32 results about "Cerebral microvessel" patented technology

The invention discloses an application of 3,5,4'-trihydroxy-stilbyl-3'-O-glucoside in the preparation of microcirculatory disturbance improvement medicines. The microcirculatory disturbance improvement medicines comprise 3,5,4'-trihydroxy-stilbyl-3'-O-glucoside as an effective active component, and one or more pharmaceutically acceptable auxiliary agents, especially gastrodin and / or water-soluble cyclodextrin derivatives and PEG400 and mannitol, wherein the structural formula of 3,5,4'-trihydroxy-stilbyl-3'-O-glucoside is shown in the specification. The microcirculatory disturbance improvement medicines treat 3,5,4'-trihydroxy-stilbyl-3'-O-glucoside as the effective active component, and are used for improving disturbances caused by cerebral microvascular damages and / or disturbances caused by ischemia reperfusion damages and / or disturbances caused by leukocyte adhesion damages, and / or disturbances caused by peroxides. Normal mice of Kunming species and artificially induced microcirculatory disturbance model mice undergo tail vein injection treatment, and results of the observation of arteriole and venule systole and capillary network under a microcirculatory microscope show that 3,5,4'-trihydroxy-stilbyl-3'-O-glucoside has an obvious expansion effect on the blood vessels of the normal mice, can obviously resist the reduction of the arteriole and venule systole and capillary network opening number of the microcirculatory disturbance model mice and can obviously resist the reduction of the blood flow speed.

The invention discloses an application and preparation method of a metastatic encephaloma targeted nano drug delivery system with effects of LRP1 up-regulation and targeting. By a biologically-degradable high polymer material serving as a basic carrier, internally-loaded functional small molecules capable of up-regulating low-density lipoprotein receptor related protein 1 (LRP1), and an LRP1 targeting ligand for surface modification, the nano drug delivery system is capable of realizing targeted delivery of the internally-loaded LRP1 up-regulation molecules under the action of the surface ligand so as to specifically up-regulate the surface LRP1 level of cerebral microvascular endothelial cells and metastatic encephaloma cells, accumulation of the LRP1 targeting ligand modified nano drug delivery system in metastatic encephaloma is promoted, and accordingly the nano drug delivery system forms a self-promoted drug delivery system. The nano drug delivery system which loads antitumor drugs realizes delivery of drugs in therapeutic concentration, and the preparation method is simple and high in operability and economic benefit.

The invention provides a bionic object testing platform of a human brain microvascular system blood flow. The bionic object testing platform comprises the components of a container; a bracket assemblywhich is mounted in the container; an accommodating chamber which is mounted at the bracket assembly and is accommodated in the container; wherein the accommodating chamber comprises a first sub-chamber and a second sub-chamber which are separately arranged, and the first sub-chamber is above the second sub-chamber; the first sub-chamber and the second sub-chamber respectively extend outwards forforming a pipe; the first sub-chamber and the second sub-chamber are internally provided with blocking members; and a probe mounting member which is arranged at top of the first sub-chamber. Throughthe container, the bracket assembly, the accommodating chamber and the components of the probe mounting member, a bionic object of the human brain microvascular system blood flow is formed, and a technical gap in the technical solution is filled.

Brain microvascular endothelial cells (BMECS) can be generated from pluripotent stem cells, and possess membrane barrier functions along with capability for maturation into other developing tissues. This cell type has not been successfully frozen with loss of significant viability and / or BMEC functional properties. For example, BMECs can be used to model barrier function in blood brain barrier, by calculating the trans-endothelial resistance (TEER). However, thawed primary BMECs lose TEER resistance. By optimizing cell preparation, freezing media selection, and the controlled freezing, the Inventors have achieved complete recovery of frozen cells, achieving proper tight junction protein expression and physiologically relevant TEER. The freezing methods and compositions described herein, thereby allow for BMECs to be manufactured, frozen and distributed at scale.

