60 results about "Disseminated coagulopathy" patented technology

The novel amidino derivatives of the formula (I):wherein all the symbols are as in specification defined;have an inhibitory activity of a blood coagulation factor VIIa and are useful for treatment and / or prevention of several angiopathy caused by enhancing a coagulation activity, such as disseminated intravascular coagulation, coronary thrombosis, cerebral infarction, cerebral embolism, transient ischemic attack, cerebrovascular disorders, pulmonary vascular diseases, deep venous thrombosis, peripheral arterial obstruction, thrombosis after artificial vascular transplantation and artificial valve transplantation, post-operative thrombosis, reobstruction and restenosis after coronary artery bypass operation, reobstruction and restenosis after PTCA or PTCR, thrombosis by extracorporeal circulation and procoagulative diseases such as glomerlonephriitis.

A compound represented by the general formula (1):Q1-Q2-T0-N(R1)-Q3-N(R2)-T1-Q4  (1)wherein R1 and R2 are hydrogen atoms or the like; Q1 is a saturated or unsaturated, 5- or 6-membered cyclic hydrocarbon group which may be substituted, or the like; Q2 is a single bond or the like; Q3 is a groupin which Q5 is an alkylene group having 1 to 8 carbon atoms, or the like; and T0 and T1 are carbonyl groups or the like; a salt thereof, a solvate thereof, or an N-oxide thereof.The compound is useful as an agent for preventing and / or treating cerebral infarction, cerebral embolism, myocardial infarction, angina pectoris, pulmonary infarction, pulmonary embolism, Buerger's disease, deep venous thrombosis, disseminated intravascular coagulation syndrome, thrombus formation after valve or joint replacement, thrombus formation and reocclusion after angioplasty, systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), thrombus formation during extracorporeal circulation, or blood clotting upon blood drawing.

Aiming at the conditions that heparin has severe bleeding side effects in clinical practice and clinical application thereof is restricted, the invention discloses a technique for producing ultra-low molecular heparin sodium (calcium). The technique comprises the following steps of: taking heparin sodium solution, adding sodium nitrite solution for cracking; adjusting the lysis buffer by using alkaline; absorbing impurities by using an anion-exchange column; washing for obtaining ultra-low molecular heparin calcium; carrying out filtration by using an ultrafiltration membrane and obtaining a precipitate by using alcohol; and after desalting, dehydration, re-precipitation, cooling and drying, obtaining a finished product of ultra-low molecular heparin calcium. The product has better and safer antithrombotic effect under low level of anticoagulation, and can be widely used for preventing and treating diseases such as deep vein thrombosis, pulmonary embolism, disseminated intravascular coagulation, and the like.

This invention relates to novel antibodies that bind with greater affinity to the factor VIIa / tissue factor (FVIIa / TF) complex than to tissue factor (TF) alone, do not compete for binding to TF with FVII and FX, an inhibit FX activation. The antibodies bind at the site of injury and prevent the initiation of thrombosis. The antibodies can be used to treat a variety of thrombotic conditions including but not limited to deep vein thrombosis, disseminated intravascular coagulation, and acute coronary syndrome.

In one aspect, the invention provides methods of inhibiting the effects of MASP-2-dependent complement activation in a living subject. In one embodiment, the invention provides methods of treating a subject suffering from a complement mediated coagulation disorder, such as disseminated intravascular coagulation. The methods comprise the step of administering, to a subject in need thereof, an amount of a MASP-2 inhibitory agent effective to inhibit MASP-2-dependent complement activation. In some embodiments, the MASP-2 inhibitory agent inhibits cellular injury associated with MASP-2-mediated alternative complement pathway activation, while leaving the classical (C1q-dependent) pathway component of the immune system intact. In another aspect, the invention provides compositions for inhibiting the effects of lectin-dependent complement activation, comprising a therapeutically effective amount of a MASP-2 inhibitory agent and a pharmaceutically acceptable carrier.

