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Title:
A HEMOCOMPATIBLE COATED POLYMER AND RELATED ONE-STEP METHODS
Document Type and Number:
WIPO Patent Application WO/2004/035677
Kind Code:
A2
Abstract:
A polymer with a hemocompatible film or coating is manufactured by a one-step method comprising polymerizing monomer droplets comprising at least one crosslinking agent to form a polymer and simultaneously coating the resulting polymer using at least one dispersing agent to thereby form a hemocompatible coated polymer.

Inventors:
ALBRIGHT ROBERT L (US)
Application Number:
PCT/US2003/032813
Publication Date:
April 29, 2004
Filing Date:
October 16, 2003
Export Citation:
Click for automatic bibliography generation   Help
Assignee:
ALBRIGHT ROBERT L (US)
International Classes:
B01J13/00; B01J13/02; B01J13/14; B05D7/00; B32B3/06; B32B3/26; B32B5/16; B32B5/18; B32B15/02; C08F2/16; C08F2/18; C08F2/20; C08F2/22; C08F2/24; C08G2/00; C08K9/00; C08K9/08; C08K9/10; C08L; (IPC1-7): C08L/
Foreign References:
US6531523B12003-03-11
US6419830B22002-07-16
US20020037983A12002-03-28
US6423024B12002-07-23
US4435524A1984-03-06
US5773384A1998-06-30
US6303702B12001-10-16
US5563214A1996-10-08
Attorney, Agent or Firm:
De La, Rosa Dan M. (Suite 27H New York, NY, US)
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Claims:
CLAIMS: What Is Claimed Is:
1. A hemocompatiblecoated polymer comprising at least one crosslinking agent and at least one dispersing agent whereby said dispersing agent forms a hemocompatible surface on said polymer.
2. The polymer of Claim 1 wherein said dispersing agent comprises a biocompatibilizing polymer.
3. The polymer of Claim 2 wherein said biocompatibilizing polymer comprises poly (N vinylpyrrolidinone).
4. The polymer of Claim 2 wherein said biocompatibilizing polymer is selected from a group consisting of poly (hydroxyethyl methacrylate), poly (hydroxyethyl acrylate), poly (dimethylaminoethyl methacrylate), salts of poly (acrylic acid), salts of poly (methacrylic acid), poly (diethylaminoethyl methacrylate), poly (hydroxypropyl methacrylate), poly (hydroxypropyl acrylate), poly (N vinylpyrrolidinone), poly (vinyl alcohol) and mixtures thereof.
5. The polymer of Claim 1 wherein said dispersing agent is selected from a group consisting of hydroxyethyl cellulose, hydroxypopyl cellulose, poly (hydroxyethyl methacrylate), poly (hydroxyethyl acrylate), poly (hydroxypropyl methacrylate), poly (hydroxypropyl acrylate), poly (dimethylaminoethyl methacrylate), poly (dimethylaminoethyl acrylate), poly (diethylamimoethyl methacrylate), poly (diethylaminoethyl acrylate), poly (vinyl alcohol), salts of poly (methacrylic acid), and salts of poly (acrylic acid) and mixtures thereof.
6. The polymer of Claim 1 wherein said crosslinking agent is selected from a group consisting of divinylbenzene, trivinylbenzene, divinylnaphthalene, trivinylcyclohexane, divinylsulfone, trimethylolpropane trimethacrylate, trimethylolpropane dimethacrylate, trimethylolpropane triacrylate, trimethylolpropane diacrylate, pentaerythrital dimethacrylates, pentaerythrital trimethacrylates, pentaerythrital tetramethacrylates, pentaerythritol diacrylates, pentaerythritol triiacrylates, pentaerythritol tetraacrylates, dipentaerythritol dimethacrylates, dipentaerythritol trimethacrylates, dipentaerythritol tetramethacrylates, dipentaerythritol diacrylates, dipentaerythritol triacrylates, dipentaerythritol tetraacrylates, divinylformamide and mixtures thereof.
7. The polymer of Claim 1 wherein said crosslinking agent comprises divinylbenzene.
8. The polymer of Claim 1 wherein said crosslinking agent comprises trivinylcylohexane.
9. The polymer of Claim 1 wherein said crosslinking agent comprises trivinylbenzene.
10. The polymer of Claim 1 wherein said crosslinking agent comprises copolymers of divinylbenzene with comonomers being selected from a group consisting of styrene, ethylstyrene, acrylonitrile, butyl methacrylate, octyl methacrylate, butyl acrylate, octyl acrylate, cetyl methacrylate, cetyl acrylate, ethyl methacrylate, ethyl acrylate, vinyltoluene, vinylnaphthalene, vinylbenzyl alcohol, vinylformamide, methyl methacrylate, methyl acrylate and mixtures thereof.
11. The polymer of Claim 1 wherein said hemocompatible surfaced polymer is a porous polymer.
12. The polymer of Claim 1 wherein said hemocompatible surfaced polymer is an ion exchange polymer.
13. The polymer of Claim 2 wherein said biocompatibilizing polymer becomes grafted to a surface of said polymer to provide said hemocompatible surfaced polymer.
14. A biocompatible coated polymer manufactured by a method comprising: polymerizing monomer droplets comprising at least one crosslinking agent to form a polymer and simultaneously coating said resulting polymer using at least one dispersing agent to thereby form a biocompatible coated polymer.
15. The polymer of Claim 14 wherein said crosslinking agent is polymerized with at least one vinyl monomer.
16. The polymer of Claim 14 wherein said dispersing agent forms a hemocompatible coating on a surface of said polymer.
17. The polymer of Claim 14 wherein said dispersing agent comprises a biocompatibilizing polymer.
18. The polymer of Claim 17 wherein said biocompatibilizing polymer is poly (N vinylpyrrolidinone).
19. The polymer of Claim 17 wherein said biocompatibilizing polymer is poly (vinyl alcohol).
20. The polymer of Claim 17 wherein said biocompatibilizing polymer is selected from a group consisting of poly (hydroxyethyl methacrylate), poly (hydroxyethyl acrylate), poly (dimethylaminoethyl methacrylate), salts of poly (acrylic acid), salts of poly (methacrylic acid), poly (diethylaminoethyl methacrylate), poly (hydroxypropyl methacrylate), poly (hydroxypropyl acrylate), poly (N vinylpyrrolidinone), poly (vinyl alcohol) and mixtures thereof.
21. The polymer of Claim 14 wherein said dispersing agent is selected from a group consisting of hydroxyethyl cellulose, hydroxypopyl cellulose, poly (hydroxyethyl methacrylate), poly (hydroxyethyl acrylate), poly (hydroxypropyl methacrylate), poly (hydroxypropyl acrylate), poly (dimethylaminoethyl methacrylate), poly (dimethylaminoethyl acrylate), poly (diethylamimoethyl methacrylate), poly (diethylaminoethyl acrylate), poly (vinyl alcohol), salts of poly (methacrylic acid), and salts, of poly (acrylic acid) and mixtures thereof.
22. The polymer of Claim 14 wherein said crosslinking agent is selected from a group consisting of divinylbenzene, trivinylbenzene, divinylnaphthalene, trivinylcyclohexane, divinylsulfone, trimethylolpropane trimethacrylate, trimethylolpropane dimethacrylate, trimethylolpropane triacrylate, trimethylolpropane diacrylate, pentaerythrital dimethacrylates, pentaerythrital trimethacrylates, pentaerythrital tetramethacrylates, pentaerythritol diacrylates, pentaerythritol triiacrylates, pentaerythritol tetraacrylates, dipentaerythritol dimethacrylates, dipentaerythritol trimethacrylates, dipentaerythritol tetramethacrylates, dipentaerythritol diacrylates, dipentaerythritol triacrylates, dipentaerythritol tetraacrylates, divinylformamide and mixtures thereof.