The invention discloses an in vitro construction method for simulating the blood-brain barrier of human brain microvascular formation, which comprises the following steps: preparing human brain microvascular endothelial cell suspension and human brain astrocyte suspension, and preparing fibrinogen mother liquor and thrombin mother liquor ; Mix endothelial cell suspension, astrocyte suspension, DMEM medium, fibrinogen mother solution and thrombin mother solution to prepare a mixed cell gel solution; inject the mixed cell gel solution into the microfluidic chip After incubating at a constant temperature until gelation, adding endothelial cell growth medium to the microfluidic chip to construct a 3D cell culture chip; continuously culturing the 3D cell culture chip so that the endothelial cells and astrocytes The plasmocytes grow to form the microvascular network structure of the brain, which corresponds to the generation of a simulated blood-brain barrier. The technical solution provided by the invention has successfully established an in vitro model of the blood-brain barrier, which more clearly and accurately reflects the characteristics of the blood-brain barrier.

The invention discloses a pharmaceutical composition for resisting cerebral ischemia-reperfusion injury and its application. The pharmaceutical composition is composed of the following components at final concentrations: 1-10 μg / mL verbascoside, 0.1-1 μg / mL formononetin, 0.5-5 μg / mL7-2'-dihydroxy-3',4 '‑Dimethoxyisoflavane. In the present invention, by optimizing the proportion of the three effective active ingredients in Buyang Huanwu Decoction, the anti-cerebral ischemia-reperfusion injury effect of the pharmaceutical composition is significantly enhanced, and the cell apoptosis caused by cerebral ischemia-reperfusion injury can be alleviated. , improve the survival rate of brain microvascular endothelial cells, and can increase the expression levels of vascular endothelial growth factor, fibroblast growth factor, lactate dehydrogenase and superoxide dismutase in brain microvascular endothelial cells, and help restore brain function, It can be used to prepare medicines or preparations for preventing or treating ischemic cerebral apoplexy, and has broad application prospects.

The invention aims at disclosing polyester cotton for cranial nerve microvascular decompression and application of the polyester cotton, the polyester cotton with an unspecific three-dimensional shape is developed, the polyester cotton is of a cotton-fiber-shaped structure and comprises a plurality of wavy polyester fibers, the fineness d of the polyester fibers ranges from 100 D to 200 D, and the fineness d of the polyester fibers ranges from 100 D to 200 D. The number f of filaments of the polyester fibers is equal to (0.2-2) * d, the density of the polyester cotton is 0.003-0.01 g / cm < 3 >, and the filaments of the polyester fibers are in a separated state, the polyester cotton has the advantages that the polyester cotton is soft and fluffy, has certain elasticity, can be shaped at will in the clinical process, can be used in combination with the polyester cotton of different sizes, and has the advantages of being simple in structure and convenient to use. Compared with the prior art, the polyester cotton with the proper size and shape can be quickly selected according to the space structure between the cranial nerve and the cerebral microvessel, the shaped polyester cotton is placed between the cranial nerve and the cerebral microvessel, isolation of the cranial nerve and the cerebral microvessel is achieved, and cranial neuropathy of a patient is treated.

The invention discloses a method for separating and purifying brain microvessels, which comprises the following steps: (1) taking fresh whole brain tissue of mice, and grinding it up and down for 12-15 times with a Dounce homogenizer to prepare tissue homogenate; (2) homogenizing the tissue The slurry was double-filtered with sterile glass magnetic beads and a 70 μm nylon cell filter to obtain brain blood vessels and microvascular tissues. The method of the invention can not only effectively improve the integrity, quantity and purity of the isolated cerebral microvessels, but also not destroy the content of each target protein in the cerebral microvessels.

The invention discloses a use of a single targeted reduction-responsive vesicle nano-drug in preparation of a drug for treating brain tumors. Through reduction-responsive reversibly crosslinked vesicles of block polymers such as PEG-P(TMC-DTC), PEG-P(LA-DTC), PEG-P(TMC-DTC)-PEI, PEG-P(LA-DTC)-PEI, PEG-P(TMC-DTC)-Sp and PEG-P(LA-DTC)-Sp and a targeting polymer using ApoE as a targeting molecule, small-molecule chemotherapeutic drugs, protein drugs and gene drugs sensitive to brain glioma cells are efficiently encapsulated. The drug-carrying targeting vesicles can efficiently target multiple receptors (including LRP-1, LRP-2 and LDLR) that are highly expressed on the surfaces of brain microvascular endothelial cells in tumor regions thereby efficiently penetrating the blood-brain barrier andbeing efficiently enriched in the brain tumor region. ApoE-targeting related receptors are also highly expressed on the surfaces of glioma cells so that the drug-carrying targeting vesicles can be efficiently endocytosed by glioma cells and fast release drugs to induce apoptosis.

