109 results about "Thrombotic disease" patented technology

The invention relates to a monoclonal antibody with anticoagulant activity and application thereof, the antibody or fragment comprises a light chain variable region and a heavy chain variable region, and the amino acid sequence of the light chain variable region of the antibody or fragment is as shown in SEQ ID NO: 1; the amino acid sequence of the variable region of the heavy chain is as shown in SEQ ID NO: 3. The monoclonal antibody disclosed by the invention has the effect of inhibiting the activity of a co-coagulation pathway in a coagulation cascade reaction, and can be applied to prevention and treatment of thrombotic diseases.

The invention provides a coding gene of coral-derived anticoagulant polypeptide and application, and belongs to the technical field of bioactive peptides. The invention provides an anticoagulant polypeptide GcKuz1. The anticoagulant polypeptide GcKuz1 comprises a mature peptide fragment as shown in SEQ ID No.1. The invention also provides a preparation method of the anticoagulant polypeptide GcKuz1. The polypeptide GcKuz1 is combined with KLKB1 in a thrombin system, so that the anti-thrombus and anti-coagulation effects are achieved, and the polypeptide does not cause hemolysis and cytotoxicity, has no bleeding risk and has good biological safety. The anticoagulant polypeptide disclosed by the invention has the effect of treating thrombotic diseases, such as arterial thrombotic diseases, venous thrombotic diseases and capillary thrombotic diseases.

Provided are an siRNA which inhibits plasma coagulation factor XI gene expression, a pharmaceutical composition containing the siRNA, a conjugate, a reagent kit, and a use of the siRNA, the pharmaceutical composition thereof and the conjugate in preparing a drug used for treating and / or preventing thrombotic diseases and ischemic strokes.

The invention relates to a pharmaceutical preparation of plasma protein, especially ADAMTS-13 protein, and a composition composed of the pharmaceutical preparation and used for preventing or treating thrombotic diseases. According to the pharmaceutical preparation, the stability of the plasma protein can be remarkably improved, and the risk that the plasma protein is immediately polluted and denatured after being separated and purified from blood is very high, so that the pharmacological activity and quality of the plasma protein can be reduced in the long-term storage process. Particularly, the pharmaceutical preparation disclosed by the invention can keep the colloidal stability, the refrigeration stability, the purity and the aggregation inhibition property of the plasma protein at a relatively high level, and the appearance of the pressed powder obtained after freeze drying can be kept good for a long time. Therefore, the pharmaceutical preparation disclosed by the invention can be well used for long-term preservation and storage of the ADAMTS-13 protein without losing the effective treatment dose of the protein, and the ADAMTS-13 protein is an important treatment resource for various thrombotic diseases.

The present disclosure relates to a method for treating or preventing a thrombotic disorder, comprising administering to a subject in need thereof an effective amount of the Compound (1) or a pharmaceutically acceptable salt thereof, at a dose in the range of 0.01-0.3 mg / kg, inclusive. The present disclosure further relates to compositions for use in such a method.

The invention relates to the field of protein, in particular to earthworm protein with fibrinolytic activity and application of the earthworm protein. The earthworm protein with fibrinolytic activity has at least one of amino acid sequences as shown in 1)-3): 1) at least one of amino acid sequences as shown in SEQ ID NO: 1 or SEQ ID NO: 2; 2) an amino acid sequence obtained by substituting, deleting or adding one or more amino acids to the amino acid sequence as shown in SEQ ID NO: 1 or SEQ ID NO: 2; and 3) an amino acid sequence having at least 90% consistency with the amino acid sequence as shown in SEQ ID NO: 1 or SEQ ID NO: 2. The earthworm protein has the activity of directly hydrolyzing fibrin, and can activate plasminogen, so that the activity of hydrolyzing fibrin is further enhanced, the formation of thrombus can be effectively inhibited, the dissolution of thrombus can be promoted, and the earthworm protein can be applied to preparation of food, medicines or health care products for preventing and / or treating thrombotic diseases.

