Abstract: The catalytic active site of Factor VII is modified to produce a compound which effectively interrupts the blood coagulation cascade. The modifications render Factor VIIa substantially unable to activate plasma Factors X or IX. Pharmaceutical compositions of the modified Factor VII are used to treat a variety of coagulation-related disorders.

Abstract: The invention relates to the compounds of formula (I) (SEQ ID NO: I:H-phe-A.sub.1 -Arg-Pro-(Gly).sub.4 -Asn-Gly-Asp-Phe-Glu-Abo-Ile-Pro-Glu-Glu-A.sub.2 -Leu-glu-OH(I)in which A.sub.1 and A.sub.2 are as defined in the description. Medicinal products containing the same are useful as anticoagulants.

Abstract: The use of triterpensaponins, like notoginsenoside R1 (NR1) and/or astragaloside (ASIV) for the production of medicaments for stimulating the fibrinolytic activity and blocking the endotoxin effect, especially for the treatment of patients and animals which suffer from endotoxin shock or to limit the endotoxin shock. Corresponding medicaments are also suitable prophylactive and therapeutic treatment of patients of coronary heart disease, peripheral arterial disease for patients who suffer from angina pectoris and for the prevention of such diseases in healthy persons.

Abstract: A method of treating a patient with a medical device having immobilized heparin on a blood-contacting surface in which the covalently attached heparinized surface is provided with an adsorbed protein which may be activated by the immobilized heparin to block the coagulation of fibrinogen. Antithrombin III is the preferred adsorbed protein. The adsorbed protein is maintained on the immobilized heparin surface until the medical device is placed into contact with the patient's blood. When in contact with the patient's blood, the adsorbed protein will prevent initial thrombin formation at the biomaterial-blood interface. The preadsorption of ATIII is accomplished under conditions advantageous to maximum heparin/ATIII binding. When the preadsorbed surface comes in contact with whole blood, the maximum advantage of prophlactic properties of ATIII/heparin are obtained.

Abstract: A lupus anticoagulant like protein obtained from Agkistrodon halys brevicaudus venom, methods and tests for detecting the presence of lupus anticoagulant in blood and methods of treating antiphospholipid syndrome and thrombotic disorders using the protein are disclosed.

Abstract: The invention presents an antithrombotic resin which is prepared by blending at least one type of antithrombotics, in polyurethane or polyurethane urea polymerized by using at least one type of polyether diol selected from the group consisting of polyol containing a polyoxyethylene group expressed in formula (I).paren open-st.CH.sub.2 CH.sub.2 O.paren close-st..sub.n (I)(where n is a number-average degree of polymerization of 1 to 100) and polyol containing a polyoxyethylene group expressed in formula (II).paren open-st.CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 O.paren close-st..sub.m(II)(where m is a number-average degree of polymerization of 1 to 100). This antithrombotic resin is capable of eluting the antithrombotic in the blood for a long time at high concentration. By using the antithrombotic resin of the invention, antithrombotic tube, antithrombotic film, antithrombotic coat, and others are obtained.

Abstract: The coordinated therapeutic use of L-carnitine, lower alkanoyl L-carnitines or the pharmacologically acceptable salts thereof with resveratrol, resveratrol derivatives or resveratrol-containing natural products is disclosed for producing a medicament for the prophylaxis and treatment of cardiovascular disorders, peripheral vascular diseases and peripheral diabetic neuropathy.

Abstract: Antithrombotic materials and methods are provided for the treatment of thrombotic disorders, in which therapeutically effective amounts of BPI protein products are administered.

Abstract: A tissue factor protein mutant capable of neutralizing the ability of endogenous tissue factor to induce coagulation is provided. A representative tissue factor mutant designated K165A, K166A TF is useful in a method for inhibiting thrombin-induced platelet aggregation in a mammal, either separately or in combination with a thrombolytic agent, an anticoagulant, or a GPII.sub.b III.sub.a inhibitor.

Abstract: A method of inhibiting platelet aggregation with an agent which is able to normalize and enhance platelet reactivity without adversely affecting the bleeding time. The method additionally prevents adrenaline-induced platelet aggregation.

Abstract: The present invention provides a one-stage assay which uses soluble thrombomodulin for directly determining the functional status in plasma of the protein C system. The activity of the protein C system is used to determine the risk of thrombosis in the host individual. Alternatively, the activity of the protein C system is used to determine the presence of a malignant cancer and other pathologies. In another embodiment of the invention, a heparin adsorbent step is added to the assay process which reveals the existence of an additional component in protein C activation, and thus the existence of an additional component in the regulation of blood coagulation.

