42 results about "Ischemic disease" patented technology

The present invention relates to a human pluripotent stem cell-derived senomorphic extracellular vesicle composition for treating cellular senescence and stem cell degeneration. Specifically, the present invention relates to a senomorphic composition comprising stem cell-derived extracellular vesicles as an active ingredient, the composition being characterized by restoring a function or morphology of senescent cells to that of normal cells, and to a pharmaceutical composition comprising the senomorphic composition as an active ingredient for preventing or treating nerve injury and ischemic diseases.

The invention discloses a handheld rapid three-dimensional fundus blood supply imaging system and method.The system comprises an upper computer, a laser excitation module, a probe, a data collection module and a space positioning module, the laser excitation module, the probe, the data collection module and the space positioning module are connected with the upper computer, and the laser excitation module conducts wavelength conversion on input pump laser through the stimulated Raman scattering principle to generate excitation light; the exciting light is then transmitted to the probe for high-speed scanning, the probe receives real-time pose feedback of the space positioning module at the same time so as to eliminate the influence of operation jitter, the data acquisition module pre-processes a photoacoustic signal acquired by the probe and then transmits the photoacoustic signal to the upper computer, and a distribution diagram is generated through an image reconstruction algorithm and analyzed. According to the invention, four clinical troubles of poor molecular specificity, depth-resolution imbalance, low clinical adaptability and deficiency of quantitative standards in the existing imaging technology are fundamentally solved, and a universal tool is provided for early screening of eye ground ischemic diseases.

The embodiment of the application provides an interventional stent conversion assembly, an interventional hemostatic stent and an assembling method, and belongs to the technical field of medical devices. The interventional stent conversion assembly comprises an inner lining and an elastic member sleeved on the inner lining. The inner lining comprises a main body portion for supporting the elastic member and a pulling portion. The main body portion is a cylindrical structure formed by spirally winding a strip-shaped member. The main body portion has opposite first and second ends. The main body portion has a cavity extending in the axial direction. One end of the pulling portion is connected to the strip-shaped member forming the first end of the main body portion, and the other end extends out of the second end of the main body portion through the cavity of the main body portion. The elastic member is a sleeve structure and can be elastically deformed in the radial direction. When the elastic member is sleeved on the main body portion, the elastic member is expanded in the radial direction and attached to the main body portion. The interventional stent conversion assembly can quickly convert a common interventional stent into an interventional hemostatic stent, thereby completing rapid response treatment of sudden ischemic diseases.

A pro-inflammatory and vasoconstrictor and endothelin-1 (ET-1) are pathogenic molecules related to a series of cardiovascular diseases. Unlike ET-1 signaling for vasoconstriction of the main artery, we have proven herein that coronary microvessels exhibit a unique signaling mechanism for constriction (independent of PKC, CPI-17, and intracellular calcium storage). The pathophysiological level of ET-1 acts preferentially on the microvessels to exert persistent vasoconstriction by activating Rho kinase upon binding to ETAR of the ET-1 receptor. The ETAR antagonist BQ123 only blocks but cannot reverse vasoconstriction against ET-1. In contrast, ROCK inhibitors (e.g., H-1152) are effective to reverse arteriolar systole against ET-1. Thus, ROCK inhibition is a potent and specific choice for the treatment of coronary ischemic disease (abnormal vasoconstriction) associated with microvascular dysfunction due to excessive production of ET-1. The ROCK inhibitors may also be used to treat microvascular diseases associated with diabetic retinopathy as well as microvascular dysfunction caused by cancer therapy or immunosuppressive drugs. Since H-1152 can also reduce the basal tension of microvessels, a ROCK inhibitor is also a good diagnostic agent when used during angiography or by a non-invasive method.

