WO2000043120A1 - Surface modified divinylbenzene resin having a hemocompatible coating - Google Patents
Surface modified divinylbenzene resin having a hemocompatible coating Download PDFInfo
- Publication number
- WO2000043120A1 WO2000043120A1 PCT/US1999/028073 US9928073W WO0043120A1 WO 2000043120 A1 WO2000043120 A1 WO 2000043120A1 US 9928073 W US9928073 W US 9928073W WO 0043120 A1 WO0043120 A1 WO 0043120A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- resin
- meth
- blood
- acrylate
- acrylamide
- Prior art date
Links
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/22—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising organic material
- B01J20/26—Synthetic macromolecular compounds
- B01J20/261—Synthetic macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D17/00—Separation of liquids, not provided for elsewhere, e.g. by thermal diffusion
- B01D17/02—Separation of non-miscible liquids
- B01D17/0202—Separation of non-miscible liquids by ab- or adsorption
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/22—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising organic material
- B01J20/26—Synthetic macromolecular compounds
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/22—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising organic material
- B01J20/26—Synthetic macromolecular compounds
- B01J20/264—Synthetic macromolecular compounds derived from different types of monomers, e.g. linear or branched copolymers, block copolymers, graft copolymers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
- B01J20/28002—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties characterised by their physical properties
- B01J20/28004—Sorbent size or size distribution, e.g. particle size
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
- B01J20/28014—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties characterised by their form
- B01J20/28016—Particle form
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
- B01J20/28054—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties characterised by their surface properties or porosity
- B01J20/28057—Surface area, e.g. B.E.T specific surface area
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
- B01J20/28054—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties characterised by their surface properties or porosity
- B01J20/28069—Pore volume, e.g. total pore volume, mesopore volume, micropore volume
- B01J20/28076—Pore volume, e.g. total pore volume, mesopore volume, micropore volume being more than 1.0 ml/g
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
- B01J20/28054—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties characterised by their surface properties or porosity
- B01J20/28078—Pore diameter
- B01J20/28083—Pore diameter being in the range 2-50 nm, i.e. mesopores
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/30—Processes for preparing, regenerating, or reactivating
- B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
- B01J20/3202—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the carrier, support or substrate used for impregnation or coating
- B01J20/3206—Organic carriers, supports or substrates
- B01J20/3208—Polymeric carriers, supports or substrates
- B01J20/321—Polymeric carriers, supports or substrates consisting of a polymer obtained by reactions involving only carbon to carbon unsaturated bonds
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/30—Processes for preparing, regenerating, or reactivating
- B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
- B01J20/3231—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the coating or impregnating layer
- B01J20/3242—Layers with a functional group, e.g. an affinity material, a ligand, a reactant or a complexing group
- B01J20/3268—Macromolecular compounds
- B01J20/327—Polymers obtained by reactions involving only carbon to carbon unsaturated bonds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
- A61M1/3615—Cleaning blood contaminated by local chemotherapy of a body part temporarily isolated from the blood circuit
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
- A61M1/3679—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits by absorption
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2220/00—Aspects relating to sorbent materials
- B01J2220/50—Aspects relating to the use of sorbent or filter aid materials
- B01J2220/58—Use in a single column
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S210/00—Liquid purification or separation
- Y10S210/902—Materials removed
- Y10S210/903—Nitrogenous
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S210/00—Liquid purification or separation
- Y10S210/902—Materials removed
- Y10S210/903—Nitrogenous
- Y10S210/905—Protein
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/29—Coated or structually defined flake, particle, cell, strand, strand portion, rod, filament, macroscopic fiber or mass thereof
- Y10T428/2913—Rod, strand, filament or fiber
- Y10T428/2933—Coated or with bond, impregnation or core
- Y10T428/2964—Artificial fiber or filament
- Y10T428/2967—Synthetic resin or polymer
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/29—Coated or structually defined flake, particle, cell, strand, strand portion, rod, filament, macroscopic fiber or mass thereof
- Y10T428/2913—Rod, strand, filament or fiber
- Y10T428/2973—Particular cross section
- Y10T428/2978—Surface characteristic
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/29—Coated or structually defined flake, particle, cell, strand, strand portion, rod, filament, macroscopic fiber or mass thereof
- Y10T428/2982—Particulate matter [e.g., sphere, flake, etc.]
- Y10T428/2991—Coated
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/31—Surface property or characteristic of web, sheet or block
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/31504—Composite [nonstructural laminate]
- Y10T428/31855—Of addition polymer from unsaturated monomers
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/31504—Composite [nonstructural laminate]
- Y10T428/31855—Of addition polymer from unsaturated monomers
- Y10T428/31909—Next to second addition polymer from unsaturated monomers
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/31504—Composite [nonstructural laminate]
- Y10T428/31855—Of addition polymer from unsaturated monomers
- Y10T428/31909—Next to second addition polymer from unsaturated monomers
- Y10T428/31913—Monoolefin polymer
- Y10T428/3192—Next to vinyl or vinylidene chloride polymer
Definitions
- the present invention relates to adsorbents for removing toxicants from blood or plasma, and also for a method of producing such adsorbents.
- Hemoperfusion involves the passage of the contaminated blood over a solid surface of a detoxicant particulate mass that separates the contaminant by sorption or by ion exchange.
- Another procedure, plasma perfusion involves separation of blood cells prior to contacting plasma with the adsorbent.
- treated blood, or both cells and treated plasma have to be returned to the patient's blood circulation system.
- selective adsorbents can be employed which incorporate ligands specially designed to attract and bind the target species.
