225 results about "THROMBIN HUMAN" patented technology

The present invention provides compounds of Formula (I): or a stereoisomer or pharmaceutically acceptable salt or solvate form thereof, wherein the variables A, B, L1, L2, X1, X2, X3, X4, X5, R4, and W are as defined herein. The compounds of Formula (I) are useful as selective inhibitors of serine protease enzymes of the coagulation cascade and / or contact activation system; for example thrombin, factor Xa, factor XIa, factor IXa, factor VIIa and / or plasma kallikrein. In particular, it relates to compounds that are selective factor XIa inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and / or inflammatory disorders using the same.

The present invention provides compounds of Formula (I):or a stereoisomer or pharmaceutically acceptable salt or hydrate form thereof, wherein the variables A, B, L1, L2, X1, X2, X3, X4 and W are as defined herein. The compounds of Formula (I) are useful as selective inhibitors of serine protease enzymes of the coagulation cascade and / or contact activation system; for example thrombin, factor Xa, factor XIa, factor IXa, factor VIIa and / or plasma kallikrein. In particular, it relates to compounds that are selective factor XIa inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and / or inflammatory disorders using the same.

Compounds of formula (I) are useful as inhibitors of trypsin like serine protease enzymes such as thrombin, factor VIIa, factor Xa, TF / FVIIa, and trypsin. These compounds could be useful to treat and / or prevent clotting disorders, and as anticoagulating agents.

The present invention relates to porous freeze-dried plasma protein matrices having an open channel structure and a concentration gradient of plasma proteins crosslinked by the action of thrombin, and methods of producing said matrices. The compositions of the present invention are useful clinically, per se or as cell-bearing implants.

The invention relates to the inhibition of blood coagulation, especially during organ rejection, and in particular the inhibition of delayed vascular rejection. The invention provides anticoagulant proteins which are anchored to cell membranes. The anticoagulant function preferably provided by heparin, antithrombin, hirudin, TFPI, tick anticoagulant peptide, or a snake venom factor. These anticoagulant proteins are preferably prevented from being constitutively expressed at the cell surface. In particular, expression at the cell surface is regulated according to cell activation, for instance by targeting the protein to a suitable secretory granule. Expression of these proteins renders cells, tissues and organs less vulnerable to rejection after transplantation (e.g. after xenotransplantation).

The present invention provides compounds of Formula (I):or a stereoisomer or pharmaceutically acceptable salt or solvate form thereof, wherein the variables A, L, Z, X1, X2, X3, X4, and X5 are as defined herein. The compounds of Formula (I) are useful as selective inhibitors of serine protease enzymes of the coagulation cascade and / or contact activation system; for example thrombin, factor Xa, factor XIa, factor IXa, factor VIIa and / or plasma kallikrein. In particular, it relates to compounds that are selective factor XIa inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and / or inflammatory disorders using the same.

There are provided inter alia multisubstituted aromatic compounds useful for the inhibition of thrombin and / or kallikrein, which compounds include substituted triazolyl. There are additionally provided pharmaceutical compositions. There are additionally provided methods of treating and preventing certain diseases or disorders, which diseases or disorders are amenable to treatment or prevention by the inhibition of thrombin and / or kallikrein.

There is provided compounds of formula I,wherein R1 and R2 have meanings given in the description, which are useful as prodrugs of inhibitors of trypsin-like proteases, such as thrombin, and in particular in the treatment of conditions where inhibition of thrombin is required (eg thrombosis) or as anticoagulants.

The present invention provides compounds of Formula (I):or a stereoisomer or pharmaceutically acceptable salt form thereof, wherein the variables A, B, L1, L2, X1, X2, X3, X4, R4, R5, R13, R14, R15 and R16 are as defined herein. The compounds of Formula (I) are useful as selective inhibitors of serine protease enzymes of the coagulation cascade and / or contact activation system; for example thrombin, factor Xa, factor XIa, factor IXa, factor VIIa and / or plasma kallikrein. In particular, it relates to compounds that are selective factor XIa inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and / or inflammatory disorders using the same.

