 436/531, 436/532, 436/533, 436/534
• US Class Current: 435/7.21
• 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 2446/84 Polymer coating, e.g. gelatin
• CPC Class Codes: G01N 2446/86 the coating being pre-functionalised for attaching immunoreagents, e.g. aminodextran
• CPC Class Codes: G01N 2446/90 characterised by small molecule linker used to couple immunoreagents to magnetic particles
• CPC Class Codes: G01N 33/531 Production of immunochemical test materials
• CPC Class Codes: G01N 33/54313 the carrier being characterised by its particulate form
• CPC Class Codes: G01N 33/5434 using magnetic particle immunoreagent carriers which constitute new materials per se
• CPC Class Codes: G01N 33/54393 Improving reaction conditions or stability, e.g. by coating or irradiation of surface, by reduction of non-specific binding, by promotion of specific binding
• CPC Class Codes: Y10S 977/829 Organic or biological core coated with inorganic shell
• CPC Class Codes: Y10S 977/897 Polymerization
• CPC Class Codes: Y10S 977/898 Enzymatic
• CPC Class Codes: Y10T 428/2991 Coated
• CPC Class Codes: Y10T 428/2998 including synthetic resin or polymer
• CPC Class Codes: Y10T 436/24 Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry

Abstract

Gelatin and aminodextran coated polymer core particles useful in immunoassays and methods of making the same are disclosed. The preparation of aminodextrans having varying amounts of amine groups is also described, as is a method of crosslinking gelatin and aminodextran without the use of a stabilizer.

Claims

1. A process for the preparation of colloidal particles having (A) a hydrophobic non-gelatin, non-aminodextran polymeric core coated with a substance selected from the group consisting of type A, acid cured gelatin of Bloom in the range 60 to 300 and an aminodextran having a molecular weight in the range of 10,000 to 2 million, and (B) a plurality of functional groups pendent from said gelatin or aminodextran coating, said process comprising:

(a) coating said gelatin or aminodextran onto the surface of a polymeric core selected from the group consisting of a polymeric substance having amine-reactive functional groups and a polymeric core not having amine-reactive functional groups, said coating being by the method of;

(i) adsorbing said gelatin or aminodextran onto the surface of said core or

(ii) convalently coupling said aminodextran to said core by reaction of aminodextran amine groups and said amine-reactive groups present on said core;

(b) (i) crosslinking the gelatin or aminodextran coating of step (a) (i) by reaction of said coating with a chemical crosslinking agent, or

(ii) selectively crosslinking or not crosslinking the aminodextran coating of step (a) (ii), said crosslinking being by reaction of said coating with a chemical crosslinking agent;

(c) blocking free, unreacted crosslinking agent functional groups present on the surface of any step (b) crosslinked product by reaction of said groups with a polyamine such that at least one polyamine --NH₂ group reacts with the unreacted crosslinking agent functional groups and at least one polyamine --NH₂ group remains unreacted; and

(d) washing the particles of step (c) or the uncrosslinked particles of step (b) (ii) to obtain colloidal particles having a solid polymer core coated with gelatin or aminodextran and having pendent amine groups.

2. The process in accordance with claim 1 wherein said core is in the size range of about 0.1 to 5.0 microns.

3. The process in accordance with claim 1 wherein said core is in the size range of about 0.1 to 1.0 microns.

4. The process in accordance with claim 1 wherein the polymeric core is magnetic.

5. Particles in accordance with claim 1, 2, 3 or 4 wherein said polymeric substance is polystyrene latex.

6. The process in accordance with claim 5 wherein said coating is selected from the group consisting of 1X-, 2X-, 3X- and 5X-aminodextran.

7. The process in accordance with claim 5 wherein said coating is 5X-aminodextran.

8. The process in accordance with claim 5 wherein the product of step (d) is derivatized to have pendent functional groups selected from the group consisting of maleimidyl groups, sulfhydryl groups, polyclonal antibodies, monoclonal antibodies and biological cells.

9. The process in accordance with claim 5 wherein said polyamine is selected from the group consisting of ethylenediamine, 1,3-diaminopropane, 1,4-cyclohexanediamine, 1,4-cyclohexenediamine, 1,4-phenylenediamine, diethylene-triamine and aminodextrans.