A method is disclosed for predicting the presence of haemostatic dysfunction. At least one time-dependent measurement on an unknown sample is performed and a respective property of the sample is measured over time so as to derive a time-dependent measurement profile. One or more predictor variables, including initial slope, are defined which sufficiently define the data of the time-dependent measurement profile. A model is then derived that represents the relationship between the abnormality and the set of predictor variables. Subsequently, the model is utilized to predict haemostatic dysfunction, such as septicemia or disseminated intravascular coagulation (DIC).

This invention relates to novel fusion proteins which are comprised of a targeting protein that binds tissue factor (TF), which is operably linked to the thrombomodulin (TM) EGF456 domain alone or in combination with at least one other TM domain selected from the group consisting of the N-terminal hydrophobic region domain, the EGF123 domain, the interdomain loop between EGF3 and EGF4, and the O-glycosylated Ser / Thr-rich domain, or analogs, fragments, derivatives or variants thereof. The fusion protein binds at the site of injury and prevents the initiation of thrombosis. The fusion protein can be used to treat a variety of thrombotic conditions including but not limited to deep vein thrombosis, disseminated intravascular coagulation, and acute coronary syndrome.

This invention relates to novel fusion proteins which are comprised of a targeting protein that binds tissue factor (TF), which is operably linked to the thrombomodulin (TM) EGF456 domain alone or in combination with at least one other TM domain selected from the group consisting of the N-terminal hydrophobic region domain, the EGF123 domain, the interdomain loop between EGF3 and EGF4, and the O-glycosylated Ser / Thr-rich domain, or analogs, fragments, derivatives or variants thereof. The fusion protein binds at the site of injury and prevents the initiation of thrombosis. The fusion protein can be used to treat a variety of thrombotic conditions including but not limited to deep vein thrombosis, disseminated intravascular coagulation, and acute coronary syndrome.

This invention relates to novel fusion proteins which are comprised of a targeting protein that binds tissue factor (TF), which is operably linked to the thrombomodulin (TM) EGF456 domain alone or in combination with at least one other TM domain selected from the group consisting of the N-terminal hydrophobic region domain, the EGF123 domain, the interdomain loop between EGF3 and EGF4, and the O-glycosylated Ser / Thr-rich domain, or analogs, fragments, derivatives or variants thereof. The fusion protein binds at the site of injury and prevents the initiation of thrombosis. The fusion protein can be used to treat a variety of thrombotic conditions including but not limited to deep vein thrombosis, disseminated intravascular coagulation, and acute coronary syndrome.

A compound represented by the general formula (1): Q1-Q2-T0-N(R1)-Q3-N(R2) -T1-Q4   (1) wherein R1 and R2 are hydrogen atoms or the like; Q1 is a saturated or unsaturated, 5- or 6-membered cyclic hydrocarbon group which may be substituted, or the like; Q2 is a single bond or the like; Q3 is a group in which Q5 is an alkylene group having 1 to 8 carbon atoms, or the like; and T0 and T1 are carbonyl groups or the like; a salt thereof, a solvate thereof, or an N-oxide thereof. The compound is useful as an agent for preventing and / or treating cerebral infarction, cerebral embolism, myocardial infarction, angina pectoris, pulmonary infarction, pulmonary embolism, Buerger's disease, deep venous thrombosis, disseminated intravascular coagulation syndrome, thrombus formation after valve or joint replacement, thrombus formation and reocclusion after angioplasty, systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), thrombus formation during extracorporeal circulation, or blood clotting upon blood drawing.

A compound represented by formula (1):Q1-Q2-T0-N(R1)-Q3-N(R2)-T1-Q4  (1)[wherein R1 and R2 are hydrogen atoms or the like; Q1 is a saturated or unsaturated, 5- or 6-membered cyclic hydrocarbon group which may be substituted, or the like; Q2 is a single bond or the like; Q3 represents the following group:(wherein Q5 is an alkylene group having 1 to 8 carbon atoms, or the like); and T0 and T1 are carbonyl groups or the like], a salt thereof, a solvate thereof, or an N-oxide thereof.The compound is useful as an agent for preventing and / or treating cerebral infarction, cerebral embolism, myocardial infarction, angina pectoris, pulmonary infarction, pulmonary embolism, Buerger's disease, deep venous thrombosis, disseminated intravascular coagulation syndrome, thrombus formation after artificial valve or joint replacement, thrombus formation and reocclusion after angioplasty, systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), thrombus formation during extracorporeal circulation, or blood clotting upon blood drawing.