Provided is a pharmaceutical composition and application thereof, specifically, said pharmaceutical composition comprises: salvianolic acid B as a first active ingredient; and ginsenoside Rg1 as a second active ingredient, and the weight ratio of the first active ingredient to the second active ingredient being 5:(1-4.5). The pharmaceutical composition has a better active-ingredient proportion than the prior art, has a better therapeutic efficacy in preventing and / or treating ischemic diseases, and ischemia-reperfusion tissue or organ damage, and can be used for treating ischemia and / or ischemia-reperfusion damage of different tissues and organs.

The invention discloses papaverine hydrochloride sustained-release microspheres for injection and a preparation method of the papaverine hydrochloride sustained-release microspheres, and relates to the technical field of pharmaceutical preparations. The sustained-release microsphere comprises an active component, a composite carrier, a composite stabilizer and a freeze-drying protective agent. The composite carrier is a compound formed by grafting a polylactic acid-glycolic acid copolymer and hyaluronic acid, the composite stabilizer is a mixture of an antioxidant and an amino acid compound, the freeze-drying protective agent is a mixture of polyol and saccharides, and the surface of the microsphere is provided with a hydrophilic-hydrophobic gradient coating composed of a hydrophobic layer, an amphiphilic layer and a hydrophilic layer. The preparation method comprises the steps of primary emulsion preparation, multiple emulsion preparation, step-by-step curing, surface modification and freeze-drying treatment, and adopts the processes of gradient emulsification, step-by-step curing, layer-by-layer grafting, gradient cooling and segmented sublimation. According to the technical scheme, the drug encapsulation efficiency and the drug loading capacity are effectively improved, the burst release rate is reduced, long-acting stable slow release is realized, the storage stability and the biocompatibility are enhanced, and a safe and effective drug administration choice is provided for treatment of ischemic diseases.

The invention discloses a new application of Apo-EVs, and particularly discloses an application of Apo-EVs from endothelial cells (ECs) in promoting differentiation of endothelial progenitor cells (EPCs) and wound healing. The Apo-EVs is rich in miR-30a-5p, and can significantly promote the differentiation of EPCs to ECs and accelerate the angiogenesis through targeted regulation of EGFR / PI3K / AKT / VEGF signal channels. In a mouse wound healing model, the Apo-EVs is adopted for intervention, and the wound healing time can be effectively shortened. The invention provides a natural, efficient and low-toxicity wound repair biological agent, and provides a new strategy for treatment of ischemic diseases and refractory wounds.

The invention relates to the technical field of biology, in particular to a method for modular assembly of artery blood vessel type organs and construction of tissue microcirculation of the artery blood vessel type organs. The method comprises the following steps: inducing human pluripotent stem cells to differentiate through a mesoderm stage to form an arterial specific vascular organoid module (AVO), and then carrying out modular assembly on the AVO in vivo or in vitro so as to quickly reconstruct a tissue microcirculation network with arterial characteristics. The obtained artery blood vessel organoid is uniform in form, the diameter of the artery blood vessel organoid is intensively distributed at about 200 microns, SOX17 and CXCR4 artery endothelial markers are expressed at the same time, and the artery blood vessel organoid has polarity and a complete basilar membrane. Transplanting experiments show that the organ can be integrated with host blood vessels in a short time, and ischemic tissue blood perfusion is recovered. The defects that existing organoid is irregular, difficult to splice, delayed in perfusion and the like are overcome, and a new strategy is provided for revascularization and acute ischemic disease repair.

MicroRNA modified umbilical cord mesenchymal stem cells and exosomes and applications. The present application provides a treatment technology based on miR-210 mutant umbilical cord mesenchymal stem cells and exosomes. By specifically modifying the miR-210 sequence, a mutant with enhanced stability and targeting efficiency is obtained. After being introduced into umbilical cord mesenchymal stem cells, exosomes with high expression of the mutant can be prepared. The exosomes show significant therapeutic effect in various disease models, including promoting angiogenesis, accelerating wound repair and neuroprotection. The present application simultaneously protects the mutant sequence, recombinant vector, recombinant cell and its preparation method, and the application of the exosomes in the preparation of drugs for treating ischemic diseases and tissue damage. This technology optimizes the sequence and delivery system of miR-210, providing a new solution for tissue repair.

