38 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.

Systems and methods relate to processing optical tomography coherence (OCT) images to predict characteristics of a treatment to be administered to effectively treat age-related macular degeneration. The processing can include pre-processing the image by flattening and / or cropping the image and processing the pre-processed image using a neural network. The neural network can include a deep convolutional neural network. An output of the neural network can indicate a predicted frequency and / or interval at which a treatment (e.g., anti-vascular endothelial growth factor therapy) is to be administered so as to prevent leakage of vasculature in the eye.

The invention relates to the technical field of drug delivery, and discloses a multilayer drug-loaded microsphere for intraocular sustained-release therapy and a preparation process thereof.The multilayer drug-loaded microsphere comprises a core layer, a middle layer and a shell layer, the core layer is composed of a polylactic acid-glycolic acid copolymer (PLGA) and a first hydrophobic drug, the middle layer is formed by wrapping the core layer with carboxymethyl chitosan, and the shell layer is composed of a first hydrophobic drug and a second hydrophobic drug. The first hydrophobic drug comprises a first therapeutic drug, the middle layer comprises a second therapeutic drug, the shell layer is composed of a polylactic acid-caprolactone copolymer PLCL and a third hydrophilic drug, and the first hydrophobic drug, the second therapeutic drug and the third hydrophilic drug are different from one another. Through the layered design of the core layer, the middle layer and the shell layer and in combination with differential degradation rates of PLGA, carboxymethyl chitosan and PLCL materials, gradient release of hydrophobic and hydrophilic drugs is achieved, a drug release curve is matched with the pathological stage of intraocular diseases, macular degeneration rapidly inhibits vascular leakage in the early stage and continuously resists inflammation in the later stage, and the effect of treating macular degeneration is achieved. And the layered slow-release synergistic treatment effect is verified.

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 present invention discloses engineered platelets carrying platelet activation inhibitor nanoparticles, a preparation method and application thereof, which belongs to the field of pharmaceutical technology and relates to a preparation method of engineered platelets carrying ticagrelor nanoparticles and its therapeutic use in malignant solid tumors. The preparation of the engineered platelets described in the present invention includes the steps of extracting and purifying platelets, preparing gelatin nanoparticles loaded with platelet activation inhibitors, anchoring the nanoparticles to the outer surface of platelets, etc. The engineered platelets of the present invention are targeted to reach the tumor site by recruiting tumor-associated platelets in the body, and specifically respond to matrix metalloproteinases to release the carried platelet activation inhibitor, thereby inhibiting the activation of platelets in the tumor microenvironment, enhancing tumor vascular leakage, alleviating the immunosuppressive microenvironment, and effectively enhancing the effects of chemotherapy and immunotherapy.

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 application belongs to the field of biological medicine, and discloses an artificially synthesized Sema4D / PlexinB1 inhibitor and application thereof in preparation of a medicine for treating and preventing fundus vascular diseases. The applicant screens Sema4D inhibitors capable of combining with sSema4D and blocking sSema4D-PlexinB1 by using an OBOC library, and finally obtains a protein small peptide KWIIVGA which has high affinity to sSema4D and has a good inhibiting effect on fundus vascular leakage and fundus vascularization of mice in a mouse experiment. The small peptide can effectively inhibit fundus vascularization and leakage, and provides a new idea for the treatment of fundus vascularization and leakage diseases such as diabetic retinopathy.

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.

A method of reducing the risk of a sepsis-induced vascular leak, tissue edema or organ dysfunction is provided. The method involves administering an effective amount of a composition selected from the group consisting of Lipocalin 10 (SEQ ID NO: 1), a truncated Lipocalin 10 (Lcn10) protein having the amino acid sequence SEQ ID NO: 2, Lcn 10-expressing vectors for full length / truncated Lcn10, or combinations thereof to the subject, The method is also useful for reducing the risk of a heart attack-induced cardiac dysfunction, atherosclerosis, inflammatory bowel disease or diabetes-induced cardiomyopathy.

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 present invention relates to the field of biomedicine technology, and in particular to a culture medium, culture method and application for endothelial progenitor cells. The present invention improves the culture medium for endothelial progenitor cells, and the endothelial progenitor cells prepared therefrom have higher proliferation activity and better angiogenesis ability, and their ability to promote the secretion of active factors is the strongest. Factors such as IL-10 and TGF-β secreted by EPCs have the potential to inhibit mast cell degranulation, reduce the release of histamine and inflammatory mediators, and thus relieve wheals and itching. In addition, EPCs promote endothelial cell proliferation by secreting factors such as VEGF and Ang-1, repair damaged vascular endothelium, and reduce vascular leakage and edema. In urticarial vasculitis, EPCs can inhibit excessive proliferation of the vascular endothelium and relieve chronic inflammation. The culture medium of the present invention can be used for endothelial progenitor cell culture, which is helpful for screening potential drugs for treating urticaria and has great application value.