Abstract: A biocompatible material comprising a substrate and a phospholipid moiety covalently attached thereto in an amount and orientation effective to provide an improved nonthrombogenic surface relative to the substrate without the phospholipid moiety covalently attached thereto is provided. In particularly preferred embodiments, the biocompatible material has the following structure: ##STR1## wherein: R.sup.1 is a (C.sub.1 -C.sub.30)alkyl group; R.sup.2 is a (C.sub.1 -C.sub.30)alkylene group; m is 1-4; n is 1-4; and L is a divalent linking group covalently bonded to the substrate and to the phospholipid moiety.

Abstract: A method for modulating, regulating and/or neutralizing heparin-dependent anticoagulant reactions by administration of lactoferrrin or polypetide fragments thereof. Said method may be used to correct the "heparin-induced" prolongation of blood coagulation and other coagulapathies in cardiopulmonary bypass, cardiac catheterization and hemodialysis patients. Said method may further be used to treat disorders and diseases related to unregulated or unmodulated heparin activity. Said method of treatment is comprised of administration of lactoferrin or fragments thereof comprised of the heparin binding domain(s) of lactoferrin.

Abstract: Process for preventing activation of enzyme systems such as coagulation and activation of complement system or bradykinin system in extracorporeal blood circulation in haemodialysis and similar procedures, by means of sequential anticoagulation, which comprises adding in the first 15 to 30 minutes of haemodialysis or of similar procedure, sodium citrate or nafamostat mesylate, into a dialysis line as anticoagulant, then stopping the addition of citrate or nafomostat mesylate, and adding heparin in the conventional total dose, until the end of dialysis.By using this process, a universal routine haemodialysis or a similar procedure, is made possible without further adaptations according to the kind of patient.

Abstract: A protein isolated from crude extracts of Hirudo medicinalis is disclosed, which strongly inhibits the binding to collagen of platelets and their subsequent activation, which leads to platelet aggregation and thrombus formation. Additionally the protein prevents binding of von Willebrand factor to collagen. Described is a method for isolation and purification of the protein as well as its use for blocking collagen-stimulated platelet aggregation. The new protein (Brandinin) has a molweight of approximately 15 kD, binds to collagen but has no collagen-cleaving activity. The protein is useful in the prophylaxis, prevention and treatment of thrombotic diseaeses and for coating of blood-contacting materials, rendering them thromboresistant.

Abstract: A novel composition, P.sup.1, P.sup.4 -dithio-P.sup.2, P.sup.3 -monochloromethylene 5', 5'"-diadenosine P.sup.1, P.sup.4 -tetraphosphate, is disclosed. The composition is useful as a therapeutic agent for prevention of thrombosis and for modulating a thrombolytic effect in a mammal.

Abstract: An oligosaccharide containing about 20 monosaccharide units is provided. This oligosaccharide designated (M.sub.9 G).sub.2 is a copolymer .beta.-D-(1.fwdarw.4) connected mannuronopyranose units and an .alpha.-L-(1.fwdarw.4) connected guluronic acid unit at a ratio of 9:1. In addition, 40-60% of the carboxylic functional groups are esterified with propanol, 2-propanol or methanol, and substantially all of the C.sub.2 carbons and about 50% of the C.sub.3 positions of the residues are sulfated, such that the resulting compound contains about 7-13% organic sulfur. The compounds are used for the prevention and therapy of thrombosis-induced ischemic vascular diseases of the heart and the central nervous system, for treating acute thrombosis-induced brain infarction and in coronary ischemia-induced angina, and for treating hyperlipoproteinemia and lowering the relative amount of cholesterol.

Abstract: The use of human Protein C for the prevention and treatment of deposition or aggregation of thrombocytes, microparticles of thrombocytes, and leucocytes is described. In addition, an improved method for the extra-corporeal treatment of body fluids is disclosed.

Abstract: The present invention is directed to non-peptidic factor Xa inhibitors which are useful for the treatment of arterial and venous thrombotic occlusive disorders, inflammation, cancer, and neurodegenerative diseases. The factor Xa inhibitors provide compounds of structure: ##STR1## wherein each R.sup.1 is independently one of alkyl, substituted alkyl, cycloalkyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl;each R.sup.2 and R.sup.3 is independently one of hydrogen, alkyl, aryl or arylalkyl;Y is a bond, or is one of --(CH.sub.2).sub.p --, cycloalkyl, aryl or C.sub.2-10 heterocycle; andm, n and p are each independently 1 to 10.

