77 results about "Ischemic disease" patented technology

The invention discloses a natural product-induced artificial nano-vesicle derived from human umbilical cord mesenchymal stem cells and application of the natural product-induced artificial nano-vesicle in ischemic diseases. The preparation method of the nano vesicle derived from the human umbilical cord mesenchymal stem cells comprises the following steps: S1, inoculating the human umbilical cord mesenchymal stem cells to a 3D microcarrier; then adding traditional Chinese medicine active ingredients to activate the human umbilical cord mesenchymal stem cells, continuing to culture, cracking the microcarrier, and harvesting cells; s2, dispersing the human umbilical cord mesenchymal stem cells obtained in S1 to obtain a suspension, extruding the suspension through a polycarbonate film, and then discarding large particles by adopting a gradient centrifugation method to obtain the nano-vesicles. Compared with naturally secreted exosomes, the exosome has the advantages that the yield is increased, the treatment efficiency is improved, the production cost is reduced, and compared with stem cells, the problems of low transplantation rate and the like are avoided. The stem cells are pretreated based on the traditional Chinese medicine, the vesicles are extracted by utilizing an extrusion method, and the yield and the treatment efficiency of the nano vesicles are remarkably improved.

The invention belongs to the technical field of biological medicines, and relates to application of a PAPSS1 agonist and an endogenous protein sulfation modification up-regulating agent in preparation and screening of medicines for treating ischemic diseases. According to the application, the association between PAPSS1 up-regulation / excitation and histone sulfation modification mediated by PAPSS1 up-regulation / excitation and ischemic diseases is disclosed for the first time, and a new prevention and treatment thought is provided for ischemic cerebral apoplexy and other ischemic diseases.

The invention provides a PARP1 inhibitor as shown in a formula (I), or pharmaceutically acceptable salts, isotope variants, tautomers, stereoisomers, prodrugs, polymorphs, hydrates or solvates of the PARP1 inhibitor. The invention also provides a preparation method of the compound, a pharmaceutical composition containing the compound, and an effect of the compound in prevention and treatment of cancers, ischemic diseases or neurodegenerative diseases. # imgabs0 #

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.

The invention relates to hypoxia response therapeutic VEGFA (vascular endothelial growth factor A) mRNA (messenger Ribonucleic Acid) and application thereof. The mRNA comprises a 5'end cap, a 5 'UTR (Untranslated Region) containing a Kozak sequence, VEGFA ORF (Open Region Fragment), a 3' UTR containing an RNA (Ribonucleic Acid) binding protein HuR binding site, a RhoBAST fluorescent aptamer at the tail end of the 3 'UTR and a PolyA tail. According to the design, through a HuR hypoxia-dependent nuclear plasma transport mechanism, the stability of mRNA in hypoxic cells is improved by 2.5 times, the protein expression quantity is improved by 2 times, and proliferation of endothelial cells is remarkably promoted. Further disclosed is a VEGFA mRNA delivery system based on engineered extracellular vesicles (EVs): EVs surface modified kidney targeting peptide LTH. The system is efficiently accumulated in ischemic kidneys, VEGFA expression is remarkably enhanced, and abnormal vascular hyperplasia of external renal organs is avoided. Animal experiments prove that the survival rate of a renal ischemia-reperfusion injury model can be increased to 100% by intravenous injection of drug-loaded EVs, and the capillary density is remarkably increased 7 days after treatment. The invention is suitable for treating ischemic diseases, organ ischemia reperfusion injury or chronic wounds and the like, and has the advantages of accurate targeting, hypoxia response, high stability and safety.

The invention discloses an application of trimethylamine oxide (TMAO) in predicting collateral circulation establishment, if collateral circulation is established, the concentration of TMAO in plasma is reduced, and if the concentration of TMAO is increased, collateral artery formation after myocardial infarction or lower limb artery occlusion can be remarkably inhibited. The invention discloses for the first time that TMAO directly hinders formation of ischemic tissue collateral circulation by inhibiting reperfusion and remodeling of middle and small arteries; the TMAO level is reduced through diet limitation or drug inhibition, and collateral artery generation and blood flow recovery of a mouse heart and lower limb ischemia model can be remarkably promoted. The invention discloses the TMAO as a novel biomarker of collateral circulation disorder and a pathological mechanism of the TMAO, and provides a theoretical basis and a technical support for non-surgical treatment and precise intervention of ischemic diseases.

