Abstract: A compound of formula I or a pharmaceutically acceptable salt thereof in which R1 and R2 are independently H or methyl (for example N,N-dimethyl-1-[1-(4-chlorophenyl) cyclobutyl]-3-methylbutyl amine hydrochloride optionally in the form of its monohydrate) is used for decreasing platelet adhesiveness.

Abstract: The invention is a fibrin glue that avoids the use of fibrinogen and thus eliminates the need for premixing and premature clot formation. The fibrin glue of the invention comprises thrombin, thromboplastin and calcium and may have clotting Factors, VII, IX and X, and the like. The invention also comprises a biosealant for use with the fibrin glue without fibrinogen or for use alone. The biosealant is a two component mixture of gelatin/resorcinol and glyoxal/glutaraldehyde/4-(p-maleimidophenyl) butyric acid. The two components are mixed on use.

Abstract: A method is provided for elevating the stability of peptides containing the sequence -Asp-Gly- or -Asn-Gly- by preventing these sequences from changing into succinimide compounds or &bgr;-transition compounds. The method comprises adding an organic acid to a solution of peptides containing these sequences to bring the pH value of the solution to a pH of between 5 and 6.5 followed by freeze-drying. In one embodiment, sucrose or mannitol is added together with the organic acid. Freeze-dried medicinal compositions obtained by using the method have excellent stability. In one embodiment of the invention, compositions produced by the method are provided and comprise hirudin or hirudin variants.

Abstract: 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.

Abstract: A method for inhibiting the effects of cardiovascular disorders and diseases in a host susceptible to or suffering from a cardiovascular disorder or disease comprising administering to the host, a therapeutically effective amount of a first substance characterized as simulating a heparin-like effect, and a therapeutically effective amount of a second substance characterized as simulating an arginine-like effect; and a formulation for use in treating a host susceptible to or suffering from the effects of cardiovascular disorders and diseases comprising a therapeutically effective amount of a first substance characterized as simulating a heparin-like effect, and a second substance characterized an simulating an arginine-like effect, an described.

Abstract: An adhesive for tissue capable of uniformly forming a high concentration of fibrin so as to provide a high closing effect is disclosed. The adhesive for tissue comprises a fibrinogen solution and a thrombin solution which solutions are separated from each other. The adhesive is to be mixed and spray coated together with a sterile gas and has a volume ratio of the fibrinogen solution to the thrombin solution of about 2:1 to 10:1. This adhesive is to be sprayed together with a sterile gas for the adhesion or closing of living tissue of a human being or animal.

Abstract: The present invention provides a blood-compatible composition containing an ionic complex consisting of an organic cationic compound and heparin or a derivative thereof, wherein the organic cationic compound is an ammonium or a phosophonium bound with four aliphatic alkyl groups, the four aliphatic alkyl groups having a total number of carbon atoms of 24 to 32, and has at least 2 alkyl groups having not less than 10 carbon atoms. A medical device capable of long-term sustention of antithrombogenicity can be produced by coating the surface of the medical device with the composition.

Abstract: 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.

Abstract: It has been found that agents which inhibit the interaction between the band 3 protein and its ligand (hereafter sometimes referred to as “interaction inhibitors” or “inhibitors”), CD36/thrombospondin, can also be used to enhance thrombolysis. The inhibitors can be peptides which contain sequences present in exofacial loops of the band 3 protein, or can be non-natural, D-isomer forms of the same sequences, or can be peptides, peptidomimetics, or non-peptidic molecules which interfere with band 3 protein—ligand interactions. One preferred group of such inhibitors comprises peptides characterized by the sequence motif Z2Z3Z2UX−UUUX− (SEQ ID NO:44), wherein Z2 represents a hydrophobic residue, U represents unobstructive residues, Z3 is either Z2 or an unobstructive residue and X− represents negatively charged residues.

Abstract: The invention is a fibrin glue that avoids the use of fibrinogen and thus eliminates the need for premixing and premature clot formation. The fibrin glue of the invention comprises thrombin, thromboplastin and calcium and may have clotting Factors, VII, IX and X, and the like. The invention also comprises a biosealant for use with the fibrin glue without fibrinogen or for use alone. The biosealant is a two component mixture of gelatin/resorcinol and glyoxal/glutaraldehyde/4-(p-maleimidophenyl) butyric acid. The two components are mixed on use.