Abstract: The present invention is directed to N-sulfonyl arginine alpha-keto-amide derivatives, their pharmaceutically acceptable salts and compositions thereof which are useful as antithrombotic agents in mammals and also the use of these compounds as antithrombotic agents. Also, disclosed are methods of using these inhibitors in their various embodiments as therapeutic agents for disease states characterized by disorders of the blood coagulation process. Further disclosed are compounds useful as intermediates in the preparation of these compounds.

Abstract: A medicament for the treatment and/or prophylaxis of restenosis and arterial sclerosis after percutaneous transluminal angioplasty, characterized in that the medicament contains batroxobin as an effective component.

Abstract: Methods of preventing or treating thrombotic conditions by administering pharmaceutical compositions containing hyaluronic acid are described.

Abstract: The invention relates to novel polypeptides with antithrombin activity obtainable from extracts of tissues or secretions of leeches of the order Rhynchobdellida, particularly of the species Theromyzon tessulatum. The polypetides have molecular weights of about 14 kD, 9 kD and 3 kD and can be used in pharmaceutical compositions for the treatment of thrombosis related disorders and events.

Abstract: The present invention concerns glycoprotein IIa/IIIb antagonists and platelet aggregation inhibitors of the formula (I): ##STR1## wherein R.sup.1 is aryl which may have one or more suitable substituent(s),R.sup.2 is carboxy(lower)alkyl or protected carboxy(lower)alkyl,R.sup.3 is carboxy or protected carboxy,A.sup.1 is alkylene which may have one or more suitable substituent(s),A.sup.2 is a group of the formula: ##STR2## (wherein R is lower alkyl), or a group of the formula:--NHCH.sub.2 CH.sub.2 CO--,A.sup.3 is lower alkylene which may have one or more suitable substituent(s),l, m and n are each the same or different an integer of 0 or 1,with proviso that A.sup.2 is not a group of the formula:--NHCH.sub.2 CH.sub.2 CO--,when l is an integer of 0.

Abstract: A medical device and a method for its manufacture. The function of the medical device requires exposure of the device to the tissue of a patient. The device has a tissue-exposed portion constructed to release an agent that inhibits adverse reaction to the presence of the device defined by a polymeric surface-layer overlying in a supported manner a polymer defining a reservoir. The reservoir incorporates the agent in a manner that permits substantially free outward release of the agent from the reservoir and the overlying layer defines metering outward passages constructed to control the outward migration of the agent to enable prolonged release of the agent from the surface of the medical device to prevent the adverse reaction due to the presence of the device.

Abstract: This invention relates to physiologically acceptable emulsions of perfluorocarbon ether hydrides having 8 to 12 carbon atoms. These novel emulsions have various medical applications. They are especially useful medically as contrast media for various biological imaging modalities such as nuclear magnetic resonance, .sup.19 F-magnetic resonance imaging, ultrasound, x-ray, and computed tomography, as oxygen transport agents or "artificial bloods" in the treatment of heart attack, stroke, and other vascular obstructions, as adjuvants to coronary angioplasty and in cancer radiation treatment and chemotherapy.

Abstract: This invention relates to novel polyfluorinated alkyl derivatives of certain tripeptides, to the methods for their preparation, the intermediates therefore, to their use in inhibiting thrombin and lung tryptase and in their end-use application as anti-coagulants useful in treating thrombophlebitis and coronary thrombosis and in the treatment of asthma.

Abstract: A biocompatible material comprising a substrate and a phospholipid moiety covalently attached thereto in an amount and orientation effective to provide an improved nonthrombogenic surface relative to the substrate without the phospholipid moiety covalently attached thereto is provided. In particularly preferred embodiments, the biocompatible material has the following structure: ##STR1## wherein: R.sup.1 is a (C.sub.1 -C.sub.30)alkyl group; R.sup.2 is a (C.sub.1 -C.sub.30)alkylene group; m is 1-4; n is 1-4; and L is a divalent linking group covalently bonded to the substrate and to the phospholipid moiety.

Abstract: An anticoagulant for blood contains sodium hydroxide, citric acid and sodium hexametaphosphate. A method of preventing the clotting of blood using the anticoagulant also is disclosed.

Abstract: The invention relates to an agent for the preservation, storage and suspension of cells, especially erythrocytes, which contains a chelating agent for multiply charged metal ions, in addition to other substances known to those skilled in the art, such as, for example, electrolytes and sugars.

Abstract: In a method for the determination of coagulation parameters in sample material via a reaction cascade in which a thrombin-catalyzed formation of a fibrin clot from fibrin monomers occurs and the formation of the fibrin clot is measured, an inhibitor of F XIII is added. By this means the reaction vessel can be used several times for coagulation tests.