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 a salicylic acid compound as well as a pharmaceutical composition and application thereof. The salicylic acid derivative disclosed by the invention can be used for remarkably improving ischemia symptoms of cerebral ischemia reperfusion model rats, and has a wide application prospect in preparation of medicines for preventing and treating cardio-cerebral ischemic diseases, improving cardio-cerebral circulatory disorder, resisting thrombus and the like.

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 traditional Chinese medicine composition for treating ischemic diseases of lower limbs and also provides a preparation method of the traditional Chinese medicine composition, the synergistic combination effect of the two medicines is exerted, the curative effect of a single medicine is obviously improved, and the anticoagulant effect is far greater than that of the independent administration of caltrop; the sum of the action intensity of two independent administration is achieved, and the in-vitro anticoagulation effect and the effect of improving the ischemic blood flow of the lower limbs can be remarkably improved; blood vessel growth factors are remarkably increased, the activity of creatine kinase and lactic dehydrogenase is reduced, and tissue damage is relieved; glutathione peroxidase is promoted, malondialdehyde and active oxygen are inhibited, and the anti-oxidation effect is achieved; hypoxia and mitochondrial functions can be improved by inhibiting hypoxia-inducible factors (hypoxia-inducible factors)-1 alpha and mitochondrial compounds 3; the anti-inflammatory effect can be achieved by inhibiting CRP, IL-1beta and TNF-alpha; the rat lower limb ischemia can be obviously improved and treated.

The invention discloses an isobenzofuran-1 (3H)-ketone derivative and application thereof, and relates to the isobenzofuran-1 (3H)-ketone derivative as shown in a formula (I), and an isotope form, a stereoisomer, a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate, a hydrate, a prodrug and a polymorphic substance of the isobenzofuran-1 (3H)-ketone derivative, the invention also discloses a preparation method of the compound and application of the compound in cardiovascular ischemic diseases. # imgabs0 #

The invention provides an application of a TRIM56 inhibitor in treatment of cerebral ischemic diseases, explores TRIM56 as a potential target gene for preventing and / or treating cerebral ischemic diseases by verifying a mutual relationship between TRIM56 expression and cerebral ischemia, provides an application of TRIM56 in preparation of drugs for preventing and / or treating cerebral ischemic diseases, provides a new application of TRIM56 as a treatment target, and provides a new application of TRIM56 in preparation of drugs for preventing and / or treating cerebral ischemic diseases and a new application of TRIM56 in preparation of drugs for preventing and / or treating cerebral ischemic diseases. And theoretical basis and practical support are provided for research and development of cerebral ischemia drugs.

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 present invention discloses a compound with RIPK1 inhibitory activity, a preparation method, and uses thereof. The compound structure is shown in Formula I, and the definitions of the substituents are as described in the specification and claims. The compound of the present invention can be used to treat inflammatory diseases, ischemic diseases, neurodegenerative diseases, tumors, and other conditions and diseases associated with receptor-interacting protein kinase 1.

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.

The invention discloses pyridone alkaloid and a preparation method and application thereof, and belongs to the field of biological medicine. The method comprises the following steps: fermenting an Acremonium dichromoporum YP-213 strain, and separating and purifying a fermentation product by using silica gel column chromatography and a high performance liquid chromatography (HPLC) technology, so as to finally obtain a target compound. Pharmacological evaluation of a zebra fish model shows that the compound can effectively promote angiogenesis. The discovery lays a foundation for the development of drugs for preventing and treating cardiovascular diseases (such as ischemic diseases), and expands a research approach for searching angiogenesis-promoting active molecules.

The present invention relates to a human implant for inducing regeneration of body vessels and a method for treating lymphedema or ischemic diseases using the same. The structure of the present invention not only provides appropriate physical strength and mechanical support to prevent re-injury of body vessels such as lymphatic vessels or blood vessels during regeneration, but also structurally and functionally mimics in vivo body vessel tissue by promoting the flow of body fluids through capillary action using a simple rod structure with irregularities (e.g., H-beams) or lumens (e.g., tubular). Furthermore, the structure of the present invention is implanted into the lesion and decomposes at an appropriate time after the completion of body vessel regeneration, making it useful as an efficient treatment for various pathological conditions caused by blocked lymphatic flow or reduced blood flow.

