59 results about "Plasmin activity" patented technology

The invention provides a dilution buffer solution for chemiluminescence detection of a blood sample. The dilution buffer solution contains 0.05 to 1 weight percent of plasmin and 0.005 to 0.02 weight percent of a de-foaming agent. The dilution buffer solution provided by the invention can reduce the jump value phenomenon in chemiluminescence detection of a blood sample, especially a repeatedly frozen and thawed blood sample, so that a correct and reliable detection result is provided for clinic, and the clinical detection time can be saved.

It is disclosed a method for determining the biological activity of defibrotide, which comprises the steps of: a) bringing into contact defibrotide, mammalian euglobulin and a substrate specific for the plasmin which, by reaction with the plasmin, provides a measurable product; and b) measuring the amount of product formed at successive times, to thereby determine the biological activity of the defibrotide. Liquid defibrotide formulations are also disclosed, preferably water solutions, having a defined biological activity and, in particular, having an activity of 25 to 35 IU / mg of defibrotide, preferably from 27 to 32 IU / mg and, more preferably, from 28 to 32 IU / mg.

It is disclosed a method for determining the biological activity of defibrotide, which comprises the steps of: a) bringing into contact defibrotide, mammalian euglobulin and a substrate specific for the plasmin which, by reaction with the plasmin, provides a measurable product; and b) measuring the amount of product formed at successive times, to thereby determine the biological activity of the defibrotide. Liquid defibrotide formulations are also disclosed, preferably water solutions, having a defined biological activity and, in particular, having an activity of 25 to 35 IU / mg of defibrotide, preferably from 27 to 32 IU / mg and, more preferably, from 28 to 32 IU / mg.

The invention discloses a plasmin lumbrukinase peptide dietary therapy formula suitable for rehabilitation of cardiovascular and cerebrovascular diseases, blood circulation promoting, blood stasis removing, thrombolysis, collateral dredging and microcirculation improving, and relates to the technical field of medicine and food homology dietary therapy. Soybean protein isolate and earthworm protein are used as core thrombolytic active raw materials, isomaltooligosacharide, xylitol, German Jilida collagen peptide, soybean peptide powder, Belgian imported inulin, red yeast rice and natto powder are compounded, microcrystalline cellulose and magnesium stearate are used as auxiliary materials, and probiotics / metabiotics strains such as rhamnolactobacilli JYLR-005 and the like can be selectively added. The raw materials have a synergistic effect through precise matching, plasmin and lumbrukinase peptide in earthworm protein can directly dissolve thrombus fibrin, natto powder and red yeast rice assist in lowering lipid and dissolving thrombus, multiple active peptides and prebiotics regulate intestinal microecology to improve microcirculation of the whole body, probiotics / metabiotics further strengthen the metabolic capacity of the body, no chemical medicine is added in the whole process, and the traditional Chinese medicine composition is free of toxic and side effects and free of toxic and side effects. The safety is high; the dietary therapy composition can achieve postoperative rehabilitation conditioning of cardiovascular and cerebrovascular diseases through daily consumption, effectively promote blood circulation to remove blood stasis, dissolve thrombus and dredge collaterals, improve microcirculation and relieve various discomfort caused by blood vessel clogging, raw materials are easy to obtain, compatibility is scientific, and the dietary therapy composition is suitable for large-scale production and popularization.

The invention belongs to the technical field of food, and particularly relates to application of nisin in inhibiting plasmin activity and improving quality of milk and / or dairy products. The nisin disclosed by the invention can be used for remarkably inhibiting the activity of plasmin. The nisin disclosed by the invention is a food additive allowed to be used, the INS number is 234, and the nisin is high in safety. Plasmin is a key enzyme causing deterioration of milk and milk quality, and the nisin disclosed by the invention improves the quality of milk and / or dairy products from the source by inhibiting the activity of plasmin.

