Functionalized porous substrate for binding chemical and biological moieties

• US 6,808,908 B2
• Filed: 05/30/2001
• Issued: 10/26/2004
• Est. Priority Date: 05/30/2001
• Status: Expired due to Term

• Current Assignee: Porex Technologies Corporation
• Original Assignee: Porex Technologies Corporation
• Inventors: Mao, Guoqiang, Li, Xingguo, Greene, George Warren IV, Yao, Li
• Primary Examiner(s): Naff, David M.
• Application Number:
  US09/866,842
• Publication Number:
  US 20030100086A1
• Time in Patent Office: 1,245 Days
• Field of Search: 435/176, 435/177, 435/180, 435/181, 435/182, 530/402, 530/811, 530/815, 530/816, 424/486, 436/524, 436/531, 436/532
• US Class Current: 435/181
• CPC Class Codes: A61L 27/446 with other specific inorganic fillers other than those covered by A61L27/443 or A61L27/46
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 31/128 containing other specific inorganic fillers not covered by A61L31/126 or A61L31/127
• CPC Class Codes: A61L 31/146 Porous materials, e.g. foams or sponges
• CPC Class Codes: Y10S 530/811 Peptides or proteins is immobilized on, or in, an inorganic carrier
• CPC Class Codes: Y10S 530/815 Carrier is a synthetic polymer
• CPC Class Codes: Y10S 530/816 Attached to the carrier via a bridging agent
• CPC Class Codes: Y10T 428/249953 Composite having voids in a component [e.g., porous, cellular, etc.]
• CPC Class Codes: Y10T 428/249986 Void-containing component contains also a solid fiber or solid particle
• CPC Class Codes: Y10T 428/31855 Of addition polymer from unsaturated monomers

Abstract

The invention relates to porous polymeric materials, methods of making them, and applications in medical devices. A specific embodiment of the invention encompasses a material comprising a porous polyolefin substrate containing inclusions of a material to which chemical or biological moieties are attached directly or via a spacer.

Claims

1. A material comprising:

a porous substrate comprising a sintered mixture of polymer particles and functional additive particles, wherein the porous substrate has a surface that comprises at least one of the functional additive particles;

a spacer covalently bound to the at least one functional additive particle; and

a biological or chemical moiety covalently or non-covalently bound to the spacer.

2. The material of claim 1, wherein the polymer particles are made of a polymer which is a polyolefin, polyether, nylon, polycarbonate, poly(ether sulfone), or a mixture thereof.

3. The material of claim 2, wherein the polyolefin is ethylene vinyl acetate;

ethylene methyl acrylate;

polyethylenes;

polypropylenes;

ethylene-propylene rubbers;

ethylene-propylene-diene rubbers;

poly(1-butene);

polystyrene;

poly(2-butene);

poly(1-pentene);

poly(2-pentene);

poly(3-methyl-1-pentene);

poly(4-methyl-1-pentene);

1,2-poly-1,3-butadiene;

1,4-poly-1,3-butadiene;

polyisoprene;

polychloroprene;

poly(vinyl acetate);

poly(vinylidene chloride);

poly(tetrafluoroethylene) (PTFE);

poly(vinylidene fluoride) (PVDF);

acrylonitrile-butadiene-styrene (ABS);

or a mixture thereof.

4. The material of claims 2, wherein the polyolefin is polyethylene or polypropylene.

5. The material of claim 2, wherein the polyether is polyether ether ketone (PEEK), (poly(oxy-1,4-phenylene-oxy-1,4-phenylene-carbonyl-1,4-phenylene)), polyether sulfone (PES), or a mixture thereof.

6. The material of claim 1, wherein the functional additive comprises a hydroxyl, carboxylic acid, anhydride, acyl halide, alkyl halide, aldehyde, alkene, amide, amine, guanidine, malimide, thiol, sulfonate, sulfonic acid, sulfonyl ester, carbodiimide, ester, cyano, epoxide, proline, disulfide, imidazole, imide, imine, isocyanate, isothiocyanate, nitro, or azide functional group.

7. The material of claim 6, wherein the functional additive comprises a hydroxyl, amine, aldehyde, or carboxylic acid functional group.

8. The material of claim 7, wherein the functional additive comprises a hydroxyl functional group.

9. The material of claim 1, wherein the functional additive is silica powder, silica gel, chopped glass fiber, controlled porous glass (CPG), glass beads, ground glass fiber, glass bubbles, kaolin, alumina oxide, or a mixture thereof.

10. The material of claim 1, wherein the spacer is a silane, functionalized silane, diamine, alcohol, ester, glycol, anhydride, dialdehyde, terminal difunctionalized polyurethane, dione, macromer, or a multifunctional polymer.

11. The material of claim 10, wherein the spacer is of Formula I:

wherein R¹ and R² are each independently hydrogen, substituted or unsubstituted alkyl, aryl, or aralkyl; and

n is an integer from about 1 to about 18.

