81 results about "Urokinase" patented technology

The invention provides a separation and purification method of urokinase, and relates to the technical field of separation and extraction. The separation and purification method comprises the following steps: S1, regulating the pH value of male urine to 8.5, standing, and taking supernate; s2, mixing the supernate with an adsorption material, and eluting with an eluent to obtain a urokinase crude product solution; the adsorption material is a core-shell silica gel polymer, Fe3O4atSiO2-NH2 is taken as a core, and polystyrene is taken as a shell; the eluent is a sodium citrate buffer solution with the concentration of 0.5 to 0.15 M, acetonitrile with the concentration of 1 to 5 weight percent and EDTA (Ethylene Diamine Tetraacetic Acid) with the concentration of 0.5 to 1.5 mM; and S3, carrying out anion exchange column chromatography on the urokinase crude product solution, eluting with an eluent, and precipitating to obtain the urokinase. The urokinase prepared by the method has the advantages of high polymer urokinase content, high recovery rate and high activity yield.

The present invention includes a method of treating a subject having relapsing-remitting multiple sclerosis (RRMS) that is undergoing relapse, comprising: determining a level of expression for two or more biomarkers selected from urokinase plasminogen activator (uPA), kallikrein-8 (hK8), kallikrein-11 (hK11), or desmoglein-3 (DSG3) in a biological sample of a subject when compared to the same type of sample from a subject or a population of subjects that do not have RRMS; diagnosing that the subject in undergoing relapse if the level of expression of the two or more biomarkers has decreased in the subject; and administering a therapeutically effective amount of treatment for RRMS to the subject.

Methods and compositions for treating acute kidney injury in a subject are provided. The methods include measuring or having measured a level of soluble urokinase plasminogen activator receptor (suPAR) in a biological sample from the subject, determining or having determined the level of suPAR in the sample compared to a control suPAR level, and administering a therapeutically effective amount of an agent that antagonizes soluble urokinase plasminogen activator receptor (suPAR) to the subject having an elevated level of suPAR relative to the control suPAR level.

This invention belongs to the field of urea preparation technology and discloses a large-particle urea, composed of the following raw materials in a specific ratio: a 50% concentration of dilute urine solvent, a urokinase activity inhibitor, and a pigment, in a ratio of 100:6:5. This solution, through the careful design of the 50% concentration of dilute urine solvent, the urokinase activity inhibitor, and the pigment, enhances the soil dissolution rate and utilization rate. The addition of the urokinase activity inhibitor effectively inhibits the rapid hydrolysis of urea, reduces ammonia nitrogen loss, improves nitrogen utilization, mitigates negative environmental impacts, and contributes to soil ecological balance. The use of large-particle morphology and strict moisture control technology ensures the product's moisture resistance and storage stability, extending its shelf life. During production, the temperature is precisely controlled at 30℃, which avoids urine crystallization, ensures the full dissolution of the urokinase activity inhibitor, avoids odors generated at high temperatures, reduces environmental pollution, and improves the product's environmental friendliness.

There is provided a positron-emitting radionuclide labelled peptide for non-invasive PET imaging of the Urokinase-type Plasminogen Activator Receptor (uPAR) in humans. More specifically the invention relates to human uPAR PET imaging of any solid cancer disease for diagnosis, staging, treatment monitoring and especially as an imaging biomarker for predicting prognosis, progression and recurrence.

Methods and compositions for treating acute kidney injury in a subject are provided. The methods include measuring or having measured a level of soluble urokinase plasminogen activator receptor (suPAR) in a biological sample from the subject, determining or having determined the level of suPAR in the sample compared to a control suPAR level, and administering a therapeutically effective amount of an agent that antagonizes soluble urokinase plasminogen activator receptor (suPAR) to the subject having an elevated level of suPAR relative to the control suPAR level.

