Heparin Or Derivative Patents (Class 536/21)
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Patent number: 6495148Abstract: New high molecular weight salts of hyaluronic acid, especially salts having as a counterion a natural amino acid are described. They are prepared starting from high molecular weight hyaluronic acid or its salts. These high molecular weight salts of hyaluronic acid are advantageously employed in cosmetic and pharmaceutical uses.Type: GrantFiled: January 29, 2001Date of Patent: December 17, 2002Inventor: Giuliana Abbiati
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Patent number: 6491965Abstract: Novel conjugates of glycosaminoglycans, particularly heparin and dermatan sulfate, and amine containing species and therapeutic uses thereof are described. In particular, mild methods of conjugating heparins to proteins, such as antithrombin III and heparin cofactor II, which provide covalent conjugates which retain maximal biological activity are described. Uses of these conjugates to prevent thrombogenesis, in particular in lung airways, such as found in infant and adult respiratory distress syndrome, and on surfaces in contact with blood are also described.Type: GrantFiled: December 17, 1996Date of Patent: December 10, 2002Assignee: Hamilton Civic Hospitals Research Development, Inc.Inventors: Leslie Berry, Maureen Andrew
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Publication number: 20020160098Abstract: A nucleic acid coating composition including a polyanion bound, directly or through one or more intermediates, to a medical device surface, with a condensate comprising a polycation and nucleic acid bound to the polyanion, devices incorporating such coating compositions, and methods for making. In one embodiment, a silyl-heparin complex is provided, bound to a medical device surface by hydrophobic interaction with the silyl moiety, with a polycation and nucleic acid condensate bound to the heparin by electrostatic interaction.Type: ApplicationFiled: January 22, 2002Publication date: October 31, 2002Inventors: Paul O. Zamora, Ray Tsang, Shigemasa Osaki
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Patent number: 6440934Abstract: The present invention has multiple aspects. In particular, in one aspect, the present invention is directed to a unit dose composition comprising 0.2 &mgr;g/kg to 48 &mgr;g/kg of an FGF-2 of SEQ ID NO: 2, or an angiogenically active fragment or mutein thereof in a pharmaceutically acceptable carrier. In another aspect, the present invention is directed to a method for treating a human patient for coronary artery disease, comprising administering into one or more coronary vessels or a peripheral vein of a human patient in need of treatment for coronary artery disease a safe and angiogenically effective dose of a recombinant FGF-2, or an angiogenically active fragment or mutein thereof. The single unit dose composition of the present invention provides an angiogenic effect in a human CAD patient that lasts six months before re-treatment is required. In another aspect, the present invention is directed to a method of administration which optimizes patient's safety.Type: GrantFiled: August 27, 1999Date of Patent: August 27, 2002Assignee: Chiron CorporationInventor: Martha Jo Whitehouse
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Publication number: 20020115836Abstract: The present invention provides an anti-thrombogenic and cellular-adhesion coating composition for blood-contacting surfaces.Type: ApplicationFiled: January 14, 2002Publication date: August 22, 2002Inventors: Ray Tsang, Shigemasa Osaki
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Publication number: 20020111331Abstract: The present invention relates to a method and apparatus for isolating anticoagulant heparin or heparan sulfate by binding the anticoagulant heparin or anticoagulant heparan sulfate onto an affinity matrix and separating the non-bound material from the bound material. The affinity matrix is made of a fibroblast growth factor immobilized on a support. The invention also relates to a method and composition for neutralizing anticoagulation catalyzed by heparin, a heparin mimic, or a heparin derivative, by contacting heparin, a heparin mimic, or a heparin derivative with a fibroblast growth factor.Type: ApplicationFiled: November 21, 2001Publication date: August 15, 2002Inventors: Wallace L. McKeehan, Yongde Luo