The invention provides plasmin-targeted complement C3 derived anticoagulant polypeptide and application thereof, and belongs to the technical field of biological medicine. The present invention provides a complement C3-derived anticoagulant polypeptide (C3-HK10) and a modified peptide (C3-moHK10), which reduce nerve injury by enhancing the activity of plasmin in degrading fibrin thrombus and promoting the production of matBDNF (matured brain-derived neurotrophic factor), thereby protecting a host from dual threats of inflammatory thrombosis and neurological dysfunction, and also provides a method for preparing the anticoagulant polypeptide (C3-HK10) and a modified peptide (C3-moHK10). And good safety is shown. In conclusion, it is found for the first time that the complement C3 polypeptides C3-HK10 and C3-moHK10 have the characteristic of promoting plasmin activity, have the functions of inhibiting inflammation, thrombus and ischemic cerebral apoplexy injury and relieving nerve injury, and have the potential of becoming anti-inflammatory, thrombus and stroke treatment and neurological function drugs.

To provide a drug that inhibits the interaction between urokinase receptor and urokinase, focusing on various physiological actions caused by the inhibition of plasmin action.SOLUTION: Provided is 1-(2-hydroxyethyl)-2-imidazolidinone (HEI) or derivatives thereof, or salts thereof, as a drug that inhibits the interaction between urokinase receptor and urokinase. 1-(2-hydroxyethyl)-2-imidazolidinone (HEI) or derivatives thereof, or salts thereof, inhibits the action of plasmin through inhibition of the interaction between urokinase receptor and urokinase, and exerts various physiological actions such as inhibition of inflammation, prevention of the degradation of extracellular matrix, and inhibition of cancer invasion.SELECTED DRAWING: Figure 2

The present invention relates to a plasmin inhibitor, a preparation method thereof and an application in the pharmaceutical field. Specifically, the present invention provides a compound represented by formula I, a preparation method thereof and an application in the pharmaceutical field, which relates to the field of medicinal chemistry. In formula I, R1 is H or halogen; R2 and R3 are each independently selected from H, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroalicyclic group, substituted or unsubstituted heteroaryl; n = 0, 1 or 2. The compound provided by the present invention has high blood coagulation and hemostasis activities, high blood drug concentration and exposure in vivo, good safety, and has good clinical application prospects.

The present invention relates to an isolated antibody or antigen-binding fragment thereof that binds to human A2AP. The isolated antibody or antigen-binding fragment according to the present invention i) cross-reacts with rabbit and / or cynomolgus A2AP, ii) does not inhibit human plasmin activity, and iii) increases plasmin mediated clot lysis in the presence of A2AP.

The present application relates to a method for promoting the degradation of pathological TDP-43 protein, comprising administering to a subject a therapeutically effective amount of one or more compounds selected from components of the plasminogen activation pathway, compounds that can activate plasminogen directly or indirectly by activating upstream components of the plasminogen activation pathway, compounds that mimic the activity of plasminogen or plasmin, compounds that can upregulate the expression of plasminogen or plasminogen activators, plasminogen analogs, plasmin analogs, tPA or uPA analogs, and antagonists of fibrinolysis inhibitors. The present application also relates to agents that promote the degradation of pathological TDP-43 protein and uses thereof.

This invention discloses a multi-enzyme preparation for industrial cell dissociation, its usage method, and applications, belonging to the field of seed cell extraction technology for industrial meat culture. The invention employs a multi-enzyme preparation composed of component 1 and component 2; component 1 includes neutral protease, hyaluronidase, and elastase; component 2 includes matrix metalloproteinase, papain, and plasmin. The invention also discloses the preparation method and applications of the multi-enzyme preparation. The rational enzyme ratio and optimized treatment conditions of this invention help protect cell membrane integrity, maintain high cell activity, and significantly improve dissociation efficiency and cell recovery. The compound enzyme preparation is highly adaptable, applicable to various tissue types and dissociation requirements, and facilitates standardized and large-scale production. Combined with automated dissociation equipment, the compound enzyme preparation enables efficient and stable industrial operation, providing important technical support and broad application prospects for the cultured meat industry, tissue engineering, and cell therapy.