23. The polymer of Claim 14 wherein said crosslinking agent comprises divinylbenzene.
24. The polymer of Claim 14 wherein said crosslinking agent comprises trivinylcylohexane.
25. The polymer of Claim 14 wherein said crosslinking agent comprises trivinylbenzene.
26. The polymer of Claim 14 wherein said crosslinking agent comprises copolymers of divinylbenzene with comonomers being selected from a group consisting of styrene, ethylstyrene, acrylonitrile, butyl methacrylate, octyl methacrylate, butyl acrylate, octyl acrylate, cetyl methacrylate, cetyl acrylate, ethyl methacrylate, ethyl acrylate, vinyltoluene, vinylnaphthalene, vinylbenzyl alcohol, vinylformamide and mixtures thereof.
27. The polymer of Claim 14 wherein said hemocompatible coated polymer is a porous polymer.
28. The polymer of Claim 14 wherein said hemocompatible coated polymer is an ion exchange polymer.
29. The polymer of Claim 17 wherein said biocompatibilizing polymer becomes grafted to a surface of said polymer to provide said hemocompatible coated polymer.
30. The polymer of Claim 14 wherein said polymer is processed in nonpyrogenic water. r.
31. A polymer with a hemocompatible surface coating, said polymer being manufactured by a one step process comprising: simultaneously coating and polymerizing monomer droplets in a suspension polymerization procedure with at least one dispersing agent having encapsulated said droplets with a hemocompatible coating to thereby form a polymer with a hemocompatible surfacecoating grafted onto the surface of said polymer, said dispersing agent being a biocompatibilizing polymer.
32. The polymer of Claim 31 wherein said monomer droplets is selected from a group consisting of divinylbenzene, styrene, ethylstyrene, acrylonitrile, butyl acrylate, butyl methacrylate, vinyltoluene, vinylnaphthalene, octyl methacrylate, octyl acrylate, cetyl methacrylate, cetyl acrylate, ethyl methacrylate, ethyl acrylate, vinylbenzyl alcohol, vinylformamide andmixtures thereof.
33. The polymer of Claim 31 wherein said biocompatibilizing polymer is selected from a group consisting of poly (hydroxyethyl methacrylate), poly (hydroxyethyl acrylate), poly (dimethylaminoethyl methacrylate), salts of poly (acrylic acid), salts of poly (methacrylic acid), poly (diethylaminoethyl methacrylate), poly (hydroxypropyl methacrylate), poly (hydroxypropyl acrylate), poly (N vinylpyrrolidinone), poly (vinyl alcohol) and mixtures thereof.
34. The polymer of Claim 31 wherein said dispersing agent is selected from a group consisting of hydroxyethyl cellulose, hydroxypopyl cellulose, poly (hydroxyethyl methacrylate), poly (hydroxyethyl acrylate), poly (hydroxypropyl methacrylate), poly (hydroxypropyl acrylate), poly (dimethylaminoethyl methacrylate), poly (dimethylaminoethyl acrylate), poly (diethylamimoethyl methacrylate), poly (diethylaminoethyl acrylate), poly (vinyl alcohol), salts of poly (methacrylic acid), salts of poly (acrylic acid) and mixtures thereof.
35. A method of manufacturing a biocompatible coated polymer, said method comprising: polymerizing monomer droplets comprising at least one crosslinking agent to form a polymer and simultaneously coating said resultant polymer using at least one dispersing agent to thereby form a biocompatible coated polymer.
36. The method of Claim 35 wherein said polymer is formed using a suspension polymerization procedure.
37. The method of Claim 35 wherein said polymer is formed using emulsion polymerization procedure.
38. The method of Claim 35 wherein said dispersing agent comprises a biocompatibilizing polymer.
39. The method of Claim 35 wherein said biocompatibilizing polymer is poly (Nvinylpyrrolidinone).
40. The method of Claim 35 wherein said biocompatibilizing polymer is poly (vinyl alcohol).
41. The method of Claim 35 wherein said biocompatibilizing polymer is selected from a group consisting of poly (hydroxyethyl methacrylate), poly (hydroxyethyl acrylate), poly (dimethylaminoethyl methacrylate), salts of poly (acrylic acid), salts of poly (methacrylic acid), poly (diethylaminoethyl methacrylate), poly (hydroxypropyl methacrylate), poly (hydroxypropyl acrylate), poly (N vinylpyrrolidinone), poly (vinyl alcohol) and mixtures thereof.
42. The method of Claim 35 wherein said dispersing agent is selected from a group consisting of hydroxyethyl cellulose, hydroxypopyl cellulose, poly (hydroxyethyl methacrylate), poly (hydroxyethyl acrylate), poly (hydroxypropyl methacrylate), poly (hydroxypropyl acrylate), poly (dimethylaminoethyl methacrylate), poly (dimethylaminoethyl acrylate), poly (diethylamimoethyl methacrylate), poly (diethylaminoethyl acrylate), poly (vinyl alcohol), salts of poly (methacrylic acid), and salts of poly (acrylic acid) and mixtures thereof.
43. The method of Claim 35 wherein said crosslinking agent comprises copolymers of divinylbenzene with comonomers being selected from a group consisting of styrene, ethylstyrene, acrylonitrile, butyl methacrylate, octyl methacrylate, butyl acrylate, octyl acrylate, cetyl methacrylate, cetyl acrylate, ethyl methacrylate, ethyl acrylate, vinyltoluene, vinylnaphthalene, vinylbenzyl alcohol, vinylformamide and mixtures thereof.
44. The method of Claim 35 wherein said crosslinking agent is hydrophobic prior to coating and said external surface of said polymer is rendered hydrophilic and biocompatible after coating.
45. The method of Claim 38 wherein said biocompatibilizing polymer becomes grafted to a surface of said hemocompatible coated polymer.
46. The method of Claim 35 wherein said polymer is processed in nonpyrogenic water.
47. The method of Claim 35 wherein said crosslinking agent is polymerized with at least one vinyl monomer.
Description:
A HEMOCOMPATIBLE COATED POLYMER AND RELATED ONE-STEP METHODS BACKGROUND OF THE INVENTION: FIELD OF THE INVENTION: The present invention relates to a polymer with a hemocompatible coating comprising at least one crosslinking agent for making the polymer and at least one dispersing agent whereby the dispersing agent forms a hemocompatible surface coating on the polymer. More specifically, the present invention relates to a hemocompatible coated polymer manufactured by a method comprising simultaneously polymerizing and coating with at least one crosslinking agent for making the polymer and using at least one dispersing agent to form a hemocompatible coated polymer.