In one aspect, the invention provides compositions and methods for preventing, reducing, and / or treating a disease, disorder or condition associated with fibrin-induced activation of the complement system and the associated activation of the coagulation and / or contact systems comprising administering a therapeutic amount of a MASP-2 inhibitory antibody to a subject in need thereof. In some embodiments, the methods of the invention provide anticoagulation and / or antithrombosis and / or antithrombogenesis without affecting hemostasis. In one embodiment of this aspect of the invention, the compositions and methods are useful for treating a subject is suffering from, or at risk of developing, a disease, disorder or condition associated with complement-related inflammation, excessive coagulation or contact system activation initiated by fibrin or activated platelets.

The invention belongs to the technical field of biological medicines, and relates to a Rubicon permeable membrane peptide and application thereof. Specifically, the permeable membrane peptide fragment sequence is designed on the basis of an amino acid sequence of interaction of Rubi protein and Btk, and seven permeable membrane sections of arginine are connected to the tail end of the permeable membrane peptide fragment sequence through disulfide bonds. Immunofluorescence experiments prove that the peptide fragment can efficiently penetrate a platelet membrane to enter cells, and co-immunoprecipitation experiments prove that the peptide fragment has strong affinity with Btk. Platelet aggregation experiments show that the peptide fragment can significantly inhibit platelet activation under collagen stimulation. In an animal model, the peptide fragment is injected before instantaneous middle cerebral artery occlusion or reperfusion of a mouse, and ischemia-reperfusion injury can be effectively relieved. The invention provides a novel potential drug candidate for treating thrombotic diseases and ischemia-reperfusion injury.

The invention provides a pharmaceutical composition. The pharmaceutical composition is prepared from aspirin, atorvastatin, valsartan, hydrochlorothiazide, folic acid substances and pharmaceutically acceptable auxiliary materials. The pharmaceutical composition provided by the invention has the advantages that the pharmaceutical composition provided by the invention has a multi-target synergistic prevention effect on vascular diseases, especially cerebral embolism, that is, the composition not only can reduce blood pressure, blood fat and blood homocysteine level, but also has an effect of preventing thrombosis, and reduces the risk of cerebral apoplexy. In addition, the form of the pharmaceutical composition is beneficial to improving the medication compliance of patients.

A series of sofalcone derivatives are provided.SOLUTION: A series of sofalcone derivatives provided by the present invention are, for example, compounds having a structure of formula (I), and have platelet aggregation inhibitory and antithrombotic effects. The sofalcone derivatives of the present invention are TxA2 receptor antagonists, have an inhibitory effect on platelet agglutination, and do not easily affect the hemostatic function. The present invention also provides a method for preparing the sofalcone derivative, and a method for using the sofalcone derivative for preventing or treating thrombotic diseases, or for inhibiting platelet aggregation.SELECTED DRAWING: None

The present invention discloses a trimer of Asn-Gly-Pro, namely [Asn-Gly-Pro]3, discloses its preparation method and its application in the treatment of venous thrombotic diseases. Experiments have proved that [Asn-Gly-Pro]3 of the present invention not only has a good anti-venous thrombosis effect, but also the anti-venous thrombosis effect is significantly stronger than that of Asn-Gly-Pro. Therefore, it is proposed that the present invention provides an effective technical means for anti-venous thrombosis.

This invention relates to the fields of molecular biology and biomedicine, disclosing plasma-active peptides with antithrombotic effects and their uses. The invention obtains various active peptides from plasma through screening and solid-phase synthesis, and confirms their biological activity through in vitro platelet aggregation experiments and in vivo arterial thrombosis model experiments. Results show that peptides 1957, 1960, and 1961 significantly inhibit collagen-induced platelet aggregation, exhibiting good antiplatelet activity; animal experiments show that peptides 1955, 1957, 1960, and 1961 significantly inhibit arterial thrombosis. These active peptides are derived from endogenous plasma components, belonging to natural antithrombotic substances, possessing good physiological compatibility and safety advantages, and reducing the risk of immunogenicity and adverse reactions. These peptides can exert antithrombotic effects without relying on traditional antiplatelet drugs, providing a new source of active molecules and treatment options for the prevention and treatment of thrombotic diseases.