A marker for characterizing an EPC subpopulation, an EPC subpopulation, and a use thereof. Indicators for distinguishing EPC subpopulations comprise CD144, vWF, CD133, or phagocytic capacity. On the basis of these indicators, identification, sorting, separation, or enrichment of EPC subpopulations can be achieved. Also provided are a use of late EPC in the preparation of a drug for treating stroke, erectile dysfunction, and ischemic diseases, and a method for treating stroke, erectile dysfunction, and ischemic diseases.

This invention discloses a method for preparing and applying nanochloroplasts with targeted mitochondrial repair function, belonging to the field of biomedical technology. The preparation method includes the following steps: mixing energy module nanoparticles and catalytic module nanoparticles with a cell membrane solution, and co-encapsulating them in a compartmentalized manner using membrane extrusion technology to form a nanochloroplast core; then, co-modifying the surface of the nanochloroplast core with upconversion nanoparticles through asymmetric modification. The nanochloroplasts of this invention can simulate the partitioned structure of natural chloroplasts, achieving phototaxis, energy supply, and carbon fixation functions, and can target mitochondria for restoring mitochondrial metabolism. This system can reconstruct the mitochondrial oxygen-carbon metabolism network in an ischemic model and is expected to develop into a novel nanomaterial for more effective treatment of ischemic diseases.

The present invention relates to a therapeutic freeze-dried or frozen cell in which the cell surface is treated with a polyphenol, a method for preparing the same, and a pharmaceutical composition comprising the same. The polyphenol-treated lyocell for treatment of the present invention can act as a biological repository for controlling the release of a variety of physiologically active molecules including endogenous substances and therapeutic drugs in the cell. Furthermore, the polyphenol-treated frozen cells for treatment contain an intracellular physiologically active substance increased and / or concentrated, for example, a growth factor, an immunomodulatory factor or the like, and can be used as a composition for preventing or treating ischemic diseases by an angiogenesis promoting effect. The composition can be used as a composition for preventing, ameliorating or treating inflammatory diseases by the improved immunomodulatory function. Meanwhile, when the therapeutic cell (lyocell) is used as an appropriate drug delivery technique before freezing (drying), it is expected to construct a cell drug system that can be simply and efficiently used.

The invention provides for compositions comprising phosphorous containing tricyclic compounds, including phthalazin-1(2H)-one derivatives. The compounds are potent inhibitors of the enzyme poly(ADP-ribose)polymerase (PARP), particularly PARP-1 and potentially PARP-2. The also show good cellular activity in inhibiting poly(ADP-ribose) oligomer formation. The compounds may be useful as mono-therapy or in combination with other therapeutic agents in the treatment conditions where PARP is implicated, such as cancer, inflammatory diseases and ischemic conditions. Thus, also provided are methods for the treatment of a condition where PARP is implicated comprising administering to an effective amount of a compound of the invention to an individual in need thereof.

The present invention provides a PARP1 inhibitor represented by formula (I), or a pharmaceutically acceptable salt, isotopic variant, tautomer, stereoisomer, prodrug, crystalline polymorph, hydrate, or solvate thereof. The present invention also provides a method for producing the compound, a pharmaceutical composition containing the compound, and the effect of the compound in the prevention and treatment of cancer, ischemic disease, or neurodegenerative disease. [C1] TIFF2026501329000048.tif53156

This invention provides compounds for use in treating diseases and conditions involving CK2α. [Solution] A compound of formula I is provided. The compound is an inhibitor of casein kinase 2 alpha (CK2α) and is useful for treating proliferative disorders (e.g., cancer), viral infections, inflammation, diabetes, vascular and ischemic disorders, neurodegeneration, and regulating circadian rhythms. JPEG2026122953000357.jpg73170

The present invention relates to nitrogen-containing heterocyclic compounds, processes for their preparation and their use. The nitrogen-containing heterocyclic compounds have the structure of general formula I, wherein the substituents are defined as described in the specification and claims. The nitrogen-containing heterocyclic compounds of the present invention are useful as therapeutic agents for the treatment of inflammatory diseases, ischemic diseases, degenerative diseases, tumor-related conditions and diseases.