DESCRIPTION OF RELATED ART: It has been known and practiced in the art of suspension polymerization to manufacture polymers with a hemocompatible coating using a two-step process. In the first step of the two-step process, polymeric beads are manufactured by polymerizing monomer droplets using suspension polymerization. In the second step of the process, a hemocompatibilizing film is applied onto the exterior surface of the polymer to provide the hemocompatible coating. Unlike the prior art, the polymers of the present invention have aqueous and organic phases where the organic phase is immiscible in the aqueous phase, and the dispersing agent used in the aqueous phase forms a hemocompatible surface on the polymer.

SUMMARY OF THE INVENTION : The present invention provides for hemocompatible coated polymer system comprising an organic phase and an aqueous phase. In one embodiment, the organic phase comprises polymerizable monomers and at least one initiator and the aqueous phase comprises at least one dispersing agent, at least one free radical inhibitor and at least one buffering agent. In another embodiment, the organic phase of the system of the present invention is immiscible in the aqueous phase, and the dispersing agent forms a hemocompatible surface on the polymer.

In still another embodiment, the monomer is a monofunctional monomer, and the monofunctional monomer is selected from a group consisting of styrene, ethylstyrene, acrylonitrile, butyl methacrylate, octyl methacrylate, butyl acrylate, octyl acrylate, cetyl methacrylate, cetyl acrylate, ethyl methacrylate, ethyl acrylate, vinyltoluene, vinylnaphthalene, vinylbenzyl alcohol, vinylformamide, methyl methacrylate, methyl acrylate and mixtures thereof.

In yet another embodiment, the monomer is a polyfunctional monomer, and the polyfunctional monomer is selected from a group consisting of divinylbenzene, trivinylbenzene, divinylnaphthalene, trivinylcyclohexane, divinylsulfone, trimethylolpropane trimethacrylate, trimethylolpropane dimethacrylate, trimethylolpropane triacrylate, trimethylolpropane diacrylate, pentaerythritol dimethacrylate, pentaerythritol trimethacrylate, pentaerythritol tetramethacrylate, pentaerythritol diacrylate, pentaerythritol triiacrylate, pentaerythritol tetraacrylate, dipentaerythritol dimethacrylate, dipentaerythritol trimethacrylate, dipentaerythritol tetramethacrylate, dipentaerythritol diacrylate, dipentaerythritol triacrylate, dipentaerythritol tetraacrylate, divinylformamide and mixtures thereof.

In still yet another embodiment, the initiator of the system of the present invention is selected from a group consisting of diacyl peroxides, ketone peroxides, peroxyesters, dialkyl peroxides, peroxyketals, azoalkylnitriles, peroxydicarbonates and mixtures thereof. In a further embodiment, the dispersing agent is selected from a group consisting of poly (N-vinylpyrrolidinone), hydroxyethyl cellulose, hydroxypopyl cellulose, poly (hydroxyethyl methacrylate), poly (hydroxyethyl acrylate), poly (hydroxypropyl methacrylate), poly (hydroxypropyl acrylate), poly (dimethylaminoethyl methacrylate), poly- (dimethylaminoethyl acrylate), poly (diethylamimoethyl methacrylate), poly- (diethylaminoethyl acrylate), poly (vinyl alcohol), salts of poly (methacrylic acid), and salts of poly (acrylic acid) and mixtures thereof.

In still a further embodiment, the free radical inhibitor is selected from a group consisting of p-nitrosophenoxide salts, sodium nitrate, N-hydroxy-N-methylglucamine, N-nitroso-N- methylglucamine and mixtures thereof. In yet a further embodiment, the buffering agent is selected from a group consisting of carbonate salts, bicarbonate salts, boric acid salts, salts of phosphoric acid and mixtures thereof. In still yet a further embodiment, the organic phase further comprises at least one porogen, and the porogen is selected from a group consisting of aliphatic hydrocarbons, dialkyl ketones, aliphatic carbinols and mixtures thereof. In another further embodiment, the polymer is a porous polymer.

In still another further embodiment, the present invention relates to a hemocompatible surface coated polymer system comprising an organic phase and an aqueous phase, the system being manufactured by a method comprising: forming the organic phase comprising polymerizable monomers and at least one initiator; forming the aqueous phase comprising at least one dispersant agent, at least one free radical inhibitor, and at least one buffering agent ; dispersing the organic phase into the aqueous phase to thereby form organic phase droplets; and polymerizing the organic phase droplets coated with the dispersing agent to thereby form the hemocompatible surface coating on the polymer. In yet another further embodiment, the polymerization of the organic phase is formed by heating a mixture of the organic and aqueous phases.

In still yet another further embodiment, the present invention relates to a method of manufacturing a hemocompatible surface coated polymer system comprising an organic phase and an aqueous phase, the method comprising : forming the organic phase comprising polymerizable monomers and at least one initiator; forming the aqueous phase comprising at least one dispersant agent, at least one free radical inhibitor, and at least one buffering agent; dispersing the organic phase into the aqueous phase by agitation to form a suspension of organic droplets; and polymerizing the organic phase by heating the suspension of the organic phase droplets coated with the dispersing agent to thereby form the hemocompatible surface coating on the polymer.

