31 results about "Vascular leakage" patented technology

The invention relates to the technical field of medical image information processing, discloses an ICG fluorescence image and MRCP three-dimensional model registration fusion display method and system, effectively solves the problems of deep biliary tract structure blurring and form distortion caused by liver tissue scattering effect in intraoperative fluorescence imaging, uses a preoperative model as anatomical prior, and improves the accuracy of the intraoperative fluorescence imaging. A viewpoint correlation optical path depth field is constructed through reverse ray tracing, a spatial variation point spread function is generated accordingly, physical reverse recovery of scattering halo in a fluorescence image is achieved, non-specific background noise such as vascular leakage is effectively inhibited in combination with topological gravitational constraint of a central skeleton, and the detection accuracy is improved. The real pipe diameter and the center line position of the deep bile duct are accurately recovered, non-rigid registration correction is performed on the three-dimensional model based on the recovered high-fidelity image, and projection errors caused by respiratory movement and soft tissue deformation are eliminated.

This invention provides a monoclonal antibody 6G2 against DENV NS1 protein and its application. The CDR amino acid sequence of the heavy chain of the monoclonal antibody 6G2 against DENV NS1 protein is shown in SEQ ID No. 1, and the CDR amino acid sequence of the light chain is shown in SEQ ID No. 3. This invention also provides the application of the above antibody in the preparation of drugs for treating dengue virus infection. The monoclonal antibody 6G2 against DENV NS1 protein of this invention has the ability to competitively bind to DENV1-4NS1 protein, inhibit vascular leakage symptoms, and protect against lethal damage from DENV infection in vivo, thus possessing significant potential value in the treatment of severe dengue fever. The monoclonal antibody 6G2 developed by this invention has important significance and application potential for the prevention and treatment of dengue virus infection, including severe dengue fever.

Benzyl derivative compounds having peroxisome proliferator-activated receptor alpha (PPARα) agonist activity, kits and compositions containing such compounds, and methods of using them to enhance PPARα activity to treat diseases and / or conditions involving inflammation and / or angiogenesis, particularly diseases and / or conditions of the eye such as, but not limited to, retinal inflammation, retinal neovascularization, retinal vascular leakage, retinopathy of prematurity, diabetic retinopathy, age-related macular degeneration, and diabetic macular edema.

Benzyl derivative compounds having peroxisome proliferator-activated receptor α (PPARα) agonistic activity, kits and compositions containing such compounds, and methods of their use in enhancing PPARα activity for treating diseases and / or conditions involving inflammation and / or angiogenesis, particularly ocular diseases and / or conditions such as but not limited to retinal inflammation, retinal neovascularization, retinal vascular leakage, retinopathy of prematurity, diabetic retinopathy, age-related macular degeneration, and diabetic macular edema.

This invention provides a monoclonal antibody 6D11 and its applications. The CDR amino acid sequence of the heavy chain of the anti-monoclonal antibody 6D11 is shown in SEQ ID No. 1, and the CDR amino acid sequence of the light chain is shown in SEQ ID No. 2. This invention also provides the application of monoclonal antibody 6D11 in the preparation of drugs for treating dengue virus infection. The monoclonal antibody 6D11 of this invention has advantages such as competitive binding to DENV1-4NS1 protein, inhibition of vascular leakage symptoms, and protection against lethal damage from DENV infection in vivo, and has significant potential therapeutic value against dengue virus.

The invention provides an application of USP7 (ubiquitin-specific protease 7) as a target spot in preparation of drugs for treating vascular abnormal leakage diseases, and relates to the technical field of biomedicine, USP7 (ubiquitin-specific protease 7) as a deubiquitination enzyme not only regulates tumor, nerve and immune related diseases, but also is closely related to vascular endothelial cell functions. In the vascular homeostasis, the USP7 can maintain the integrity of a vascular barrier and inhibit pathological leakage by stabilizing endothelial connexin such as VE-cadherin and beta-catenin; under the inflammation or hypoxia condition, through deubiquitination of HIF-1alpha or NF-kappa B pathway components (such as I kappa B alpha), vascular endothelial cell activation can be promoted, VEGF signal-driven abnormal angiogenesis or release of inflammatory factors can be aggravated, and diabetic retinopathy, tumor vascular hyperplasia and sepsis-related vascular leakage can be participated. According to the application, verification experiments prove that USP7 has a certain protection effect on vascular permeability, and a treatment strategy is provided for vascular abnormal leakage diseases clinically.