- adsorbents such as Protein-A
- removal of circulating toxins and tumor antigens for example, a-fetoprotein associated with hepatic cancer, carcinoembrionic antigen associated with various carcinomas, thioesterase or cytokeratins associated with breast cancer
- adsorbents such as immobilized monoclonal antibodies and specific immobilized ligands
- removal of protein bound toxins and drugs for example, in the case of psychotomimetic or narcotic drug overdose
- Hemoperfusion and plasma perfusion on non-specific activated carbon-type sorbents was shown to be helpful in treatment of schizophrenia (Kinney, U.S. Pat. No. 4,300,551, 1981), pulmonary hypertension (SU 1507-397-A, 1989), multiple sclerosis (SU 1466-754-A, 1989), treatment of rhesus-conflict in obstetrics (SU 1533-697-A, 1989), for detoxication of organism of patients who have undergone extensive surgery (SU 1487-909- A, 1989).
- Bodden U.S. Pat. No. 5,069,662, December 1991
- high concentrations of anti-cancer agents can be perfused through a body organ containing a tumor and then removed from the organ with effluent blood.
- the contaminated blood is then transported to an extracorporeal circuit, purified from contaminations and returned to the body.
- This permits safe infusion of greater than usual concentrations of chemotherapeutic agents and delivering lethal doses of the agents to the tumor while preventing toxic levels of the agents from entering the body's general circulation.
- the process is applicable to the treatment of a number of tumors such as those of kidney, pancreas, bladder, pelvis and, in particular, the liver.
- chemotherapeutic agents for use in the practice are Adriamycin (doxorubicin), fluorinated pyrimidines (5- fluorouracyl 5-FU or floxuridine FURD), cisplatin, Mytomycin C, cyclophosphamide, methotrexate, vincristine, Bleomycin, FAMT, and any other anti-cancer agent.
- Blood detoxication most effectively can be achieved by hemoperfusion through a cartridge with a non-specific sorbent, for example, activated carbon, able to clear the blood from the above antineoplastic agents.
- the sorbent such as active carbon
- the biological defense system of blood may be activated and react in several ways: the blood may coagulate to form a clot, or thrombus, the immune system may respond unfavorably, and white blood cells may act to encapsulate the artificial device.
- Clark U.S. Pat. No. 4,048,064, September 1977 describes formation of a semipermeable polymeric coating on the carbon particles by polymerization of various hydrophilic monomers, in particular hydroxyethylmethacrylate (HEMA) and acrylamide. Moreover, he includes heparin into the coating polymer, in order to minimize complement activation and aggregation of platelets.
- HEMA hydroxyethylmethacrylate
- Nakashima, et al. U.S. Pat. No.
- thin integral membranes on the surface of the adsorbent can be better prepared from hydrophobic, insoluble in water polymer, in turn coated by a second, but water-soluble polymer.
- activated carbon was coated with a polyelectrolyte complex prepared from a polycation (DEAE-cellulose) and heparin and precipitated on the surface of carbon beads (Nalueva, et al., SU 844-569, 1981).
- Polymeric hydrophobic materials may serve as non-selective adsorbents. Endotoxins were observed to adsorb on porous polypropylene and polyethylene (Harris, U.S. Pat. No. 4,059,512, November 1977). Macroporous styrene-divinylbenzene copolymers were shown to be useful for blood detoxication from barbiturates and glutethimides (Kunin, et al., U.S. Pat. No. 3,794,584, February 1974).
- Polystyrene polymers prepared by an extensive crosslinking of polystyrene chains with rigid bi-functional cross-linking reagents such as dichlorodimethyl ether are taught by U.S. Patent 5,773,384.
- U.S. Patent 5,051,185 discloses a double-layered structure comprising a water- insoluble core coated with a blood compatible polymer.
- a water-insoluble core there is disclosed a spherical or particulate polymer having a particle size from 25 to 2500 ⁇ m having a specific surface area from 5 to 55 m /g.
- the water-insoluble core is preferably porous, displaying an average pore size of from 20 to 5,000A.
- the present invention has as an objective to provide an adsorbent for removing toxicants from blood or plasma, which is rendered hemocompatible through reaction of hemocompatible monomers or polymers with pendant vinyl groups on the adsorbent resin.
- the resin may be shaped to a convenient physical dimension for use. Bead form and fiber form are physical shapes convenient for exposure to blood or plasma for removal from blood of an absorbable component thereof.
- one feature of the present invention resides, in an adsorbent for removing toxicants from blood or plasma, of resin prepared from monomeric reactants of aromatic compounds, which resin has a surface and pore structure modified so as to prevent adsorption of large proteins and platelets and to minimize activation of blood complement system, without affecting noticeably the accessibility of the inner adsorption space of the beads for small and middle- size toxicant molecules.
- Preparation of the polymeric resin beads useful for this invention may follow known methods of addition polymerization. Helfferich. F., Ion Exchange, McGraw-Hill Book Company, Inc., 1962, p. 34 - 36 to produce resin heads of known sizes: 25 to 2500 ⁇ m, preferably from 50 to 1500 ⁇ m.
- divinylbenzene is the preferred material. As noted by Helfferich, pure divinylbenzene is not readily accessible. Commercially available sources are mixtures of divinylbenzene isomers (40 to 60 percent) and ethylstyrene (60 to 40 percent). Nominal DVB content is referenced as the mole percent of pure divinylbenzene monomer in the polymerization starting materials.
- the monomeric starting materials are combined with an addition type catalyst such as benzoyl peroxide, lauroyl peroxide, t-butyl hydroperoxide, or asobisisobutyronitrile present from 0.5 to 5 percent by weight of the monomeric reactants present.
- the hydrophobic monomeric starting materials are formed into small droplets, such as by agitation in water to which a suspension stabilizer such as: geletin, polyvinyl alcohol, an oleate salt, or a methacrylate salt has been added.
- a suspension stabilizer such as: geletin, polyvinyl alcohol, an oleate salt, or a methacrylate salt has been added.