In another embodiment, the present invention relates to a polymer with a hemocompatible coating comprising at least one crosslinking agent for making the polymer and at least one dispersing agent whereby the dispersing agent forms a hemocompatible surface on the polymer.

In another embodiment, the biocompatibilizing polymer comprises poly (N- vinylpyrrolidinone). In still another embodiment, the biocompatibilizing polymer is selected from a group consisting of poly (hydroxyethyl methacrylate), poly (hydroxyethyl acrylate), poly (dimethylaminoethyl methacrylate), salts of poly (acrylic acid), salts of poly (methacrylic acid), poly (diethylaminoethyl methacrylate), poly (hydroxypropyl methacrylate), poly (hydroxypropyl acrylate), poly (N-vinylpyrrolidinone), poly (vinyl alcohol) and mixtures thereof. In another embodiment, the salts may be sodium and potassium salts and in still another embodiment, the salts are water-soluble salts.

In yet another embodiment, the dispersing agent is selected from a group consisting of hydroxyethyl cellulose, hydroxypopyl cellulose, poly (hydroxyethyl methacrylate), poly (hydroxyethyl acrylate), poly (hydroxypropyl methacrylate), poly (hydroxypropyl acrylate), poly (dimethylaminoethyl methacrylate), poly (dimethylaminoethyl acrylate), poly (diethylamimoethyl methacrylate), poly (diethylaminoethyl acrylate), poly (vinyl alcohol), salts of poly (methacrylic acid), and salts of poly (acrylic acid) and mixtures thereof.

In still another embodiment, the crosslinking agent is selected from a group consisting of divinylbenzene, trivinylbenzene, divinylnaphthalene, trivinylcyclohexane, divinylsulfone, trimethylolpropane trimethacrylate, trimethylolpropane dimethacrylate, trimethylolpropane triacrylate, trimethylolpropane diacrylate, pentaerythrital tetra-, tri-, and dimethacrylates, pentaerythritol tetra-, tri-and diacrylates, dipentaerythritol tetra, tri-, and dimethacrylates, dipentaerythritol tetra-, tri-, and diacrylates, divinylformamide, and mixtures thereof.

In still yet another embodiment, the crosslinking agent comprises divinylbenzene. In a further embodiment, the crosslinking agent comprises trivinylcylohexane. In yet a further embodiment, the crosslinking agent comprises trivinylbenzene.

In still a further embodiment, the crosslinking agent comprises copolymers of divinylbenzene with comonomers being selected from a group consisting of styrene, ethylstyrene, acrylonitrile, butyl methacrylate, octyl methacrylate, butyl acrylate, octyl acrylate, cetyl methacrylate, cetyl acrylate, ethyl methacrylate, ethyl acrylate, vinyltoluene, vinylnaphthalene, vinylbenzyl alcohol, vinylformamide, methyl methacrylate, methyl acrylate and mixtures thereof.

In still yet a further embodiment, the polymer with the hemocompatible surface is a porous polymer. In another further embodiment, the polymer with the hemocompatible surface is an ion exchange polymer. In a further embodiment, the polymer is an affinity polymer. In yet another further embodiment, the biocompatibilizing polymer becomes grafted to the surface of the polymer to provide a polymer with the hemocompatible surface. For purposes of this invention, the term "grafting"is defined as chemically bonded with potential entanglement such that the dispersing agent is physically restricted from leaving the surface of the polymer.

In another embodiment, the present invention relates to a polymer manufactured by a process comprising: simultaneously polymerizing and coating with at least one crosslinking agent for making the polymer and using at least one dispersing agent to form a hemocompatible coated polymer.

For purposes of this invention, the term"hemocompatibility"is defined as a condition whereby a material, when placed in contact with whole blood and blood components or physiological fluids, results in clinically acceptable physiological changes. In another embodiment, the dispersing agent is a biocompatibilizing polymer. A"biocompatibilizing polymer"is defined as a polymer, which forms a surface over a non-biocompatible material, making the polymeric system compatible with physiological fluids and tissues. The term"crosslinking agent"is defined as a linking agent such as a polyfunctional monomer that links two or more polymer chains or segments of the same polymer chain together. The term"dispersing agent"is defined as a substance that imparts a stabilizing effect upon a finely divided array of immiscible particles suspended in a fluidizing medium. The immiscible particles can be a solid, liquid or gas and the fluidizing medium can be a liquid or a gas.

In another embodiment, the crosslinking agent is polymerized with at least one vinyl monomer. In a further embodiment, the dispersing agent forms a hemocompatible coating on a surface of the polymer. In yet a further embodiment, the coating of the polymer is equivalent to the surface of the polymer.

In still a further embodiment, the polymer is processed in non-pyrogenic water. For purposes of this invention, "non-pyrogenic"shall be defined by U. S. P. 25, Monograph (151) Pyrogenic Test, U. S. Pharmacopeia National Formulary.

In still yet another embodiment, the polymer of the present invention is prepared by suspension polymerization. For purposes of the invention, suspension polymerization is defined as the polymerization of monomer droplets dispersed in an immiscible liquid. Based upon an Elemental Analysis of the Polymer's Surface by X-Ray Photoelectron Spectroscopy (XPS), the dispersing agent becomes chemically grafting onto the surface of the polymer as the monomer droplets are transformed into polymeric beads. Polymers coated with poly (N-vinylpyrrolidinone) have been found to be biocompatible and hemocompatible. The hemocompatible polymers of the present invention pass the Lee White clotting tests and the tests for the hemolysis of red blood cells.

In another embodiment, the polymer of the present invention is a porous polymer. The term "porous polymers defined as a polymer particle having an internal pore structure with a porosity resulting from voids or holes throughout the polymer matrix. In still another embodiment, the polymer is an ion exchange resin or polymer. An ion exchange resin or polymer is a resin or polymer carrying ionogenic groups that are capable of exchanging ions or of sequestering ions. The ion exchange polymers of the present invention are beneficial when used with blood for removing and isolating varying ions and ionogenic molecules. in still yet another embodiment, the present invention relates to a polymer with a hemocompatibilizing surface coating. In a further embodiment, the coated polymer is manufactured by a one step process comprising: simultaneously coating and polymerizing monomer droplets in a suspension polymerization procedure with at least one dispersing agent having encapsulated the droplets with a hemocompatible coating to thereby form a polymer with a hemocompatible surface- coating grafted onto the surface of the polymer beads.