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Patent number: 6406894Abstract: A process for preparing polyvalent, physiologically degradable carbohydrate-containing polymers by enzymatic glycosylation reactions is described. The carbohydrate-containing polymers thus prepared may be used for preparing carbohydrate building blocks. The polyvalent carbohydrate-containing polymers of the invention cause no intolerance reactions in vivo, either in their intact form or in the form of degradation products. The carbohydrate side chain of the carbohydrate-containing polymer is assembled by enzymatic glycosylation reactions in homogeneous aqueous buffer systems directly on a biodegradable polymer. The yields of the glycosylation reaction are significantly improved over known processes, and are often quantitative. This also provides a significant increase in the loading densities. A process for preparing free oligosaccharides by means of the carbohydrate-containing polymers of the invention is also described.Type: GrantFiled: December 11, 1997Date of Patent: June 18, 2002Assignee: Glycorex ABInventors: Brigitte Hoersch, Michael Ahlers, Gerhard Kretzschmar, Eckart Bartnik, Dick Seiffge
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Patent number: 6388060Abstract: This present invention provides methods of sulfating uronic acid-containing polysaccharides. High levels of sulfation can be obtained using the methods of the present invention.Type: GrantFiled: November 4, 1999Date of Patent: May 14, 2002Assignee: Vascular Therapeutics Inc.Inventors: Steven Y. C. Guo, Edward H. Conrad
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Publication number: 20020055621Abstract: Alkali and alkali-earth metal salts of polysaccharides derived from heparin, their method of preparation and the pharmaceutical compositions containing them.Type: ApplicationFiled: July 23, 2001Publication date: May 9, 2002Inventors: Jacques Diaz, Christelle Pecquet, Elisabeth Perrin, Christian Viskov
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Patent number: 6384021Abstract: Compositions of heparins of very low molecular weight, with the formula I, in which, n may vary between 1 and 12; R1=H or SO3Na; R2=SO3Na or COCH3. Such compositions of heparin are composed of mixtures of oligosaccharides or fragments of heparin and are characterised by having anti-Xa activity and anti-factor IIa activity and because they can be used as anti-thrombic medicaments.Type: GrantFiled: November 3, 1999Date of Patent: May 7, 2002Assignee: Laboratorios Farmaceuticos RoviInventor: Jean Mardiguian
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Publication number: 20020040013Abstract: The invention concerns the use of low molecular weight heparin for preventing and/or treating motor neuron diseases.Type: ApplicationFiled: June 14, 2001Publication date: April 4, 2002Inventors: Jean-Marie Stutzmann, Andre Uzan
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Publication number: 20020019021Abstract: The application relates to a method for determining the anticoagulatory potential of a sample by adding thrombomodulin and thromboplastin in a coagulation test.Type: ApplicationFiled: November 6, 1998Publication date: February 14, 2002Inventor: MICHAEL KRAUS
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Publication number: 20020016308Abstract: The present invention is related to heparin-like compounds characterized by their capacity of inhibiting collagen-induced platelet aggregation in flowing whole blood and their use for prophylactic treatment of arterial thrombosis associated with vascular or microvascular injury and interventions. Said properties are related to a high coupling density of negatively charged heparin or heparin-like glycosaminoglycan molecules, present in multiple heparin or heparin-like glycosaminoglycans as well as in proteoglycans containing said multiple heparin or heparin-like glycosaminoglycans or lower-molecular-weight heparin or heparin-like glycosaminoglycans connected directly or through spacer/linker molecules to globular core molecules. Heparin-like compounds, with said properties are obtainable from mammalian mast cells, by tissue extraction or cell cultivation.Type: ApplicationFiled: January 20, 1999Publication date: February 7, 2002Inventors: RIITTA LASSILA, PETRI KOVANEN, KEN LINDSTEDT
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Publication number: 20020012928Abstract: An object of the present invention is to provide a novel method for suppressing the action of nucleic acid synthesis inhibitory substances and thereby amplifying a nucleic acid in a sample efficiently.Type: ApplicationFiled: March 16, 2001Publication date: January 31, 2002Applicant: SHIMADZU CORPORATIONInventor: Hiroshi Tonoike