Abstract: There is disclosed a pharmaceutical preparation for treating blood coagulation disorders which comprises purified prothrombinase factors, in particular purified prothrombin and optionally purified factor Xa as active component.

Abstract: Azole derivatives of formula (I): ##STR1## are disclosed as useful in treating platelet-mediated thrombotic disorders.

Abstract: This invention relates to peptide aldehyde derivatives of formula (I): D-Xaa-Pro-Arg-H, wherein Xaa represent a 2-cycloheptyl-2-hydroxyacetyl or 2-cyclopentyl-2-hydroxyacetyl group, Pro represents an L-prolyl residue and Arg represents an L-arginyl residue, their acid-additon salts formed with an organic or inorganic acid and pharmaceutical compositions containing the same. The compounds of formula (I) of the invention have therapeutic, particularly anticoagulant, antiplatelet and antithrombotic properties.

Abstract: Compounds of this invention have the formula:X--(CH.sub.2).sub.n --C(O)NH--A--C(COOR.sup.5)R.sup.3 R.sup.4or a pharmaceutically acceptable salt thereof, e.g. ##STR1## which are useful for inhibiting fibrinogen binding to blood platelets, thereby inhibiting platelet aggregation.

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: This invention relates to the diagnosis of congenital defects in the anticoagulant protein C system. Methods that are disclosed are based on the detection of mutations at the cleavage sites of coagulation factors that are under control of activated protein C (APC). Diagnostic tests include analysis of the APC-cleavage sites of factor V and factor VIII, by using specific primers to amplify selectively from RNA, cDNA derived from RNA or chromosomal DNA, parts of factor V and factor VIII that contain cleavage sites for APC. Methods that monitor the presence of mutations at the cleavage sites for APC and their utility in the diagnosis of thrombo-embolic disease are disclosed. The invention further discloses methods for correcting the defects detected according to the invention, as well as novel therapeutic agents which can be used in the treatment of bleeding disorders, which agents are based on the "defective" Factor V and Factor VIII proteins leading to the thrombotic disorders described hereinabove.

Abstract: The invention is drawn to anti-thrombin proteins from the salivary glands of the species, Simulium. Methods for recombinant production of the protein as well as biomedical uses are provided.

Abstract: The present invention relates generally to protein molecules and to derivatives, homologues, analogues and mimetics thereof capable of inducing or facilitating inhibition of blood clot formation and more particularly platelet aggregation. The present invention also contemplates genetic sequences encoding said protein molecules and derivatives, homologues, analogues and mimetics thereof. The molecules of the present invention are useful inter alia in a range of therapeutic and prophylactic applications.

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: A method and compositions for reducing post-surgical adhesion formation/reformation in mammals following surgical injury to a body cavity or organs situated therein. The aqueous compositions comprising pentoxifylline and a polyoxyalkylene block copolymer are applied to the injured areas subsequent to surgical injury.

Abstract: Substances comprising disaccharides and substances comprising carboxylated and/or sulfated oligosaccharides in substantially purified form, and methods of using same, are disclosed for the regulation of cytokine activity in a host. For instance, the secretion of active Tumor Necrosis Factor Alpha (TNF-.alpha.) can be either inhibited or augmented selectively by administration to the host of an effective amount of a substance of the invention. Thus, the present invention also relates to pharmaceutical compositions and their use for the prevention and/or treatment of pathological processes involving the induction of active cytokine secretion, such as TNF-.alpha.. The invention also relates to the initiation of a desirable immune system-related response by the host to the presence of activators, including pathogens. The substances and pharmaceutical compositions of the present invention may be administered daily, at very low effective doses, typically below 0.

Abstract: The specification describes a pharmaceutical combination consisting of dipyridamole or mopidamol and acetylsalicylic acid or the physiologically acceptable salts thereof, processes for preparing this pharmaceutical combination and the use thereof for the controlled prevention of clot formation.