To provide an antigen-binding protein comprising an antigen-binding domain that binds to plasmin. Also provided are compositions comprising the antigen binding proteins, as well as uses thereof and methods of treatment comprising the same.SOLUTION: To provide antigen-binding proteins or antigen-binding fragments thereof that specifically bind to the serine protease domain of plasmin and inhibit or reduce plasmin activity via interaction with the catalytic site of the protein.SELECTED DRAWING: None

This invention discloses the application of the plasmin inhibitor NKI10 in the preparation of drugs for preventing and treating excessive inflammatory responses, belonging to the field of biomedical technology. The amino acid sequence of the plasmin inhibitor NKI10 disclosed in this invention is shown in any one of SEQ ID NO. 1 to 10. The plasmin inhibitor NKI10 can significantly inhibit the production of IL-6, IL-1β, and TNF-α in animal and cellular inflammation models. Since the plasmin inhibitor NKI10 can inhibit excessive inflammatory responses, it can be prepared for use as a drug for preventing and treating excessive inflammatory responses.

The application provides a plasmin alpha2 plasmin inhibitor complex antibody 4C1 and 2D5, the sequence of the heavy chain variable region of the antibody 4C1 is shown as SEQ ID NO:1, and the light chain variable region is shown as SEQ ID NO:2; the sequence of the heavy chain variable region of the antibody 2D5 is shown as SEQ ID NO:9, and the light chain variable region is shown as SEQ ID NO:10. The detection sensitivity of the antibody is high.

The invention discloses plasmin based on hermetia illucens and application thereof, and belongs to the technical field of biology. The plasmin based on the hermetia illucens is obtained by grinding and centrifuging larvae of the hermetia illucens in a PBS (Phosphate Buffer Solution) and extracting supernate. The invention further provides application of the plasmin based on the hermetia illucens in preparation of thrombolytic drugs. The plasmin is extracted from the hermetia illucens, and the hermetia illucens is short in breeding cycle, high in reproductive capacity, capable of being massively extracted in a short time and low in cost; the extracted plasmin has a remarkable thrombolysis effect and has a very good utilization value; the plasmin can be used for directly dissolving thrombus and degrading fibrinogen.

The invention discloses a tranexamic acid-tyrosinase inhibitor hybrid conjugate as well as a preparation method and application thereof, belongs to the technical field of cosmetics and biological medicines, and particularly relates to a tranexamic acid-tyrosinase inhibitor hybrid conjugate shown in a formula (I) and a skin composition taking the compound as an active component. According to the hybrid conjugate, tranexamic acid and a tyrosinase inhibitor are integrated into a single-structure molecule through an ester bond, so that the transdermal efficiency can be improved and the transdermal dynamic difference limitation of a traditional compound preparation can be broken through by adjusting the hydrophilic-hydrophobic balance of the compound; and plasmin activity can be inhibited through cooperation of tranexamic acid, so that melanin generation signal transmission capability and tyrosinase inhibition capability of tyrosinase inhibitor specificity are reduced, and efficient and mild multi-channel whitening and spot fading are realized. As a whitening active matter, the tranexamic acid-tyrosinase inhibitor hybrid conjugate disclosed by the invention has a great application prospect in the aspects of whitening and freckle removing effects.

The present disclosure provides an ADC comprising a plasmin cleavage site. The ADC according to the present disclosure can have a hydrophobic portion between an antibody and a plasmin cleavage site, and the hydrophobic portion includes no uncharged hydrophilic polymers such as polyethylene glycol (PEG).

The present disclosure provides compositions for hemostasis blood testing, as well as related methods, systems, kits, and sample holders. The compositions include any one or more of (a) a plurality of phospholipids, (b) a plurality of activators, (c) a blood coagulation initiator, and (d) plasmin or a precursor thereof. In some embodiments, the composition further includes one or more of (e) a buffer, (f) a sugar, (g) a protein concentration reference standard, and (h) CaCl2.

The present invention belongs to the field of biomedicine technology, and specifically relates to a novel recombinant protein Plasminogen-CTM and its application. The present invention first provides a novel recombinant protein Plasminogen based on natural Plasminogen protein, and after the amino acid sites 742-810 of the natural Plasminogen protein are mutated in a combined manner, multiple recombinant protein mutants are obtained. The novel recombinant protein Plasminogen provided by the present invention has enzyme activity without activation by an activator, and can therefore be an effective means to replace natural plasmin directly isolated from plasma.