There is provided compounds of formula I,wherein R1, Rx, Y, Ry, n and B have meanings given in the description which are useful as competitive inhibitors of trypsin-like proteases, such as thrombin, and in particular in the treatment of conditions where inhibition of thrombin is required (e.g. thrombosis) or as anticoagulants.

The present invention provides compounds of Formula (I): or a stereoisomer or pharmaceutically acceptable salt or solvate form thereof, wherein the variables A, L, Z, X1, X2, X3, X4, and X5 are as defined herein. The compounds of Formula (I) are useful as selective inhibitors of serine protease enzymes of the coagulation cascade and / or contact activation system; for example thrombin, factor Xa, factor XIa, factor IXa, factor VIIa and / or plasma kallikrein. In particular, it relates to compounds that are selective factor XIa inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and / or inflammatory disorders using the same.

A method for promoting the foling of a polypeptide selected from thrombin and a precursor thereof comprising contacting the polypeptide with a molecular chaperone and a foldase is provided.

For defects that existing hemostasis research and products cannot intelligently perform self-propelling or cannot be driven to forward deep in the wound under the action of external field force, the invention provides a preparation method for a janus structure based rapid hemostatic agent having a directional propulsion function. The preparation method includes performing esterification on microporous starch to unidirectionally grow calcium carbonate particles so as to obtain esterified microporous starch / calcium carbonate Janus particles; fixedly assembling thrombin on the surfaces of the esterified microporous starch / calcium carbonate Janus particles to obtain esterified microporous starch / calcium carbonate Janus particles assembled with the thrombin; mixing the esterified microporous starch / calcium carbonate Janus particles assembled with the thrombin and protonated tranexamic acid powder so as to obtain the janus structure based rapid hemostatic agent having a directional propulsion function. Through the formation of the biphasic heterogeneous Janus structure, the unidirectional and intelligent self-propulsion of hemostatic starch can be realized by cooperating with the protonated tranexamic acid, so that rapid three-dimensional hemostasis on deep wounds, penetrating wounds and irregular wounds such as aortic / venous rupture can be realized.

The present invention provides compounds of Formula (I):or a stereoisomer, tautomer, pharmaceutically acceptable salt or solvate form thereof, wherein the variables A, L1, M and R11 are as defined herein. The compounds of Formula (I) are selective inhibitors of serine protease enzymes of the coagulation cascade and / or contact activation system; for example thrombin, factor Xa, factor XIa, factor IXa, factor VIIa and / or plasma kallikrein. In particular, it relates to compounds that are selective factor XIa inhibitors or dual inhibitors of fXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and / or inflammatory disorders using the same.

A variety of polymeric synthetic hernia mesh prosthesis with surface treatment on at least one tissue-facing surface to control tissue adhesion are disclosed including heparin surface treatment which provides heparin present in an amount to yield heparin bioactivity of at least one of i) an ATIII binding of at least 2 pmol / cm2, and ii) a thrombin deactivation of at least 0.2 IU / cm2; an acrylic surface treatment for coupling thereto of a heparin surface treatment, a collagen surface treatment or both; and an amino-functional polysiloxane surface treatment for coupling thereto of a heparin surface treatment. The synthetic hernia mesh may be formed of monofilament or multifilament polypropylene or polyester, and may be formed as a multi-layer prosthesis with an outer layer formed of a polymeric synthetic hernia mesh with surface treatment to control tissue adhesion coupled to one or more polymeric synthetic hernia meshes without such surface treatments.