Abstract: The present invention relates to methods for inhibiting the complement pathway in a mammal comprising administering an effective dose of a composition comprising an active ingredient selected from the group consisting of isolated sea cucumber (Phylum Echinodermata, Class Holothuroidea) body wall, isolated sea cucumber epithelial layer, isolated sea cucumber flower, sea cucumber fucosylated chondroitin sulfate, combinations thereof, active derivatives thereof or combinations of active derivatives thereof.

Abstract: An adhesive for tissue capable of uniformly forming a high concentration of fibrin so as to provide a high closing effect is disclosed. The adhesive for tissue comprises a fibrinogen solution and a thrombin solution which solutions are separated from each other. The adhesive is to be mixed and spray coated together with a sterile gas and has a volume ratio of the fibrinogen solution to the thrombin solution of about 2:1 to 10:1. This adhesive is to be sprayed together with a sterile gas for the adhesion or closing of living tissue of a human being or animal.

Abstract: The compound of formula ##STR1## is useful as chain extender in the preparation of polymers, in particular of linear and cross-linkable, heparinizable, biocompatible polymers.

Abstract: Methods of using relaxin (RLX), a peptide hormone of the insulin family, which has been found to produce effects on the walls of blood vessels, on blood clotting and on blood lipids and electrolytes, per se, and through the stimulation of the synthesis and release of the two powerful substances: nitric oxide (NO) and atrial natriuretic peptide (ANP), are contemplated whereby RLX is administered to a patient for increasing blood flow, producing dilation of the arteries, influencing blood clotting and fibrinolysis, reducing blood lipids, inducing reduction of blood osmolarity and sodium concentration, and through NO for inhibiting release of histamine from mast cells. RLX is accordingly used as a therapeutic agent in methods for treating arteriosclerosis and vascular diseases, ischemia and thrombosis, hypertension and pregnancy's gestosis, and other diseases, or allergic and inflammatory disorders as dysfunctions in fluid and electrolyte balance.

Abstract: The present invention relates to peptide of the amino acid sequence of formula (I):82 85 90 Glu Thr His Lys Asp Asp Gln Leu Ile 95 100 Cys Val Asn Glu Asn Gly Gly Cys Glu Gln 105 110 Tyr Cys Ser Asp His Thr Gly Thr Lys Arg 115 120 Ser Cys Arg Cys His Glu Gly Tyr Ser Leu 125 128 Leu Ala Asp Gly Val Ser Cys Thr (SEQ ID NO. 1)and functional equivalents thereof in which amino acids in the above stated sequence are modified or absent and wherein at least one of the cysteine residues may be blocked or replaced and wherein any cysteine residues which remain unblocked or unreplaced may be present in a disulphide bonded state. The invention also includes slats and derivatives of said peptides. The peptides and their salts and derivatives are useful in the treatment of blood clotting disorders.

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: Disclosed are methods of treating, inhibiting or preventing vascular thrombosis or arterial restenosis in a mammal. The disclosed methods include causing the mammal to inhale a therapeutically-effective concentration of gaseous nitric oxide (NO). Also disclosed are methods that include the administration of the following types of agents in conjunction with inhaled nitric oxide: compounds that potentiate the beneficial effects of inhaled nitric oxide, and antithrombotic agents that complement or supplement the beneficial effects of inhaled nitric oxide.

Abstract: A polypeptide which is capable of inhibiting binding of von Willebrand factor (vWF) to platelets and comprising an amino acid sequence that corresponds to the amino acid sequence of that fragment of mature von Willebrand factor subunit having its amino terminus at about Cys.sup.509 and its carboxy terminus at about Cys.sup.695, said polypeptide comprising optionally a second and/or a third domain, the second domain corresponding to the amino acid sequence of that fragment of mature vWF subunit having its amino terminus at about Thr.sup.450 and its carboxy terminus at about Tyr.sup.508, or a subfragment or combination of subfragments thereof, and a third domain corresponding to the amino acid sequence of that fragment of mature vWF subunit having its amino terminus at about Asp.sup.696 and its carboxy terminus at about Gly.sup.