- the aqueous phase including the droplets of catalyzed monomer of DNB and divinylbenzene are maintained at a temperature (40 to 110°C, preferably from 60 to 90°C) sufficient for polymerization.
- pressurization will be necessary to polymerize the monomers in liquid water at temperatures greater than 100°C.
- the beads can be externally sized in order to provide a more narrow particle size distribution as described in U.S. Patent 4,444,961.
- resin isformed from momomeric starting materials comprising DNB of 40 percent or more. Further, is not necessary or desirable to subject the resin to a solvent swelling and subsequent cross-linking step with a Lewis acid catalyst. Rather, DNB resin can be prepared with porosity suitable for absorbing the contaminants in blood by variation of the known parameters for preparation of DNB resins: temperature, solvent amount and choice of catalyst, and reaction time. Upgrading of the DNB monomer from commercially available values to 65 to 90 mole percent DNB can provide the skilled artisan another parameter useful to benefit pore size, porosity, and surface area.
- Rendering DNB resin hemocompatible also varies from the prior art of U.S. Patent 5,773,384.
- Several approaches to chemically modify the bead surface of an adsorbent are suggested to render the resin hemocompatibile. These approaches include: the formation of lipid-like layers on the surface of polystyrene beads in an attempt to simulate the structure of biomembranes by forming co-polymers of 2-methacryloyloxyethyl-phosphorylcholine with n- butyl-methacrylate grafted on the surface of a polystyrene resin.
- Groups of phosphatidylcholine are formed on the surface of polystyrene beads, without a preliminary grafting of the hydrophilic copolymer suggested by Ishihara, et al.
- heparin deposited on the surface of the polystyrene beads are believed to inhibit activation of the blood complement system and prevent formation of clots.
- long hydrophilic polymer chains on the surface are believed to prevent contacts between blood proteins and cells with the hydrophobic polystyrene surface.
- a fourth approach is to deposit high molecular weight fluorinated polyalkoxyphosphazene on the outer surface of the beads.
- the DNB resins of the instant invention are readily rendered hemocompatible by coating the resin by reaction of vinyl reactive and hemocompatible monomers and polymers with unreacted vinyl groups of the DNB resins. Also in contrast to the water-insoluble carrier of particulate or spherical form according to U.S.
- Patent 5,051,185 the inventive resins while having a surface area from 20 to 500 m 2 /g, a pore size from 20 to 500A, preferably from 20 to 300A, and a pore volume less than 2.5 cc/g, preferably less than 2.0 cc/g, but more than 1.0 cc/g, the instant resins can be manufactured having a surface area from 200 to 1,600 m 2 /g, preferably from 500 to 1,200 m 2 /g, more preferably 700 to 1,000 m 2 /g.
- Suitable hemocompatible coating may be prepared from a wide variety of such reactants capable of reacting with vinyl groups.
- Suitable nitrogen containing reactants include: primary amines, secondary amines, tertiary amines, quaternary amines and nitrogen- containing aromatic cyclic compounds such as pyridines, and imidazols.
- aromatic cyclic compounds include vinyl derivatives of such nitrogen containing compounds such as 2-vinylpyridine, 4-vinylpyridine, 2-methyl-5-vinylpyridine, 4-vinylimidazole, ⁇ -vinyl- 2-ethylimidazole, vinylpyrrolidinone, ⁇ -vinyl-2-methylimidazole.
- acrylic or (meth)acrylic acid derivatives including: dimethylaminoethyl (meth)acrylate, diethylaminoethyl (meth)acrylate, dimethylaminopropyl (meth)acrylate, 3-dimethylamino-2- hydroxypropyl (meth)acrylate), acrylamide or methacrylamide derivative.
- Acrylamide and methacrylamide such as N-dimethylaminoethyl (meth)acrylamide, N-diethylaminoethyl (meth)acrylamide.
- alkyl (meth)acrylates that is, 2- hydroxyethyl methacrylate, methyl (meth)acrylate, ethyl (meth)acrylate, and n- butyl(meth)acrylate.
- alkyl (meth)acrylates that is, 2- hydroxyethyl methacrylate, methyl (meth)acrylate, ethyl (meth)acrylate, and n- butyl(meth)acrylate.
- N-methyl (meth)acrylamide, N-vinylpyrrolidone, vinyl acetate, and vinylpyridine are also useful alone or as a co-polymer as a hemocompatible coating.
- Reaction conditions for coating the DNB resin beads with a vinyl reactive additive reactant are similar to the reaction conditions for formation of the DNB resin: a suitable catalyst such as are generally known, a suitable solvent, heating the DNB resin, catalyst, solvent, and additive reactant to the reactive temperature: generally from 40 to 110°C, for a time sufficient for reaction, from 8 hours to Vi hour.
- Such divinylbenzene resins avoid cross-linking of styrene-divinylbenzene copolymers with monochlorodimethyl ether as a bifunctional reagent, or cross-linking of such resin using chloromethylation taught by U.S. Patent 5,773,384. Consequently, the concerns for removing unreacted cross-linker can be avoided.
- the adsorbents prepared in accordance with this invention are charged to a column or cartridge for use to removal contaminants from blood or plasma.
- the column should preferably be provided with an inlet and an outlet designed to allow easy connection with the blood circuit, and with two porous filters set between the inlet and the absorbent layer, and between the absorbent layer and the outlet.
- the column may be made of a biocompatible material, glass, polyethylene, polypropylene, polycarbonate, polystyrene. Of these, polypropylene and polycarbonate are preferred materials, because the column packed with the sorbent can be sterilized (for example, autoclave and alpha -ray sterilization) before use.
- the resin By adjusting the pore size of the DNB resin and rendering the resin hemocompatible, the resin is useful to remove blood components having molecular weights of between 100 and 20,000 daltons including proteins, glycosated proteins, including degranulation inhibitory protein, advanced glycosylation endproducts, hormones such as parathyroid hormone and endotoxins such as those toxins which cause sepsis.
