Abstract: A multiple coagulation test system and method for determining an appropriate coagulation promoting substance for administration to a patient as a therapy for improving clotting function in said patient has at least three sample wells. One of the wells is for testing a baseline clotting indicator time of a patient's blood to serve as a control sample. Each of the other wells are for testing clotting indicator times of different coagulation promoting substances when mixed with the patient's blood. The coagulation promoting substances are agents or combination of agents capable of improving clotting function in the patient. An appropriate therapy for improving clotting function in the patient is determined by comparison of the baseline control clotting indicator time with the clotting indicator times of the coagulation promoting substances mixed with the patient's blood. Generally, the agent giving the lowest clotting indicator time is selected as an appropriate treatment for reducing hemorrhaging begun.

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: A process for forming a surface modification on a polymer substrate and polymer substrates having such surface modifications. The process comprises the steps of absorbing a swelling monomer into the polymer substrate for a period of time in order to swell the polymer substrate; removing the swollen polymer from the swelling monomer; transferring the swollen polymer to a reaction mixture containing at least one functional monomer; polymerizing the functional monomer in the reaction mixture containing the swollen polymer substrate for a period of time; and removing the polymer from the reaction mixture. Because the surface modification produced by the process is a surface interpenetrating polymer network, the process is not sensitive to the reactive groups located on the surface of the polymer substrate. Further, the surface interpenetrating network bonds to the polymer substrate through caternary connections or other forms of chain entanglement and thus is quite stable.

Abstract: A method of treatment for human patients with an acquired hypercoagulable state or acquired protein C deficiency associated with sepsis, purpura fulminans, meningococcal sepsis, bone marrow and other transplantations, severe burns, pregnancy, major surgery, severe trauma, or ARDS, which comprises administering activated protein C providing a highly selective therapeutic agent with a low potential for causing bleeding complications.

Abstract: Compositions useful in the delivery of active agents are provided. These delivery compositions include (a) an active agent; and either (b)(1) a carrier of (i) at least one amino acid and (ii) at least one diketopiperazine or (b)(2) at least one mono-N-substituted, di-N-substituted, or unsubstituted diketopiperazine. Methods for preparing these compositions and administering these compositions are also provided.

Abstract: Disclosed is a medicinal composition, which comprises a peptide as an effective ingredient and as bases, epsilon aminocaproic acid or tranexamic acid and an ethylene oxide-propylene oxide block copolymer represented by the following formula (I):HO(C.sub.2 H.sub.4 O).sub.a --(C.sub.3 H.sub.6 O).sub.b --(C.sub.2 H.sub.4 O).sub.c H (I)wherein a, b and c stand for integers of 1 or greater, respectively. According to this medicinal composition, the peptide can be absorbed at a high rate through the mucosa and further, its pharmacological effects are prolonged over for a long time.

Abstract: Methods are provided for the treatment of a host suffering from a cellular proliferative disease through administration of a chemotherapeutic agent in conjunction with a cell membrane permeant. Optionally, the cell membrane permeant and/or chemotherapeutic agent will be present in a pharmaceutically acceptable vehicle capable of acting as a depot. In the subject methods, the chemotherapeutic agent and membrane permeant are administered at least proximal to a target site of the host. Administration of chemotherapeutic agents in accordance with the subject methods results in improved efficacy of, and/or decreased host toxicity to, the intralesionally administered chemotherapeutic agent.

Abstract: The catalytic active site of Factor VII is modified to produce a compound which effectively interrupts the blood coagulation cascade. The modification renders 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: This invention relates to novel cyclic compounds linked by a heterocyclic ring system, which are useful as antagonists of the platelet glycoprotein IIb/IIIa complex, to pharmaceutical compositions containing such cyclic compounds, and to methods of using these compounds for the inhibition of platelet aggregation. A representative compound of the invention is cyclo-(D-Val-N(Me)Arg-Gly-Asp-?5-aminomethyl!-2-furoate).