Abstract: The present invention relates to a water-soluble conjugate having antithrombin-binding activity comprising a substantially straight-chained organic polymer backbone having at least 30 molecules of sulfated glycosaminoglycans distributed along the polymer backbone, wherein the sulfated glycosaminoglycans are attached to the polymer backbone at a single point of attachment which is not responsible for the antithrombin-binding activity. The present invention also relates to a surface having antithrombin-binding properties prepared with the conjugate and methods of preparing said conjugate and said surface.

Abstract: The present invention comprises a method of alleviating restenosis, post-PTCA or other coronary arterial intervention, and more particularly, to the use of ancrod to prevent restenosis in the coronary arteries.

Abstract: A novel thrombin-inhibitory protein from assassin bugs with a molecular weight of about 12,000 dalton and the N terminus Glu-Gly-Gly-Glu-Pro-Cys-Ala-Cys-Pro-His-Ala-Leu-His-Arg-Val-Cys-Gly-Ser-As p is described. The protein is suitable for controlling diseases.

Abstract: A method of inhibition of cellular and molecular level biological interactions which are dependent on RGD interactions is disclosed. The method comprises administering a compound of the formula IH.sub.2 N--C(.dbd.NH)--NH--CH.sub.2 --A--CH.sub.2 --CO.sub.2 H (I)and pharmaceutically acceptable salts thereof, wherein A is a chain of 9 atoms selected from the group consisting of: ##STR1## wherein each of x, n and m is at least 1; in chains (i) and (ii) n is at most 6; in chains (iii) and (iv) the sum of x+n+m is 5; and the sum of n+m is 4 in chain (v) and 3 in chain (vi).

Abstract: The present invention relates to aqueous depot formulations of hirudin, particularly desulphatohirudin, which are very stable. These formulations contain water, hirudin, and calcium, magnesium, or zinc ions in the form of water insoluble salts, the salts being in a concentration of from 100 mM to 600 mM.

Abstract: Methods for inhibiting the attachment of platelets to a site of an injury are provided. The methods involve administering to a subject that has sustained an injury an effective amount of a platelet binding-site agent. Preferred platelet binding-site agents are platelets that are substantially free of platelet substances contained in lysosomes, dense granules or alpha granules.

Abstract: The present invention provides a method for surface modifying a substrate, such as an implant, to provide the substrate with anticoagulant activity and resistance to the deposition of plasma proteins; and the resulting substrate. The surface of the substrate is modified by first depositing a film of a plasma polymer such as plasma polymerized N-vinyl-2-pyrrolidone or allyl alochol on the surface of the substrate. Optionally, a neutral hydrophilic spacer molecule is attached to the plasma polymer. An anticoagulant, such as heparin, is attatched either directly to the substrate or indirectly to the substrate via attatchment to the spacer molecule, when such spacer molecule is present.

Abstract: A composition and method of treatment of hemoglobinopathies, such as, for example, sickle cell disease and thalassemia, wherein an inventive extract used in such treatment is obtained from alfalfa and other certain plant materials, preferably using a hydroxide base and hexane. In the most preferred embodiment, the plant material is first extracted with 1,1,1-trichloroethane and a hydroxide base, followed by extraction with hexane. The polar acidic compounds present in alfalfa and other plant materials selectively dissolve in the hexane phase and exhibit good antisickling activity in vitro. Further, these active compounds which comprise the inventive extract are effective in vivo by significantly alleviating the many clinical manifestations of sickle cell disease and thalassemia experienced by the affected patients.

Abstract: A medical device and a method for its manufacture. The function of the medical device requires exposure of the device to the tissue of a patient. The device has a tissue-exposed portion constructed to release an agent that inhibits adverse reaction to the presence of the device defined by a polymeric surface-layer overlying in a supported manner a polymer defining a reservoir. The reservoir incorporates the agent in a manner that permits substantially free outward release of the agent from the reservoir and the overlying layer defines metering outward passages constructed to control the outward migration of the agent to enable prolonged release of the agent from the surface of the medical device to prevent the adverse reaction due to the presence of the device.

Abstract: Compounds of formula I relate to the peptide sequence of human fibrogen A.alpha. chain, with modified positions 14 through 17 (P.sub.3 -P.sub.1.sup.1), which may be a useful inhibitor of thrombin. The antithrombin and anticoagulant compounds of this invention, therefore, have therapeutic potential in treatment or prophylaxis of thrombosis and related atherosclerotic diseases. A procedure for the synthesis of peptides according to formula I is also described.