- blood components having molecular weights of between 100 and 20,000 daltons including proteins, glycosated proteins, including degranulation inhibitory protein, advanced glycosylation endproducts, hormones such as parathyroid hormone and endotoxins such as those toxins which cause sepsis.
- Such compounds as creatinine, barbiturate, phenobarbital, sodium salicylate, amphetamines, morphine sulfate, meprobamate, glutethimide, etc. can also be effectively and rapidly removed from the blood by the disclosed resin rendered hemocompatible.
- the hemocompatible resin will absorb cytochrome C, ⁇ - 2-microglob
- Divinylbenzene/ethyl vinylbenzene copolymer beads having a ratio of DNB to ENB of 80 to 20 on a weight basis were dried at 70°C in a vacuum oven for 24 hours. lOOg of the resulting beads were placed into a flask with 650 ml of methanol. The reaction mixture was heated to 65°C and this temperature maintained until 200 ml of distillate removed. 200 ml methanol was then added to the flask. After cooling to ambient temperature, l-vinyl-2- pyrrolidinone (1.0 g., 9.0mMole) and 75 ml of methanol was added, followed by 0.237 g.
- Divinylbenzene/ethyl vinylbenzene copolymer beads having a ratio of DNB to ENB of 80 to 20 on a weight basis were dried at 70°C in a vacuum oven for 24 hours. lOOg of the resulting beads were placed into a flask with 650 ml of ethanol. The reaction mixture was heated to 78°C and this temperature maintained until 200 ml of distillate removed. 200 ml ethanol was then added to the flask. After cooling to ambient temperature, polyvinylpyrrolidinone molecular weight, 10,000 (1.0 g., 9.0mMole) available from Aldrich P.O. 2060 Milwaukee WI 53201 United States solid was added, followed by .02 g.
- the polymer beads when contacted with blood were compatible. Blood does not clot on contact. The beads remove blood contaminants such as ⁇ -2-microglobulin.
Abstract
Description
Claims
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2000594570A JP2003506111A (en) | 1999-01-22 | 1999-11-23 | Surface-modified divinylbenzene resin with blood compatible coating |
CA002358949A CA2358949A1 (en) | 1999-01-22 | 1999-11-23 | Surface modified divinylbenzene resin having a hemocompatible coating |
AU19232/00A AU1923200A (en) | 1999-01-22 | 1999-11-23 | Surface modified divinylbenzene resin having a hemocompatible coating |
DE69942282T DE69942282D1 (en) | 1999-01-22 | 1999-11-23 | SURFACE-MODIFIED DIVINYL BENCH RESIN WITH HEMO-COMPATIBLE COATING |
EP99962883A EP1148944B1 (en) | 1999-01-22 | 1999-11-23 | Surface modified divinylbenzene resin having a hemocompatible coating |
AT99962883T ATE464947T1 (en) | 1999-01-22 | 1999-11-23 | SURFACE MODIFIED DIVINYLBENZENE RESIN WITH HEMOCOMPATIBLE COATING |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US23615399A | 1999-01-22 | 1999-01-22 | |
US09/236,153 | 1999-01-22 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2000043120A1 true WO2000043120A1 (en) | 2000-07-27 |
Family
ID=22888346
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1999/028073 WO2000043120A1 (en) | 1999-01-22 | 1999-11-23 | Surface modified divinylbenzene resin having a hemocompatible coating |
Country Status (8)
Country | Link |
---|---|
US (5) | US6238795B1 (en) |
EP (2) | EP2189213A1 (en) |
JP (1) | JP2003506111A (en) |
AT (1) | ATE464947T1 (en) |
AU (1) | AU1923200A (en) |
CA (1) | CA2358949A1 (en) |
DE (1) | DE69942282D1 (en) |
WO (1) | WO2000043120A1 (en) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE10221055A1 (en) * | 2002-05-10 | 2003-11-27 | Hemoteq Gmbh | New aminated oligo- or polysaccharide derivatives obtained from heparin, chitosan or chitin, useful for producing hemocompatible coatings on medicinal products, especially stents |
EP1463548A2 (en) * | 2001-12-21 | 2004-10-06 | Renaltech International LLC | Selective adsorption devices and systems |
EP2866854A4 (en) * | 2012-06-29 | 2016-03-30 | Cytosorbents Corp | Methods of using polymers |
US10064406B2 (en) | 2011-01-06 | 2018-09-04 | Cytosorbents Corporation | Polymeric sorbent for removal of impurities from whole blood and blood products |
Families Citing this family (63)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20020159995A1 (en) | 1997-07-30 | 2002-10-31 | Renal Tech International | Devices, systems, and methods for reducing levels of pro-inflammatory or anti-inflammatory stimulators or mediators in the blood, generated as a result of extracorporeal blood processing |
US20020197250A1 (en) * | 2001-04-10 | 2002-12-26 | Renal Tech International | Biocompatible devices, systems, and methods for reducing levels of pro-inflammatory or anti-inflammatory stimulators or mediators in the blood |
US20020197249A1 (en) * | 2001-04-10 | 2002-12-26 | Renal Tech International | Devices, systems, and methods for reducing levels of pro-inflammatory or anti-inflammatory stimulators or mediators in blood products |
US8329388B2 (en) * | 1997-07-30 | 2012-12-11 | Cytosorbents, Inc. | Biocompatible devices, systems, and methods for reducing levels of proinflammatory of antiinflammatory stimulators or mediators in the blood |