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: Compositions useful in the delivery of active agents are provided. These delivery compositions include (a) an active agent; and either (b)(1) a carrier of (i) at least one amino acid and (ii) at least one diketopiperazine or (b)(2) at least one mono-N-substituted, di-N-substituted, or unsubstituted diketopiperazine. Methods for preparing these compositions and administering these compositions are also provided.

Abstract: A method of making a platelet releasate product is disclosed involving performing an assay on a platelet releasate sample for a component of the releasate and forming platelet releasate product by comparing the assay results to a predetermined range of amounts of the component to be contained in the product. A method of treatment of tissue is disclosed involving the topical application of such product.

Abstract: A treatment of ischemia and the attendant reperfusion injury entails the administration plasmin and plasmin-forming proteins, including lys-plasminogen and similar substances. Lys-plasminogen, which can be obtained from the proteolytic cleavage of glu-plasminogen, has been found to have a protective effect on tissue that has been injured by ischemic conditions. The administration of lys-plasminogen alone, in a dosage of about 10-1000 caseinolytic units/kg, can be used to treat subjects during the time of reperfusion and after reperfusion has already occurred. Lys-plasminogen also can be administered in conjunction with clot lysis therapies, such as those that employ tissue plasminogen activator and the like. Lys-plasminogen can also lessen cerebral edema which results from cerebral ischemia.

Abstract: A liquid preparation of antithrombin-III (AT-III), comprising an AT-III and an organic acid, a salt thereof, a sugar sulfate or a surfactant as a stabilizer, and a liquid preparation of AT-III, having a pH of 9-10. The preparation of the present invention is stable after long-term preservation and poses no clinical problems in terms of pharmacological effects and safety. The preparation is more advantageous than lyophilized preparations in that it does not require dissolution in injectable distilled water and can be used easily. Accordingly, the preparation is clinically very useful.

Abstract: Stabilized and activated Factor VIII is used as a therapeutic agent to treat patients with a Factor VIII deficiency. This includes hemophilia A patients as well as patients with Factor VIII inhibitors which block the hemostatic activity of Factor VIII. The stabilized and activated Factor VIII is also prepared in a therapeutic composition with a therapeutically acceptable adjuvant.

Abstract: A treatment of ischemia and the attendant reperfusion injury entails the administration plasmin and plasmin-forming proteins, including lys-plasminogen and similar substances. Lys-plasminogen, which can be obtained from the proteolytic cleavage of glu-plasminogen, has been found to have a protective effect on tissue that has been injured by ischemic conditions. The administration of lys-plasminogen can used to treat subjects during the time of reperfusion and after reperfusion has already occurred. Lys-plasminogen also can be administered in conjunction with clot lysis therapies, such as those that employ tissue plasminogen activator and the like.

Abstract: A flowable demineralized bone powder composition is provided for use in surgical bone repair.

Abstract: Blood coagulation is accelerated by contacting blood with an accelerator of hydrolase activity. The activation of the precursors of serine protease including Factor XII and the enzyme activity of serine protease is accelerated. The accelerator is a metal complex containing a ligand which is a cyclic compound having a five- or six-membered ring containing carbonyl groups adjacent to each other. Examples of such ligands are oxidized alkylgallate, partially or totally oxidized ellagic acid, partially or completely oxidized 1,4- di(3,4-dihydroxyphenyl) 2,3-dimethylbutane, 1,2,3-triketohydroindene and isatin. The metal of the complex is preferably Fe, Co, Ni, or Al. The complex may be combined with a hydrolase as a co-accelerator of coagulation, an organic acid having an amino salt and/or a quaternary nitrogen or an antifibrinolysis agent and/or an anti-plasmin agent.

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: A process and apparatus for one-step preparation of the fibrinogen component of an adhesive is described. The fibrinogen is precipitated directly from plasma using polyethylene glycol. This permits preparation of autologous fibrinogen from the patient during surgery which can be combined with calcium, ion and thrombin and used as an adhesive.

