Macroporous particles as biocompatible chromatographic supports

• US 5,168,104 A
• Filed: 09/13/1991
• Issued: 12/01/1992
• Est. Priority Date: 09/13/1991
• Status: Expired due to Fees

• Current Assignee: Alberta Research Council
• Original Assignee: Chembiomed, Ltd.
• Inventors: Li, Nai-Hong, Mazid, M. Abdul
• Primary Examiner(s): Foelak, Morton
• Application Number:
  US07/759,576
• Time in Patent Office: 445 Days
• Field of Search: 521/91, 521/92, 521/95, 521/96, 521/122, 521/123, 521/141, 521/146, 521/147, 521/149, 521/150, 523/218, 523/219
• US Class Current: 521/64
• CPC Class Codes: B01J 20/08 comprising aluminium oxide or hydroxide; comprising bauxite
• CPC Class Codes: B01J 20/103 comprising silica
• CPC Class Codes: B01J 20/26 Synthetic macromolecular compounds
• CPC Class Codes: B01J 20/261 obtained by reactions only involving carbon to carbon unsaturated bonds macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds per se C08F
• CPC Class Codes: B01J 20/264 derived from different types of monomers, e.g. linear or branched copolymers, block copolymers, graft copolymers
• CPC Class Codes: B01J 20/267 Cross-linked polymers
• CPC Class Codes: B01J 20/28004 Sorbent size or size distribution, e.g. particle size
• CPC Class Codes: B01J 20/28019 Spherical, ellipsoidal or cylindrical
• CPC Class Codes: B01J 20/28069 Pore volume, e.g. total pore volume, mesopore volume, micropore volume
• CPC Class Codes: B01J 20/28078 Pore diameter
• CPC Class Codes: B01J 20/28097 being coated, filled or plugged with specific compounds
• CPC Class Codes: B01J 20/285 based on polymers
• CPC Class Codes: B01J 20/286 Phases chemically bonded to a substrate, e.g. to silica or to polymers
• CPC Class Codes: B01J 20/3064 Addition of pore forming agents, e.g. pore inducing or porogenic agents
• CPC Class Codes: B01J 20/3071 Washing or leaching
• CPC Class Codes: B01J 20/3078 Thermal treatment, e.g. calcining or pyrolizing
• CPC Class Codes: B01J 20/3085 Chemical treatments not covered by groups B01J20/3007 - B01J20/3078
• CPC Class Codes: B01J 20/3092 Packing of a container, e.g. packing a cartridge or column of chromatography columns B01D15/206
• CPC Class Codes: B01J 20/321 consisting of a polymer obtained by reactions involving only carbon to carbon unsaturated bonds
• CPC Class Codes: B01J 20/3217 Resulting in a chemical bond between the coating or impregnating layer and the carrier, support or substrate, e.g. a covalent bond
• CPC Class Codes: B01J 20/3219 : involving a particular spacer or linking group, e.g. for attaching an active group
• CPC Class Codes: B01J 20/3248 : the functional group or the linking, spacer or anchoring group as a whole comprising at least one type of heteroatom selected from a nitrogen, oxygen or sulfur, these atoms not being part of the carrier as such
• CPC Class Codes: B01J 20/3251 : comprising at least two different types of heteroatoms selected from nitrogen, oxygen or sulphur
• CPC Class Codes: B01J 20/3255 : comprising a cyclic structure containing at least one of the heteroatoms nitrogen, oxygen or sulfur, e.g. heterocyclic or heteroaromatic structures
• CPC Class Codes: B01J 20/3274 : Proteins, nucleic acids, polysaccharides, antibodies or antigens
• CPC Class Codes: B01J 2220/46 : Materials comprising a mixture of inorganic and organic materials materials coated or impregnated on a carrier B01J20/32
• CPC Class Codes: B01J 2220/54 : Sorbents specially adapted for analytical or investigative chromatography
• CPC Class Codes: B01J 2220/58 : Use in a single column
• CPC Class Codes: C08J 9/26 : by elimination of a solid phase from a macromolecular composition or article, e.g. leaching out
• CPC Class Codes: C12N 11/082 : obtained by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: C12N 11/084 : Polymers containing vinyl alcohol units
• CPC Class Codes: C12N 11/087 : Acrylic polymers

Abstract

A method to prepare uniform populations of macroscopic beads containing pores of at least 0.1 microns diameter is described. The beads consist essentially of a copolymer of a monoethylenically unsaturated monomer and a crosslinking polyethylenically unsaturated monomer, said resulting copolymer optionally being derivatized with functional groups, linking moieties, and/or affinity ligands. The macroporous beads are obtained by utilizing, as porogen in the polymerization reaction, porous inorganic particles which have been preabsorbed with a blowing agent. The blowing agent is not activated until after the polymerization takes place; when the blowing agent is activated, the organic polymer which isolates the inorganic porogen particles from each other in the bead is destroyed. Upon subsequent dissolution of the inorganic porogen, a network of pores throughout the organic copolymer-formed particle is formed. The resulting beads are useful in a variety of chromatographic, analytical and biomedical techniques.

Claims

1. A method to prepare crosslinked organic polymer rigid, porous beads, which method comprises polymerizing a suspension containing at least one monoethylenically unsaturated monomer and at least one polyethylenically unsaturated monomer in the presence of inorganic particles containing pores, which (inorganic particles have a diameter of at least 0.1 microns are preabsorbed with sufficient blowing agent to fill said pores,

under conditions wherein said blowing agent is inert;

followed by

activating said preabsorbed blowing agent;

followed by

dissolution of said inorganic particles.

2. The method of claim 1, wherein said inorganic particles are porous silica or alumina.

3. The method of claim 1, wherein the blowing agent is a peroxide or an azoisonitrile.

4. The method of claim 1 wherein the monoethylenically monomer is styrene, an acrylic ester, a methacrylic ester, vinyl acetate, vinyl propionate or vinylbenzyl chloride.

5. The method of claim 1, wherein the polyethylenically unsaturated crosslinking monomer is divinyl benzene, triallyl isocyanurate or pentaerythritol trimethacrylate.

6. The method of claim 1, wherein the volume of blowing agent is substantially the same as the pore volume of said inorganic particles.

7. The method of claim 1, wherein said blowing agent is activated at elevated temperatures and said polymerization is conducted at a temperature below that at which the blowing agent is activated.