US20020198487A1 (en) * | 2001-04-10 | 2002-12-26 | Renal Tech International | Devices, systems, and methods for reducing levels of pro-inflammatory or anti-inflammatory stimulators or mediators in physiologic fluids |
EP2189213A1 (en) | 1999-01-22 | 2010-05-26 | Dow Global Technologies Inc. | Method for producing a surface modified divinylbenzene resin having a hemocompatible coating |
US6960178B2 (en) * | 2000-02-02 | 2005-11-01 | Xepmed, Inc. | Apparatus for enhanced plasmapheresis and methods thereof |
DE10045434B4 (en) * | 2000-09-14 | 2005-07-14 | Fresenius Hemocare Gmbh | Adsorbent with differently modified surface areas, process for its preparation and use thereof |
US6878127B2 (en) | 2001-04-10 | 2005-04-12 | Renaltech International, Llc | Devices, systems, and methods for reducing levels of pro-inflammatory or anti-inflammatory stimulators or mediators in the blood |
CA2462244C (en) * | 2001-10-04 | 2010-11-09 | Toray Industries, Inc. | A hydrophilic substance and a production method thereof |
CA2484374C (en) * | 2002-05-09 | 2011-05-17 | Hemoteq Gmbh | Medical products comprising a haemocompatible coating, production and use thereof |
US20040102732A1 (en) * | 2002-06-19 | 2004-05-27 | Morteza Naghavi | Dialysis system for treatment of vulnerable patients and methods of use |
US20040044300A1 (en) * | 2002-09-03 | 2004-03-04 | Donnie Rudd | Method of replenishing cells damaged by treatment for cancer |
US20040077985A1 (en) * | 2002-09-03 | 2004-04-22 | Donnie Rudd | Method of replenishing cells damaged by treatment for cancer |
US6884829B2 (en) * | 2002-10-18 | 2005-04-26 | Robert L. Albright | Hemocompatible coated polymer and related one-step methods |
US7629049B2 (en) * | 2002-10-18 | 2009-12-08 | Medasorb, Inc. | Hemocompatible polymer systems and related devices |
US7112620B2 (en) * | 2002-10-18 | 2006-09-26 | Albright Robert L | Hemocompatible polymer systems & related methods |
DE10261910A1 (en) * | 2002-12-30 | 2004-07-15 | Polymerics Gmbh | Adsorber material for blood, blood plasma and albumin purification processes |
US7507442B2 (en) * | 2003-11-04 | 2009-03-24 | Guardian Industries Corp. | Heat treatable coated article with diamond-like carbon (DLC) and/or zirconium in coating |
CN1886464B (en) * | 2003-11-28 | 2010-12-08 | 大赛璐化学工业株式会社 | Dispersed material and process for production of colored organic solid particle |
CA2575731C (en) | 2003-12-24 | 2014-07-15 | Chemica Technologies, Inc. | Dialysate regeneration system for portable human dialysis |
DE102004024140A1 (en) * | 2004-05-14 | 2005-12-08 | Fresenius Medical Care Deutschland Gmbh | Preservative for medical devices |
US20080044333A1 (en) * | 2004-07-30 | 2008-02-21 | Hakka Leo E | Method and apparatus for NOx and Hg removal |
US7208080B2 (en) * | 2004-09-16 | 2007-04-24 | Thermaco, Inc. | Low cost oil/grease separator |
US7297278B2 (en) * | 2004-10-20 | 2007-11-20 | Baker Hughes Incorporated | Methods for removing metals from water |
US20060193839A1 (en) * | 2005-02-28 | 2006-08-31 | Donnie Rudd | Method of providing readily available cellular material derived from peripheral blood, and a composition thereof |
US20080075704A1 (en) * | 2005-02-28 | 2008-03-27 | Wolf David A | Method of providing readily available cellular material derived from peripheral blood, and a composition thereof |
US20090204051A1 (en) * | 2005-03-30 | 2009-08-13 | Kaneka Corporation | Method of removing lymphocyte growth inhibitor |
US20100300971A1 (en) * | 2005-05-18 | 2010-12-02 | Sequant Ab | Zwitterionic stationary phase as well as method for using and producing said phase |
US20080035568A1 (en) * | 2005-10-03 | 2008-02-14 | Zhongping Huang | Apparatus and Method for Filtering Fluids |
WO2007041430A2 (en) * | 2005-10-03 | 2007-04-12 | Emv Technologies, Llc | Apparatus and method for enhanced hemodialysis performance |
US20100135976A1 (en) * | 2006-06-16 | 2010-06-03 | Rune Nilsson | Adsorption device |
US7875182B2 (en) * | 2006-11-20 | 2011-01-25 | Cytosorbents, Inc. | Size-selective hemoperfusion polymeric adsorbents |
US8211310B2 (en) * | 2006-11-20 | 2012-07-03 | Cytosorbents, Inc. | Size-selective polymer system |
US9604196B2 (en) | 2006-11-20 | 2017-03-28 | Cytosorbent, Inc. | Size-selective hemocompatible polymer system |
US8660800B2 (en) * | 2007-09-04 | 2014-02-25 | Koninklijke Philips N.V. | Multi-treatment planning apparatus and method |
WO2009158027A1 (en) * | 2008-06-26 | 2009-12-30 | Cytosorbents, Inc. | Removal of myoglobin from blood and/or physiological fluids |
US20100030196A1 (en) * | 2008-07-29 | 2010-02-04 | Medtronic, Inc. | Apheresis of a target molecule from cerebrospinal fluid |
US20110033463A1 (en) * | 2009-08-06 | 2011-02-10 | Medtronic, Inc. | Apheresis, administration of agent, or combination thereof |
US8383319B2 (en) | 2009-08-25 | 2013-02-26 | Eastman Kodak Company | Lithographic printing plate precursors and stacks |
WO2016187217A2 (en) | 2015-05-18 | 2016-11-24 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and compositions for treating aging-associated impairments |