In another embodiment, the present invention relates to a method of manufacturing a biocompatible and hemocompatible surface coated polymer. In still another embodiment, the method comprises: polymerizing monomer droplets comprising at least one crosslinking agent and simultaneously coating the resulting polymer beads using at least one dispersing agent, to form a biocompatible surface coated polymer. In still another embodiment, the coated polymers are hemocompatible. In yet another embodiment, the polymer is formed using a suspension polymerization procedure. In another embodiment, the polymer is formed using an emulsion polymerization procedure followed by growing the particles with additional monomer feed.

In still another embodiment, the present invention relates to an application of use whereby the hemocompatible surface coated polymers of the present invention are utilized for medical applications. In another embodiment, the hemocompatible polymers of the present invention may be used to isolate and/or remove target substances from blood and physiological fluids and for specific treatments. In a further embodiment, the hemocompatible polymers of the present invention may be used in preserving organs. In yet another embodiment, the present invention relates to an apparatus for isolating blood components and for purifying blood using the hemocompatible surface coated polymers of the present invention. In one embodiment, the apparatus comprises a cartridge containing the hemocompatible polymers of the present invention.

In yet a further embodiment, the present invention relates to a polymer with a hemocompatible surface coating, the polymer being manufactured by a method comprising: polymerizing monomer droplets comprising at least one crosslinking agent to form a polymer and developing a surface coating on the polymer by using at least one dispersing agent carrying hydroxyl groups followed by a reaction of hydroxyl groups with a vinyl monomer or polymer to thereby form the hemocompatible surface coating on the polymer.

In still yet a further embodiment, the present invention also relates to a method of manufacturing a hemocompatible surface coated polymer using a one step process, the method comprising: polymerizing monomer droplets comprising at least one crosslinking agent to form a polymer and developing a surface coating on the polymer by using at least one dispersing agent carrying hydroxyl groups followed by a reaction of hydroxyl groups with a vinyl monomer or polymer to thereby form the hemocompatible surface coating on the polymer.

In another embodiment, the present invention relates to a polymer having a hemocompatible- coated surface, the polymer being manufactured by a two-step process comprising: polymerizing monomer droplets comprising at least one crosslinking agent and at least one dispersing agent to form a polymer; and coating the surface of the polymer by crosslinking a monovinyl monomer and a polyfunctional monomer mixture over the surface of the polymer bead to thereby form the hemocompatible coating on the surface of the polymer.

In a further embodiment, the present invention relates to a method comprising: polymerizing monomer droplets comprising at-least one crosslinking agent and at least one dispersing agent to form a polymer; and coating the surface of the polymer by crosslinking a monovinyl monomer and a polyfunctional monomer mixture over the surface of the polymer bead to thereby form the hemocompatible coating on the surface of the polymer.

In another embodiment, the present invention relates to a hemocompatible system comprising an organic phase and an aqueous phase, wherein the organic phase composed of the polymerizable monomers and the porogen are dispersed into a slurry of droplets by agitation throughout the aqueous phase which is formulated to effect the stability of the droplets by the water-miscible dispersant and to quench polymer growth in the aqueous phase by carrying a water-soluble free radical inhibitor.

DETAILED DESCRIPTION OF THE INVENTION : As required, detailed embodiments of the present invention are disclosed herein; however, it is to be understood that the disclosed embodiments are merely exemplary of the invention that may be embodied in various forms. The figures are not necessary to scale, some features may be exaggerated to show details of particular components. Therefore, specific structural and functional details disclosed herein are not to be interpreted as limiting, but merely as a basis for the claims and as a representative basis for teaching one skilled in the art to variously employ the present invention.

The specific example below will enable the invention to be better understood. However, they are given merely by way of guidance and do not imply any limitation.

EXAMPLE 1 The first polymer synthesis was targeted at an aqueous to organic volume ratio of 1.0. Table 1 below illustrates the targeted dispersion mixture designed for Example 1 using a fifty (50) liter reaction.

TABLE 1: Dispersion Mixture Desires for 50 Liters Aqueous/Organic Volume Ratio 1.0 Volume of Organic Phase, ml 25,000. 0 Volume of Aqueous Phase, ml 25, 000. 0 Density of Organic Phase, g/ml 0.83490 Weight of Organic Phase, g 20,872. 5 Density of Aqueous Phase, g/ml 1.005 Weight of Aqueous Phase, g 25,125. 0 Polymeriable Monomers, DVB plus EVB, g 8766.45 Total Volume of Organic & Aqueous Phases, ml 50,000. 0 Total Weight of Organic & Aqueous Phases, g 45,997. 5 The procedure for the polymerization in Example 1 is initiated by the preparation of an aqueous phase and an organic phase. Table 2 and 3 below illustrate the components of the aqueous phase composition for the polymer synthesis by weight percent (%) and by quantity of the components in grams (g), respectively.

TABLE 2 Aqueous Phase Composition Ultrapure Water, wt. % 98.089 Water from Aqueous 45% Solution of 0. 611 Poly (N-vinylpyrrolidinone), wt. % Poly (N-vinylpyrrolidinone) Pure, wt. % 0.500 Sodium Carbonate, wt. % 0.500 Sodium Nitrite, wt. % 0.300 Other dispersants, such as poly (vinyl alcohol) have been used as a substitute for the poly (N- vinylpyrrolidinone).

TABLE 3 Aqueous Phase Charges Ultrapure Water, g 24,644. 83 Water from Aqueous 45% Solution of (153.542) Poly (N-vinylpyrrolidinone), g Poly (N-vinylpyrrolidinone) Pure, g (125.625) Aqueous Poly (N-vinylpyrrolidinone) Solution, 279.167 45 wt. %, g Sodium Carbonate, g 125.625 Sodium Nitrite, g 75.375 Weights in parenthesis are part of other charged materials Total Weight of Aqueous Phase, g 25,124. 997 Table 4 and 5 illustrate the components of the organic phase composition for the polymer synthesis by weight percent (5) and by quantity of the components in grams (g), respectively.

TABLE 4 Organic Phase Composition Divinylbenzene (DVB), wt. % 26.998 Ethylvinylbenzene (EVB), wt. % 15.0024 Inerts, wt. % 0. 41567 Toluene, wt. % 27.134 Isooctane, wt. % 30.450 Benzoyl Peroxide, wt. % of polymerizable monomers 1.03 Other immiscible porogens such as isooctane, cyclohexane and nonane have been substituted, both singularly and in combination with one another, for the mixture of toluene and isooctan.