A thrombus suction negative pressure suction device comprises an injection needle tube, a piston is arranged in the injection needle tube in a sliding mode, the head end of the injection needle tube is connected with a connecting sleeve, the head end of the injection needle tube is connected with symmetrically-distributed air outlet tubes, a limiting frame is arranged in each air outlet tube, an air blocking plate is arranged on each limiting frame in a sliding mode, and the air blocking plates are connected with the connecting sleeves in a sliding mode. The air blocking plate is used for sealing the air outlet pipe, the air blocking plate is sleeved with a first elastic piece, and a first ball valve is arranged in the connecting sleeve. By arranging the liquid storage tube on the injection needle tube, a urokinase solution can be directly injected into the suction catheter without additionally using a three-way valve, the overall operation is simpler, and the injection needle tube and the suction catheter can be blocked through the first ball valve, so that the injection needle tube and the suction catheter can be independently operated; and the injection needle tube can exhaust internal air through the air blocking plate, negative pressure is achieved, air is prevented from entering the suction catheter, and therefore it is guaranteed that the suction catheter is in a stable negative pressure state.

This invention discloses a fusion protein targeting the urokinase-type plasminogen activator receptor and its application in the field of anti-aging. The fusion protein is composed of a hepatocyte growth factor active domain and a humanized anti-uPAR single-domain antibody linked by a flexible linker peptide, and its specific amino acid sequence is SEQ ID NO:3. This fusion protein can specifically bind to uPAR, which is highly expressed on the surface of senescent cells, with intramolar affinity, achieving targeted delivery of the hepatocyte growth factor active domain. In vitro experiments have demonstrated that this protein can significantly reverse the aging phenotype of human fibroblasts, effectively reduce aging-related β-galactosidase activity, p16INK4a protein expression, and interleukin-6 secretion, and promote cell proliferation. In a rapidly aging mouse model, this protein can systematically improve age-related physiological functional decline. The fusion protein of this invention achieves specific targeting and efficient treatment of senescent cells, providing a new solution for the development of anti-aging drugs.

The utility model relates to the field of urokinase extraction, and discloses a urine and water diverter for separating and extracting urokinase from human urine, which comprises a shell, a protective cover is arranged at the top end of the shell, a filter plate is arranged on the inner wall of the shell, a driving motor is fixedly connected to the top end of the protective cover, and an output shaft of the driving motor penetrates through and rotates on the inner wall of the protective cover. A cleaning assembly is arranged at the bottom end of an output shaft of the driving motor and comprises a connecting rod, the top end of the connecting rod is fixedly connected to the bottom end of the output shaft of the driving motor, and stirring blades are fixedly connected to the outer side of the connecting rod. According to the urine separating and filtering device, the driving motor, the cleaning assembly and the filtering plate are used in cooperation, when urine is separated and filtered, the cleaning brush can be driven by the driving motor to clean the filtering net, it is ensured that the filtering efficiency is continuous and stable, then the urine is stirred through the stirring blades, and therefore dispersion of impurities in the urine is promoted; and the risk of blockage of the filter screen is reduced.

Provided are antibodies that specifically bind to human urokinase-type plasminogen activator receptor (uPAR). In some cases, the antibodies are cross-reactive with one or more non-human animal uPAR polypeptides, such as non-human primate uPAR, e.g., cynomolgus monkey uPAR. Fusion proteins and conjugates comprising the antibodies of the present disclosure are also provided. Methods of using the antibodies, fusion proteins, and conjugates of the present disclosure to treat conditions associated with uPAR expression and / or activity are also provided. In some embodiments, the condition associated with uPAR expression and / or activity is cancer. Non-limiting examples of such cancers include cancers characterized by cancer cells expressing uPAR on their surface, cancers characterized by stromal cells within the tumor microenvironment expressing uPAR on their surface, and the like.