Disclosed herein are 3D printed vascular tissues and compositions and methods for making the 3D printed vascular tissues. The 3D printed vascular tissues can be used to model vascular tissue damage (e.g., vascular leakage) and in screening assays for agents that cause or inhibit or treat vascular tissue damage.

The invention belongs to the technical field of medicines, and particularly relates to application of a pigment epithelium-derived factor (PEDF) in synergistically enhancing a hepatocyte growth factor (HGF) in resisting pulmonary arterial hypertension (PH). Research finds that the HGF can improve pulmonary artery remodeling in PH, but can aggravate vascular leakage through a VEGF / VEGFR2 pathway. The PEDF can be combined with VEGFR2 (vascular endothelial growth factor receptor 2) to inhibit VEGF-induced endothelial cell activation and permeability increase. Meanwhile, a specific region of the PEDF is combined with the VEGFR2 under the action of a hydrogen bond and the like, and a derivative peptide fragment of the PEDF can block a VEGF / VEGFR2 signal. Compared with single HGF, cotransfection of the PEDF and the HGF can better inhibit angiogenesis and leakage and delay PH progress. Researches prove that the PEDF counteracts the leakage promoting side effect of the HGF through specific binding with the VEGFR2, and a theoretical basis is provided for developing a PH treatment strategy of the HGF combined with the PEDF derived peptide.

This invention provides an antibody fusion protein comprising a binding construct that targets and is capable of binding to Ang-2, IL-6 receptors, and at least one VEGF family member; or an antigen-binding fragment or domain of the antibody fusion protein. The antibody fusion protein comprises an antibody or binding peptide against Ang-2, an antibody against IL-6R, and multiple extracellular domains of the VEGF receptor as binding components. The antibody fusion protein is suitable for treating or controlling ocular or systemic diseases, symptoms, or conditions caused by abnormal angiogenesis, increased vascular leakage, or inflammation.

Microvascular leak plays a critical role in the outcome of sepsis. Counteracting vascular leakage has recently raised a huge interest in the field but therapeutic targets and translation studies are crucially lacking. The inventors hypothesized that ANGPTL4 might counteract lipopolysaccharide-induced vascular hyperpermeability. Mechanistically, the inventors show that the C-terminal fragment of ANGPTL4 recapitulates full-length ANGPTL4 inhibition of vascular permeability by stabilizing endothelial cell adherent junctions whereas the N-terminus has no such effect. The inventors further demonstrate that giving human recombinant c- ANGPTL4 to mice prevents microvascular leak and mortality induced by LPS. In humans, the inventors describe the association between ANGPTL4 plasma level at time of inclusion and 90- day mortality in sepsis or septic shock patients French and European Outcome Registry in Intensive Care Units (FROG-ICU). In conclusion, the inventors demonstrate that suppressing vascular permeability by c-ANGPTL4 could be a novel therapeutic for the treatment of sepsis capillary leak syndrome. Either alone or in combination with existing drugs, c-ANGPTL4 could contribute to the reduction of mortality in patients with shock states.

Microparticulate (MP) formulations formed from one or more poly(hydroxyacid) polymers having a molecular weight ranging from 5kD to 60kD, and one or more active agents are injected into the eye of a subject to address eye disorders. The MP formulations assure high drug loading and extended delivery of the active agent of six to twelve months. The active agents may include peroxisome proliferator-activated receptor alpha (PPARα) signaling agonists such as PPARα agonist A190 (IUPAC name 3-((4-((4-fluorobenzyl)oxy)- 3- methylbenzyl)amino)benzoic acid). The formulations have therapeutic and protective effects against retinal degeneration diseases such as age-related macular degeneration (AMD), but may also be used for treating or relieving the symptoms of retinal inflammation, retinal neovascularization, retinal vascular leakage, retinopathy of prematurity (ROP), diabetic retinopathy (DR), and diabetic macular edema (DME).

