21 results about "Neutrophil elastase" patented technology

The present invention relates to a binding agent capable of specifically binding and competitively inhibiting neutrophil elastase, the binding agent comprising an immunoglobulin single variable domain (ISVD), as well as related products, methods and uses, for example, methods and uses, particularly for the prevention, treatment or diagnosis of inflammatory diseases.

The present invention relates to an anti-neutrophil elastase (NE) antibody or antigen-binding fragment thereof that specifically binds to NE, wherein the anti-NE antibody or antigen-binding fragment thereof comprises: a heavy chain variable region (VH) including a heavy chain CDR1 represented by the amino acid sequence of SEQ ID NO: 1, 7, or 13, a heavy chain CDR2 represented by the amino acid sequence of SEQ ID NO: 2, 8, or 14, and a heavy chain CDR3 represented by the amino acid sequence of SEQ ID NO: 3, 9, or 15; and a light chain variable region (VL) including a light chain CDR1 represented by the amino acid sequence of SEQ ID NO: 4, 10, or 16, a light chain CDR2 represented by the amino acid sequence of SEQ ID NO: 5, 11, or 17, and a light chain CDR3 represented by the amino acid sequence of SEQ ID NO: 6, 12, or 18. The antibody of the present invention exhibits excellent NE neutralizing activity, and thus can be used for preventing or treating NE hyperactivation-related diseases.

The present disclosure is directed to methods of treatment, including treatment of a myopathy by administering to a subject in need thereof an elastase inhibitor in combination with a glucocorticoid. The present disclosure is also directed to pharmaceutical compositions that include an elastase inhibitor that can be used in such treatment.

The invention discloses nucleotide of fusion protein for coding neutrophil elastase and application of the nucleotide. A nucleotide sequence for coding the fusion protein is as shown in SEQ ID NO. 8; the nucleotide sequence of mRNA (messenger ribonucleic acid) for coding the fusion protein is as shown in SEQ ID NO. 12; the fusion protein comprises an optimized human neutrophil elastase (ELANE) fragment and an optimized human alpha2-macroglobulin (A2M) fragment. The mRNA preparation which is encapsulated by the nano-lipid particles and is used for coding the wild type ELANE can achieve a tumor elimination effect only by complex intratumor injection. According to the mRNA preparation which is encapsulated by the nano-lipid particles and is used for coding the ELANE fusion protein, tumor elimination in a mouse body can be realized only through intramuscular injection administration, the operation is simpler and more convenient, and the mRNA preparation is beneficial to treatment of scattered and tiny tumor focuses in the body.

The present invention relates to a novel method of treating pulmonary emphysema in patients suffering from alpha-1 antitrypsin deficiency (AATD), a genetic disorder that causes low levels of alpha-1 antitrypsin (AAT), a protein that protects the lungs from damage by neutrophil elastase. The invention consists of aerosolizing nanoparticles composed of apolipoprotein A1 enriched with AAT (A1NP). The invention aims to deliver these nanoparticles directly to the lungs, where they can interact with the alveolar surface and modulate the inflammatory and proteolytic processes that lead to emphysema. In particular, the inventors report that said nanoparticles are not cytotoxic, have anti-inflammatory and anti-elastase properties, can cross alveolar epithelial cells, and are not immunogenic in mice.

The present invention provides a pyrimidinone-containing compound, a pharmaceutical composition thereof, and a use thereof. Specifically, disclosed is a compound as shown in formula (I) or a pharmaceutically acceptable salt thereof. The compound of the present invention has strong inhibitory activity against hNE, and the compound or the pharmaceutical composition thereof can be used for treating related diseases caused by an abnormal increase in neutrophil elastase.

The objective was to develop a novel neutrophil elastase measurement method that can measure neutrophil elastase with high sensitivity. [Solution] A method for measuring human neutrophil elastase in a sample is provided, comprising contacting the sample with two or more antibodies or antigen-binding fragments thereof that recognize different epitopes on a complex with human neutrophil elastase. A reagent or kit for immunological measurement of human neutrophil elastase is also provided, comprising two or more antibodies or antigen-binding fragments thereof that recognize different epitopes on a complex with human neutrophil elastase and its inhibitor.

The application provides an activatable hydrophilic near-infrared fluorescent probe, a liposome fluorescent probe, a cell membrane fluorescent probe, a preparation method and application thereof, and relates to the field of biomedical new materials.The activatable hydrophilic near-infrared fluorescent probe is obtained after grafting of an activatable fluorescent probe and a hydrophilic polymer; the activatable fluorescent probe is a fluorescent probe that specifically responds to neutrophil elastase; and the activatable fluorescent probe comprises a hemicyanine fluorescent group and a fluorescent shielding group.The activatable hydrophilic near-infrared fluorescent probe, the liposome fluorescent probe and the cell membrane fluorescent probe provided by the application can be activated by neutrophil elastase that is highly expressed in an inflammatory environment, have the advantages of wide application range, various detection modes, accurate detection effect, good biocompatibility and the like.The application has the ability of active targeting of an inflammatory site, and can realize real-time detection of early inflammation under the guidance of fluorescence imaging.