Abstract: Topically applicable pharmaceutical/therapeutic alcoholic solution compositions, well suited for percutaneous/transdermal antithrombotic therapy, comprise an effective antithrombotic amount of acetylsalicylic acid ("ASA") or salt thereof, formulated into primary alcohol (e.g., isopropanol) and secondary ester (e.g., isopropyl myristate) solvents therefor, optionally in the presence of penetration enhancers and/or ASA hydrolysis inhibitors.

Abstract: Methods for binding heparin to biological or synthetic materials which are to be implanted within a mammalian body. In instances where connective tissue proteins or other components of the material having adequate carboxyl groups present thereon, the method comprises a) contacting the material with a carboxyl-activating agent, b) contacting the material with a polyamine compound to form amide-bound polyarnine side chains at the sites of the previously activated carboxyl groups, and c) contacting the material with heparin such that heparin will become bound to the amino groups on the polyamine side chains.

Abstract: A method for increasing the placental blood flow, which comprises administering a human-originated antithrombin-III. The human-originated antithrombin-III increases the placental blood flow in mammals and particularly improves intrauterine growth retardation caused by a decreased blood flow. The method is highly safe to the mother and fetus, since it uses human-originated AT-III as an active ingredient, thereby enabling effective and safe treatment of intrauterine growth retardation (IUGR) and the like.

Abstract: The invention provides a process of manufacture of a recombinant protein called Asp-Pallidipin. Asp-Pallidipin inhibits the collagen-induced platelet aggregation of mammalian platelets. The Asp-Pallidipin comprises(i) a protein (Pallidipin) selected from the group of Pallidipin proteins, and(ii) the amino acid aspartic acid,wherein the aspartic acid is connected by a peptide bond with the N-terminal end of Pallidipin.

Abstract: A transdermal therapeutic system (TTS) comprises compounds releasing carbon monoxide in organisms to increase the CO-concentration in the organism.

Abstract: A potent serine protease inhibitor capable of inhibiting Factor VIIa, Factor XIa, plasma kallikrein, or plasmin is provided. The inhibitor is provided in a pharmaceutical composition for treatment of diseases where inhibition of Factor VIIa, Factor XIa, plasma kallikrein, or plasmin is indicated.

Abstract: The invention concerns fractions from echinoderms of the class Holothuroidea (sea cucumber) that can be used directly as active therapeutic agents or as raw materials in producing biologically active derivatives thereof. The fractions can be used alone or in combination and are derived from a) the epithelial layer, free of muscle and collagenous tissues, b) the isolated flower, or c) the whole body wall substantially free muscle, viscera and flower. The invention also concerns processes for obtaining these fractions that involve the use of thermal/mechanical and/or enzymatic means.

Abstract: A microcapsule contains a pharmaceutically effective amorphous water-soluble 2-piperazinone-1-acetic acid compound or salt thereof and a polymer binder and a method of preparing said microcapsule. The microcapsule is produced by dispersing in an aqueous phase a dispersion of the amorphous water-soluble 2-piperazinone-1-acetic acid compound or salt thereof in a solution of a polymer in an organic solvent to give an s/o/w type emulsion and subjecting the emulsion to in-water drying. The sustained-release microcapsule entraps 2-piperazinone-1-acetic acid compound or the salt thereof, as a drug, in high concentration, and in reducing the initial release of the drug, thereby reducing undesirable side effects of the drug.

Abstract: The invention relates to carbohydrate derivatives having the formula I, ##STR1## wherein R.sup.1 is H or CH.sub.2 OSO.sub.3.sup.-, R.sup.2 and R.sup.3 are independently H, (1-6C)alkyl or SO.sub.3.sup.- ; R.sup.4 is OSO.sub.3.sup.- or NHSO.sub.3.sup.- ; n is 0 or 1; p is 1 or 2; or a pharmaceutically acceptable salt thereof The compounds of the invention have antithrombotic activity and may be used for inhibiting smooth muscle cell proliferation.

Abstract: The present invention is directed to novel 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, described are methods of using these inhibitors as inhibitors of coagulation proteases and as therapeutic agents for disease states characterized by abnormal thrombus formation and/or disorders of the blood coagulation process. Further described herein are compounds useful as intermediates in the preparation of these compounds.