The invention belongs to the technical field of medicines, and discloses application of pantethine in preparation of medicines for preventing and / or treating thrombotic diseases or medicines for inhibiting platelet activation or regulating vascular endothelial cell functions. In-vivo and in-vitro experiments prove that pantethine can remarkably relieve thrombus load in a mouse thrombus model, down-regulate expression of vWF (von Willebrand Factor), up-regulate expression of TFPI (Tissue Factor Path Inhibitor) and TH BD (Thromboregulatory Protein), and antagonize platelet adhesion, aggregation and activation induced by a platelet activator. The action mechanism is closely related to inhibition of reactive oxygen species (ROS) generation and NF-kappa B signal channel activation, and improvement of endothelial cell functions. It can be known from the invention that pantethine plays an antithrombotic role from multiple aspects, and is suitable for preparation of antithrombotic drugs for prevention or treatment. The invention provides a new drug choice for prevention and treatment of thrombotic diseases.

The application provides a highland thrombosis disease risk early warning system, comprising: a sensing acquisition module, which is used for acquiring patient characteristic data, the patient characteristic data including physical sign data and individual baseline data; an index analysis module, which is used for preprocessing the patient characteristic data and generating risk indexes; a risk assessment module, which is used for assessing a risk coefficient according to the risk indexes; and a risk early warning module, which is used for obtaining a risk degree corresponding to the risk coefficient according to a pre-constructed risk classification standard, and implementing corresponding risk early warning according to the risk degree. The application solves the problem in the prior art that a portable health monitoring device cannot accurately measure core hemodynamic parameters closely related to thrombosis, and also cannot accurately perform risk early warning on highland thrombosis diseases according to the acquired parameters.

The invention discloses a recombinant human serum albumin-arteplase nano-drug (rHSA-HSAbp-rt-PA) as well as a preparation method and an application of the recombinant human serum albumin-arteplase nano-drug (rHSA-HSAbp-rt-PA). The nano-drug comprises arteplase (rt-PA), human serum albumin adhesion peptide (HSAbp) and recombinant human serum albumin (rHSA), and the sequence of the human serum albumin adhesion peptide is VGPLGPHYYYCAADLWRL. According to the present invention, the recombinant human serum albumin-arteplase nano-drug is connected through the human serum albumin adhesion peptide, such that the chemical cross-linking step is avoided, the preparation method is simple, and the recombinant human serum albumin-arteplase nano-drug has the half-life period of as long as 29 min, has good treatment effect, and has wide application prospects in the treatment of thrombotic diseases.

The present invention relates to a fluorescent probe based on a lanthanide metal organic framework, a preparation method and an application, and belongs to the field of nanomaterial technology. The fluorescent probe provided by the present invention is obtained by covalently cross-linking a lanthanide metal organic framework with a neutrophil elastin binding peptide and a P-selectin binding peptide, and the surface of the lanthanide metal organic framework is modified with a tetracyclic antibiotic and arginine. The fluorescent probe prepared by the present invention specifically targets activated platelets and neutrophils, does not affect cell survival rate, does not cause hemolysis of red blood cells, and can be applied to the preparation of diagnostic products for thrombotic diseases. The use of a fluorescent probe loaded with urokinase achieves stable and efficient delivery of urokinase, inhibits platelet aggregation, slows down blood clot contraction, has a good thrombolytic effect, and has the potential to be used in the preparation of drugs for the treatment of thrombotic diseases. The materials required for the present invention are easy to obtain, the preparation method is simple, and a new method is provided for the diagnosis and treatment of thrombotic diseases.

The invention relates to the field of biological polypeptides, in particular to an earthworm polypeptide for treating thrombotic diseases and application of the earthworm polypeptide. The amino acid sequence of the earthworm polypeptide disclosed by the invention is selected from at least one of sequences as shown in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 5 or SEQ ID NO: 6. The polypeptide disclosed by the invention can significantly promote fibrinolysis, has significant effects in inhibiting thrombosis and anticoagulation, and can effectively prevent and treat thrombotic diseases.

The invention discloses an application of a TBOA analogue in preparation of a kit for testing platelet stress self-regulating force, and the platelet stress self-regulating force is reflected by the aggregation degree of platelets after being intervened by the TBOA analogue. The application focuses on a new mechanism of platelet activation, that is, when platelets are stimulated by activators such as thrombin, normal reactions of activation and aggregation are driven and maintained by adjusting uptake of glutamic acid by EAATs. Due to the clear action mechanism, the application can provide indexes and methods with higher specificity in diagnosis, treatment and prognosis evaluation of thrombotic diseases, and the pertinence is extremely high. According to the application, the influence of the TBOA analogue on the platelet aggregation degree is utilized to test the stress self-regulating force of the platelet, and new clinical application of the TBOA analogue is developed.

