WO2005016976A2

WO2005016976A2 - Hemocompatible polymer systems and related methods

Info

Publication number: WO2005016976A2
Application number: PCT/US2004/016159
Authority: WO
Inventors: Robert L. Albright
Original assignee: Albright Robert L
Priority date: 2003-05-27
Filing date: 2004-05-24
Publication date: 2005-02-24
Also published as: WO2005016976A3

Abstract

A polymer system with a hemocompatible film or coating is provided, the system comprises an organic phase and an aqueous phase, 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, the organic phase is immiscible in the aqueous phase, and the dispersing agent forms a hemocompatible surface on the polymer.

Description

HEMOCOMPATIBLE POLYMER SYSTEMS & RELATED METHODS

RELATED APPLICATION: This application is a continuation-in-part application of U. S. Application Serial No. 10/273249, entitled "A Hemocompatible Coated Polymer & Related One-Step Methods" which was filed on October 18, 2002.

BACKGROUND OF THE INVENTION:

FIELD OF THE INVENTION:

The present invention relates to a hemocompatible surface coated polymer system comprising an organic phase and an aqueous phase. More specifically, the present invention relates to polymer having organic and aqueous phases, where the organic phase i 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, and the organic phase is immiscible in the aqueous phase, and the dispersing agent forms a hemocompatible surface on the 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 methaciylate, butyl acrylate, octyl aciylate, cetyl methacrylate, cetyl acrylate, ethyl methacrylate, ethyl acrylate, vinyltoluene, vinyl aphthalene, vinylbenzyl alcohol,

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 trimethaciylate, 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, divmylformamide 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, diaϊkyl 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(dύτιethylaminoethyl methacrylate), poly- (dimethylaminoethyl acrylate), poly(diethylanώnoethyl 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-hychoxy-N-methyiglucamine, 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 Horn 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: fbπning 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 hemσcompatibfe 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 orgamc 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- vinylpyrroUdinone). In still another embodiment, the biocompatibilizing polymer is selected from a group consisting of poly(hydroxyethyl methacrylate), poly(hydroxyethyl acrylate), poly(dimethylanτinoethyl methacrylate), salts of ρoly(acrylic acid), salts of poly(methacrylic acid), poly(diethylaminoethyl methacrylate), polyφydroxypropyl methacrylate), poly(hydroxypropyl acrylate), poly(N-vinylpyrrohdinone), 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(dime ylaminoethyI acrylate), poIy(diethy!amimoethyI methacrylate), poly(diethylaminoethyl acrylate), ρoly(vinyl alcohol), salts of ρoly(methacrylic acid), and salts of ρoly(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, divinylfoπnamide, 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, v yffomiamide, 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 polymer" is 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 hemocompatϊble-coated surface, the polymer being manufactured by a two-step process comprising: ulverizing 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 Polymerizable 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 orgamc 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-vinyIpyrrolidinone) 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-vinylpyrroUdinone). 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

Ethyivinyibenzene (EVB), wt. % 15.0024

Inerts, wt. % 0.41567

Toluene, t. % 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 isooctane. TABLE 5 Orεanic Phase Charges Divinylbenzene, Pure, g (5635.069) Ethylvinylbenzene, Pure, g (3131.381) Commercial DVB, Dow 63.5%, g 8853.211

Inerts, 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 orgamc 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:

^1

Ό

o

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 speci-Scally disclosed herein.

Claims

CLAIMS: What Is Claimed Is:

1. A hemocompatible surface coated polymer system comprising an organic phase and an aqueous phase, said organic phase comprising polymerizable monomers and at least one initiator and said aqueous phase comprising at least one dispersing agent, at least one free radical inhibitor and at least one buffering agent, said organic phase being immiscible in said aqueous phase, said dispersing agent forms a hemocompatible surface on said polymer.

2. The system of Claim I wherein said monomer is a monofunctional monomer, said 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.

3. The system of Claim 1 wherein said monomer is a polyfunctional monomer, said 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.

4. The system of Claim 1 wherein said initiator is selected from a group consisting of diacyl peroxides, ketone peroxides, peroxyesters, dialkyl peroxides, peroxyketals, azoalkylnitriles, peroxydicarbonates and mixtures thereof

5. The system of Claim 1 wherein said dispersing agent is selected from a group consisting of poly(N-vinylpyrrolidinone), hydroxyethyl cellulose, hydroxypopyl cellulose, poly(hydroxyethyl methacrylate), poly(hydroxyethyl acrylate), polyfhydroxypropyl methacrylate), poly(hydroxypropyl acrylate), poly(dimethylaminoethyl methacrylate), poly- (di ethylaniinoethyl acrylate), poly(die ylamimoethyl methacrylate), poly- (diethylaminoethyl acrylate), poly(vinyl alcohol), salts of poly(methacrylic acid), and salts of poly(acrylic acid) and mixtures thereof.

6- The system of Claim 1 wherein said 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.

7. The system of Claim 1 wherein said buffering agent is selected from a group consisting of carbonate salts, bicarbonate salts, boric acid salts, salts of phosphoric acid and niixtures thereof.