Disclosed herein, are peptides that bind urokinase-type plasminogen activator receptors. The peptides may comprise amino acid sequences of IPPWEAPK (SEQ ID NO: 1), DLAQCQTPTQAAPPTPVSPR (SEQ ID NO: 2), or LHVPLMPAQPAPPK (SEQ ID NO: 3), or retro-inverso amino acid sequences of the above enumerated sequences. Also described herein, are methods of administering compounds comprising peptides that bind urokinase-type plasminogen activator receptors to subjects for the treatment of ovarian cancer and improving wound closure.

This invention relates to the field of biotechnology, specifically to a TruC-T cell that secretes and expresses IL-7 and PF4 to enhance anti-tumor activity and targets uPAR, and its application. Interleukin-7 (IL-7) can effectively promote the development, survival, and proliferation of T cells, while platelet factor 4 (PF4 / CXCL4) can regulate the immune response and chemotactically attract leukocytes to specific sites; the synergistic effect of the two can enhance the anti-tumor function and persistence of T cells. Meanwhile, urokinase-type plasminogen activator receptor (uPAR) is highly expressed in various solid tumors and hematological malignancies, making it an ideal target for tumor therapy; TruC-T cells targeting uPAR can precisely act on tumor tissue, and combined with the immune-enhancing effects of IL-7 and PF4, can significantly improve the efficacy of anti-tumor immune responses, prolong the duration of therapeutic effects, and reduce tumor recurrence.

The current invention relates to a polypeptide comprising an immunoglobulin single variable domain and an urokinase-type plasminogen activator (uPA) domain wherein the immunoglobulin single variable domain is able to bind to fibrin via a fibrin-binding domain.

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 disclosure provides urokinase plasminogen activator receptor (uPAR) binding polypeptides (e.g., uPAR antigen binding proteins), and fusion proteins comprising said uPAR binding polypeptides and a cytokine or variant thereof. The disclosure further provides pharmaceutical compositions comprising the uPAR binding polypeptides and fusion proteins of the disclosure and methods of treating cancer with the same. The disclosure further provides engineered IL-12 p35 and p40 polypeptides.

The application discloses an engineered exosome targeting human urokinase-type plasminogen activator receptor uPAR and a preparation method and application thereof. Firstly, a high-affinity anti-human uPAR single-domain antibody VHH is prepared; then, a human umbilical cord mesenchymal stem cell engineering cell line expressing a VHH-PTGFRN fusion protein is constructed, and the engineered exosome is prepared and purified by combining three-dimensional hypoxic culture, chemical induction and size-exclusion chromatography technology. The engineered exosome comprises four comparative samples, wherein the core sample Exo^(VHH / miR) can simultaneously display the anti-uPAR VHH on the membrane surface to realize targeted delivery and enrich miR-193b-3p in the chamber to realize gene silencing, and the synergistic effect of the two can efficiently remove the uPAR high-expression senescent cells and inhibit the senescence-associated secretory phenotype SASP. The engineered exosome has the advantages of standardized preparation process, high yield and high purity, strong targeting, excellent curative effect and good safety, and can be used for preparing a treatment preparation for anti-aging and aging-related diseases, and has important clinical application value.

The invention provides a preparation method of an aprotinin affinity chromatographic column. Specifically, the aprotinin is used as a raw material and is coupled with CNBr activated agarose gel Focurose 4FF to prepare the aprotinin affinity chromatographic column. The coupling reaction in the preparation method is simple and easy to control, the reaction condition is mild, the operation is convenient, the repeatability is high, and industrial amplification is easy. The affinity column prepared by the invention can completely remove human urinary kallidinogenase in urokinase, and can be repeatedly used for multiple times.