Abstract: A potent serine protease inhibitor capable of inhibiting Factor VIIa, Factor XIa, plasma kallikrein, or plasmin is provided. The inhibitor is provided in a pharmaceutical composition for treatment of diseases where inhibition of Factor VIIa, Factor XIa, plasma kallikrein, or plasmin is indicated.

Abstract: A multimer peptide from a snake venom has an activity to inhibit binding between von Willebrand factor and platelets. The multimer peptide is used to obtain a single strand peptide which does not substantially cause decrease in platelets at a minimum dose for exhibiting the activity in vivo. The single strand peptide is obtained by allowing the multimer peptide to exist together with a protein-denaturing agent, and glutathione and/or cysteine, and thereby disconnecting disulfide bonds between peptide chains for constituting the multimer peptide while substantially preserving disulfide bonds within the peptide chains. Alternatively, the single strand peptide, a mutant thereof, or a part thereof is produced by genetic engineering techniques by using genes coding for them.

Abstract: This invention relates to mixtures of sulfated oligosaccharides which possess antithrombotic properties and are useful for the treatment and prevention of venous and arterial thrombosis, prevention of arterial thrombotic accidents, and in the prevention of thrombosis in surgical equipment, to pharmaceutical compositions including such mixtures, to processes for preparing such mixtures, and to the use of such mixtures in the prevention of thrombosis in surgical equipment.

Abstract: This invention relates to novel propenone oxime ethers, methods of preparing them and pharmaceutical compositions containing them. The compounds have the formula: ##STR1## wherein R.sup.1 is H, or glucuronide;R.sup.2 and R.sup.3 are independently H or methyl;R.sup.4 is 0, or glucuronide, andn is 0 or 1, provided that when R.sup.1 is H, n is 1.

Abstract: A pharmaceutical preparation contains protein C and a thrombolytically active substance that does not activate protein C. This preparation prevents reocclusion usually occurring in the course of thrombolysis therapy.

Abstract: A novel thrombin-inhibitory protein from ticks with a molecular weight of about 8000 Dalton and the N terminus Leu-Asn-Val-Leu-Cys-Asn-Asn-Pro-His-Thr-Ala-Asp-Cys-Asn-Asn-Asp-Ala-Gln-Va l-Asp is described. The protein is suitable for controlling diseases.

Abstract: The present invention relates to the single-chain thrombomodulin ("TM") and analogs thereof that are not susceptible to cleavage by proteases and retain the biological activity of thrombomodulin, as well as methods of use in, for example, antithrombotic therapy. Novel proteins, nucleic acid gene sequences, pharmaceuticals and methods of inhibiting thrombotic activity are disclosed.

Abstract: Methods of preventing tissue damage associated with decreased blood flow in a human by administering AICA riboside or a prodrug thereof in an amount which provides a blood plasma concentration of between 1 .mu.g/ml and 20 .mu.g/ml of AICA riboside for a time sufficient to reduce the risk of said tissue damage in said human. Methods of preventing an adverse clinical outcome, such as an adverse cardiovascular and/or cerebrovascular event, in a patient at risk for such outcome by administering AICA riboside or a prodrug thereof in an amount which provides a blood plasma concentration of between 1 .mu.g/ml and 20 .mu.g/ml of AICA riboside for a time sufficient to reduce the risk for said patient.

Abstract: The prevention and therapy of pulmonary embolism with pharmaceutical compositions containing low molecular weight dermatan sulfate is described. These pharmaceutical compositions are administered by subcutaneous, intramuscular or intravenous route at a daily dosage between 200 and 3000 mgs of active principle. The low molecular weight dermatan sulfate preferred in carrying out the invention has an average molecular weight equal to 5500.+-.1100 Daltons and is obtained by depolymerization of the dermatan sulfate of natural origin in the presence of hydrogen peroxide and cupric ions.

Abstract: Compounds of the formula: ##STR1## wherein R.sup.1 --R.sup.4, R.sup.7 --R.sup.8, R.sup.a, R.sup.b, R.sup.c, Y, Z, n and m are set forth in the specification, as well as hydrates, solvates or pharmaceutically acceptable salts thereof, that inhibit a number of proteolytic enzymes are described. Also described are methods for preparing the compounds of Formula I.