Abstract: A multiple coagulation test device has a plurality of tubes, each tube having associated coagulation detection means, and containing a treatment dosage of a coagulation enhancing agent. Whole blood samples are placed in the tubes which are mixed and warmed to 37.degree. C., with the time to coagulation determined. The agent giving the lowest clotting time is selected as the most effective treatment for reducing hemorrhaging within a few minutes and the selected treatment begun. Utilizing the inventive device eliminates the need to use a multiple agent approach, by identifying the most effective course of action.

Abstract: A method of inhibiting oxytocin from acting at its receptor site by administering oxytocin receptor antagonist compounds of the formula ##STR1## wherein X is oxygen or sulfur; Y is hydrogen or lower alkyl; R.sup.

Abstract: A shaped piece of swollen demineralized bone which can also be plasticized is provided for use in surgical bone repair.

Abstract: A method for the treatment of bone lesions or bone deficiencies in a living mammal comprising administering a composition comprising an inorganic phase and an organic phase wherein the inorganic phase comprises a porous particulate TCP ceramic or a nonporous or microporous particulate HAP ceramic or a mixture of porous particulate TCP ceramic and nonporous or microporous particulate HAP ceramic, wherein the organic phase comprises a purified hydrated collagen product which is mixed with and forms a continuous or substantially continuous surface coating over said inorganic phase(s) and a hydrated collagen-demineralized bone product which is mixed with and forms a substantially continuous surface coating over said purified hydrated collagen product surface coating or the organic phase comprises a hydrated collagen-demineralized bone product which is mixed with and forms a continuous or substantially continuous surface coating over said inorganic phase and a purified hydrated collagen product which is mixed with

Abstract: A method for treating patients suffering from bleeding disorders not caused by clotting factor defects or clotting factor inhibitors, as well as a novel composition for use in treating bleeding disorders as disclosed. The method includes administering to a patient a composition comprising an effective haemostatic amount of factor VIIa, and is particularly effective in treating patients suffering from thrombocytopenia and von Willebrand's disease, as well as other platelet disorders. A composition suitable for use in treating such bleeding disorders comprises purified factor VIIa in a concentration of at least 25 .mu.g/ ml.

Abstract: A stable thrombin composition for oral administration having an excellent solubility is prepared with thrombin as a hemostatic ingredient, gelatin, albumin and glycine as a stabilizer and sucrose and/or sugar alcohol as a carrier. The thrombin composition is effective for the treatment of hemorrhage in the upper alimentary canal, is stable even at room temperature conditions for long periods of time, has excellent solubility and can be orally administered in a simple manner.

Abstract: Disclosed is a method for purifying a fibroblast growth factor (FGF) protein with use of a crosslinked polysaccharide sulfate. The FGF protein is preferable a mutein, in which at least one human basic FGF-constituent amino acid is substituted by at least one different amino acid. The crosslinked polysaccharide sulfate is preferably a crosslinked cellulose sulfate, a crosslinked agarose sulfate or a crosslinked dextran sulfate. According to the present invention, FGF can be highly purified on a commercial scale, and therefore preparations containing the FGF protein can be advantageously formulated.

Abstract: Human blood coagulation factor XIII allows the prevention of intraventricular hemorrhage when administered to premature infants, preferably by intravenous injections.

Abstract: Disclosed herein are methods for using a proteinaceous material present in kinin free high molecular weight kininogen to treat surfaces to prevent or minimize adhesion by blood components and/or animal cells. For example, in medical applications, one can treat plastic tubes or other conduits that carry blood to reduce the tendency of the blood to block the conduit. Also disclosed is an improved method of purifying kinin free high molecular weight kininogen.

Abstract: A method of determining the presence of epithelial lesions is provided wherein a sample of a body fluid taken from an epithelial region suspected to have said lesions is tested for the presence of a proteolytic activity. The lesion is then treated by applying a therapeutically effective amount of a proteinase inhibitor in the form of a physiologically acceptable preparation, a pharmaceutical preparation of aprotinin being particularly preferred.