The invention discloses application of dihydropyridine in preparation of a medicine for treating choroidal neovascularization, and belongs to the technical field of biological medicines.The proliferation, migration and lumen formation of human choroidal endothelial cells under the hypoxia condition are inhibited through dihydropyridine, and blood vessel leakage, area and volume of laser-induced choroidal neovascularization of mice are reduced; the formation of laser-induced choroidal neovascularization of mice is relieved through dihydropyridine, and the proliferation, migration and lumen formation of hypoxia-induced human choroidal endothelial cells can be down-regulated, so that the PHD has a treatment effect on CNV.

The present disclosure relates to a composition for preventing, alleviating or treating an eye disease, which contains (7S)-(+)-cyclopentylcarbarmic acid, 8,8-dimethyl-2-oxo-6,7-dihydro-2H,8H-pyrano[3,2-g]chromen-7-yl-ester as an active ingredient. The (7S)-(+)-cyclopentylcarbarmic acid, 8,8-dimethyl-2-oxo-6,7-dihydro-2H,8H-pyrano[3,2-g]chromen-7-yl-ester of the present disclosure exhibits the effect of remarkably reducing intraocular vascular leakage and, as such, can be advantageously used in a composition for preventing, alleviating or treating an eye disease.

The present invention relates to a method for preparing a novel vascular leakage inhibitor with high yield. The preparation method is easy to react and more productive and economical than the conventional method, using an intermediate agent that can easily remove impurities generated during the reaction. In addition, the preparation method can produce a novel vascular leakage inhibitor with high yield, using a new reagent that has not been used in the isomerization step in the past, and is particularly advantageous in the production of a high-quality active pharmaceutical ingredient.

The invention discloses a method for reprogramming fibroblasts into pericyte-like cells (PCLCs) through a chemical small molecule combination, and an application of the method in preparation of a medicine for treating vascular leakage diseases, and particularly relates to a method for reprogramming fibroblasts into the PCLCs. According to the preparation method, a chemical reprogramming strategy without genetic modification is adopted, an endogenous signal channel is regulated and controlled in a time sequence mode, and fibroblasts are efficiently induced into PCLCs with high expression of pericyte related marker genes such as EMILIN3, LAMC3, GDF10, AHR, CD109, NQO1 and QPRT. When the obtained PCLCs is used for treating vascular leakage diseases, multiple biological functions such as inflammation resistance, oxidation resistance, immunoregulation and tissue barrier protection can be achieved, so that the pathological condition is improved, and the death rate is reduced. The invention provides a novel safe cell drug strategy without gene manipulation for the treatment of vascular leakage diseases.

This invention proposes compounds of formula IA, IB, IC, ID, IE, IF, IG, IH, or IJ for the treatment or prevention of the following vascular endothelial dysfunction or vascular leakage diseases:

The present invention provides methods for treating mucosal inflammation or vascular leakage in a subject. The methods involve administering to the subject a pharmaceutical composition comprising RADA16 self-assembling peptide.

The present application relates to methods of treating ocular diseases. In particular, the present application provides the use of a combination therapy of administering a thymidylate synthetase inhibitor and a vascular endothelial growth factor inhibitor and a monotherapy of administering capecitabine in ocular diseases. The diseases have one or more of the following characteristics: ocular vascular leakage, ocular vascular pathology, retinal fibrosis, scarring, and retinal inflammation. Representative diseases include neovascular age-related macular degeneration, diabetic retinopathy, and retinal vein occlusion.