The present application relates to a DNA drug, a gene targeting delivery system and its application in the treatment of lower extremity peripheral arterial disease. Specifically, the present application relates to a microcrystalline nanocarbon targeted drug delivery system and a plasmid containing human interleukin-4 gene loaded thereon. The delivery system comprises a matrix microcrystalline nanocarbon, and folate, polyethyleneimine and polyethylene glycol modified on the surface thereof. The matrix microcrystalline nanocarbon has a size of 5-20 nanometers, a crystallinity of >80%, a rich mesoporous structure, a high specific surface area and good biocompatibility. The present application also provides a preparation method of the system, which comprises the steps of synthesizing a matrix by pulse modulation radio frequency plasma enhanced chemical vapor deposition, surface functionalization modification and plasmid loading. After injection into the lower extremity muscle, the system can actively target the macrophages in the ischemic site, realize long-term expression of the IL-4 gene at the lesion site. It can effectively promote stable, mature functional angiogenesis by inducing macrophages to polarize to the repair M2 phenotype and regulating the OSM / GSNOR / ENG signal axis, thereby improving limb ischemia. The present application has important application value in the field of gene therapy for ischemic diseases, especially peripheral arterial disease and severe limb ischemia.

Provided are compounds of the Formula I, and salts, hydrates and solvates thereof:wherein R1, Q, Ra, Rb, Rc, Rd and Re are each as defined in the specification. The compounds are inhibitors of Casein Kinase 2 alpha (CK2α) and are useful for the treatment and / or prevention of diseases and conditions in which CK2α activity is implicated, such as, for example, but not limited to, the treatment and / or prevention of proliferative disorders (e.g. cancer), viral infections, inflammation, diabetes, vascular and ischemic disorders, neurodegeneration and the regulation of circadian rhythm. The present invention also relates to pharmaceutical compositions comprising the compounds defined herein, to processes for synthesising these compounds and to their use for the treatment of diseases and / or conditions in which CK2α activity is implicated.

The present invention relates to an umbilical cord blood-derived vascular endothelial progenitor cell and a composition for preventing or treating ischemic diseases comprising the same, and more specifically, to an umbilical cord blood-derived vascular endothelial progenitor cell and a composition for preventing or treating ischemic diseases, the present invention relates to a high-purity umbilical cord blood-derived vascular endothelial progenitor cell exhibiting specific surface antigen characteristics, a method for obtaining an umbilical cord blood-derived vascular endothelial progenitor cell by pre-treating umbilical cord blood, and a composition for preventing and treating ischemic diseases comprising the umbilical cord blood-derived vascular endothelial progenitor cell. The high-purity umbilical cord blood-derived vascular endothelial progenitor cell of the present invention exhibits colony formation, high proliferation ability, and high potential for angiogenesis in vivo, and thus can exhibit an excellent effect on the prevention or treatment of various ischemic diseases induced by blood vessel contraction or occlusion.

The present application provides a class of PARP1 inhibitors represented by formula (I), or a pharmaceutically acceptable salt, isotopic variant, tautomer, stereoisomer, prodrug, polymorph, hydrate or solvate thereof. The present application also provides a preparation method of the compound, a pharmaceutical composition comprising the compound, and the role of the compound in the prevention and treatment of cancer, ischemic disease or neurodegenerative disease.