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Patent number: 6342591Abstract: The present invention provides an anti-thrombogenic and cellular-adhesion coating composition for blood-contacting surfaces. The coating comprises a covalent complex of from 1 to 30 hydrophobic silyl moieties of Formula I: wherein R1 is an C1-18 alkyl or C6-32 aryl group, each R2 is independently selected from the group consisting of C1-18 alkyl and C6-32 aryl, R3 is N or O, n is a number from 1 to 10, directly bound to a heparin molecule via covalent bonding, with an adhesive molecule directly bound to the heparin molecule. In one embodiment, the coating comprises benzyl-(1,2 dimethyl)disilyl heparin, wherein an adhesive molecule, such as fibronectin, is bound to the heparin.Type: GrantFiled: July 31, 2000Date of Patent: January 29, 2002Assignee: BioSurface Engineering Technologies, Inc.Inventors: Paul O. Zamora, Shigemasa Osaki, Ray Tsang
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Publication number: 20020009782Abstract: A method of preparing low molecular weight heparin or low molecular weight heparan sulfate, the method is effected by digesting unfractionated or partially fractionated heparin or heparan sulfate having a given preponderant molecular mass with heparanase, thereby obtaining beparin or heparan sulfate of a lower preponderant molecular mass. A product obtained by implementing the method and a pharmaceutical composition including the latter are also described.Type: ApplicationFiled: September 4, 2001Publication date: January 24, 2002Inventor: Daphna Miron
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Patent number: 6340675Abstract: A process is disclosed for the production of an anticoagulant composition which allows for the accurate analysis of blood electrolyte concentrations. Also disclosed is the anticoagulant composition produced in accordance with the disclosed method and an apparatus containing said composition useful in the selection and sampling of blood.Type: GrantFiled: September 11, 1996Date of Patent: January 22, 2002Assignee: Sherwood Services AGInventors: Edward Mancilla, Elizabeth M. Lagwinska
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Patent number: 6339074Abstract: Hyaluronic acid, hyaluronate esters and salts thereof are sulfated such that the number of sulfate groups per monomeric unit is in the range of from 0.5 to 3.5. The sulfated derivatives exhibit anticoagulant and cell adhesion reduction properties, and may be used to prepare biomaterials.Type: GrantFiled: November 23, 1999Date of Patent: January 15, 2002Assignee: Fidia Advanced Biopolymers, SrlInventors: Gloria Cialdi, Agnese Magnani
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Patent number: 6329351Abstract: Sulphaminoheparosansulphates obtainable from the Escherichia coli K5 polysaccharide by deacetilation and the subsequent sulfation with the sulphuric anhydride/trimethylamine adduct carried out at 0° C., for times ranging from 0.25 to 2 hours and using a reactant/polysaccharide ratio (SO3 equivalents/available OH groups equivalents) equal to 5 have been found having high anti-metastatic activity and low anticoagulant activity.Type: GrantFiled: December 20, 1999Date of Patent: December 11, 2001Assignee: Istituto Scientifico Di Chimica E Biochimica “G. Ronzoni”Inventors: Annamaria Naggi, Giangiacomo Torri
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Patent number: 6326476Abstract: The invention relates to new heparin derivatives from bovine or porcine heparin which have a molecular weight equal to or larger than the standard heparin, show a sulfur content which is equal to or higher than that of the starting heparin or at least 13% w/w, have an anticoagulant activity in the anti-FXa assay of less than 10% of the standard heparin it was made from, show a ratio of APTT activity over anti-FXa activity of 3-35, show a reduced prolongation of bleeding time compared to the standard heparin it was made from as measured in the rat tail after i.v. administration and show enhancement of the rate of development of coronary collaterals in dogs equal to or better than clinically used heparin. The invention also relates to processes for preparation of the new bovine and porcine heparin derivatives.Type: GrantFiled: May 10, 1995Date of Patent: December 4, 2001Assignee: Pharmacia ABInventors: Christer Jan Mattsson, Carl Magnus Erik Svahn, Michael Per Weber
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Publication number: 20010046974Abstract: The present invention provides compositions and methods for the treatment of cardiovascular diseases. More particularly, the present invention relates to modifying thrombus formation by administering an agent which, inter alia, is capable of (1) inactivating fluid-phase thrombin and thrombin which is bound either to fibrin in a clot or to some other surface by catalyzing antithrombin; and (2) inhibiting thrombin generation by catalyzing factor Xa inactivation by antithrombin III (ATIII). The compositions and methods of the present invention are particularly useful for preventing thrombosis in the circuit of cardiac bypass apparatus and in patients undergoing renal dialysis, and for treating patients suffering from or at risk of suffering from thrombus-related cardiovascular conditions, such as unstable angina, acute myocardial infarction (heart attack), cerebrovascular accidents (stroke), pulmonary embolism, deep vein thrombosis, arterial thrombosis, etc.Type: ApplicationFiled: June 6, 2001Publication date: November 29, 2001Applicant: Hamilton Civic Hospitals Res Dev., Inc.Inventors: Jeffrey Weitz, Jack Hirsh