TABLE 5 Organic Phase Charges Divinylbenzene, Pure, g (5635.069) Ethylvinylbenzene, Pure, g (3131.381) Commercial DVB, Dow 63.5%, g 8853.211 Inets g (86.761) Toluene, g 5663.613 Isooctane, g 6355.676 Weights in parenthesis are part of commercial DVB Total Weight of Organic Phase, g (excluding BPO) 20, 872.50 Benzoyl Peroxide, BPO, Pure, g 90.294 75 weight percent BPO, g 120.393 97 weight oercent BPO, g 93.087 Upon preparation of the aqueous and organic phases, the aqueous phase is introduced into the reactor. The reactor is set at an agitation rate sufficient to produce droplet slurry throughout the reaction volume. The aqueous phase is then heated to 65 degrees Celsius with agitation and a nitrogen sweep through the headspace in order to displace oxygen from the reactor space. The organic phase is then introduced into the reactor by pouring or pumping the organic phase onto the aqueous phase under agitation at a stirring rate of at least 86 revolutions per minute. The droplet dispersion is then stirred at 86 revolutions per minute for at least fifteen (15) minutes to set the droplet size and allow the droplet slurry to equilibrate as the temperature is raised from about 65 degrees to about 70 degrees Celsius. Once the droplet dispersion is homogenous throughout the reaction volume, the slurry is then heated to about 75 plus or minus 2.0 degrees Celsius and held at that temperature for ten (10) hours.

The slurry is cooled to about 70 degrees Celsius and the stirrer is turned off, and the polymer beads are allowed to collect at the top of the fluid bed. The mother liquor is then removed from the bottom of the reactor via a pump until the bead bed approaches within about one (1) inch from the bottom of the reactor. The mother liquor is discarded.

A sufficient amount of ultrapure water at ambient temperature is added to fluidize the bead bed and the slurry is heated to 60%. The quantity of water needed to wash the beads will be approximately one (1) bed volume or about 25 liters of water. Upon adding the water, the stirrer is then restarted and agitated at a stir rate of 106 revolutions per minute for about thirty (30) minutes while being heated to 60%. The stirring is stopped and the beads are allowed to collect at the top of the fluid bed.

The liquor is then drained from the bottom of the reactor via a pump until the bead bed approaches within about one (1) inch from the bottom of the reactor. The wash liquor is discarded.

The beads are then washed with the 60 degree Celsius ultrapure water for at least five (5) washes or until the bulk fluid is transparent and free of junk polymer (a clear liquor is achieved). The water- wet bead slurry is transferred to a column that is fitted with a solid-liquid separator at the bottom of the column. The separator may be a mesh or screen made from Teflon, nylon, polypropylene, stainless steel, or glass with pore openings in the size from about 100 to about 300 microns.

The porogen mixture is displaced from the beads by a downflow treatment with ten (10) bed volumes of isopropyl alcohol at a flow rate of one (1) bed volume per hour. The isopropyl alcohol is displaced from the beads with water at a downflow treatment with ten (10) bed volumes of ultrapure water (pyrogen and endotoxin free) at a flow rate of one (1) bed volume per hour. The polymer beads are then transferred from the column into plastic containers for transport to the thermal steam- flux cleaner.

Alternatively, the porogen is displaced from the beads by a thermal-gas-flux treatment in which the porogen filled beads are heated from about 150 degrees to about 180 degrees Celsius under an upflow gas flux for approximately six (6) hours. The hot gas flux can be either super heated stream or hot nitrogen gas. The dried, cleaned, porogen free beads are wetted out with an aqueous solution of isopropyl alcohol in water for further handling prior to being packed into containers.