The present invention provides a hemostatic material which is excellent in hemostatic property, biodegradability and bioabsorbability, uniformity and stability of the quality, as well as reduces a risk of contamination with a pathogenic organism derived from an animal. The hemostatic material comprises a thrombin and a synthetic polypeptide capable of forming a triple helical structure. The polypeptide may show a peak of the molecular weight in the range from 5×104 to 100×104 in the molecular weight distribution. The polypeptide may contain at least a peptide unit represented by the formula: -Pro-X-Gly- (in the formula, X represents Pro or Hyp). The thrombin may be a recombinant. In the hemostatic material, the proportion of the thrombin may be about 0.1 to 500 units (U) relative to 1 mg of the polypeptide. The hemostatic material may further comprise a binder component having biodegradability and bioabsorbability. The hemostatic material may be formed on a substrate.

The invention discloses a thrombin detection method based on a splitter adapter and a water-soluble conjugated polymer. According to the method, a super-molecular detection platform based on a water-soluble conjugated polymer / nucleic acid adapter is designed by virtue of the sensitivity of the water-soluble polymer on a comformational change of a deoxyribonucleic acid (DNA) chain and according to the characteristics that the nucleic acid adapter has specific binding ability and the like. Two sequences cannot form a G-four-chain structure when thrombin does not exist in a solution or other nonspecific proteins exist in the solution, the distance from a compound to the polymer is small, and thus effective energy transfer between the compound and the polymer can be realized; when the thrombin exists in the solution, the thrombin induces the two sequences to form the G-four-chain structure, and the distance between the compound and the polymer is increased, so that effective energy transfer cannot be carried out. The method disclosed by the invention is simple, convenient and fast, is high in sensitivity and selectivity, and has important significance in the aspect of thrombin detection.

Provided are spray-dried thrombin powders comprising microcapsules, methods of preparation and uses thereof.

The invention provides a terpenoid shown by the formula I or pharmaceutically acceptable salt, ester or hydrate thereof. The invention also provides a preparation and application of the terpenoid. In the invention, a carbon-drop diterpene new compound separated from leonurus is carbon-drop labdane diterpene obtained from the nature for the first time. The compound can obviously shorten the PT (prothrombin time), APTT (activated partial thromboplastin time) and TT (thrombin time) in vitro and obviously increase the amount of FIB (fibrinogen) in blood, and realizes a certain effect on enhancing the coagulation function, thereby providing a new option for developing a novel natural coagulation drug.

The present invention relates to compositions and methods for cell transplantation. In particular, the present invention provides a composition comprising procoagulant cells and at least one factor Xa inhibitor, preferably rivaroxaban, as well as at least one thrombin inhibitor, preferably bivalirudin.

The invention discloses a method for preparing human thrombin from cold-removing glue plasma. Firstly, anion resins are used to absorb prothrombin in the cold-removing glue plasma, then elution and filtering are conducted, and a prothrombin solution is obtained; secondly, the prothrombin solution is activated through a CaCL2 solution, and a thrombin solution is obtained; thirdly, S / D viral inactivation is conducted on the thrombin solution; fourthly, chromatography is conducted through cation columns, and a purified thrombin solution is obtained; fifthly, ultrafiltration, dialysis and concentrate are conducted on the thrombin solution, and the thrombin solution with the titer meeting the product specification requirement is obtained; sixthly, a filter element of 20 nm in size is used to conduct virus removal filtering; seventhly, sterilization filtering is conducted through a filter element of 0.22 microns in size, and then subpackage is conducted according to the required specifications; eighthly, freeze-drying is conducted, and dry heat viral inactivation is conducted on freeze-drying powder, and a human thrombin product is obtained. According to the method, the thrombin is purified through the one-step cation columns, operation is simple, thrombin specific activity is high, and safety of clinic use of the product is guaranteed through a three-step virus elimination mode.

A process is disclosed for preparing an autologous platelet gel and membranes thereof comprising mixing a platelet concentrate with a calcium salt and batroxobin. This process encompassing the use of batroxobin as the gel activator allows to overcome the prior art processes drawbacks connected with the use for the same purpose of human of bovine thrombin. A kit is also described for carrying out this process.