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 invention discloses application of a plasmin inhibitor NKI10 in preparation of a medicine for preventing and treating excessive inflammatory reaction, and belongs to the technical field of biological medicine. The invention discloses application of a plasmin inhibitor NKI10 in preparation of a medicine for preventing and treating excessive inflammatory reaction. The amino acid sequence of the plasmin inhibitor NKI10 is shown as any one of SEQ ID NO.1-10. The plasmin inhibitor NKI10 can be used for remarkably inhibiting the generation of IL-6, IL-1beta and TNF-alpha in an animal inflammation model and a cell inflammation model. The plasmin inhibitor NKI10 can inhibit the excessive inflammatory reaction, so that the plasmin inhibitor NKI10 can be applied to preparation of drugs for preventing and treating the excessive inflammatory reaction.

The invention relates to the technical field of in-vitro diagnosis, and discloses a plasmin-alpha 2 plasmin inhibitor compound detection kit and a preparation method and application thereof.The plasmin-alpha 2 plasmin inhibitor compound detection kit comprises a reagent M, a reagent R1, a reagent R2, a calibration product and a quality control product, and the reagent M comprises a plasmin-alpha 2 plasmin inhibitor compound antibody coated Tosyl magnetic bead suspension; the R1 reagent is a phosphate buffer solution; the reagent R2 comprises an acridinium ester labeled plasmin-alpha 2 plasmin inhibitor compound antibody, and the reagent R2 comprises an acridinium ester labeled plasmin-alpha 2 plasmin inhibitor compound antibody; the calibrator is prepared from a plasmin-alpha 2 plasmin inhibitor compound; and the quality control product comprises a plasmin-alpha 2 plasmin inhibitor compound. According to the invention, the accuracy of the detection result of the plasmin-alpha 2 plasmin inhibitor compound can be improved.

The invention provides a method for detecting plasmin in dairy products, which comprises the following steps: firstly dissociating plasmin in milk in a buffer solution (containing a dissociating agent), and then hydrolyzing non-fluorescent coumarin peptide by using the dissociated plasmin to release 7-amino-4-methyl coumarin (AMC). And determining the activity of plasmin in the sample by measuring the concentration change of the fluorescence product AMC. According to the present invention, the dissociation reagent, the detection mode (dynamic and non-dynamic), the detection instrument parameter, the specific detection process and the like are subjected to the experimental invention improvement, and the detection method suitable for the experimental matrix is established so as to provide the more accurate detection data; results show that the standard curve obtained by the method is excellent in linearity and relatively good in repeatability, and the detection result is not influenced by the milk turbidity and is stable.

The invention relates to a plasmin inhibitor as well as a preparation method and application thereof, in particular to a compound which can inhibit plasmin activity and delay fibrinolysis, has blood coagulation and hemostasis activity and is shown in a formula (I), pharmaceutically acceptable salts, hydrates, isomers, prodrugs and mixtures thereof, and X, R1 to R5 are defined in the specification.

The invention discloses a fermented soybean fermentation process for high-yield plasmin and thrombolysis application thereof. According to the method, black beans are used as raw materials, water is added for soaking and sterilization, bacillus subtilis is added, the mixture is put into a constant-temperature and constant-humidity incubator for fermentation, according to plasmin activity, the fermentation temperature, humidity, time, inoculation amount, loading capacity and solid-liquid ratio are subjected to a single-factor test, the solid-state fermentation conditions are optimized, and the plasmin solid-state fermentation effect is improved. An optimal solid-state fermentation process is determined by combining an orthogonal test, high-plasmin-yield fermented soybean is obtained through an ultralow-temperature freeze-drying technology, and finally, the safety and thrombolysis effect of the plasmin of the fermented soybean are verified through in-vivo and in-vitro thrombolysis experiments. Compared with the traditional processing process, the fermented soybean processed by the method disclosed by the invention has the advantages that the influence of seasonal and environmental conditions is reduced by utilizing the principle of pure fermentation, the quality stability of the fermented soybean is improved, and meanwhile, the production of the fermented soybean with high plasmin yield lays a foundation for the development of thrombolytic drugs.