The invention provides a near-infrared NIR-II region fluorescence ratio probe based on tumor-associated neutrophil and application of the near-infrared NIR-II region fluorescence ratio probe. The nanoprobe is a rare earth doped down-conversion nanocrystal with a core-shell structure, the surface of the rare earth doped down-conversion nanocrystal is modified with a response unit and a targeting unit, and the response unit can release a fluorescence signal through enzymatic cleavage of neutrophil elastase; and the targeting unit is used for targeting a tumor microenvironment integrin receptor. The nanoprobe has high specificity and sensitivity, high anti-interference capability and self-calibration capability, can realize NIR-IIb region ratio imaging, provides a key basis for early curative effect judgment, achieves accurate individual stratification, fills the technical blank of cancer immunotherapy curative effect monitoring, and promotes the development of a tumor immune microenvironment molecular imaging technology.

The invention discloses a fusion protein of neutrophil elastase as well as a preparation method and application of the fusion protein. The fusion protein comprises an optimized human neutrophil elastase (ELANE) fragment and an optimized human alpha2-macroglobulin (A2M) fragment; the amino acid sequence of the fusion protein is as shown in SEQ ID NO.8. The use of ELANE is limited due to intolerance to serine protease inhibitors (such as alpha-1-antitrypsin, A1AT). The optimized ELANE fragment and the optimized A2M fragment are connected to form the fusion protein, the fusion protein has high enzymatic activity, the tolerance to A1AT is greatly improved, and 83.3% of enzyme activity can still be maintained after the fusion protein acts for 2 hours through high-concentration A1AT (19200 nM). The fusion protein can efficiently eliminate mouse tumors and is safe to mice. The fusion protein is simple in preparation process and easy to industrially amplify, and a new strategy is provided for tumor treatment.

To provide an improved method for treating IdiopathicPulmonaryFibrosis (IPF).SOLUTION: The invention features a polypeptide comprising a variant of plasminogen-activator inhibitor-1 (PAI-1) having a reduced capacity to bind vitronectin, a reduced capacity to interact with the PAI-1 clearance receptor LDL-receptor-related-protein 1 (LRP1), and a capacity to efficiently inhibit neutrophil elastases in presence of neutrophil extracellular traps (NETs). In some embodiments, a polypeptide of the present invention comprises a PAI-1 variant optionally fused to an Fc domain monomer or moiety. The invention also features pharmaceutical compositions and methods of using the polypeptides to treat diseases and conditions characterized by aberrant neutrophil elastase activity (as an example, idiopathic pulmonary fibrosis).SELECTED DRAWING: Figure 1

The application relates to a polypeptide functionalized gold nanocluster targeting neutrophils, a preparation method thereof and application thereof in preparation of an anti-thrombus drug, and belongs to the field of biomedical nanomaterials. The nanocluster is formed by Au-S coordination self-assembly of a thiol-containing targeting polypeptide and gold atoms. The polypeptide can specifically recognize neutrophil elastase (NE), realizes targeting of activated neutrophils and inhibits enzyme activity of the neutrophils. The nanocluster inhibits formation of neutrophil extracellular traps (NETs) induced by phorbol ester (PMA) or activated platelets, and shows reduction of histone citrullination (CitH3) level, extracellular DNA release and active oxygen (ROS) generation. In-vivo experiments show that the gold nanocluster is enriched at a thrombus site, and significantly reduces thrombus load in a deep vein thrombosis model and an FeCl3-induced arterial thrombosis model. The application plays an anti-thrombus role by inhibiting NETs.

The present invention relates to the dipeptidyl-peptidase I (DPPI or Cathepsin C) inhibitor of formula (I), which is useful in the prevention and / or treatment of bronchiectasis with certain underlying aetiologies, in the prevention and / or treatment of anti-neutrophil cytoplasmic anti- body-associated vasculitis or hidradenitis suppurativa using therapeutically efficacious dosages and to polymorphs of Compound (I) as well as to pharmaceutical compositions comprising Compound (I) and its polymorphs.

Embodiments are directed to: (i) neutrophil secreted factors that have the capacity to kill a broad range of cancer cells without affecting the viability of non-cancer cells. Two neutrophil killing factors have been identified by the inventors: (1) eosinophil cationic protein (ECP) and (2) neutrophil elastase (ELANE); or (ii) therapeutic compositions that include CD95 degrading polypeptide components and methods of treating cancer with the same.

Embodiments are directed to: (i) neutrophil secreted factors that have the capacity to kill a broad range of cancer cells without affecting the viability of non-cancer cells. Two neutrophil killing factors have been identified by the inventors: (1) eosinophil cationic protein (ECP) and (2) neutrophil elastase (ELANE); or (ii) therapeutic compositions that include CD95 degrading polypeptide components and methods of treating cancer with the same.