12. The material of claim 1, wherein the chemical or biological moiety is a drug, hydrophilic moiety, catalyst, antibiotic, antibody, antimycotic, carbohydrate, cytokine, enzyme, glycoprotein, lipid, nucleic acid, nucleotide, oligonucleotide, peptide, protein, ligand, cell, ribozyme, or a combination thereof.

13. The material of claim 10 wherein the spacer to which the porous substrate and biological or chemical moiety is attached is of Formula VIII:

wherein the porous substrate is bound to the oxygen atom;

R¹ and R² each independently is hydrogen, substituted or unsubstituted alkyl, aryl, or aralkyl;

X is OH, NH₂, CHO, CO₂H, NCO, or epoxy;

n is an integer from about 1 to about 5;

m is an integer from about 1 to about 5; and

o is an integer from 0 to about 3.

14. The material of claim 13 wherein X is CHO or NH₂.

15. The material of claim 10 wherein the spacer to which the porous substrate and biological or chemical moiety is attached is of Formula IX:

wherein the porous substrate is bound to the oxygen atom;

R¹ and R² each independently is hydrogen, substituted or unsubstituted alkyl, aryl, or aralkyl; and

n is from about 1 to about 18.

16. A material comprising:

a porous substrate comprising sintered polyethylene particles and having a surface in which at least one particle of a functional additive has been embedded; and

a spacer precursor of Formula II covalently attached to the at least one particle of functional additive;

wherein R¹, R² and R⁴ are each independently hydrogen, substituted or unsubstituted alkyl, aryl, or aralkyl;

n is an integer from about 1 to about 18; and

X is OH, NH₂, CHO, CO₂H, NCO, or epoxy.

17. A material comprising:

a porous substrate comprising sintered polyethylene particles and having a surface in which at least one particle of a functional additive has been embedded; and

a spacer of Formula I;

wherein R¹ and R² are each independently hydrogen, substituted or unsubstituted alkyl, aryl, or aralkyl; and

n is an integer from about 1 to about 18; and

wherein the spacer is covalently attached to the at least one particle of functional additive and to a chemical or biological moiety.

18. The material of claim 17, wherein the chemical or biological moiety is a nucleotide, oligonucleotide, polynucleotide, peptide, cell, ligand, or protein.

19. A method of providing a material which comprises:

sintering particles of a polymer and particles of a functional additive having functional groups to provide a porous substrate having a surface, wherein the surface comprises at least one of the functional groups;

attaching a spacer to at least one particle of functional additive by contacting a functional group of the at least one particle of functional additive with the spacer under reaction conditions suitable for the formation of a covalent bond between an atom of the functional group and an atom of the spacer; and

contacting the spacer with a chemical or biological moiety under reaction conditions suitable for the formation of a covalent or non-covalent bond between an atom of the spacer and an atom of the chemical or biological moiety.

20. The method of claim 19, wherein the functional group is hydroxyl, carboxylic acid, anhydride, acyl halide, alkyl halide, aldehyde, alkene, amide, amine, guanidine, malimide, thiol, sulfonate, sulfonic acid, sulfonyl ester, carbodiimide, ester, cyano, epoxide, proline, disulfide, imidazole, imide, imine, isocyanate, isothiocyanate, nitro, or azide.

21. The method of claim 19, wherein the porous substrate is formed by sintering the particles of functional additive and then attaching the spacer, or attaching the spacer to at least one of the particles of functional additive prior to sintering the particles.

22. A method of providing a material which comprises:

sintering particles of a polymer and particles of a functional additive having functional groups to provide a porous substrate having a surface, wherein the surface comprises at least one of the functional groups; and

contacting the at least one at the functional groups with a compound of Formula II;

wherein each of R¹, R², and R⁴ each independently is hydrogen, substituted or unsubstituted alkyl, aryl, or aralkyl;

n is an integer from about 1 to about 18; and

X is OH, NH₂, CHO, CO₂H, NCO, or epoxy under conditions suitable for the formation of a material of Formula III;

wherein Surface is the surface of the porous substrate.

23. The method of claim 22 wherein the material of Formula III is contacted with a chemical or biological moiety having an amine group if X is an aldehyde or carboxylic acid, or a chemical or biological moiety having an aldehyde or carboxylic acid group if X is an amine, under reaction conditions suitable for the formation of a material of Formula IV:

wherein Moiety is the chemical or biological moiety, and wherein Surface is the surface of the porous substrate.

24. The method of claim 22 wherein X is NH₂ in the material of Formula III, and the material is contacted with a compound of Formula V:

25. The method of claim 24, wherein Spacer is a hydrophilic polyurethane, polyethylene glycol, or polyelectrolyte and wherein Z is isocyanurate, aldehyde, amino, carboxylic acid, or N-hydroxysuccimide.