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Publication number: 20010034336Abstract: Coatings are provided in which biopolymers may be covalently linked to a substrate. Such biopolymers include those that impart thromboresistance and/or biocompatibility to the substrate, which may be a medical device. Coatings disclosed herein include those that permit coating of a medical device in a single layer, including coatings that permit applying the single layer without a primer. Suitable biopolymers include heparin complexes, and linkage may be provided by a silane having isocyanate functionality.Type: ApplicationFiled: May 23, 2001Publication date: October 25, 2001Inventors: Chirag B. Shah, Laurel L. Wolfgang
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Patent number: 6303585Abstract: A carrier and a method for preparing it are provided for use in the delivery of therapeutic agents. A polysaccharide is reacted with an oxidizing agent to open sugar rings on the polysaccharide to form aldehyde groups. The aldehyde groups are reacted to form covalent oxime linkages with a second polysaccharide and each of the first and second polysaccharide is selected from the group consisting of hyaluronic acid, dextran, dextran sulfate, chondroitin sulfate, dermatan sulfate, keratan sulfate, heparan, heparan sulfate and alginate.Type: GrantFiled: July 1, 1998Date of Patent: October 16, 2001Assignee: Orquest, Inc.Inventors: Robert C. Spiro, Andrea Y. Thompson, LinShu Liu
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Patent number: 6291671Abstract: A method for preparing a drug complex in which a polysaccharide derivative having carboxyl groups and a residue of a drug compound are bound to each other by means of a spacer comprising an amino acid or a spacer comprising peptide-bonded 2 to 8 amino acids, or a drug complex in which a polysaccharide derivative having carboxyl groups and a residue of a drug compound are bound to each other without the spacer, characterized in that an organic amine salt of the polysaccharide derivative having carboxyl groups is reacted with the drug compound or the spacer bound to the drug compound in a non-aqueous system. The reaction between the polysaccharide derivative having carboxyl groups and the drug compound bound with the spacer or the like can be carried out in high yields, and when a drug compound having a lactone ring is subjected to the reaction, side reactions can be reduced.Type: GrantFiled: March 22, 1999Date of Patent: September 18, 2001Assignee: Daiichi Pharmaceutical Co., Ltd.Inventors: Kazuhiro Inoue, Hiroshi Susaki, Masahiro Ikeda
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Patent number: 6288044Abstract: Process for the preparation of O-sulfated K4, K5 and K40 polysaccharides useful for the treatment of tumoral, HIV-1 and coagulation pathologies and in cosmetic preparations, wherein the K4, K5 or K40 polysaccharide in the form of sodium salt is suspended in an aprotic solvent and directly submitted to the reaction of O-sulfation with a pyridine-sulphur trioxide or trimetylamine-sulphur trioxide adduct or with chlorosulfonic acid.Type: GrantFiled: July 23, 1999Date of Patent: September 11, 2001Assignee: INALCO S.p.A.Inventors: Giorgio Zoppetti, Pasqua Oreste, Giovanni Cipolletti
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Patent number: 6255277Abstract: A method for preventing adverse effects associated with the use of a medical device in a patient by introducing into the patient a device of which at least a portion includes a prophylactic or therapeutic amount of a nitric oxide adduct. The nitric oxide adduct can be present in a matrix coating on a surface of the medical device; can be coated per se on a surface of the medical device; can be directly or indirectly bound to reactive sites on a surface of the medical device; or at least a portion of the medical device can be formed of a material, such as a polymer, which includes the nitric oxide adduct. Also disclosed is a method for preventing adverse effects associated with the use of a medical device in a patient by introducing the device during a medical procedure and before or during said procedure locally administering a nitric oxide adduct to the site of contact of said device with any internal tissue.Type: GrantFiled: May 10, 1995Date of Patent: July 3, 2001Assignees: Brigham and Women's Hospital, NitroMed, Inc.Inventors: Jonathan Stamler, Joseph Loscalzo, John D. Folts