The invention relates to application of Lignicol in preparation of a product for preventing or treating ischemic diseases, and belongs to the technical field of biological medicines. The invention discovers that Lignicol has the effect of treating ischemic diseases, such as ischemic cardiovascular diseases, ischemic cerebrovascular diseases, limb ischemic diseases, peripheral artery occlusion diseases and the like, for the first time. The application of zebra fish as experimental animal detection finds that Lignicol can effectively relieve vascular injury caused by Vatalanib base (PTK787) in an organism, has a remarkable angiogenesis promoting effect, can be applied to treatment of ischemic diseases, and is small in toxic and side effects. The invention can provide candidates for drugs for treating ischemic diseases, and has wide market prospects.

The present invention belongs to the field of biomedicine and discloses the application of EPC subsets in ischemic diseases. The present invention discovers for the first time the indicators for distinguishing EPC subsets: CD144, vWF, CD133 or phagocytic ability. Based on the above indicators, the present invention discloses methods for identifying, sorting, separating or enriching EPC subsets.

The invention relates to application of a gaultheria yunnanensis extract in preparation of a medicine for treating cerebral diseases, and particularly relates to application of a gaultheria yunnanensis extract in clinical treatment of Alzheimer's disease, cerebral ischemic disease, Parkinson's disease dementia, traumatic brain injury, chronic traumatic encephalopathy and other diseases. Meanwhile, the clinical disease treatment range of the gaultheria yunnanensis extract is further expanded. Particularly, the traditional Chinese medicine composition has a remarkable curative effect in clinical application of treating the Alzheimer's disease.

A cell preparation that is an effective therapeutic for ischemic disease. The cell preparation includes CD18-positive cells. A method to produce the cell preparation includes obtaining a buffy coat layer from a sample containing hematopoietic stem cells, obtaining mononuclear cells by removing, from the buffy coat layer, inhibitory cells that inhibit a therapeutic effect, obtaining, from the mononuclear cells, CD34+ mononuclear cells that are CD34-positive, and obtaining, from the CD34-positive mononuclear cells, CD34+CD18high mononuclear cells in which CD18 is highly expressed.

The proinflammatory and vasoconstrictor agent endothelin-1 (ET-1) is a pathogenic molecule involved in an array of cardiovascular diseases. Different from ET-1 signaling for vasoconstriction in large arteries, we demonstrate herein that the coronary microvasculature exhibits unique signaling mechanisms (independent of PKC, CPI-17, and intracellular calcium storage) for constriction. The pathophysiological levels of ET-1 preferentially act on the microvasculature to exert long-lasting vasoconstriction through the activation of Rho kinase after binding to the ET-1 receptor ETAR. The ETAR antagonist BQ123 only blocks but is not able to reverse the vasoconstriction to ET-1. In contrast, ROCK inhibitors (e.g., H-1152) effectively reverse arteriolar constriction to ET-1. Therefore, ROCK inhibition is a potent and specific choice for treating coronary ischemic diseases (abnormal vasoconstriction) associated with microvascular dysfunction with overproduced ET-1. ROCK inhibitors may also be used to treat microvascular diseases related to diabetic retinopathy and microvascular dysfunction from cancer therapy or immunosuppressive medications. Since H-1152 can also reduce the basal tone of the microvasculature, ROCK inhibitors are also good diagnostic agent(s) when used during angiogram or by noninvasive methods.

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 a phthalide ring-opening derivative as shown in a formula (I-1) and a stereoisomer or pharmaceutically acceptable salt thereof and application thereof. Experimental results show that the compound disclosed by the invention has excellent pharmacokinetic properties, and the release of butylphthalide and dexcanthanol in vivo is superior to that of single drug butylphthalide and dexcanthanol and is also superior to that of a compound composition. The compound disclosed by the invention has an excellent brain protection effect and can greatly reduce the cerebral infarction area; the compound can be used for preventing and treating nerve injury, degenerative diseases and ischemic diseases. # imgabs0 #