The present invention mainly addresses the problem of providing an antibody against semaphorin 3A protein, said antibody enabling effective prevention and / or treatment of a disease, in which Sema 3A protein participates, such as a neurodegenerative disease, autoimmune disease, inflammatory disease, cancer, infectious disease, etc. or disseminated intravascular coagulation syndrome. An anti-Sema 3A antibody comprising CDRs having specific amino acid sequences (SEQ ID NOS: 1-6, 60-62, 64-66, 68-70, 72-74, 76-78, 80-82, 84-86 and 88-90) enables effective prevention and / or treatment of a disease, in which Sema 3A protein participates, such as a neurodegenerative disease, autoimmune disease, inflammatory disease, cancer, infectious disease, etc. or disseminated intravascular coagulation syndrome and, therefore, remarkably ameliorates symptoms associated with such a disease.

A compound of formula (I) wherein R<1> and R<2> are as defined in the description, R<2> being an aromatic group, useful in the treatment and condition selected from the group consisting of the group meningitis and salpingitis, septic shock, disseminated intravascular coagulation, and / or adult respiratory distress syndrome, acute or chronic inflammation, arthritis, cholangitis, colitis, encephalitis, endocarditis, glomerulonephritis, hepatitis, myocarditis, pancreatitis, pericarditis, reperfusion injury, vasculitis, acute and delayed hypersensitivity, graft rejection, and graft-versus-host disease, auto-immune diseases including Type 1 diabetes mellitus and multiple sclerosis, periodonate diseases, interstitial pulmonary fibrosis, cirrhosis, systemic sclerosis, keloid formation tumors which produce IL-1 as an autocrine growth factor, cachexia, Alzeimer's disease, percussion injury, depression, atherosclerosis, osteoporosis in a mammal, including a human.

The present invention relates to a use of a pharmaceutical composition in the manufacture of medicament for treating related diseases caused by endotoxemia. The pharmaceutical composition comprises 3-methyl-1-phenyl-2-pyrazolin-5-one or pharmaceutically acceptable salt thereof and borneol. The diseases include, but are not limited to, systemic inflammatory response syndrome, sepsis, severe sepsis, septic shock, sepsis related disseminated intravascular coagulation, acute lung injury, acute respiratory distress syndrome, multiple organ failure syndrome, septic brain injury and inflammatory lung injury caused by other reasons, including but not limited to bacterial pneumonia.

This invention relates to novel antibodies that bind with greater affinity to the factor VIIa / tissue factor (FVIIa / TF) complex than to tissue factor (TF) alone, do not compete for binding to TF with FVII and FX, an inhibit FX activation. The antibodies bind at the site of injury and prevent the initiation of thrombosis. The antibodies can be used to treat a variety of thrombotic conditions including but not limited to deep vein thrombosis, disseminated intravascular coagulation, and acute coronary syndrome.

A compound represented by the following formula (1): Q1—Q2—To—N(R1)—Q3—N(R2)—T1—Q4  (1) [wherein, R1 and R2 are hydrogen atoms or the like; Q1 is a saturated or unsaturated, 5- or 6-membered cyclic hydrocarbon group which may have a substituent, or the like; Q2 is a single bond or the like; Q3 represents the following group: —C(R3a)(R4a)—{C(R3b)(R4b)}m1—{C(R3c)(R4c)}m2—{C(R3d)(R4d)}m3—{C(R3e)(R4e)}m4—C (R3f)(R4f)— (in which, R3a to R4e represent hydrogen or the like); T0 represents a carbonyl group or the like; and T1 represents —COCONR— or the like]; or salt thereof, solvate thereof, or N-oxide thereof. The compound is useful as a preventive and / or therapeutic agent for cerebral infarction, cerebral embolism, myocardial infarction, angina pectoris, pulmonary infarction, pulmonary embolism, Buerger's disease, deep venous thrombosis, disseminated intravascular coagulation syndrome, thrombus formation after valve or joint replacement, thrombus formation and reocclusion after angioplasty, systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), thrombus formation during extracorporeal circulation, or blood clotting upon blood drawing.