The invention discloses preparation and application of macrophage targeting nanoparticles entrapped with a cell burial function accelerant. The medicine for enhancing the intercellular function of the macrophages is a liver X receptor stimulant, and the liver X receptor stimulant comprises at least one of T0901317, GW3965, Ouabagenin and LXR-623. The surface of the targeting nanoparticle is coated with a macrophage cell membrane, and meanwhile, a urokinase type plasminogen activator receptor (uPAR) targeting ligand is modified. The nanoparticle can be efficiently accumulated at an inflammatory focus part by utilizing a macrophage cell membrane, and the modified targeting ligand is used for targeting the macrophage with damaged cell burial function, so that the cell burial function of the macrophage is enhanced, the polarization of the macrophage to an anti-inflammatory phenotype is promoted, the release of anti-inflammatory and proinflammatory cytokines is regulated, and the anti-inflammatory effect of the nanoparticle is improved. And finally, the inflammatory microenvironment of a focus part is regulated and controlled, so that a good effect of treating autoimmune diseases is achieved.

Provided are modified u-PA polypeptides and fusion proteins containing the modified u-PA polypeptides. The u-PA polypeptides are modified to have altered activity and / or specificity so that they cleave a complement protein, such as complement protein C3, to thereby inhibit complement activation. The modified u-PA polypeptides and fusion proteins that inhibit complement activation can be used for treatment of diseases and conditions that are mediated by complement activation, or in which complement activation plays a role. These disorders include ischemic and reperfusion disorders, including myocardial infarction and stroke, sepsis, autoimmune diseases, diabetic retinopathies, age-related macular degeneration, transplanted organ rejection, inflammatory diseases and diseases with an inflammatory component.

The invention provides a composite microsphere, a preparation method and application thereof, and a urokinase purification method, and belongs to the field of bioengineering and chemical engineering. The composite microsphere is prepared from the following raw materials: modified nano ferroferric oxide, polylactic acid, polylysine and arginine. According to the invention, the composite microspheres comprising modified nano ferroferric oxide, polylactic acid, polylysine and arginine are used as chromatographic column filler, and a urokinase raw material solution is subjected to chromatographic column treatment, so that the adsorption capacity to endotoxin can be effectively improved, and the activity of urokinase is improved.

A product, composition, suspension and / or method to dissolve vaso-occlusive clots in vivo in a sickle diseased subject utilizing Target-specific Thrombolytic Urokinase Spheres (TTUS). The TTUS can target vaso-occlusive clots in vivo and then lyse the obstructive blood clots with high efficiency can be intravenously administered to a subject in need thereof. The TTUS are configured to dissolve vaso-occlusive clots by converting plasminogen in blood of the subject into plasmin molecules that dissolves the clot. The nanospheres can encapsulate an enzymatically active bioreactive agent, such as urokinase. Since the active enzyme is targeting and binding essentially only to obstructive clots, there is minimal risk of side-effects to the subject. The nanospheres are less than one micron in diameter, resulting in a size much smaller than red blood cells.

The utility model discloses a urokinase eluent recovery device which comprises a base, a mounting rack is arranged above the base, an elution tank is fixedly arranged on the base, four groups of symmetrically distributed liquid collecting tanks are arranged on the mounting rack, the liquid collecting tanks and the elution tank are correspondingly distributed, a mounting ring is arranged above the elution tank, and the mounting ring is arranged on the mounting rack. A mounting ring is arranged below the elution tank, a scraping rod is fixedly mounted on the mounting ring, the scraping rod is attached to the inner wall of the elution tank, a cleaning block is arranged on the scraping rod, the cleaning block is in sliding connection with the scraping rod, a rotating ring is arranged below the elution tank, a plurality of groups of annularly distributed bottom plates are arranged below the elution tank, and the plurality of groups of bottom plates are rotationally connected with the elution tank through mounting shafts; the multiple sets of annularly-distributed bottom plates are matched with the scraping rods and the cleaning blocks, so that complete cleaning of kieselguhr on the inner wall of the elution tank is achieved, and the situation that the next use of the eluent recovery device is affected due to the fact that residual kieselguhr cannot be completely cleaned is avoided.