US20160208011A1 (en) | 2010-01-28 | 2016-07-21 | The Board Of Trustees Of The Leland Stanford Junior University | Ccr3 modulation in the treatment of aging-associated impairments, and compositions for practicing the same |
WO2017120461A1 (en) | 2016-01-08 | 2017-07-13 | The Board Of Trustees Of The Leland Stanford Junior University | Ccr3 modulation in the treatment of aging-associated impairments, and compositions for practicing the same |
US10487148B2 (en) | 2010-01-28 | 2019-11-26 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and compositions for treating aging-associated impairments |
EP2655443A1 (en) * | 2010-12-20 | 2013-10-30 | DSM IP Assets B.V. | Bio-renewable vinyl beads |
RU2452562C1 (en) * | 2011-04-05 | 2012-06-10 | Государственное образовательное учреждение высшего профессионального образования "Башкирский государственный университет" ГОУ ВПО "БашГУ" | Method of producing sorbent |
US9161968B2 (en) | 2011-04-08 | 2015-10-20 | The Board Of Trustees Of The Leland Stanford Junior University | Methods of neuroprotection involving macrophage colony stimulating factor receptor agonists |
CN102603984B (en) * | 2012-01-16 | 2014-01-15 | 南开大学 | Synthesis of high specific surface area hydroxy resin and method for extracting stevioside by high specific surface area hydroxy resin |
EP2945994B1 (en) | 2013-01-18 | 2018-07-11 | Basf Se | Acrylic dispersion-based coating compositions |
JP2016063846A (en) * | 2013-02-08 | 2016-04-28 | テルモ株式会社 | Medical coating material and medical device |
EP2783748B1 (en) | 2013-03-27 | 2019-05-08 | Biotage AB | Use of a sorbent for extracting mycotoxins |
EP3043640B1 (en) * | 2013-12-03 | 2020-02-05 | Biofishency Ltd | Mechanical-biological filter |
EA035336B1 (en) | 2013-12-09 | 2020-05-29 | Зе Боард Оф Трастиз Оф Зе Леланд Стэнфорд Джуниор Юниверсити | Method for treating aging-associated cognitive disorder or disease |
US10905779B2 (en) | 2013-12-09 | 2021-02-02 | The Board Of Trustees Of The Leland Stanford Junior University | Methods for screening human blood products comprising plasma using immunocompromised rodent models |
EA201890020A1 (en) | 2015-06-15 | 2018-05-31 | Зе Боард Оф Трастиз Оф Зе Леланд Стэнфорд Джуниор Юниверсити | METHODS AND COMPOSITIONS FOR THE TREATMENT OF ASSOCIATED WITH AGING STATES |
CN105504131B (en) * | 2016-01-26 | 2018-07-17 | 重庆希尔康血液净化器材研发有限公司 | β is removed for blood purification2The preparation method of the resin of microglobulin |
US11911551B2 (en) | 2016-03-02 | 2024-02-27 | Exthera Medical Corporation | Method for treating drug intoxication |
US10786615B2 (en) * | 2016-03-02 | 2020-09-29 | Exthera Medical Corporation | Method for treating drug intoxication |
US11065600B2 (en) | 2016-05-26 | 2021-07-20 | Cytosorbents Corporation | Use of a hemocompatible porous polymer bead sorbent for removal of endotoxemia-inducing molecules |
CN108311121B (en) * | 2018-01-25 | 2021-05-14 | 健帆生物科技集团股份有限公司 | Adsorption resin for blood perfusion, preparation method thereof and perfusion apparatus |
CN111468079A (en) * | 2019-01-23 | 2020-07-31 | 重庆希尔康血液净化器材研发有限公司 | Preparation method of anticoagulant hemoperfusion adsorption material |
CN109762109A (en) * | 2019-02-18 | 2019-05-17 | 南开大学 | A kind of poly 4 vinyl pyridine function base resin and its preparation method and application |
CN115634673A (en) * | 2022-12-07 | 2023-01-24 | 盱眙凹土能源环保材料研发中心 | Preparation method of ultrahigh cross-linked resin for bilirubin adsorption and blood perfusion |
Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4048064A (en) * | 1976-04-23 | 1977-09-13 | Clark Iii William T | Biocompatible hemoperfusion system |
US4171283A (en) * | 1976-08-04 | 1979-10-16 | Kuraray Co., Ltd. | Hemoperfusion adsorbents |
US4785079A (en) | 1984-11-09 | 1988-11-15 | The Salk Institute For Biological Studies | Isolation of fibroblast growth factor |
JPH01119264A (en) | 1987-10-30 | 1989-05-11 | Kanegafuchi Chem Ind Co Ltd | Adsorbent and removing device therewith |
JPH01181875A (en) | 1988-01-14 | 1989-07-19 | Kanegafuchi Chem Ind Co Ltd | Adsorptive body of immune complex and removing device for immune complex with it |
US5149425A (en) * | 1988-11-09 | 1992-09-22 | Chembiomed, Ltd. | Affinity supports for hemoperfusion |
US5773384A (en) * | 1996-03-23 | 1998-06-30 | White Eagle International Technologies Group, Inc. | Sorbents for removing toxicants from blood or plasma, and method of producing the same |
WO1999039823A1 (en) | 1998-02-06 | 1999-08-12 | Advanced Renal Technologies, Llc | Method of producing material for purification of physiological liquids of organism, and method of producing the material |
Family Cites Families (26)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE249274C (en) | ||||
US3794584A (en) | 1970-04-09 | 1974-02-26 | Rohm & Haas | Removal of poisons and drugs from blood |
US4059512A (en) | 1974-12-27 | 1977-11-22 | Preventive Systems, Inc. | Process for removing endotoxin from biological fluids |
US4046766A (en) * | 1975-02-18 | 1977-09-06 | Rohm And Haas Company | Quinolizinium resins and monomers and methods for making them |