The present disclosure relates to a cord blood-derived vascular endothelial progenitor cell and a composition for preventing or treating ischemic diseases containing the same, and more specifically, to a highly pure cord blood-derived vascular endothelial progenitor cell exhibiting specific surface antigen properties, a method for obtaining a cord blood-derived vascular endothelial progenitor cell through preprocessing of cord blood, and a composition for preventing or treating ischemic disease containing the cord blood-derived vascular endothelial progenitor cell. The high-purity cord blood-derived vascular endothelial progenitor cell of the present disclosure exhibits colony formation and high proliferation ability and angiogenic potential in the body, and thus can exhibit excellent effects in the prevention or treatment of various ischemic diseases caused by vascular contraction or occlusion.

The invention provides application of an NCOA3 polyQ structural domain as a target spot in preparation of a medicine for relieving lower limb ischemic diseases, relates to the technical field of biomedicine, and aims to solve the problems that in the prior art, blood flow reperfusion recovery of the lower limb ischemic diseases is poor, collateral vessels are insufficient in formation, and safe and effective targeted intervention means are lacked. By constructing a mouse lower limb ischemia model, it is proved that blood flow recovery and collateral angiogenesis after ischemia are remarkably inhibited by Nco3polyQ structural domain deletion: compared with a WT mouse, postoperative blood flow perfusion of an Nco3Q / Q mouse is recovered slowly, and the blood flow of the affected side is only recovered by 60% on the 21st day after the operation; the CD31 positive region of the gastrocnemius muscle tissue on the 14th day after the operation is obviously reduced, and the mRNA expression of the blood vessel marker gene Pecam1 is reduced. On the basis, an intervention strategy aiming at the NCOA3 polyQ structural domain is used for preparing the medicine for relieving the lower limb ischemic disease, and a new treatment strategy and a potential target are provided for the ischemic limb disease.

Disclosed are an amide compound having RIPK1 inhibitory activity, a preparation method therefor, and a use thereof. The amide compound has a structure as shown in general formula I, and definitions of substituents are described in the specification and claims. The amide compound of the present application can be used for treating conditions and diseases such as inflammatory diseases, ischemic diseases, neurodegenerative diseases, tumors, and the like associated with RIPK1.

The invention discloses a preparation method and application of VEGF (vascular endothelial growth factor) engineered endothelial extracellular vesicles. The invention provides a specific preparation method, VEGF engineered endothelial extracellular vesicles (vEVs) and pharmaceutical application of the VEGF engineered endothelial extracellular vesicles. Compared with untreated common endothelial extracellular vesicles (EVs), the yield of the vEVs prepared by the invention is higher, and the vEVs are rich in higher-level angiogenesis promoting factors such as VEGF (vascular endothelial growth factor) and the like, show remarkably enhanced endothelial cell migration and tube formation promoting capability and accelerate endothelial cell uptake efficiency. The invention can be used for preparing medicines for promoting tissue repair and revascularization, and particularly has wide application prospects in the fields of diabetes wound healing, ischemic disease treatment and the like.

The invention discloses a double mRNA (messenger Ribonucleic Acid) combined targeted delivery system for treating a lower limb peripheral artery disease (PAD) and application of the double mRNA combined targeted delivery system. The system comprises a microcrystal nanocarbon targeted drug-loading delivery matrix on which messenger ribonucleic acid (mRNA) of an IL-4 gene and / or a VEGF gene is loaded. The matrix comprises matrix microcrystalline nanocarbon, and folic acid (FA), dextran sulfate (DS), polyethyleneimine (PEI) and polyethylene glycol (PEG) which are modified on the surface of the matrix microcrystalline nanocarbon. According to the system, folic acid and dextran sulfate are used for dual targeting of macrophages, so that efficient endocytosis is realized; the mRNA is used for rapidly expressing protein in cytoplasm, so that the risk of genome integration is avoided; through co-delivery of IL-4 and VEGF, functional angiogenesis and tissue repair are synergistically promoted. Preferably, the system can be entrapped in injectable hydrogel to form a gel composite system, so that slow and continuous release of the medicine is realized. The invention further provides a preparation method of the system and application of the system in preparation of drugs for treating ischemic diseases. The system has the advantages of high targeting efficiency, high expression speed, high vascular maturity, lasting effect and the like, and provides a new strategy for PAD treatment.