Abstract: A description is given of a one-component tissue adhesive containing, in aqueous solution, fibrinogen, F XIII, a thrombin inhibitor, prothrombin factors, calcium ions and, where appropriate, a plasmin inhibitor and of a process for the production thereof.This adhesive can be reconstituted from a freeze-dried form with water. It can contain all active substances in pasteurized form and is then free of the risk of transmission of hepatitis and HTLV III.

Abstract: Patients having a predisposition for thrombus formation are effectively treated with compositions of acetylsalicylic acid, citric acid, thiamine and/or a zinc salt. The combination of aspirin and citric acid has been found to be significantly more effective in inhibiting platelet aggregability than aspirin alone, and thiamine contributes to the reduction in thrombotic potential by reducing plasma fibrinogen levels. Accordingly, new methods and compositions are disclosed for reducing the thrombotic potential of human or animal subjects, such as in the prophylaxis or treatment of atherosclerosis, vascular surgery patients or other cardiovascular diseases.

Abstract: The present invention encompasses compounds of formula I: ##STR1## and the pharmaceutically acceptable non-toxic salts thereof; wherein R.sub.1 is hydrogen, lower alkyl, alkenyl, alkynyl, cycloalkyl, alkylcycloalkyl, cycloalkylalkyl, or phenylalkyl;R.sub.2 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, alkylcycloalkyl, cycloalkylalkyl, or phenylalkyl; orNR.sub.1 R.sub.2 forms a nitrogen heterocycle; andR.sub.3 is hydrogen, an amino acid or a peptide residue.These compounds may be employed as substrates in assays for determining proteolytic enzyme activity or as enzyme inhibitors. The invention also encompasses methods for determining proteolytic enzyme activity using the compounds of formula I.

Abstract: Compounds of the formula ##STR1## wherein L, M, R, T and X are set forth in the description, as well as hydrates or solvates thereof, which inhibit thrombin-induced platelet aggregation and clotting of fibrinogen in plasma, are described. The compounds of formula I are prepared by amidination or, depending on whether L is NH or O, by amide formation or esterification.

Abstract: Asp-Pro-Arg alpha-keto-amide derivatives, and their pharmaceutically acceptable salts and compositions, for use as antithrombotic agents in mammals are disclosed. The method of use of these inhibitor compounds for treatment or prevention of conditions of abnormal thrombus formation in mammals is also disclosed. Further disclosed are alpha-hydroxy amide compounds used as intermediates in the preparation of the keto-amide compounds.

Abstract: A restenosis inhibiting agent for the treatment or prevention of restenosis after percutaneous transluminal coronary angioplasty which comprises a pharmaceutically effective amount of a compound of the following general formula or a pharmaceutically acceptable salt thereof as an active ingredient: ##STR1## wherein R is an imidazolyl group, a thiazolyl group or a pyridyl group, n is an integer of 1 or 2, and m is an integer of 1 to 4.

Abstract: Non-peptidic RXD analogues are provided that inhibit biological cellular and molecular interactions which are dependent on RXD recognition, wherein X is one of the amino acid residues G, E, Y, A or F. In particular, RGD surrogates are provided having no sequence of .alpha.-natural amino acids and comprising a guanidino and a carboxyl terminal groups spaced by a chain of 11 atoms, at least 5 of which are carbon atoms. The compounds inhibit cell adhesion and are useful for the treatment of several pathological disorders, e.g., thrombosis, autoimmune diseases, metastasis, allergy, host-graft reactions and inhibition of scar tissue formation.

Abstract: An anti-thrombogenic substance is immobilized on a base of a medical device to impart anti-thrombogenic properties to the medical device. The method comprises the steps of applying a photo-reactive azide derivative macromolecular material to a base to form a bonding layer, coating the bonding layer with a macromolecular layer composed of a water-soluble photo-crosslinking macromolecular material containing the anti-thrombogenic substance, and irradiating the base with ultraviolet light with the bonding layer and the macromolecular layer formed thereon to develop inter-molecular covalent bonding in the bonding layer. The macromolecular layer containing the anti-thrombogenic substance is thus fixed onto the base. Concurrently, the anti-thrombogenic substance is immobilized in the macromolecular layer which is crosslinked. The azide derivative can be poly-m-azidostyrene, copolymers, of poly-m-aziodstyrene with styrene and copolymers of poly-m-azidostyrene with methyl methacrylate.

Abstract: Recombinant DNA expression vectors encoding a peptide which inhibits binding of von Willebrand factor to platelet membrane glycoprotein Ib, said vector including a nucleotide sequence encoding the amino acid sequence from HIS.sup.1 to LEU.sup.610, inclusive, of the amino terminal region of platelet membrane glycoprotein Ib.alpha.