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Patent number: 6245753Abstract: Polysaccharides, which are widely used as an anticoagulation drugs, especially heparin, are clinically administered only by intravenous or subcutaneous injection because of their strong hydrophilicity and high negative charge. Amphiphilic heparin derivatives were synthesized by conjugate to bile acids, sterols, and alkanoic acids, respectively. The hydrophobicity of the heparin derivatives depended on the feed mole ratio of heparin to hydrophobic agent. The heparin derivatives were slightly hydrophobic and exhibited good solubility in a water-acetone solvent, as well as water. The heparin derivatives have a high anticoagulant activity. These slightly hydrophobic heparin derivatives can be absorbed in gastric intestinal tract and can be used as oral dosage form. Also, the heparin derivatives can be used for the surface modification to prevent anticoagulation for medical devices such as extracorporeal devices and implanted devices.Type: GrantFiled: April 27, 1999Date of Patent: June 12, 2001Assignee: Mediplex Corporation, KoreaInventors: Youngro Byun, Yong-Kyu Lee
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Patent number: 6232093Abstract: The invention relates to a simplified process for the extraction of heparin from animal mucosa tissue. The method consists of an enzymatic hydrolysis step of the raw material at ambient temperature, followed by hydrolysis for up to 6 hours at a temperature of 50-75° C. Raise in temperature is obtained by easy means. The digestion mixture can be further incubated while cooling down to ambient temperature. Heparin is recovered from anion exchanger present in the protein hydrolysate.Type: GrantFiled: January 3, 2000Date of Patent: May 15, 2001Assignee: Akzo Nobel N.V.Inventors: Francois Egbert Abraham Van Houdenhoven, Adrianus Lambertus Maria Sanders, Petrus Johannes Josephus Van Zuthpen
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Patent number: 6228998Abstract: A glycosaminoglycan derivative is disclosed wherein a first amino group of a spacer compound (NH2—Y—NH2) is bonded to an aldehyde formed by reducing and partially oxidizing a reducing end sugar of a glycosaminoglycan, via an aminoalkyl bond, or a lactone formed by oxidizing and cyclodehydrating the reducing end sugar of a glycosaminoglycan, via an acid amide bond, and further a hydrocarbon compound having a allyl group at one end and a functional group at another end which is bonded to the second amino group of the spacer compound. This derivative is useful as a substrate in a process for identifying a glycosaminoglycan-degrading enzyme that gives good reproducibility and sensitivity.Type: GrantFiled: July 20, 1995Date of Patent: May 8, 2001Assignee: Seikagaku Kogyo Kabushiki KaishaInventors: Ryu Miura, Sadako Yamagata, Tatsuya Yamagata
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Patent number: 6229009Abstract: A cross-linked copolymer based on at least one non-crosslinked polycarboxylic polysaccharide and at least one second non-crosslinked polycarboxylic polymer which is not a polycarboxylic polysaccharide and a cross-linking agent having at least two amine functions.Type: GrantFiled: February 18, 1999Date of Patent: May 8, 2001Assignee: Societe de Conseils de Recherches et d'Applications Scientifiques (S.C.R.A.S.)Inventors: Nada Lambert, Denis Labarre, Hatem Fessi
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Patent number: 6221855Abstract: The present invention relates to the use of heparan sulfate, or a biological equivalent thereof, to regulate nucleic acid expression, expression of cell receptors, and infection by hepatitis B virus.Type: GrantFiled: March 11, 1999Date of Patent: April 24, 2001Assignee: Wake Forest UniversityInventor: William D. Wagner
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Patent number: 6204254Abstract: A novel group of compounds is disclosed for decorating the surface of synthetic polymeric or tissue derived prostheses to prevent adverse rejection events. The decorating molecules are obtained as derivatives of naturally occurring polysaccharides, derivatized to provide functionally reactive groups at the termini thereof, and the reacting with nucleophilic or other groups on the surface of the prosthesis in a simple one step reaction. Some of these reagents are useful in noncovalent adsorption to polyolefinic or perfluorocarbon based materials. Finally, phospholipids partially substituted with the nonantigenic polysaccharides provide a superior bipolar component for liposome formation.Type: GrantFiled: September 12, 1997Date of Patent: March 20, 2001Assignee: Baxter International, Inc.Inventors: Deanna J. Nelson, Ton That Hai, David E. Pereira, Timothy N. Estep