The present invention relates to humanized antibodies and molecular conjugates targeting Urokinase type plasminogen activator receptor associated protein (uPARAP), in particular antibody-drug conjugates (ADCs) comprising humanized antibodies directed against uPARAP and their use in delivery of active agents to cells and tissues expressing uPARAP. The invention further relates to the use of said ADCs in the treatment of diseases involving uPARAP expressing cells, such as certain cancers.

The present invention relates to a hybrid protein comprising a urokinase catalytic domain and a VHH specifically binding to vWF for use in treating a patient having elevated serum lactate dehydrogenase (LDH) levels or at risk thereof following or during a traumatic event. The treatment comprises administering the hybrid protein to reduce the serum LDH levels of the patient to a target range of less than 280 U / L. The present invention also relates to means and methods for the prevention and / or treatment (including, as mentioned herein, reducing and / or limiting the damage caused by) of tissue damage, especially tissue damage associated with the occurrence and / or formation of thrombi in circulation.

The invention relates to the technical field of urokinase, and discloses a urokinase purification method and a chromatographic column type adsorption device for extraction, the purification method comprises the following steps: S1, taking a urokinase raw material, carrying out microfiltration, adding a chitosan quaternary ammonium salt solution, carrying out directional flocculation, centrifuging, and collecting a supernatant; s2, adding the supernate in the step S1 into a weak anion exchange chromatographic column, eluting, collecting eluent with active components, and desalting the eluent; s3, adding the eluent desalted in the step S2 into a gel filtration chromatography column, eluting, and collecting the eluent; s4, the eluent in the step S3 is added to a Ni-IMAC metal chelating chromatographic column, and purified urokinase is obtained after elution. According to the method, multiple chromatographic columns are used for chromatography, and cost and operation complexity are reduced.

Provided herein are methods for safe and effective thrombolysis in therapy for human subjects with symptoms of a potential stroke or acute myocardial infarction (“AMI”) using a sequential administration of a low dose bolus of human tissue plasminogen activator (“tPA”) followed by an infusion of a mutant form of human pro-urokinase (“proUK”).

The invention relates to the technical field of separation and extraction of natural products, in particular to a method for extracting unimodal urokinase from human urine. The method sequentially comprises the following steps: human urine collection, silica gel chromatography, precipitation, aprotinin chromatography, pasteurization for virus inactivation, anisole chromatography, molecular sieve chromatography and freeze-drying. A novel purification process is designed, a specific purification technology is adopted to ensure that a final product shows a single peak in chromatographic analysis, the content of impurity protein in a high-purity product is extremely low, anaphylactic reaction and immunogenicity can be reduced, the medication safety of a patient can be improved, and the method can be directly used for development of a freeze-drying preparation or an injection and simplification of a downstream preparation process. The implementation of the scheme provided by the invention can promote the upgrading of the thrombolytic drug industry chain in China and improve the international competitiveness. The method has the advantages of high finished product purity, few impurities, simplicity and convenience in operation, concise extraction steps, reduced production time, high efficiency, small environmental pollution, low production cost and the like.

This disclosure relates to nanoparticles coated with fusion proteins comprising a domain that binds a cancer marker and a domain comprising a toxic polypeptide. In certain embodiments, the targeted cancer marker is urokinase plasminogen activator receptor (uPAR) insulin-like growth factor 1 receptor (IGF1R), EGFR, HER2, and / or other member of the ErbB family of receptors. In certain embodiments, the molecule that binds a cancer marker is an amino terminal fragment of uPA or variant capable of binding uPAR and / or IGF1 or variant capable of binding IGF1R. In certain embodiments, the toxic polypeptide is a bacterial exotoxin.

Disclosed are novel urokinase plasminogen activator receptor (uPAR) binding molecules and soluble urokinase plasminogen activator receptor (suPAR) binding molecules and methods of their use.

The invention discloses a CHO cell line and a method for producing recombinant human low molecular weight urokinase (rh-LLW-uPA) by using the CHO cell line. The method has high productivity and enables the production of low molecular weight urokinase having improved characteristics in terms of safety, quality and stability.