The application discloses a polypeptide FXIa inhibitor FXIapepin with high inhibition and high specificity. Since FXIa can be used as a low hemorrhage risk anti-thrombus treatment target, the polypeptide inhibitor can be used for preparing a drug for developing a low hemorrhage risk treatment or prevention of a thrombotic disease, and has a wide application prospect.

The invention provides an isoquinoline derivative with a novel structure, a pharmaceutically acceptable salt thereof, a preparation method of the isoquinoline derivative, a pharmaceutical composition containing the isoquinoline derivative and pharmaceutical application of the isoquinoline derivative, and belongs to the technical field of medicines. In-vitro experiments show that the isoquinoline derivative has significant inhibitory activity on arachidonic acid-induced platelet aggregation, and the antiplatelet activity of part of compounds is superior to that of aspirin. In a rat carotid artery thrombosis model induced by FeCl3, the isoquinoline derivative remarkably prolongs thrombosis time and reduces thrombus weight, and the in-vivo antithrombotic curative effect of the isoquinoline derivative is equivalent to that of aspirin and ticagrelor. A mouse tail bleeding model shows that the side effects of bleeding amount and bleeding time of the isoquinoline derivative are obviously lower than those of aspirin and ticagrelor. Therefore, the series of isoquinoline derivatives have the advantages of efficient antithrombotic effect and low bleeding risk, and have good application prospects in preparation of drugs for preventing and treating thrombotic diseases. In addition, the preparation method provided by the invention has the advantages of easily available raw materials, simple steps and strong operability, and the obtained target product has high quality and good efficiency.

The invention discloses an antithrombotic peptide Sibakazin of Simulium bannaense and application of the antithrombotic peptide Sibakazin, and belongs to the field of biomedicine. The anti-thrombus peptide Sibakazin is cyclic protein of three pairs of intramolecular disulfide bonds formed by the twenty-sixth cysteine and the fifty-first cysteine, the twenty-eighth cysteine and the forty-seventh cysteine, and the thirty-sixth cysteine and the seventy-first cysteine coded by a blood sucking insect Simulium bannaense anti-thrombus peptide gene. The amino acid sequence of the gene is shown as SEQ ID NO: 1. The antithrombotic peptide provided by the invention can inhibit platelet aggregation induced by ADP or collagen, and has a significant thrombus formation inhibition function in vivo; in addition, the antithrombotic peptide is obtained through prokaryotic expression, large-scale industrial production is easy, and the antithrombotic peptide can be applied to preparation of drugs for inhibiting platelet aggregation and treating thrombotic diseases.

This invention relates to a method for constructing a humanized FXI mouse model, comprising: (1) constructing a targeting vector expressing the humanized FXI gene; (2) designing and obtaining sgRNA targeting the mouse FXI gene; (3) co-injecting or co-electroporating the targeting vector, sgRNA, and Cas9 protein into the cytoplasm or nucleus of mouse zygotes, and transplanting the zygotes into pseudopregnant mice, performing genotyping on the pseudopregnant pups, and screening for positive F0 mice with the correct humanized fragment inserted; (4) mating the F0 mice with background mice to obtain F1 mice, and screening for the humanized FXI mouse model. The humanized FXI mouse constructed by this invention has broad application prospects in the coagulation system, thrombotic diseases, and related drug screening.

The present invention relates to using c-Src SH3 RT-loop as a target for anti-thrombosis. Specifically, the present invention provides the use of a c-Src SH3 RT-loop antagonist for preparing a composition or preparation, and the composition or preparation is used for: (a) interfering with the interaction between integrin β3 and c-Src; (b) inhibiting platelet spreading on solid-phase fibrinogen; (c) inhibiting platelet aggregation and / or adhesion; and / or (d) preventing and / or treating thrombosis. The present invention discovers for the first time that a drug combination or preparation targeting the RT-loop region of the c-Src SH3 domain can effectively treat thrombotic diseases without increasing the risk of bleeding.