EXAMPLE 2 Other experimental procedures were conducted to make the polymeric beads manufactured by similar polymerization procedures described in Example 1 and under the variations identified in the Table of Inputs (Table 6) with the resulting responses tabulated in the Tables of responses (Table 7). Tables 6 & 7 are set forth below: Experimental Program: Input Sam ! e ID Sam le ! D Sam le ID Sam le-ID Sam le ID Sam le ID Sam le ID Sam le ID Sam le 1D Sam te ID Sam le ID LDM 02-001 02-004 02-006 02-008 02-010 02-012 02-015 02-016 02-017 02-022 02-025 Drganic Phase Composition- Com osltion Monomer (DVB & EVB) Wt. % 42. 0 42. 0 42. 0 42. 0 40. 7 50. 0 40. 0 40. 0 45. 0 45. 0 Porogen Wt. % 58. 0 58. 0 58. 0 58. 0 59. 3 50. 0 60. 0 60. 0 55. 0'55. 0 55. 0 PorogenlMonomer Ratio 1. 3810 1. 3810 1. 3810 1. 3810 1. 457 1. 000 1. 500 1. 500 1. 222 1. 222 1. 222 Benzoyl Peroxide (BPO) Wt. % 1. 03 1. 03 1. 03 1. 03 1. 03 1. 03 1. 03 1. 03 1. 03 1. 03 1. 03 Porogen Compositlon Isooctane, Wt. % 52. 5 52. 5 52. 5 52. 5 53. 5 eo. o 99. 327 99. 327 99. 174 99. 174 99. 274 Tolugne, Wt. % 46. 769 46. 769 46. 769 46. 769 45. 81 38. 99 0 0 0 0 0 niBb, Wt % 0. 731 0. 731 0. 731 0. 731 0. 693 1. 010 0. 6734 0. 6734 0. 826 0. 826 0. 726 Tdgene, plus IneKs, Wt. % 47. 5 47. 5 47. 5 47. 5 46. 5 40. 0 tsoMane/Totueneptustnerts g g g g., Ra'iD Aquoeus Phase C¢rDosition Siiium Carbonte, Wt. % 0. 500 0. 500 0. 500 0. 500 0. 500 0. 500 0. 500 0. 500 0. 500 0. 500 0. 500 Sodium Nltrite, Wot. % 0. 300 0. 300 0. 300 0. 300 0. 300 0. 300 0. 300 0. 300 0. 300 0. 300 0. 300 P§k. 500 0. 500 0. 450 0. 400 0. 400 0. 400 0. 100 0. 400 1 o. soo 1 0. 500 1. 000 Wt. %-- P K 30, 45-55 Kdaftons, 0 p 0 0 0 0 0 0 0 0. 250 1. 000 PVK 60, 400-500 Kdattons. QgQQ QgQQ ogo oo QOQ QQQ Qo 000 QgQQ QgQ Q wYeMK 60, 400-500 Kdaltons, 0. 500 0. 500 0. 450 0. 400 0. 400 0. 400 0. 100 0. 400 0. 500 0. 250 0 % Poli lnyl alcohol), Wt. % 0. 01 0. Q1 0. 05 0. 100 0. 100 0. 100 0. 400 0. 100 0 0 0 MM3cular Size, Kdaltons 88. 0 88. 0 95. 0 95. 0 95. 0 95. 0 95. 0 95. 0 Afunt H drolized, °Jo 85 85 95 95595 95 95 95 "" Afftunt Hydmlized, % eouslOrgantc Phase 0. $ p, g 0. 9 0. 9 0. 9 0. 9 0. 9 0. 9 0. 9 1. 1 1. 1 Vo ! ume Ratto niume Ratio Experimental Program: Input Sam le ID Sam 1e ID Sam le ID Sam le ID Sam le ! D Sam le ID Sam 1e ID Sam) e 1D Sam le ID Sam le ID Sam ! e ID Sam le ID LDM02-028 02-029 02-030 02-031 02-032 02. 033 02. 034 02-036 02-038 02-040 02-042 02-044 Organ ! c Phase Composition Monomer (DVB&EVB) Wt. % 45. 0 45. 0 45. 0 45. 0 45. 0 50. 0 55. 0 55. 0 55. 0 55. 0 55. 0 55. 0 Porogen Wt. % 55. 0 55. 0 55, 0 55. 0 55. 0 50. 0 45. 0 45. 0 45. 0 45. 0 45. 0 45. 0 orogen/Monomer Ratio _ 1 2æ 1. 222 1. 222 1. 222 1. 222 1. 000 0. 8182 0. 8182 0. 8182 0. 8182 018182 0. 6182 oyl Pemxlde (BPO) Wt. % 3 1. 03 1. 03 1. 03 1. 03 1. 03 Porogen Composition ! sooctane, Wt. % 99. 274 99. 274 99. 274 99. 274 99. 274 99. 112 98. 915 98. 915 98. 915 98. 915 98. 915 98. 915 I'SC) To) uenWt. % 000000000000 inertes,-% 0. 726 0. 726 0. 726 0. 726 0. 726 0. 8878 1. 085 1. 085 1. 085 1. 085 1. 085 1. 085 Toluere : tus Inerts, Wt, 'o ° Isooctårte/Toluene plus Inerts Ratlo A ; qu s Phase ComXsitlon I- Sodluh¢5Narbonte, Wt. % 0. 500 0. 500 0. 500 0. 500 0. 500 0. 500 0. 500 0. 500 0. 500 0. 500 0. 500 0. 500 Sod) um : N) Mte. Wt. % 0. 300 0. 300 0. 300 0. 300 0. 300 0. 300 0. 300 0. 300 0. 300 0. 300 0. 300 0. 300 Potv (nyfpyrroMone), 00 ogoo., 0 00 gOQ ooo OgQO 3QQ Q QQQ 0 03 Poly (", nylpyrroltdione), 0. 700 0. 900 1. 000 1. 000 1. 500 1. 000 0. 500 1. 300 1. 100 1. 000 0. 200 0. 300 Wt. %.. :. PVP I=D, 45-55 Kdaftcns, p. T00 0. 900 1. 000 1. 000 1. 500 0. 9 0 1. OOD 1. 000 0. 800 0 0 Wt % =_- P K- :-60. 40D-500 Kdaltons, 0 0 0 0 0 0. 100 0. 500 0. 300 0. 100 0. 200 0. 200 0. 300 t. °/. Pu Mo (ecutar Size, o Amourtt'Hydrolized, °, AmoHydrolked, % qubuslorçlanlc Phase 1, 2 1. 2 1. 1AS 1. 2 1. 2 1. 1 1. 1 1. 0 1. 0 1. 0 1. 0 1. 0 Vo (u Ratio Experimental Program: Input , Sample ID Sample ID Sample iD Sample ID Sample ID Sample ID Sample ID Sample ID Sample ID Sample ID Sampfe ID Sample ID 02-b52 9 02-061 1 b2-073 02-074 2-075 02-079 rgan ! c Phase omposition- ; onomer (DVB & EVB) Wt. % 55. 0 55. 0 55. 0 55. 0 55. 0 55. 0 55. 0 55. 0 55. 0 55, 0 55. 0 55. 0 svrogen Wt. % 45. 0 4s 0 4s, 0 45 0 45 0 45. 0 45. 0 45. 0 45. 0 45. 0 45. 0 45. 0 'orogen/Monomer Ratlo 0. 8182 0. 8182 0. 8182 0. 8182 0. 8182 0. 8182 0. 8182 0. 8182 0. 8182 0. 8182 0. 8182 0. 8182 zoyl Peroxlde (BPO) Wt. % 1. 03 1. 03 1. 03 1. 03 1. 03 1. 03 1. 03 1. 03 1. 03 1. 03 1. 03 1. 03 Porogen, . Composltion Isooctane, Wt. % 98. 915 98. 915 98. 915 98. 915 98. 915 98. 915 98. 915 98. 915 98. 915 98. 915 98. 915 98. 915 TolueW 0 0 0 0 0 0 0 Inerts, Wt % 1. 085 1. 085 1. 085 1. 085 1. 085 1. 085 1. 085 1. 085 1. 085 1. 085 1. 085 1. 085 Toluerze, plus Inerts, Wt. % Isoocta_ oluene pius Ratio _ : . : SquoeUs Phase ComsMon Sodium Darbonte, Wt. % 0. 300 0. 100 0. 500 0. 500 0. 500 0. 500 0. 500 0. 500 0. 500 0. 500 0. 500 0. 500 Sodlultrite, Wot. % 0. 300 0. 100 0. 300 0. 300 0. 300 0. 300 0. 300 0. 300 0. 300 0. 300 0. 