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Patent number: 6197951Abstract: The invention discloses a starch graft poly(meth)acrylate blast media which is effective in paint removal. The media is superior to a physical blend of the components (i.e., starch and acrylic polymers) and to either a starch polymer or an acrylic polymer used singly. The hardness of the media is between 65-90 Shore D.Type: GrantFiled: September 23, 1999Date of Patent: March 6, 2001Assignee: Archer Daniels Midland CompanyInventor: Ruben P. Lenz
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Patent number: 6197943Abstract: Glycosaminoglycans having high antithrombotic activity in vitro, obtained by various kinds of glycosaminoglycans supersulfated by the preparation of the salt of an organic base of the starting supersaturated glycosaminoglycan, by partial solvolytic desulfation of said salt and N-resulfation of said partially desulfated product.Type: GrantFiled: September 20, 1999Date of Patent: March 6, 2001Assignee: Inalco S.p.A.Inventors: Benito Casu, Annamaria Naggi, Giangiacomo Torri
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Patent number: 6194394Abstract: Coagulation control compositions suitable for use in connection with PT and/or APTT assays are disclosed along with their methods of preparation and methods of use. Preferred coagulation controls comprise plasma and an anticoagulant having activity for enhancing the activity of antithrombin III (ATIII) or of heparin co-factor II (HCII) against thrombin or against a clotting factor selected from the group consisting of factors IXa, Xa and XIa. The anticoagulant is preferably a glycosaminoglycan such as heparin, a heparin derivative or a heparin analog. The anticoagulant is preferably combined with (1) an abnormal plasma (e.g. activated plasma or factor-deficient plasma) and/or (2) a primate plasma (e.g. human plasma), and a non-primate mammalian plasma (e.g. bovine plasma). In the latter case, the non-primate mammalian plasma is preferably present in the coagulation control composition in an amount of not more than about 12% by volume, relative to total volume.Type: GrantFiled: July 1, 1998Date of Patent: February 27, 2001Assignee: Sigma-Aldrich Co.Inventor: Pamela L. Hawkins
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Patent number: 6174999Abstract: A water insoluble, biocompatible composition that is formed by a method which combines, in an aqueous mixture, a polyanionic polysaccharide, a nucleophile, and an activating agent, under conditions sufficient to form the composition. Also, a water insoluble, biocompatible composition that is formed by a method which combines, in an aqueous mixture, a polyanionic polysaccharide, a modifying compound, a nucleophile and an activating agent under conditions sufficient to form the composition.Type: GrantFiled: February 11, 1992Date of Patent: January 16, 2001Assignee: Genzyme CorporationInventors: Robert J. Miller, Xuejian Xu
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Patent number: 6174863Abstract: The invention relates to a carbohydrate derivative having formula I wherein R1 is (1-4C)alkoxy; R2, R3 and R4 are independently (1-4C)alkoxy or OSO3−, the total number of sulfate groups is 4, 5, or 6; and the twisted lines represent bonds either above or below the plane of the six-membered ring to which they are attached; or a pharmaceutically acceptable salt thereof. The compounds of the invention have antithrombotic activity and may be used for treating or preventing thrombosis and for inhibiting smooth muscle cell proliferation.Type: GrantFiled: November 18, 1998Date of Patent: January 16, 2001Assignee: Akzo Nobel N.V.Inventors: Constant Adriaan Anton van Boeckel, Maurice Petitou, Philippe Duchaussoy, Cornelia Maria Dreef-Tromp, Johannes Egbertus Maria Basten
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Patent number: 6162797Abstract: Derivatives of the K5 polysaccharide having anticoagulant activity higher than heparin, obtained by a process including the steps of reacting: with an organic base a solution of K5 polysaccharide N-deacetylated, N-sulfated and epimerized at least to an iduronic acid content of 50% treating with a sulfating agent to obtain the N-resulfation of the possible N-desulfated groups.Type: GrantFiled: November 6, 1998Date of Patent: December 19, 2000Assignee: Inalco S.p.A.Inventors: Giorgio Zoppetti, Pasqua Oreste, Giovanni Cipolletti
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Adsorbent carrier containing immobilized sulfated polysaccharide and ligand for direct hemoperfusion