The application specifically discloses a kind of nanovaccine for thrombosis prevention and its preparation method and application, it is related to thrombotic disease, especially related to the nanovaccine for treating thrombotic disease.The nanovaccine provided by the application has good immunogenicity without macromolecular heterologous protein carrier such as KLH;The process simplicity and repeatability are improved by reducing complex chemical coupling and purification steps;The dependence on traditional high-stimulating immune adjuvant is reduced, and the biological safety is improved;The stability of antigen in gastrointestinal environment is significantly improved;Active targeting delivery of M cells and dendritic cells is realized;Dendritic cell maturation and antigen presentation are promoted, and mucosal immunity and systemic immunity level are improved;The advantages such as effectively inhibiting thrombosis are realized, and a new type of oral antithrombotic vaccine system with high compliance suitable for long-term thrombosis prevention is constructed.

The present invention discloses a recombinant human serum albumin-alteplase nanodrug (rHSA-HSAbp-rt-PA), its preparation method, and application. The nanodrug comprises alteplase (rt-PA), a human serum albumin adhesion peptide (HSAbp), and recombinant human serum albumin (rHSA), wherein the sequence of the HSA adhesion peptide is VGPLGPHYYYCAADLWRL. The rHSA-alteplase nanodrug is linked via the HSA adhesion peptide, avoiding the chemical cross-linking step and simplifying the preparation method. The rHSA-alteplase nanodrug has a half-life of up to 29 minutes, exhibits improved therapeutic efficacy, and has broad application prospects in treating thrombotic diseases.

Disclosed are aptamers, aptamer antidotes, and their use in the treatment of thrombosis and other thrombotic conditions.

The present invention provides cardio-cerebrovascular drugs and their use.Specifically, the compound of the present invention has the structure represented by formula (I), where each group is defined as described in the specification.The present invention also discloses the use of said compound in treating thrombotic disease, anti-inflammation and treating neurological injury. [Formula 1] JPEG2024545920000054.jpg4242

The present invention belongs to the technical field of polypeptide preparation and application, and specifically relates to an anticoagulant earthworm polypeptide and its preparation method and application. The amino acid sequence of the earthworm polypeptide is IISNFQAR; the earthworm polypeptide preparation method adopts the following steps: (1) crushing and sieving the earthworm, adding water, heating and boiling; (2) cooling the mixed solution obtained in step (1), adjusting the pH value, enzymolysis, boiling, and separation and purification; (3) treating the purified sample obtained in step (2) and performing LC-TOF-MS analysis to obtain the active peptide IISNFQAR. The research on earthworm polypeptide in the present invention confirms its medicinal value for preparing drugs for preventing and treating thrombotic diseases, provides a solid foundation for the clinical application of earthworm polypeptide to treat thrombosis, and provides data support for the development of active peptide substances in animal medicines.

The invention discloses an antithrombotic peptide Bannaensin of Simulium bannaense and application thereof, and belongs to the field of biomedicine. The anti-thrombus peptide Bannaensin is one of the twenty-second cysteine, the seventy-second cysteine, the thirty-first cysteine, the fifty-fifth cysteine, the forty-eighth cysteine and the sixty-eighth cysteine coded by a blood sucking insect Simulium bannaense anti-thrombus peptide gene, and the other is one of the twenty-second cysteine, the thirty-first cysteine, the fifty-fifth cysteine, the forty-eighth cysteine and the sixty-eighth cysteine coded by a blood sucking insect Simulium bannaense anti-thrombus peptide gene. The 110th cysteine and the 160th cysteine, the 119th cysteine and the 1343rd cysteine, and the 1336th cysteine and the 1366th cysteine form six pairs of cyclic proteins with intramolecular disulfide bonds, and the amino acid sequence of the cyclic proteins is shown as SEQ ID NO: 1. The antithrombotic peptide of the present invention can inhibit platelet aggregation induced by ADP or collagen, and shows significant antithrombotic activity in vivo; the antithrombotic peptide is obtained through prokaryotic expression, large-scale production can be achieved, and the antithrombotic peptide can be applied to preparation of drugs for inhibiting platelet aggregation and treating thrombotic diseases.

Provided are an siRNA which inhibits plasma coagulation factor XI gene expression, a pharmaceutical composition containing the siRNA, a conjugate, a reagent kit, and a use of the siRNA, the pharmaceutical composition thereof and the conjugate in preparing a drug used for treating and / or preventing thrombotic diseases and ischemic strokes.