The invention relates to a VHH specifically binding to plasmin. The invention further relates to a compound or a pharmaceutical composition comprising the VHH and to the use thereof in the treatment, prevention or amelioration of a disease or condition characterized by a thrombotic or embolic state.

This invention belongs to the field of biomedicine and relates to a procoagulant polypeptide TPTX and its applications. The procoagulant polypeptide TPTX of this invention can exert its procoagulant and hemostatic effects by specifically inhibiting plasmin activity. Experiments have shown that TPTX exhibits significant dose-dependent procoagulant and hemostatic effects in ferric chloride-induced mouse carotid artery thrombosis models, mouse liver hemorrhage models, mouse tail hemorrhage models, and mouse saphenous vein hemorrhage models, with effects superior to the positive control drug 6-aminocaproic acid. Simultaneously, TPTX can reduce the area of ​​atorvastatin-induced cerebral hemorrhage in zebrafish and improve their motor dysfunction. Mechanistic studies show that TPTX has an inhibitory constant Ki of 17.76 nM on plasmin and has no significant effect on the activity of seven other key serine proteases in the coagulation system, demonstrating a clear target and high selectivity. The procoagulant polypeptide of this invention can be used to prepare hemostatic drugs, possessing the advantages of high efficiency, clear target, and high selectivity, with broad prospects for clinical application.

The invention provides a method for detecting plasmin activity in ultra-high-temperature sterilized cow milk, the detection method comprises the step of pretreating the ultra-high-temperature sterilized cow milk to obtain a clear and transparent sample solution, the pretreatment comprises the following steps: mixing the ultra-high-temperature sterilized cow milk with a trisodium citrate buffer solution, adjusting the pH value to 8.2, and centrifuging to remove fat, and mixing the degreased cow milk with a detection buffer solution containing epsilon-aminocaproic acid, so that plasmin is separated from casein. According to the preparation method, casein is dissociated by adding trisodium citrate, then the pH value is adjusted to 8.2, and centrifugal degreasing is performed, so that the floating speed of fat is increased, plasmin on the surface (oil-water interface) of the fat is promoted to be released into whey, and a clear solution is obtained; by adding epsilon-aminocaproic acid, plasmin is fully separated from casein, competitive inhibition of casein on a synthetic substrate is reduced, and accurate determination of plasmin activity in UHT milk with low plasmin activity is realized.

The present invention discloses a plasmin-inhibiting peptide YHX-PIP-4 derived from bovine milk protein and its application, and relates to the technical field of bioactive peptides. The present invention provides a plasmin-inhibiting peptide YHX-PIP-4 derived from β-lactoglobulin, whose amino acid sequence is shown in SEQ ID NO.1. With the help of bioinformatics technology, the present invention screened a peptide segment with plasmin inhibition ability from the β-lactoglobulin sequence through molecular docking and molecular dynamics simulation technology. This peptide segment is named plasmin-inhibiting peptide YHX-PIP-4; studies have confirmed that the plasmin-inhibiting peptide YHX-PIP-4 can inhibit the activity of plasmin, and adding it to ultra-high temperature milk can avoid the precipitation and aging gel phenomenon of milk during storage, thereby extending its shelf life.

It is disclosed a method for determining the biological activity of defibrotide, which comprises the steps of: a) bringing into contact defibrotide, mammalian euglobulin and a substrate specific for the plasmin which, by reaction with the plasmin, provides a measurable product; and b) measuring the amount of product formed at successive times, to thereby determine the biological activity of the defibrotide. Liquid defibrotide formulations are also disclosed, preferably water solutions, having a defined biological activity and, in particular, having an activity of 25 to 35 IU / mg of defibrotide, preferably from 27 to 32 IU / mg and, more preferably, from 28 to 32 IU / mg.