Patent number: 6156492Abstract: An adsorbent for use in direct hemoperfusion to adsorb and remove harmful substances from blood is prepared by immobilizing a sulfated polysaccharide and/or its salt on a water-insoluble carrier. Preferably, the sulfated polysaccharide has a limiting viscosity of 0.005 to 0.5 dl/g and a sulfur content of 5 to 22% by weight, and is immobilized on the carrier in an amount of 0.02 to 200 mg per ml of carrier. Carrier particles can have an average particle size of 30 to 5000 .mu.m, and preferably 120 to 800 .mu.m. The sulfated polysaccharide inhibits adhesion of hemocytes and exhibits an anticoagulation property to extend blood coagulation time, and has additional functions of adsorbing releasing factors released from hemocytes, adsorbing lipoproteins, and enabling reduction of carrier particle size to about 30 .mu.m. Immobilizing a ligand on the carrier with the sulfated polysaccharide makes it possible to adsorb and remove specific substances in blood that bind to the ligand.Type: GrantFiled: December 18, 1998Date of Patent: December 5, 2000Assignee: Kaneka CorporationInventors: Akira Kobayashi, Satoshi Takata -
Patent number: 6156547Abstract: This invention relates to an apparatus containing specific binary combinations of glycosyltransferases, for the synthesis of specific saccharide compositions such as, for example, oligosaccharides, polysaccharides, glycolipids, and glycopeptides.Type: GrantFiled: November 8, 1996Date of Patent: December 5, 2000Assignee: NEOSE Pharmaceuticals, Inc.Inventor: Stephen Roth
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Patent number: 6150151Abstract: An affinity chromatographic matrix for purification of a biological material is provided having an ionically charged polymeric ligand such as glycoaminoglycan non-covalently bound directly by an ionic bond to an oppositely ionically charged group on a chromatographic matrix. Having the ligand non-covalently bound to the matrix by an ionic bond, allows the ligand to be easily washed off the matrix and replaced for subsequent purifications without having to replace the matrix. A biological material in a crude mixture is purified by non-covalently binding the material to the bound ligand and dissociating the material from the ligand. Matrices that may be used include crosslinked agarose, crosslinked dextran, crosslinked cellulose, crosslinked dextran and bisacrylamide, or matrices based on silica or plastic polymers. The charged group may be a quaternary amine or diethylaminoethyl group.Type: GrantFiled: August 17, 1994Date of Patent: November 21, 2000Assignee: American Cyanamid CompanyInventor: Kiran Manohar Khandke
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Patent number: 6140481Abstract: This invention relates to a process for producing a desulfated polysaccharide, which comprises reacting a sulfated polysaccharide having a saccharide in which a primary hydroxyl group is sulfated, as a constituent sugar, with a silylating agent represented by the following formula (I) ##STR1## wherein R.sup.1 s are the same or different and each represent a hydrogen atom or a halogen atom, R.sup.2 represents a lower alkyl group, and R.sup.3 s are the same or different and each represent a lower alkyl group, an aryl group or a halogen atom,and a desulfated heparin obtained by this production process.Type: GrantFiled: December 27, 1996Date of Patent: October 31, 2000Assignee: Seikagaku CorporationInventors: Saburo Hara, Keiichi Yoshida, Masayuki Ishihara
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Patent number: 6130210Abstract: Heparin derivatives are disclosed that may be used to inhibit formation of metastases. One series of heparin derivatives of the invention are N-acylated with monocarboxylic acids or dicarboxylic acids and have molecular weights from about 1000 Daltons to about 30,000 Daltons. Another series of heparin derivatives of the invention have average molecular weights ranging from about 1000 to 3000 daltons, and are optionally N-acylated with residues from aliphatic monocarboxylic or dicarboxylic acids.Type: GrantFiled: March 31, 1998Date of Patent: October 10, 2000Assignee: Italfarmaco S.p.A.Inventors: Patrizia Caretto, Teresa Sciumbata, Flavio Leoni, Gianni Gromo
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Patent number: 6127347Abstract: A method of treating hypovolemic shock and related shock syndromes by the administration of substantially non-anticoagulant heparinoids without the hemorrhaging problems generally associated with heparin; such syndromes include degradation of the microvascular structure, immune and gastrointestinal tract dysfunction, and multiple organ failure.Type: GrantFiled: February 17, 1995Date of Patent: October 3, 2000Inventors: Irshad H. Chaudry, Kevin R. Holme