Abstract: A flowable demineralized bone powder composition is provided for use in surgical bone repair.

Abstract: An accelerator of the activity of hydrolase consisting of a coordination compound or a metal complex containing, as a ligand, an organic cyclic compound with carbonyl groups adjacent to each other in the structure shown in the following general formula I that are substantially in the same plane as each other; ##STR1## (wherein A is the cyclic compound moiety.

Abstract: A pasteurized human firbinogen which can be used therapeutically, and a process for its preparation are described.

Abstract: This invention concerns a method of preparing a cryoprecipitated suspension containing fibrinogen and Factor XIII useful as a precursor in the preparation of a fibrin glue which involves (a) freezing fresh frozen plasma from a single donor such as a human or other animal, e.g., a cow, sheep or pig, which has been screened for blood transmitted diseases, e.g., one or more of syphilis, hepatitis or acquired immune deficiency syndrome at about -80.degree. C. for at least 6 hours, preferably for at least about 12 hours; (b) raising the temperature, so as to form a supernatant and a cryoprecipitated suspension containing fibrinogen and Factor XIII; and (c) recovering the cryopricipitated suspension.

Abstract: A tissue adhesive in lyophilized form contains at least one biologically compatible tenside beside fibrinogen and factor XIII and optionally further proteins as well as adjuvants or additives. The presence of these biologically compatible tensides was found to shorten the reconstitution times of lyophilized tissue adhesive preparations without negatively affecting the biochemical, mechanical or biological properties of the preparation or of the tibrin formed therefrom.

Abstract: A composition and method for treating thrombotic disorders. The composition comprises a peptide comprising an amino acid sequence corresponding to the sequence of the amino acid residues in the EGF domain of Factor IX, or a subsequence thereof. Such peptides compete with coagulation Factors IX and IXa for endothelial binding cites and thereby inhibit thrombosis formation.

Abstract: A method for treating the vascular passage of a patient, damaged by procedures such as an endarterectomy which denude portions of the vascular passages of their endothelial cell linings, is disclosed. In this method, endothelial cells are isolated from the patient's own microvessels, the flow of blood through the patient's damaged vascular passage is interrupted, the endothelial cells isolated from the patient's microvessels are applied to the surface of the denuded portion of the patient's vascular passage in a density sufficient to provide covereage of at least about 50% of said denuded portion, and interruption of blood flow through the vascular passage is maintained for a period of time sufficient to allow the sodded cells to form an attachment to the vascular lining sufficient to withstand the shear created by resumed blood flow through the vascular passage.

Abstract: Stable factor VIII and other plasma protein formulations are provided in low ionic strength media which comprises: sodium chloride, potassium chloride or mixtures thereof; lysine hydrochloride; and histidine as the buffering agent.

Abstract: This invention relates to cosmetic, health- and body-preserving compositions of high biological value, optimizing the biological processes occurring in the skin cells and providing the most preferable function of the enzyme system of the cells connected with the age of the organism.The compositions of the invention contain in addition to the commonly used carrier and additive and/or filling materials and active ingredients, mineral waters of a native condition, medicinal waters and/or the mixtures thereof and/or the mixtures thereof with fermented or non-fermented plant juices and/or optionally inorganic materials playing the role of trace elements in the living organism as well as proteins.

Abstract: A method of determining the presence of epithelial lesions is provided wherein a sample of a body fluid taken from an epithelial region suspected to have said lesions is tested for the presence of a proteolytic activity. The lesion is then treated by applying a therapeutically effective amount of a proteinase inhibitor in the form of a physiologically acceptable preparation, a pharmaceutical preparation of aprotinin being particularly preferred.