[Object] To provide a substituted cycloalkene derivative having an action to suppress intracellular signal transduction or cell activation induced by endotoxin and to suppress cell responses due to the intracellular signal transduction and cell activation such as an excess generation of inflammatory mediators such as TNF-α, pharmacologically acceptable salts therefor, a medicament containing them as an active ingredient, a preparation method therefor, and a medicament containing the aforementioned substituted cycloalkene derivative as an active ingredient which is superior in prophylaxis and / or treatment of diseases such as sepsis (septic shock, disseminated intravascular coagulation, multiple organ failure and the like), that are associated with intracellular signal transduction or cell activation induced by endotoxin and to cell responses to the intracellular signal transduction and cell activation.[Solution] A compound represented by the general formula (I):{whereinX and Y represent a group in which X and Y together with a carbon atom to which they are bound form ring A (the ring is 3- to 7-membered heterocyclyl ring or 3- to 7-membered cycloalkyl ring), each represents a hydrogen atom, or X and Y together represent a substituent of ring B.l and m, independently from each other, represent an integer of 0 to 3, and l+m is 1 to 3.R1 is an aliphatic hydrocarbon group and the like which may be substituted with a group selected from Substituent group β and Substituent group γ. n represents an integer of 0 to 3.R2 is a C1-C6 alkyl group and the like which may be substituted with a group selected from a hydrogen atom and Substituent group β.R3 is a phenyl group, 5- to 6-membered heteroaryl group and the like which may be substituted with a group selected from Substituent group ε.R5 is a C1-C6 alkyl group and the like which may be substituted with a group selected from a hydrogen atom and Substituent group β.Provided that in the case where R3 is a phenyl group which may be substituted with a group selected from Substituent group ε, X and Y represent a group in which X and Y together with a carbon atom to which they are bound form ring A, or X and Y together represent a substituent of ring B.

The invention discloses a method for extracting hirudin by electrically stimulating living leeches. The method includes four steps of extraction of secretion, preparation of protectant, processing of secretion and drying of secretion. The product dry powder contains the main effectively active ingredient, namely hirudin, extracted from the living leeches, which can be used for preventing and treating vein thrombosis, disseminated intravascular coagulation, brain coagulation, thrombophlebitis, coronary thrombosis and the like. Compared with the prior art, the method has the advantages that hirudin production process is simplified while living leeches are maintained for extracting high-purity hirudin multiple times.

The invention relates to a method for preparing liquid fibrinogen (FIB) detection solution. The solution is mainly used for monitoring the disturbance of blood coagulation, the hemorrhagic disease, the disseminated intravascular coagulation (DIC), the diabetes, the acidosis, the atherosclerosis and other disease symptoms. Along with the wide clinical application of thrombus and hemostasis detection, the fibrinogen (FIB) detection is the routine detection item of the thrombus and hemostasis detection, and has important clinical diagnosis value. The method adopts cow thrombin as a main raw material, and uses the Von clauss method (NCCLS recommended) to prepare the novel liquid fibrinogen (FIB) detection solution. The novel stable system solves the difficulty of maintaining the stability of the solution in the liquid state, and the method has the advantages of high sensitivity, convenient use, low experimental error, high stability, favorable compatibility, low cost, and the like.

To find a compound having a tissue fibrinosis-inhibitory activity and a fibrinolytic activity, and to provide a novel compound that is useful for preventing and / or treating tissue fibrinosis diseases (pulmonary fibrosis, renal fibrosis etc.), diseases caused by pathological blood clots such as ischemic heart diseases (myocardial infarction, angina), intraatrial thrombus, pulmonary embolism, deep venous thrombosis, disseminated intravascular coagulation, ischemic cerebral diseases (cerebral infarction, cerebral bleeding) and arteriosclerosis and the like. To provide a pharmaceutical drug comprising a 5-phenyl-3-pyridazinone derivative represented by the following general formula (I):and an optical isomer thereof, or a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, useful for preventing and / or treating disease conditions or symptoms mediated by plasminogen activator inhibitor-1.