The application discloses a kind of polydopamine / drug nano composite particles and preparation method and application thereof.The polydopamine / drug nano composite particles in aqueous solution, using the synchronous process of alkaline drug molecule crystallization and dopamine oxidative polymerization, green synthesis nano drug.The polydopamine / drug nano composite particles of the application have: (1) high drug loading efficiency, simple preparation method; (2) have excellent active oxygen scavenging capacity; (3) response active oxygen controlled release drug; (4) the active oxygen of synthesis nano drug retains the activity of drug, such as nanofasudil nano drug can inhibit ROCK signal pathway; (5) good biocompatibility; can significantly reduce the ROS level in diabetic retinopathy model, reduce the expression of inflammatory factors, improve vascular leakage and inhibit neovascularization.The preparation process of the application is simple, the reaction condition is mild, and the biocompatibility is good, which provides a new nano drug delivery strategy for the treatment of diabetic retinopathy.

A fusion protein comprises two VEGF-binding units, a least one of which comprises at least an extracellular domain of at least a VEGF receptor. The other VEGF-binding unit can comprise a VEGF-C antibody or at least a different extracellular domain of at least a VEGF receptor. The fusion protein can further comprise an Ang-2-binding unit. The fusion protein is useful in treating or controlling an ocular or systemic disease, condition, or disorder that has etiology in at least one of aberrant angiogenesis, increased vascular leakage, and inflammation.

A fusion protein, or an antigen-binding fragment, or antigen-binding domain thereof comprises a binding construct targeting and being capable of binding Ang-2, IL-6, and at least one of the VEGF family members. The fusion protein comprises, as binding components, an antibody or binding polypeptide directed against Ang-2, an antibody directed against IL-6, and a plurality of extracellular domains of VEGF receptors. The fusion protein is useful in treating or controlling an ocular or systemic disease, condition, or disorder that has etiology in one of aberrant, excessive angiogenesis, increased vascular leakage, and inflammation.

The invention provides a multi-modal retinal disease intelligent auxiliary diagnosis system, which comprises an image preprocessing module used for processing a binocular fundus image uploaded by a user; the disease classification module is used for extracting global features and local lesion details by adopting a dual-channel DINOv2 model, initializing weights in a data set through transfer learning, performing fine adjustment on the fundus image data set, and performing fundus multi-label classification; and the batch processing module is used for disassembling batch binocular eye fundus image processing tasks into independent sub-tasks based on a distributed task scheduling and dynamic resource allocation technology, and distributing the independent sub-tasks to a plurality of edge computing nodes for parallel processing. According to the method, a multi-label independent classifier is designed, eight independent three-layer MLP classifiers are adopted, and each classifier focuses on single pathological feature modeling. Through parameter space decoupling design, gradient conflicts among multiple labels are avoided, and accurate capture of heterogeneity pathologies such as diabetes microvascular leakage characteristics and glaucoma optic cup morphological parameters is ensured.

This application discloses a multispecific fusion protein comprising a binding construct that targets and is capable of binding to at least one of DLL4 and VEGF family members; or an antigen-binding fragment or domain thereof. This application also discloses a multispecific fusion protein comprising an antibody against DLL4 or an antigen-binding fragment thereof, multiple extracellular domains of the VEGF receptor or an antibody against at least one VEGF family member or an antigen-binding fragment thereof, and an antibody or binding peptide against Ang-2. The multispecific fusion protein can be used to treat or control ocular or systemic diseases, conditions, or disorders caused by abnormal angiogenesis, increased vascular leakage, inflammation, fibrosis, or combinations thereof.

The invention belongs to the technical field of cancer treatment, and discloses an application of an sTREM2-NCL-AKT / eNOS axis in the vascular permeability of ovarian cancer and the formation of malignant ascites. The invention proves that the level of the sTREM2 is increased in ascites of an ovarian cancer patient, discloses the effect of the sTREM2 in promoting vascular permeability and driving ascites formation, and puts forward that the sTREM2 has double values of a prognosis biomarker and a potential treatment target. The discovery lays a foundation for developing accurate treatment for ovarian cancer and malignant ascites. In mechanism, the sTREM2 activates an AKT / eNOS signal channel through interaction with a cell surface nucleolin (NCL) protein, so that the integrity of an endothelial barrier is damaged. Targeting or blocking sTREM2 effectively mitigates vascular leakage and ascites production. According to the discovery, the sTREM2 is determined as a core driving factor of ascites pathogenesis, and the potential of the sTREM2 as an ovarian cancer treatment target is highlighted.