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Patent number: 6096525Abstract: A bio-active material such as heparin, urokinase or streptokinase is bonded via a hydrophilic spacer to a functionality on the surface of a hydrophobic, bio-compatible polymeric substrate to provide a coating of the bio-active material on the surface. The substrate surface is preferably the surface of an implantable medical device such as a vascular graft. An amine and/or hydroxyl functionality on the substrate surface is reacted with an isocyanate group at an end of the hydrophilic spacer to bond the spacer to the substrate, and the bio-active material is reacted with an isocyanate group at another end of the spacer to bond the bio-active material to the spacer. Polymeric substrates include expanded polytetrafluoroethylene and polyethylene terephthalate, and the hydroxyl and/or amine functionality may be provided on the substrate surface by plasma glow discharge. A preferred spacer is an isocyanate end-blocked poly(ethylene oxide).Type: GrantFiled: November 26, 1997Date of Patent: August 1, 2000Assignee: Meadox Medicals, Inc.Inventor: Birendra K. Patnaik
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Patent number: 6083933Abstract: Cystitis of the bladder and urinary tract, particularly interstitial cystitis, are treated using effective unit doses of chondroitin sulfate. Further, cystitis patients are screened for their response to a given cystitis treatment using a method in which patients are first challenged with an irritant and then treated with a selected cystitis therapeutic. Candidates for further treatment are identified as those patients who on receiving the selected therapeutic, report relief from at least one symptom elicited with the irritant. Also provided are kits comprising solutions for carrying out this screening method.Type: GrantFiled: April 19, 1999Date of Patent: July 4, 2000Assignee: Stellar International Inc.Inventor: Sungtack Samuel Hahn
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Patent number: 6077683Abstract: A method and medicament for the inhibition of neutrophil elastase and cathepsin G in mammals comprising administering a treatment effective amount of 2-O-desulfated heparin to a mammal in need thereof. The medicament preferably is administered by aerosolization or by intravenous (IV) injection. Preferably, the 2-O-desulfated heparin medicament includes a physiologically acceptable carrier which may be selected from the group consisting of physiologically buffered saline, normal saline, and distilled water. Additionally provided is a method of synthesizing 2-O-desulfated heparin.Type: GrantFiled: June 14, 1999Date of Patent: June 20, 2000Assignee: Carolinas HealthCare SystemInventor: Thomas P. Kennedy
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Patent number: 6075013Abstract: The present invention provides compositions and methods for the treatment of cardiovascular diseases. More particularly, the present invention relates to modifying thrombus formation by administering an agent which, inter alia, is capable of (1) inactivating fluid-phase thrombin and thrombin which is bound either to fibrin in a clot or to some other surface by catalyzing antithrombin; and (2) inhibiting thrombin generation by catalyzing factor Xa inactivation by antithrombin III (ATIII). The compositions and methods of the present invention are particularly usefull for preventing thrombosis in the circuit of cardiac bypass apparatus and in patients undergoing renal dialysis, and for treating patients suffering from or at risk of suffering from thrombus-related cardiovascular conditions, such as unstable angina, acute myocardial infarction (heart attack), cerebrovascular accidents (stroke), pulmonary embolism, deep vein thrombosis, arterial thrombosis, etc.Type: GrantFiled: June 5, 1998Date of Patent: June 13, 2000Assignee: Hamilton Civic Hospitals Research Development Inc.Inventors: Jeffrey I. Weitz, Jack Hirsh
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Patent number: 6051701Abstract: Hyaluronic acid, hyaluronate esters and salts thereof are sulfated such that the number of sulfate groups per monomeric unit is in the range of from 0.5 to 3.5. The sulfated derivatives exhibit anticoagulant and cell adhesion reduction properties, and may be used to prepare biomaterials.Type: GrantFiled: July 30, 1998Date of Patent: April 18, 2000Assignee: Fidia Advanced Biopolymers SRLInventors: Gloria Cialdi, deceased, Agnese Magnani
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Patent number: 6027741Abstract: Hyaluronic acid, hyaluronate esters and salts thereof are sulfated such that the number of sulfate groups per disaccharide unit are in the range of from 0.5 to 3.5. The sulfated derivatives exhibit anticoagulant and cell adhesion reduction properties, and may be used to prepare biomaterials.Type: GrantFiled: February 8, 1996Date of Patent: February 22, 2000Assignee: Fidia Advanced Biopolymers SRLInventors: Gloria Cialdi, deceased, Rolando Barbuci, Agnese Magnani