The present invention provides a method of detecting platelet thrombosis or organ injury in a patient suffering from disseminated intravascular coagulation (DIC) syndrome or systemic inflammatory response syndrome (SIRS) by analyzing a von Willebrand factor-degrading enzyme and / or a degrading factor thereof. A kit for detecting platelet thrombosis or organ injury in a patient suffering from DIC or SIRS which contains an antibody capable of binding specifically to a von Willebrand factor-degrading enzyme or its fragment and an antibody capable of binding specifically to a degrading factor of a von Willebrand factor-degrading enzyme or its fragment.

A method and system for the assessment of the risk of development of disseminated intravascular coagulation (DIC), in patients showing systemic inflammatory response syndrome (SIRS) or sepsis is disclosed. Specifically, the invention provides a method for early DIC assessment and preventive treatment planning, which has the potential for significantly decreasing mortality rate as well as the rate of DIC related sequelae in the SIRS / sepsis patient population and thereby improving quality of life. The risk assessment method is based on features of vital signs and / or biomarker measurements, and provides solutions for assessing the risk of DIC development 24 hours in advance or within 72 hours after ICU admittance.

A compound of formula (I)Wherein X, Y, ring A, ring B, l, m, R1, R2, R4 and R5 are as defined herein, to supress intracellular signal transduction or cell activation induced by endotoxin and to suppress cell responses due to the intracellular signal transduction and cell activation such as an excess generation of inflammatory mediators such as TNF-α, pharmacologically acceptable salts therefor, a preparation method therefor, and a medicament containing the aforementioned substituted cycloalkene derivative as an active ingredient which is superior in prophylaxis and / or treatment of diseases such as sepsis (septic shock, disseminated intravascular coagulation, multiple organ failure and the like), that are associated with intracellular signal transduction or cell activation induced by endotoxin and to cell responses to the intracellular signal transduction and cell activation.

A method for determining a condition of disseminated intravascular coagulation (DIC), by analyzing the amount and / or enzyme activity of a von Willebrand factor (vWF)-cleaving protease (ADAMTS13) (preferably also the amount of vWF) in a patient suffering from DIC, and a kit for determining a condition of DIC, comprising an antibody or a fragment thereof which specifically binds to ADAMTS13, are disclosed. According to the present invention, a differential diagnosis of patients with thrombotic thrombocytopenic purpura (TTP) can be carried out from among patients with DIC, which could not be distinguished on the basis of only clinical findings or known markers.

Hypercoagulable and hyperinflammatory responses can lead to a variety of diseases including but not limited to disseminated intravascular coagulation in sepsis, consumptive coagulopathy in trauma, thrombosis in the postsurgical setting, acute respiratory distress syndrome in lung, and other diseases or conditions. Polyphosphate is accumulated by many infectious microorganisms and may be released by damaged infectious microorganisms. In addition, polyphosphate is found in many organs and is released from activated platelets and mast cells. Polyphosphates activate the intrinsic pathway of coagulation that also induces inflammation. Hypercoagulable and hyperinflammatory challenge are mediators contributing to endothelial dysfunction, organ failure and death, which occur in many pathological conditions. As such, polyphosphates can be targeted pharmacologically by inhibitors, such as anti-polyphosphate antibodies, as well as used as biomarkers for diagnosis, prognosis, and treatment response indicators that may be used to provide guidance for alterations in treatment plans.

The present invention relates to azacycloalkylalkanoyl peptides and pseudopeptides which inhibit platelet aggregation and thrombus formation thereby being useful in the prevention and treatment of thrombosis associated with disease states such as myocardial infarction, stroke, peripheral arterial disease, and disseminated intravascular coagulation, to methods for the prevention or treatment of thrombosis in a mammal in need of such therapy comprising the administration of a therapeutically effective amount of such compounds, and to pharmaceutical compositions comprising such compounds.