| PATENT NUMBER | This data is not available for free |
| PATENT GRANT DATE | 28.11.2000 |
| PATENT TITLE |
Method of producing material for purification of physiological liquids of organism |
| PATENT ABSTRACT |
A method of producing a material for purification of physiological liquids of organism has the steps of providing a polymer which has a size, a shape, and a structure selected so as to remove toxic compounds from the physiological liquids, chemically modifying a surface of the polymer so as to provide hydrophilicity and biocompatibility, and performing the modification in a medium with a content of organic substance which is efficient for preventing endotoxins contamination of the polymer. -------------------------------------------------------------------------------- |
| PATENT INVENTORS | This data is not available for free |
| PATENT ASSIGNEE | This data is not available for free |
| PATENT FILE DATE | December 14, 1998 |
| PATENT PARENT CASE TEXT | This data is not available for free |
| PATENT CLAIMS |
What is claimed as new and desired to be protected by Letters Patent is set forth in the appended claims: 1. A method of producing a material for purification of physiological fluids of organism, comprising steps of providing a porous hydrophobic divinylbenzene copolymer with surface exposed vinyl group, which has a size, a shape, and a structure providing removal of toxic compounds from physiological liquids, chemically modifying the surface exposed vinyl groups so as to form different surface exposed groups which are hydrophilic and biocompatible; and performing chemical modification of the surface exposed vinyl groups in a medium with a content of an organic substance which is efficient for preventing endotoxins contamination of the polymer wherein the modification of the copolymers is performed by a method selected from the group consisting of (A) grafting hydrophobic polymer chains by a radical polymerization of 2-hydroxyethyl methacrylate, N-vinylpyrrolidone or N-vinylcaprolactam (B) oxidation of the vinyl groups to epoxy groups with subsequent reaction of the epoxy groups with water, ethylene glycol, amines or 2-aminoethanol and (C) depositing high-molecular weight hermicompatible poly(trifluoroethyloxy)phosphazene onto the surface of the polymeric beads. 2. A method as defined in claim 1, wherein said modifying includes a modifying with the use of the medium which contains at least 20 vol. % of the organic substance. 3. A method as defined in claim 1, wherein said modifying includes a modifying with the use of the medium which is purely organic. 4. A method as defined in claim 1, wherein said modifying includes a modifying with the use of the medium which is aqueous-organic. 5. A method as defined in claim 1, wherein said modifying includes modifying with the use of the medium selected from the group consisting of ethanol, methanol and dioxane. -------------------------------------------------------------------------------- |
| PATENT DESCRIPTION |
BACKGROUND OF THE INVENTION The present invention relates to a method of producting materials for purification of physiological liquids of organisms. It is known to use for purification of physiological liquids of organism such materials which are based on polymers with a surface modified to provide a greater hydrophilicity and biocompatibility. When physiological liquids of organisms are passed through such materials, toxicants are removed from blood, plasma and other physiological liquids. It has been found that during modification of the surface of the polymers for producing such materials, frequently a contamination with endotoxins takes place. Endotoxins is a degradation product of the cell membrane (walls) of bacteria. They are present on all surfaces, in air and in solution, even after sterilization procedure. The adsorbants have a great affinity for endotoxins. The later binds to the interior surface of the beads of the polymer avidly and is not easily removed. It is therefore very important to avoid contamination of the polymers with the bacteria and endotoxins as much as possible. SUMMARY OF THE INVENTION Accordingly, it is an object of the present invention to provide a method of producing materials for purification of physiological liquids of organism, which avoids the disadvantages of the prior art. More particularly, it is an object of the present invention to provide a method of producing materials for purification of physiological liquids of organism, which prevents contamination of the materials which endotoxins. In keeping with these objects and with others which will become apparent hereinafter, one feature of present invention resides, briefly stated, in a method of producing a material for purification of physiological liquids of organism which includes providing a polymer having a size, shape and structure selected so as to remove toxic compounds from a physiological liquid, modifying a surface of the polymer to impart to the polymer a greater hydrophilicity and a greater biocompatibility, and performing the modification in a medium with a content of an organic substance sufficient for inhibiting of endotoxins. When the method is performed in accordance with the present invention, a material for purification of physiological liquids of organism produced by the inventive method is not contaminated with endotoxins. The novel features which are considered as characteristic for the present invention are set forth in particular in the appended claims. The invention itself, however, both as to its construction and its method of operation, together with additional objects and advantages thereof. DESCRIPTION OF PREFERRED EMBODIMENTS One of the materials which can be efficiently used for purification of physiological liquids of organism is a porous hydrophobic divinylbenzene copolymer which initially has surface exposed vinyl groups, in which thereafter the vinyl groups are chemically modified so as to form different surface exposed functional groups with a greater hydrophilicity and greater biocompatibility than those of the vinyl groups. This material is disclosed in our patent application Ser. No. 09/019,583 which is incorporated here as a reference. The divinylbenzene copolymer of this material is produced in the following manner: A solution of 130 g p-ethylstyrene, 132 g divinylbenzene (a mixture of para and metha-isomers of about 1:1) and 2.62 g benzoyl peroxide in a mixture of 150 ml toluene and 100 ml iso-amyl alcohol is suspended in 4 liters of pure water containing 1% cellulose stabilizer. After 39 min stirring at room temperature, the mixture is heated at 40.degree. C. for 1 hours, 60.degree. C. for 2 hours, 80.degree. C. for 5 hours and 90.degree. C. for 2 hours. After cooling the mixture to room temperature, the beads of the material obtained are filtered and washed with hot water, methanol and water. The polymer is dried in an oven at 80.degree. C. within one day. In order to impart a greater hydrophilicity and a greater biocompatibility the surface-exposed vinyl groups of the above mentioned copolymer are modified in accordance with a modification procedure. In accordance with the present invention, the modification procedure is performed in a medium with a content of an organic substance which is a efficient for inhibition of bacterial growth and generation of endotoxins. It has been found that the content of the organic substance in the medium has to be at least 20 vol % to prevent contamination of the polymer with endotoxins. The modification of the copolymers can be performed in accordance with the following three principal directions. grafting hydrophilic polymer chains by a radial polymerization of 2-hydroxyethyl methacrylate, N-vinylpyrrolidone, N-vinylcaprolactame, or other water soluble monomers, oxidation of the vinyl groups to epoxy groups with the subsequent reaction of the epoxy groups with water, ethylene glycol, amines or 2-amonoethanol molecules, and depositing high-molecular-weight hemocompatible polymer, in particular poly(trifluorethyeoxy) phosphazene onto the surface of the polymeric beads. This was disclosed in detail in our patent application Ser. No. 09/019,583 which is incorporated here by reference. Several examples of the modification procedure are presented herein below. |
| PATENT EXAMPLES | This data is not available for free |
| PATENT PHOTOCOPY | Available on request |
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