Methods of treating an ischemic disease in a subject are provided. Accordingly there is provided a method comprising administering to the subject a therapeutically effective amount of cells with reduced level of expression and / or activity of TNFR1, thereby treating the ischemic disease in the subject. Also provided is a method comprising treating with TNFalpha cells with reduced expression and / or activity of TNFR1 and administering to the subject a therapeutically effective amount of said cells, thereby treating the ischemic disease in the subject.

The invention belongs to the technical field of medicines, and discloses an oxo aromatic heterocyclic derivative as well as a preparation method, a pharmaceutical composition and application thereof. Specifically, the invention relates to an oxo aromatic heterocyclic derivative shown as a general formula I, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, a preparation method thereof, and a composition containing one or more of the compounds. The invention also relates to application of the compounds in treatment of CD73-related diseases such as tumors, cancers, inflammation-related diseases, immune-related diseases, nervous system diseases, neurodegenerative diseases, central nervous system diseases, depression, Parkinson's disease, sleep disorders and fibrosis and cerebral and cardiac ischemic diseases.

The invention provides a cerium-based composite nano enzyme for promoting wound healing as well as a preparation method and application thereof, and belongs to the technical field of nano medicine. The cerium-based composite nano-enzyme is constructed by integrating cerium nanoclusters (CeNC) and amino acid into a cobalt-based MOF (Metal Organic Framework) framework, and the synthesized nano-material has a topological structure of ZIF-67. Wherein CeNC is fixed in pores and on the surface of a cobalt framework (Co-ZIF), and amino acid and 2-methylimidazole have a competitive coordination effect, replace part of ligands and participate in framework assembly. The cerium-based composite nano-enzyme has good inflammation inhibition and angiogenesis promotion capabilities, can effectively promote chronic wound healing, overcomes the problems of chronic wound treatment drugs in the prior art, establishes an example of a novel angiogenesis promotion nano-drug, and has a wide application prospect. Meanwhile, a technical support is provided for tissue repair and regeneration and ischemic disease treatment.

The invention discloses oligopeptide cyclic peptide and application thereof in preparation of drugs for preventing or treating hypoxia-related diseases. The amino acid sequence of the oligopeptide cyclic peptide is as shown in the following formula: cyclo (Lys-Tyr-Xaa1-Xa a2-Xaa2-Xaa2-Cys-Gly), and the amino acid sequence of the oligopeptide cyclic peptide is as shown in the specification. Wherein X < aa1 > is Asn or Gln; and Xaa2 is Ala, Leu, Me t, Ile, Pro or Val. The oligopeptide cyclic peptide disclosed by the invention has remarkable anti-hypoxia activity, can effectively prolong the survival time of mice suffering from asphyxia hypoxia and acute decompression hypoxia, has remarkable retarding and treating effects on cerebral ischemic diseases, and provides an effective alternative compound for preparing novel anti-hypoxia medicines and functional foods.

The present invention addresses the problem of providing a new ischemic disease treatment strategy targeting pericytes. As a solution, the present invention provides an inflammation suppressant or a tissue protective agent for ischemic injury, each including an inhibitor which blocks ATP-sensitive potassium (KATP) channels present in a pericyte. In particular, the KATP channel is composed of pore-forming KIR6.1 and regulatory SUR2 subunits, and it is preferable for the inhibitor to act on the KIR6.1. The inflammation suppressant or the tissue protective agent for ischemic injury is preferably used in the treatment of ischemic diseases such as cerebral infarction or ischemic cardiac disease.