204 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.

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.

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.

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 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.

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 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 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.

The invention belongs to the technical field of biomedicine, and particularly discloses a method for detecting thrombin based on a fluorescent dual-signal non-enzymatic amplification strategy of an aptamer and application of the method. The method comprises the following steps: reacting an auxiliary probe, a signal probe and a Linker chain to form a three-chain DNA reaction substrate, then mixingthe three-chain DNA reaction substrate, a fuel chain and the aptamer/ catalyst chain for reaction to form a reaction solution, thus obtaining a thrombin fluorescent detection system, and after the thrombin is added, detecting the thrombin by monitoring the change of a fluorescent signal FAM and ROX. According to the method, the release of the catalyst chain is induced through the specific combination of the thrombin and the aptamer; the catalyst chain triggers and starts a DNA cyclic amplification reaction through nucleic acid hybridization and branch migration, so that the recycling and cyclic utilization and dual-signal amplification of the catalyst chain are realized; the whole reaction process of the method does not need any protease, and the whole reaction can be completed in one reaction system in one step; and the selectivity is good, the sensitivity is high, the linear range is 1fM-1nM, and the lowest detection lower limit is 0.45fM.

The invention discloses a preparing method for pig thrombin freeze-dried powder. The preparing method comprises the following steps that anticoagulant pig plasma and gel are mixed and stirred for adsorption and pass through a column for elution, and a prothrombin solution is obtained; normal saline is added to rabbit brain powder, then the prothrombin solution and CaCl2 are added for zymogen activation, a crude thrombin enzyme solution is obtained, subjected to ultrafiltration for desalination and concentrated, viral inactivation is carried out, an obtained crude enzyme solution passes through DEAE-Sepharose Fast Flow chromatographic column, elution is carried out, target peaks are collected, and pig thrombin is obtained; the pig thrombin is added with mannitol or dextran 40, filtering, sterilizing, subpackaging, freeze drying and vacuum tamponing are carried out, an aluminum plastic combined cover is rolled, and a pig thrombin freeze-dried product is obtained; the freeze-dried product is subjected to dry heat treatment at 100 DEG C for secondary virus inactivation, and the pig thrombin freeze-dried powder is obtained after packaging. The specific activity of pig thrombin in the product is not lower than 130 U/mg, the whole process is simple in step and easy to implement, the product safety is improved, and the preparing method is suitable for industrial production.

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 antithrombin activator, preferably unfractionated heparin, as well as at least one thrombin inhibitor, preferably bivalirudin.

The invention relates to a process for preparing high activity thrombin inhibitors, which comprises subjecting hirudin, the natural specific inhibitor of thrombin to DNA family restructuring, carrying out restructuring to hirudin HV1, HV2, HV3 genes, constructing reorganization library for hirudin bacteriophage display, using thrombin as coating antigen, subjecting bacteriophage reorganization library to three rounds of enriched elutriation including adsorption, elution and expansion, obtaining a plurality of bacteriophage monoclons with high affinity with thrombin through ELISA screening, carrying out pronucleus induced expression to these clones, finally detecting the antithrombogenic activity of the purification expression product.

The present invention provides a method for treating a thrombotic or an inflammatory disorder administering to a patient in need thereof a therapeutically effective amount of at least one compound of Formula (I) or Formula (V): (I) or a stereoisomer or pharmaceutically acceptable salt or solvate form thereof, wherein the variables A, L, Z, R<3>, R<4>, R<6>, R<11>, X<1>, X<2>, and X<3> 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 provides compounds within the scope of Formula I and relates to pharmaceutical compositions comprising these compounds.

The invention discloses a protective agent of human antithrombin preparation in freezing and drying process. According to the protective agent, a protective agent solution is prepared from one of solute sucrose, amino acid or salt of the amino acid by using deionized water, wherein the amino acid is lysine or hydrochloride in the salt of the lysine, or tyrosine or one of the salts in the tyrosine, or aspartic acid or one of the salts in the aspartic acid; one of the solutes is prepared into a solution by using deionized water so as to obtain the protective agent; the protective agent is added before the human antithrombin preparation is frozen and dried, the inactivation of the main antithrombin ingredient in the preparation in the freezing and drying process is effectively prevented, the activity of the antithrombin is protected, and the antithrombin has better forming appearance and redissolving clarity of the preparation after being frozen and dried.