The invention relates to the technical field of medicine, in particular to application of tangerine seed extract in preparation of medicine for treating diabetic retinopathy. The invention finds that the tangerine seed extract can significantly reduce the glucose level of mice and can significantly improve vascular leakage and visual dysfunction caused by diabetic retinopathy, so that the invention provides the application of the tangerine seed extract in preparation of the medicine for treating diabetic retinopathy.

The application discloses application of SELE in treatment of wet age-related macular degeneration. The application research finds that SELE can significantly promote proliferation, migration and tube formation ability of vascular endothelial cells. SELE By inhibiting gene expression or activity, the application can significantly inhibit choroidal neovascularization in a wAMD mouse model, reduce abnormal vascular leakage, effectively reduce ocular inflammatory response, reduce inflammation-mediated vascular damage, target intervention of biological behavior of vascular endothelial cells, and block a key link of pathological angiogenesis. The application provides a novel molecular target for wAMD treatment and breaks the limitation of the existing anti-VEGF therapy.

The invention discloses an application of SELE in treatment of wet age-related macular degeneration. The research finds that the SELE can obviously promote the proliferation, migration and tube forming ability of vascular endothelial cells. By inhibiting SELE gene expression or activity, choroidal neovascularization in a wAMD mouse model can be significantly inhibited, and abnormal vascular leakage is reduced; meanwhile, the eye inflammatory response is effectively reduced, the inflammation-mediated vascular injury is relieved, the vascular endothelial cell biological behavior is intervened in a targeted manner, and the key link of pathological angiogenesis is blocked. The invention provides a brand new molecular target for wAMD treatment, and breaks through the limitation of the existing anti-VEGF therapy.

The invention discloses application of vitamin C, or stereoisomers, geometric isomers, tautomers, nitrogen oxides, hydrates, solvates, metabolites, pharmaceutically acceptable salts or prodrugs thereof in preparation of drugs for preventing and treating vascular injury caused by microbial infection. The invention discloses a molecular mechanism that vitamin C regulates ATP11C expression and inhibits phosphatidylserine eversion so as to improve an endothelial barrier function, and provides a new action target for treatment of infection-related endothelial injury; cell experiments and animal experiments prove that the vitamin C has remarkable effects in the aspects of improving endothelial dysfunction caused by infection, reducing vascular leakage and increasing the survival rate of infected animals, and has good application prospects and clinical transformation values; the application of the vitamin C in vascular endothelial injury caused by staphylococcus aureus, hantavirus and dengue virus infection is clearly provided for the first time, and the new medical application of the vitamin C is expanded.

The present invention relates to the technical field of biomedicine, and provides an application of asarone in the preparation of a drug for treating and / or preventing ocular diseases, and a composition and an application thereof. For the purposes of the present invention, ocular diseases include diseases characterized by retinal ganglion cell damage, macular degeneration, cataracts, or dry eye syndrome; and asarone comprises at least one of alpha-asarone, beta-asarone, or gamma-asarone. The present invention also provides an asarone composition. The asarone or the asarone composition of the present invention is administered by eye drops, orally, or by injection, and can effectively reduce intraocular pressure, protect retinal ganglion cells, improve retinal function, reduce vascular leakage in neovascular age-related macular degeneration, reduce MDA content, reduce retinal cell apoptosis, increase tear secretion volume in dry eye syndrome, and inhibit visual dysfunction caused by dry age-related macular degeneration and macular degeneration. The present invention provides an effective prevention and treatment basis for asarone in the treatment and / or prevention of the described ocular diseases.