Abstract: Skin treatment compositions are provided which counteract moisture loss and promote healing of burned or sunburned skin which include a unique moisturizing component formed of polyglycerylmethacrylate, glycerine, allantoin, panthenol, amino acid complex, and fibronectin.

Abstract: A binary complex between streptokinase and plasminogen is prepared in which the catalytic site essential for fibrinolytic activity is blocked by a group which is removable by hydrolysis such that the pseudo-first order rate constant for hydrolysis of the complex is in the range 10.sup.-6 sec.sup.-1 to 10.sup.-3 sec.sup.-1 in isotonic aqueous media at pH 7.4 at 37.degree. C. The complex is preferably a p-anisoyl streptokinase/plasminogen complex without internal peptide bond cleavage. The complex is useful in the treatment of venous thrombosis.

Abstract: Injectable aqueous suspensions of biomaterials, such as cross-linked collagen, that contain a biocompatible fluid lubricant, such as glycogen or maltose, are disclosed. The inclusion of the lubricant significantly improves the intrusion of the suspension into soft tissue.

Abstract: The invention relates to a process for the pasteurization of plasma proteins and plasma protein fractions without essentially impairing their biological activity, by subjecting a suspension of the plasma proteins or plasma protein fractions in glycerol esters of saturated or singly or multiply unsaturated fatty acids having 4-22 carbon atoms, or mixtures of these esters, as the inert heat-transfer agent, with a maximum water content of the suspension of 1% by weight, to a heat treatment at temperatures of 50.degree. to 120.degree. C.

Abstract: A method of removing lipid soluble process chemicals from biological materials containing the lipid soluble process chemicals comprising bringing the biological materials containing the lipid soluble process chemicals into contact with an effective amount of a naturally occurring oil extracted from a plant or an animal or a synthetic compound of similar chemical structure, agitating the resultant mixture, separating out an upper-phase and a lower-phase by sedimentation and decanting the upper-phase. The method is particularly useful for producing relatively virus free physiologically acceptable plasma.

Abstract: Porcine serum albumin stabilizes porcine growth hormone, and provided for sustained release of porcine growth hormone in implant devices for swine.

Abstract: Compositions containing therapeutically or immunologically active proteins are rendered substantially free from infectious agents such as viable viruses and bacteria without substantial loss of therapeutic or immunologic activity by mixing the protein composition with a complex formed from transition metal ions, such as copper ions, and an angularly-fused, polynuclear heterocyclic arene having two nitrogen atoms in a "cis-ortho" relationship, such as phenanthroline, and a reducing agent such as a thiol or ascorbic acid or ascorbate salt or mixtures of ascorbic acid or ascorbate with a thiol in amounts and at a temperature and for a time sufficient to inactivate substantially all of the viruses and bacteria contained therein. Compositions containing therapeutically active proteins substantially free from viral and bacterial infectivity, which have heretofore been unattainable, can be prepared by the method of the invention.

Abstract: This invention relates to new xylane sulfates having an apparent molar weight comprised between 7000 and 12000.This invention relates also to a process for their preparation by fractionation, and to the therapeutic application thereof as anti-thrombosis and hypolipemic agents.

Abstract: Treatment of cellular disorders involving abnormal solid cellular growths involves introduction of cytotoxic reagents dispersed in a physiologically acceptable proteinaceous matrix into the solid cellular growth or area of an existing or removed solid cellular growth. Enhanced effectiveness of the drug is observed, with reduced cytotoxic effects on cells distant from the site of introduction. Other drugs may be included to enhance therapeutic gain and reduce adverse affects to normal tissue.

Abstract: Treatment of cellular disorders involving abnormal solid cellular growths involves introduction of cytotoxic reagents dispersed in a physiologically acceptable proteinaceous matrix into the solid cellular growth or area of an existing or removed solid cellular growth. Enhanced effectiveness of the drug is observed, with reduced cytotoxic effects on cells distant from the site of introduction. Other drugs may be included to enhance therapeutic gain and reduce adverse affects to normal tissue.