GB1592702A (en) | 1976-10-28 | 1981-07-08 | Asahi Chemical Ind | Method of adsorbing a protein on a protein adsorbent comprising a porous copolymer of a cyano-group-containing monomer |
US4300551A (en) | 1978-05-02 | 1981-11-17 | Kinney Michael J | Method for treating schizophrenia |
SU844569A1 (en) | 1978-11-17 | 1981-07-07 | Всесоюзный Научно-Исследовательскийинститут Медицинских Полимеров | Method of preparing homocompatible adsorbents for blood purification from toxins |
CA1166413A (en) | 1980-10-30 | 1984-05-01 | Edward E. Timm | Process and apparatus for preparing uniform size polymer beads |
SU1533697A1 (en) | 1984-07-05 | 1990-01-07 | И.К.Деденко, О.А.Машков. М.П.Захараш ,А.В.Обухова. С.Л.Мизерна и В.Г.Николаев | Method of treating rh-conflict |
US4623706A (en) | 1984-08-23 | 1986-11-18 | The Dow Chemical Company | Process for preparing uniformly sized polymer particles by suspension polymerization of vibratorily excited monomers in a gaseous or liquid stream |
SU1487909A1 (en) | 1985-11-21 | 1989-06-23 | Nii Patologii Krovoobrashcheni | Method of detoxication of organism in post-surgery period |
SU1466754A1 (en) | 1986-03-06 | 1989-03-23 | 1-Й Ленинградский Медицинский Институт Им.Акад.И.П.Павлова | Method of treatment of disseminated sclerosis |
EP0265924B2 (en) | 1986-10-29 | 1998-04-22 | Kanegafuchi Kagaku Kogyo Kabushiki Kaisha | Uniform polymer particles |
SU1507397A1 (en) | 1987-06-01 | 1989-09-15 | Киевский Медицинский Институт Им.Акад.А.А.Богомольца | Method of drug therapy of the primary pulmonary hypertension |
EP0319144A1 (en) | 1987-11-06 | 1989-06-07 | Asahi Kasei Kogyo Kabushiki Kaisha | Adsorbent of beta 2-microglobulin |
US5069662A (en) | 1988-10-21 | 1991-12-03 | Delcath Systems, Inc. | Cancer treatment |
US5306561A (en) * | 1992-02-20 | 1994-04-26 | Cornell Research Foundation, Inc. | Preparation of surface-functional polymer particles |
JP2650013B2 (en) | 1992-09-29 | 1997-09-03 | 株式会社ティーティーティー | Driving method of display discharge tube |
US5545131A (en) | 1994-04-28 | 1996-08-13 | White Eagle International Technologies, Lp | Artificial kidney |
US5460725A (en) | 1994-06-21 | 1995-10-24 | The Dow Chemical Company | Polymeric adsorbents with enhanced adsorption capacity and kinetics and a process for their manufacture |
US5416124A (en) | 1994-06-21 | 1995-05-16 | The Dow Chemical Company | Polymeric adsorbents with enhanced adsorption capacity and kinetics and a process for their manufacture |
US5629353A (en) | 1995-05-22 | 1997-05-13 | The Regents Of The University Of California | Highly cross-linked nanoporous polymers |
US6416487B1 (en) | 1997-07-30 | 2002-07-09 | Renal Tech International Llc | Method of removing beta-2 microglobulin from blood |
US5904663A (en) | 1997-07-30 | 1999-05-18 | Braverman; Andrew | Method of removing beta-2 microglobulin from blood |
US6136424A (en) | 1998-02-06 | 2000-10-24 | Renal Tech International, Llc | Method of and material for purification of physiological liquids of organism, and method of producing the material |
EP2189213A1 (en) | 1999-01-22 | 2010-05-26 | Dow Global Technologies Inc. | Method for producing a surface modified divinylbenzene resin having a hemocompatible coating |
-
1999
- 1999-11-23 EP EP10152368A patent/EP2189213A1/en not_active Withdrawn
- 1999-11-23 CA CA002358949A patent/CA2358949A1/en not_active Abandoned
- 1999-11-23 WO PCT/US1999/028073 patent/WO2000043120A1/en active Application Filing
- 1999-11-23 AT AT99962883T patent/ATE464947T1/en not_active IP Right Cessation
- 1999-11-23 DE DE69942282T patent/DE69942282D1/en not_active Expired - Lifetime
- 1999-11-23 EP EP99962883A patent/EP1148944B1/en not_active Expired - Lifetime
- 1999-11-23 AU AU19232/00A patent/AU1923200A/en not_active Abandoned
- 1999-11-23 JP JP2000594570A patent/JP2003506111A/en active Pending
-
2000
- 2000-01-14 US US09/483,620 patent/US6238795B1/en not_active Expired - Lifetime
- 2000-12-22 US US09/746,810 patent/US6338801B2/en not_active Expired - Fee Related
-
2001
- 2001-05-21 US US09/861,969 patent/US6325939B2/en not_active Expired - Fee Related
- 2001-09-27 US US09/965,256 patent/US6419830B2/en not_active Expired - Lifetime
-
2002
- 2002-03-08 US US10/094,001 patent/US6423024B1/en not_active Expired - Lifetime
Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4048064A (en) * | 1976-04-23 | 1977-09-13 | Clark Iii William T | Biocompatible hemoperfusion system |
US4171283A (en) * | 1976-08-04 | 1979-10-16 | Kuraray Co., Ltd. | Hemoperfusion adsorbents |
US4785079A (en) | 1984-11-09 | 1988-11-15 | The Salk Institute For Biological Studies | Isolation of fibroblast growth factor |
JPH01119264A (en) | 1987-10-30 | 1989-05-11 | Kanegafuchi Chem Ind Co Ltd | Adsorbent and removing device therewith |
JPH01181875A (en) | 1988-01-14 | 1989-07-19 | Kanegafuchi Chem Ind Co Ltd | Adsorptive body of immune complex and removing device for immune complex with it |
US5149425A (en) * | 1988-11-09 | 1992-09-22 | Chembiomed, Ltd. | Affinity supports for hemoperfusion |