300 0. 300 Po (y (NIlnylpyrrolidione), 0. 010 0. 010 0 0. 05 0 0 0 0 0 0 0 0 Wt. % . = ; PVP 45-55 Kdattons, 0. 010 0. 010 0 00000000 'Wt. % _ P I , 400-500 Kdaltons, 0 0 0 0 0 0 0 0 0 0 0 0 _1./0^ o'y (y'a) coho)). Wt. % 0. 250 OAOO 0 0 0 0 0 0. 300 0. 300 0. 300 0. 300 0. 300 95 95 17D 170 170 170 170 170 >\mouydrolized, % 95 95........ 88 88 88 88 88 88 VatrosolPlus, Wt. % 0 0 0. 500 0. 300 0. 300 0. 300 0 0 0 0 0. 05 0 AqueoISIOrganic Phase 1. 0 1. 0 1. 0 1. 0 1. 0 1. 0 1 : 0-1. 0 1 : 0 1. 0 1. 0 10 Volure Ratio t Experimental Program: Input Sample ID Sample ID Sample ID Sample ID Sample ID Sample ID Sample ID Sample ID Sample ID Sample ID Sample ID Sample ID LDM 02-082 02-083 02-086 Organic Phase composition Monomer (DVB & EVB) Wt.% 55.0 55.0 55.0 Porogen Wt.% 45.0 45.0 45.0 PorogenmMonomer Ratio 0.8182 0.8182 0.8182 mzoyl Peroxide (BPO) Wt.% 1.03 1.03 1.03 Porogen Composition Isooctane. Wt.% 99.915 98.95 98.915 toluene. wt.% 0 0 0 Inerts Wt.% 1.085 1.085 1.085 toluene, plus Inerts, Wt.% .. .. .. Isocctarna/Toluene plus Inerts Ratio .. .. .. Aquosus Phase Composition Sodium carbonte. Wt.% 0.500 0.500 0.500 Sodium Artrite, Wt.% 0.300 0.300 Poly (N-Vinylpyrroldione). 0 0 0 Wt.% PVP K30, 45-55 Kadaltone, 0 0 0 Wt.% @P K-00, 400-500 Kdaltons, 0 0 0 Wt.% Poly(vinyl alcohol), Wt.% 0.300 0.300 0.3 Molecular Size. Kdallons 170 88 170 Amount Hydrolized. % 88 85 88 Natrosol Plus, Wt.% 0 0 0 Aqueous/Orgainc Phase 1.0 1.0 1.0 Volume Ratio Experimental Programs:Response Sample ID Sample ID Sample ID Sample ID Sample ID Sample ID Sample ID Sample ID Sample ID Sample ID Sample ID LDM 02-001 02-004 02-006 02-008 02-010 02-017 02-025 02-034 02-036 02-038 Surface Characteristics SEM; description (smooth, nodes nodes, nodes, nodes, nodes, nodes, no nodes, no nodes, no nodes, no nodes, nodes, present, open or closed pore closed closed closed closed closed open open open open closed structure) Internal Pore Sluqture (Dry Beads) BET Surface Area, S, m2g-1 563.5 852.8 615.7 614.4 661.4 520.9 540.0 537.2 556.6 556.6 Porosity, Pwt in ml.g- 10.9210 1.5370 1.53085 1.7245 1.7722 1.1241 1.3899 1.9069 1.9588 1.8754 Pore modes greater than 100 Å 150 250, 250 430 490 250, 390, 495 320, 440 380, 490 210, 280 210, 280, 380 diameter from desorption 400 500 550 640, 920 550, 750 620, 930 380, 500, 500, 650, 930 Isotherm. List each 1400, 1900 1200, 2900 650 Pore modes range in Å greater 100-250 100-500 100-600 100-700 100-600 100-2300 100-2900 100-1600 100-1600 100-1600 than 100 Å dameter, desorption Isotherm cytochromie C Sorption Static Assasment 500 mg/Liter Conc. Mg Cyto C sorbed/g dry polymer 15.2 43.35 42.95 63.05 79.7 135.0 155.8 86.6 82.0 54.8 at 3hr contact % of Cyto C removed from solution 19.42 53.80 51.46 66.22 73.78 82.64 82.49 85.12 85.26 57.82 at 3 hr contact Serum Albumin Sorption % Tamoved from solution with 6.1 4.15 4.38 4.9 a concentration of 35,000 mg/l of serum albumin Mg BSA (or HSA) sorbed/g dry 681.6 488.22 301.46 311.96 polymer at 3 hr contact Coatinng Assesment ESCA Measurements for Surface Componetnts Atom Frection on surface C 0.8702 0.8722 0.8917 0.8881 0.8855 0.8613 0.8520 0.8981 0.8682 .8901 O 0.0784 0.0758 0.0682 0.0729 0.0860 0.1106 0.1480 0.0778 0.0935 0.0771 N 0.0514 0.0520 0.0401 0.0390 0.0284 0.0281 none 0.0241 0.0383 0.0328 delected Experimental Programs:Response Sample ID Sample ID Sample ID Sample ID Sample ID Sample ID Sample ID Sample ID Sample ID LDM 02-040 '02-044 02-054 02-055A 02-075 02-079 02-082 02-083 02-086 Surface Characteristics SEM; description (smooth, nodes nodes, nodes, nodes, nodes, nodes present, open or closed pore closed closed closed closed closed closed structure) Internal Pore Stucture (Dry Beads) BET Surface Area, S, m2g-1 549.6 545.4 536.8 525.2 531.5 528.9 Porosily, Pwt In ml.g-1 1.8356 1.6420 1.6567 1.6957 1.5232 1.3708 Pore modes greater than 100 Å 300;390; 250;310; 280;350; 290;390; 200;310; 210;280; diameter from desorption 500;650; 450;550; 460;600; 500;640; 410;530; 380;490;620; Isotherm. List each 950 790;1200 810;1900 990 740;900;1200 900;1300 Pore modes ranges in Å greater than 100 Å diameter, description 100-1600 100-2000 100-2900 100-1700 100-2400 100-2400 Cyclochrome C Sorption Static Assesement 590 mg/Liter Conc. Mg Cyto C sorbed/g dry polymer 57.7 1.7 73.9 57.8 32.8 61.1 afther contact % of Cyclo C removed from solution 61.43 65.55 79.83 63.63 39.00 74.89 at S hr contact Serum Albumin Sorpiton % removed from solution with a concentration of 35,000 mg/l 3.07 4.12 of serum albumin Mg BSA (or HSa) sorbed/g dry 92.10 257.96 polymr at 3 hr contact Coating Assesment ESCA Measurements for Surface Components, Atom fraction on surface C 0.8586 0.8748 0.8238 0.7924 0.8441 0.8830 O 0.0982 0.0897 0.1745 0.2078 0.1559 0.1170 N 0.0432 0.355 none none none none detected detected detected detected Numerous modifications and variations of the present invention are possible in light of the above teachings. It is therefore to be understood that within the scope of the attendant claims attached hereto, this invention may be practiced otherwise than as specifically disclosed herein.