The invention discloses a preparation method and application of a prodrug-loaded brain metastases targeting drug delivery system that inhibits Mfsd2a. The nano drug delivery system is constructed with a biodegradable polymer material as the basic carrier, and functional molecules are loaded inside it to Inhibition of Mfsd2a and brain metastases intracellular enzyme-specific prodrugs, surface modification of brain microvascular endothelial cell targeting ligands and brain metastases targeting ligands; the nano drug delivery system can target ligands in brain microvascular endothelial cells and Mfsd2a inhibitory functional molecules efficiently penetrate the blood-brain barrier; after crossing the blood-brain barrier, the nano-drug delivery system can target and enter tumor cells under the guidance of the brain metastases targeting ligand; On the basis of targeted delivery, the body drug can further specifically act on tumor cells and reduce side effects on normal brain tissue and surrounding tissues. The above method is simple, operable and economical.

The invention provides a method for detection or monitoring status of silent brain ischemia (SBI) and cerebrovascular health. The assay reagents and methods described herein provide a specific indicator of cerebral microvascular disease, enabling clinicians to identify patients at risk for the development of SBI. A method of treating a subject having silent brain ischemia and / or metabolic syndromecomprises administering to the subject aspirin therapy, blood pressure therapy, body weight management, and / or a program of diet and exercise when levels of two or more SBI markers are elevated. Described herein are molecules that are produced by cerebral endothelial cells exposed to chronic vascular risk factors including obesity, hyperlipidemia, hypertension, and glucose intolerance. These stress molecules produced by cerebral endothelial cells are detectable in the serum and serve as diagnostic indicators of brain-specific endothelial cell damage and correlate with MRI indicators of silentstroke and impaired cognitive function.

In one embodiment, the present invention is a method of creating a fully-human blood-brain barrier (BBB) model, comprising the steps of (a) obtaining a mixture of neural cells and brain microvascular endothelial cells (BMECs), wherein the neural cells and BMECs that comprise the mixture were produced from the differentiation of human pluripotent stem cells (hPSCs); (b) purifying BMECs from the mixture of neural cells and BMECs of step (a); and (c) co-culturing the purified BMECs with a cell type selected from the group consisting of pericytes, astrocytes and differentiated neural progenitor cells (NPCs), wherein a blood brain barrier model is created.

Disclosed is a method for producing an in vitro model for blood-brain barrier, including (a) a culturing conditionally immortalized astrocytes on one surface of a porous membrane and culturing conditionally immortalized brain pericytes on the other surface of the porous membrane, until both of the cells become a sheet; (b) culturing conditionally immortalized brain microvascular endothelial cells in a culture vessel, until the cells become a sheet; (c) peeling off the sheet of conditionally immortalized brain microvascular endothelial cells; (d) allowing the sheet of conditionally immortalized brain microvascular endothelial cells to come into contact with the sheet of conditionally immortalized brain pericytes, so that the sheets are arranged in layers; and (e) co-culturing a cell culture comprising three layers consisting of the sheet of conditionally immortalized brain microvascular endothelial cells, the sheet of conditionally immortalized brain pericytes, and the sheet of conditionally immortalized astrocytes.

A liver-blood-brain barrier system based on a microfluidic chip for simulating metabolic processes in vivo. The microfluidic chip is mainly composed of a top chip, a porous filter membrane, and a bottom chip. The top chip is inoculated with liver cells, which can simulate the liver metabolism process of drugs in vivo; the bottom chip is mainly connected by the left main channel and the right main channel through the collagen channel, and the brain glial cell layer and the brain microvascular endothelial cell layer are seeded on the collagen interface Can simulate blood-brain barrier function. The invention integrates the construction and characterization of the in vitro blood-brain barrier model and the evaluation of the barrier permeability of the drug through the liver metabolism process, and can be used for the in vitro simulation of the blood-brain barrier model and the application of drug evaluation. The invention solves the problem of secondary inoculation and long time consumption of the cell co-culture model, adds flow conditions, is more in line with the real environment in the body, and significantly reduces the consumption of cells and reagents, and can obtain multiple experimental related parameters at the same time.