US5773384A (en) * | 1996-03-23 | 1998-06-30 | White Eagle International Technologies Group, Inc. | Sorbents for removing toxicants from blood or plasma, and method of producing the same |
WO1999039823A1 (en) | 1998-02-06 | 1999-08-12 | Advanced Renal Technologies, Llc | Method of producing material for purification of physiological liquids of organism, and method of producing the material |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1463548A2 (en) * | 2001-12-21 | 2004-10-06 | Renaltech International LLC | Selective adsorption devices and systems |
EP1463548A4 (en) * | 2001-12-21 | 2010-04-14 | Renaltech Internat Llc | Selective adsorption devices and systems |
DE10221055A1 (en) * | 2002-05-10 | 2003-11-27 | Hemoteq Gmbh | New aminated oligo- or polysaccharide derivatives obtained from heparin, chitosan or chitin, useful for producing hemocompatible coatings on medicinal products, especially stents |
DE10221055B4 (en) * | 2002-05-10 | 2007-10-25 | Hemoteq Ag | Compounds for hemocompatible coating of surfaces, process for their preparation and their use |
US10064406B2 (en) | 2011-01-06 | 2018-09-04 | Cytosorbents Corporation | Polymeric sorbent for removal of impurities from whole blood and blood products |
EP2866854A4 (en) * | 2012-06-29 | 2016-03-30 | Cytosorbents Corp | Methods of using polymers |
AU2013282320B2 (en) * | 2012-06-29 | 2017-10-19 | Cytosorbents Corporation | Methods of using polymers |
EP3673930A1 (en) * | 2012-06-29 | 2020-07-01 | Cytosorbents Corporation | Methods of using polymers |
US11602585B2 (en) | 2012-06-29 | 2023-03-14 | Cytosorbents Corporation | Methods for reducing contamination in a biological substance |
Also Published As
Publication number | Publication date |
---|---|
US6325939B2 (en) | 2001-12-04 |
ATE464947T1 (en) | 2010-05-15 |
JP2003506111A (en) | 2003-02-18 |
US20020091231A1 (en) | 2002-07-11 |
AU1923200A (en) | 2000-08-07 |
US20010032819A1 (en) | 2001-10-25 |
CA2358949A1 (en) | 2000-07-27 |
US20020017488A1 (en) | 2002-02-14 |
EP2189213A1 (en) | 2010-05-26 |
US6338801B2 (en) | 2002-01-15 |
US20010008958A1 (en) | 2001-07-19 |
US6238795B1 (en) | 2001-05-29 |
US6423024B1 (en) | 2002-07-23 |
DE69942282D1 (en) | 2010-06-02 |
EP1148944A1 (en) | 2001-10-31 |
EP1148944B1 (en) | 2010-04-21 |
US6419830B2 (en) | 2002-07-16 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US6238795B1 (en) | Surface modified polymer beads | |
US5773384A (en) | Sorbents for removing toxicants from blood or plasma, and method of producing the same | |
US6133393A (en) | Method of purification of physiological liquids of organism | |
JP4992120B2 (en) | Virus and leukocyte selective removal material and use thereof | |
US6127311A (en) | Method of producing material for purification of physiological liquids of organism | |
ES2880509T3 (en) | Size Selection Hemoperfusion Polymeric Adsorbents | |
GB2075362A (en) | Column for adsorption of blood proteins | |
JP3741320B2 (en) | Leukocyte selective removal filter material | |
US20020146413A1 (en) | System for treating patient with bacterial infections | |
EP1679117A2 (en) | Adsorption system for removing viruses and viral components from fluids, in particular from blood and blood plasma | |
JP2649224B2 (en) | Sterilization method for body fluid treatment device and sterilized body fluid treatment device | |
JP2568846B2 (en) | Myoglobin adsorbent | |
JP3330420B2 (en) | Bradykinin adsorbent | |
EP0888178A1 (en) | Sorbents for removing toxicants from blood or plasma, and method of producing same | |
JPH0595999A (en) | Adsorption body for contrast medium | |
JPH10179732A (en) | Whole blood treating device and whole blood treatment | |
JPH06126167A (en) | Transthyretin adsorbent | |
JPS6319154A (en) | Beta 2-microglobulin adsorbent | |
JPH0783767B2 (en) | Blood purification device | |
JPH0623042A (en) | Blood purifying adsorbent and blood purifying method | |
JPH0232897B2 (en) | ||
JP2511410C (en) | ||
JPH0622631B2 (en) | Granular adsorbent for removing pathogen-related substances, method for producing the same, and adsorption device using the same | |
JP2568846C (en) |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AE AL AM AT AU AZ BA BB BG BR BY CA CH CN CU CZ DE DK EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT UA UG UZ VN YU ZA ZW |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): GH GM KE LS MW SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG |
|
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
WWE | Wipo information: entry into national phase |
Ref document number: 1999962883 Country of ref document: EP |
|
ENP | Entry into the national phase |
Ref document number: 2358949 Country of ref document: CA Ref country code: CA Ref document number: 2358949 Kind code of ref document: A Format of ref document f/p: F |
|
ENP | Entry into the national phase |
Ref country code: JP Ref document number: 2000 594570 Kind code of ref document: A Format of ref document f/p: F |
|
WWP | Wipo information: published in national office |
Ref document number: 1999962883 Country of ref document: EP |
|
REG | Reference to national code |
Ref country code: DE Ref legal event code: 8642 |