8. The system of Claim 1 wherein said organic phase further comprises at least one porogen, said porogen being selected from a group consisting of aliphatic hydrocarbons, dialkyl ketones, aliphatic carbinols and mixtures thereof.

9. The system of Claim 8 wherein said polymer is a porous polymer.

10. A hemocompatible surface coated polymer system comprising an organic phase and an aqueous phase, said system being manufactured by a method comprising: forming said organic phase comprising polymerizable monomers and at least one initiator; forming said aqueous phase comprising at least one dispersant agent, at least one free radical inhibitor, and at least one buffering agent; dispersing said organic phase into said aqueous phase to thereby form organic phase droplets; and polymerizing said organic phase droplets coated with said dispersing agent to thereby form the hemocompatible surface coating on said polymer.

11. The system of Claim 10 wherein said monomer is a monofunctional monomer, said 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

12. The system of Claim 10 wherein said monomer is a polyfunctional monomer, said 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 teframetftacryjfate, dipentaerythritol diacrylate, dipeπtaeiytiiritoZ triacrylate, dipentaerythritol tetraacrylate, divmylformamide and -Mixtures thereof.

13. The system of Claim 10 wherein said initiator is selected from a group consisting of diacyl peroxides, ketone peroxides, peroxyesters, dialkyl peroxides, peroxyketals, azoalkylnitriles, peroxydicarbonates and mixtures thereof

14. The system of Claim 10 wherein said dispersing agent is selected from a group consisting of poly(N-vinylpyrroHdinone), hydroxyethyl cellulose, hydroxypopyl cellulose, poIy(hydroxyethyl methacrylate), poly(hydroxyethyI acrylate), poly(hydroxypropyl methacrylate), poly(hydroxypropyl acrylate), poly(dimemylanιuιoethyl methacrylate), poly- (dimethylaminoethyl acrylate), poly(diemylamimoethyl methacrylate), poly- (diethylaminoethyl acrylate), poIy(vinyl alcohol), salts of poly(methacrylic acid), and salts of poly(acryhc acid) and mixtures thereof.

15. The system of Claim 10 wherein said free radical inhibitor is selected from a group consisting of p-nitrosophenoxide salts, sodium nitrate, N-hydroxy-N- methyiglucamine, N-nitroso-N-methylglucamine and mixtures thereof

16. The system of Claim 10 wherein said buffering agent is selected from a group consisting of carbonate salts, bicarbonate salts, boric acid salts, salts of phosphoric acid and mixtures thereof.

17. The system of Claim 10 wherein said orgamc phase further comprises at least one porogen, said porogen being selected from a group consisting of aliphatic hydrocarbons, dialkyl ketones, aliphatic carbi ols and mixtures thereof, said porogen causing the formation of a porous polymer.

18. The system of Claim 10 wherein said polymerization of said orgamc phase is formed by heating said mixture of said organic and aqueous phases.

19. A method of manufacturing a hemocompatible surface coated polymer system comprising an organic phase and an aqueous phase, said method comprising: forming said organic phase comprising polymerizable monomers and at least one initiator; forming said aqueous phase comprising at least one dispersant agent, at least one free radical inhibitor, and at least one buffering agent; dispersing said organic phase into said aqueous phase by agitation to form a suspension of organic droplets; and polymerizing said organic phase by heating said suspension of said organic phase droplets coated with said dispersing agent to thereby form the hemocompatible surface coating on said polymer.

20. The method of Claim 19 wherein said monomer is a monofunctional monomer, said 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.

21. The method of Claim 19 wherein said monomer is a polyfunctional monomer, said 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, (hvmylformamide and mixtures thereof.

22. The method of Claim 19 wherein said initiator is selected from a group consisting of diacyl peroxides, ketone peroxides, peroxyesters, dialkyl peroxides, peroxyketals, azoalkylnitriles, peroxydicarbonates and mixtures thereof.

23. The method of Claim 19 wherein said dispersing agent is selected from a group consisting of poly(N-vinylpyrrohdinone), hydroxyethyl cellulose, hydroxypopyl cellulose, poly(hydroxyethyl methacrylate), pσIy(hydroxyethyϊ acrylate), ρoly(hydroxypropyl methacrylate), poly(hydroxypropyl acrylate), poly(dimethylaminoethyl methacrylate), poly- (dimethylaniinoethyl acrylate), poly(diethyla imoethyl methacrylate), poly- (diethylaminoethyl acrylate), poly(vinyl alcohol), salts of poly(methacrylic acid), and salts of poly(acrylic acid) and mixtures thereof.

24. The method of Claim 19 wherein said free radical inhibitor is selected from a group consisting of p-nitrosophenoxide salts, sodium nitrate, N-hydroxy-N- methylglucamine, N-nifroso-N-methylglucamine and mixtures thereof.

25. The method of Claim 19 wherein said buffering agent is selected from a group consisting of carbonate salts, bicarbonate salts, boric acid salts, salts of phosphoric acid and mixtures thereof

26. The method of Claim 19 wherein said organic phase further comprises at least one porogen, said porogen being selected from a group consisting of aliphatic hydrocarbons, dialkyl ketones, aliphatic carbinols and mixtures thereof, said porogen causing the formation of a porous polymer.