The sealant and bone generating product comprises a coagulated matrix of platelet rich plasma with a recombinant compound for generating thrombin mixed with two different phospholipids. The bone generating product comprises an effective amount of calcium containing compound dispersed in the matrix for inducing the formation of bone.

The present invention relates to a composition for transplantation in a physiologically compatible buffer solution comprising, (a) a transplant-cell selected among an adipose stem cell, an adipocyte, adipose tissues (fat tissue) and a mixture thereof; and (b) a semi-solid substance derived from a living body or a biodegradable substance selected among a hyaluronic acid, collagen, elastin, thrombin, chondroitin sulfate, albumin and a mixture thereof.

The invention discloses application of a peptide compound in rhizoma sparganii in the preparation of medicines for resisting blood coagulation and / or thrombus. The structural formula of the peptide compound is as shown in a formula (I). The invention provides the peptide compound obtained from the rhizoma sparganii through the separation and the purification and the application thereof for the first time. The peptide compound has an elongation tendency effect on prothrombin time (PT), activated partial thromboplastin time (APPT) and thrombin time (TT) and very good anticoagulation activity and provides powerful basis for the development of antithrombus natural medicines.

The present invention provides a process for producing an antithrombin III composition comprising an antithrombin III molecule having complex type N-glycoside-linked sugar chains, wherein the complex type N-glycoside-linked sugar chains have a structure in which fucose is not bound to N-acetylglucosamine in the reducing end in the sugar chains.

The invention provides an ultra-high sensitive colorimetric method for detecting thrombin; a lot of DNA (Deoxyribonucleic Acid) enzymes can be formed by adopting a rolling-circle replicating and amplifying technology; detection signals are amplified; therefore, the detection sensitivity of thrombin is increased; influence of unreacted hemin to reaction can be eliminated by adopting a 96-pore plate connection primer; the signal to noise ratio is increased; and therefore, the detection sensitivity is further increased. By adopting a sensitive colorimetric system, gold ions are reduced to be red or blue generated in a dispersed or united state by utilizing hydrogen peroxide; whether a target molecule exists can be judged directly; a nano gold solution is unnecessary to prepare in advance; the ultra-high sensitive colorimetric method is simple and feasible; complex apparatuses and equipment are unnecessary; by means of the ultra-high sensitive colorimetric method, ultra-high sensitive detection of thrombin can be realized; and the detection limit is up to 10-17 M (about six thrombin molecules).

The present invention provides a biocompatible, biodegradable graft composition for regeneration of neural tissue, comprising the following components: a) a gel scaffold formed from an isolated platelet containing fluid and an activating agent comprising calcium chloride, with or without thrombin, b) a nerve growth factor selected from BDNF, NGF, retinoic acid and combinations thereof, and c) a culture of at least 50,000 progenitor stem cells; the method of production and the uses thereof.

The invention discloses a preparation method of a photoelectrochemical biosensor based on a cyclometalated iridium complex and application of the photoelectrochemical biosensor to thrombin detection.The biosensor uses the visible light-excited iridium complex as a photoelectrically active material, and the iridium complex is located on colloidal gold to prepare a gold nanometer signal probe. Capturing hairpin DNAs are immobilized on a modified ITO electrode to prepare a working electrode of the biosensor. A thrombin recognition system includes a specific recognition hairpin HP1 and an adjuvant hairpin HP2; in the presence of thrombin, a large number of secondary targets T-DNAs are released under the action of the excision enzyme ExoIII and hybridize with the capturing hairpin DNAs on theworking electrode so as to capture the gold nanometer signal probe, thereby realizing response to photocurrent signals; thrombin with different concentrations allows the amount of the signal probe connected to the working electrode to be different, so photocurrent intensities are different, and thus, quantitative detection of thrombin is realized. The method has the advantages of high sensitivityand good selectivity.