The application discloses application of Alvelestat in preparation of a medicine for treating cerebral hemorrhage. The application is based on proteomic stratification analysis of hematoma fluid of a cerebral hemorrhage patient, finds that neutrophil elastase (NE) is a key molecule in the progression of cerebral hemorrhage, and further proposes a technical scheme of taking NE as a target and using a selective NE inhibitor Alvelestat for intervention. Animal experiments verify that Alvelestat can reduce cerebral edema, promote hematoma absorption, reduce neuron apoptosis and improve neural function defects; transcriptomics reveals that it plays a protective role by inhibiting multiple inflammation and immunity related signal pathways. The application provides a new strategy for precise targeted treatment of cerebral hemorrhage, and has clear clinical conversion value.

This invention provides an amphiphilic enzyme-sensitive polymer, its preparation method, and its applications. The amphiphilic enzyme-sensitive polymer is a neutrophil elastase-binding peptide-polyethylene glycol-matrix metalloproteinase 2-responsive peptide-polylactic acid block copolymer. This invention prepares Mal-PEG-GPLGIAGQ through a substitution reaction, then prepares Mal-PEG-GPLGIAGQ-PLA through an amidation reaction, and finally prepares NE-PEG-GPLGIAGQ-PLA through a Michael addition reaction. When this polymer is applied to prepare a nanomicelle drug system, it can self-assemble into structurally stable nanomicelles in aqueous solution and possesses targeting functionality. The prepared nanomicelle drug system exhibits excellent enzyme responsiveness, and after drug loading, it can achieve efficient and safe therapeutic effects.

The invention relates to the technical field of biological medicines, in particular to application of 5, 7, 4 '-trihydroxy-6, 3', 5 '-trimethoxyflavone, 5, 4'-dihydroxy-6, 7-dimethoxyflavone and 5, 4 '-dihydroxy-3', 6, 7-trimethoxyflavone which are separated from artemisia wissmanniana to preparation of medicines for preventing and treating lipopolysaccharide-induced acute pneumonia or acute lung injury of mice, and particularly relates to application of 5, 7, 4 '-trihydroxy-6, 3', 5 '-trimethoxyflavone, 5, 4'-dihydroxy-6, 7-dimethoxyflavone and 5, 4 '-dihydroxy-3', 6, 7-trimethoxyflavone to preparation of medicines for preventing and treating lipopolysaccharide-induced acute pneumonia or acute lung injury of mice. Experiments prove that the monomer and the composition play a remarkable comprehensive prevention and treatment role by down-regulating expression of a proinflammatory factor, promoting generation of an anti-inflammatory factor IL-10, reducing the wet-to-dry weight ratio of the lung and reducing the activity of total protein and neutrophil elastase in alveolar lavage fluid. The invention aims to provide a technical scheme for multi-target intervention of acute pneumonia through natural active molecules.

The invention relates to the technical field of biological medicine, in particular to a biomarker combination, a kit of the biomarker combination and application of the biomarker combination in diagnosis of acute Stanford B-type aortic dissection (ATBAD). The biomarker combination comprises serum amyloid protein A1 (SAA1), serum amyloid protein A2 (SAA2), C-reactive protein (CRP), neutrophil elastinase (ELANE), matrix metalloenzyme 9 (MMP9), nest protein 1 (NID1), mannose binding lectin 2 (LMAN2) and proprotein convertase subtilisin / kexin type 9 (PCSK9), and the biomarker combination can realize high-sensitivity and high-accuracy detection of ATBAD. And the anti-interference capability is excellent.

The invention discloses a preparation method and an application of a neutrophil elastase (NE) response near-infrared two-region ratiometric fluorescent probe (DCNC). According to the DCNC, the NIR-II dual-emission fluorescence characteristic of rare earth ions is combined with a ratio-type signal response mode, the sensitivity, the signal stability and the quantitative capacity of in-vivo fluorescence imaging are greatly improved, ultralow or enhanced F1525 / EX808 fluorescence signals are shown before and after interaction with NE, the F1525 / EX980 fluorescence signals are kept unchanged, and the result shows that in-vivo fluorescence imaging can be achieved through the DCNC. Therefore, the self-calibration ratio fluorescence imaging NE activity change is realized. The activated probe shows high sensitivity, high specificity and good linear response to NE activity, can realize early stratification of immune response in a Hepa1-6 mouse tumor model by monitoring infiltration conditions of tumor-related neutrophils (TANs), and provides dynamic imaging support for optimization of individualized immunotherapy strategies.

The application discloses application of a duodenum hookworm polypeptide AdKI1 in preparation of an anti-excessive inflammation reaction medicine and belongs to the technical field of biological medicines. The application discloses the application of the duodenum hookworm polypeptide AdKI1 in preparation of the anti-excessive inflammation reaction medicine, and the amino acid sequence of AdKI1 is shown as SEQ ID NO. 1 or SEQ ID NO. 2. The duodenum hookworm polypeptide AdKI1 can efficiently inhibit activities of neutrophil elastase, cathepsin G and proteinase 3, and can be applied in preparation of the anti-excessive inflammation reaction medicine. AdKI1 can significantly improve lung tissue damage of a mouse with LPS-induced acute lung injury and reduce an inflammation reaction. AdKI1 can significantly inhibit LPS-induced secretion of TNF-alpha, IL-6 and IL-1beta by macrophages and promote secretion of IL-10.