41 results about "Capillary endothelial cells" patented technology

The present invention is directed to a combination of therapeutic compounds and treatment methods and kits using the combination. In particular, one of the combination affects the NCca-ATP channel of neural tissue, including neurons, glia and blood vessels within the nervous system. Exemplary SUR1 and/or TRPM4 antagonists that inhibit the NCca-ATP channel may be employed in the combination. The combination therapy also employs one or more of a non-selective cation channel blocker and/or an antagonist of VEFG, NOS, MMP, or thrombin. Exemplary indications for the combination therapy includes the prevention, diminution, and/or treatment of injured or diseased neural tissue, including astrocytes, neurons and capillary endothelial cells, that is due to ischemia, tissue trauma, brain swelling and increased tissue pressure, or other forms of brain or spinal cord disease or injury, for example. In other embodiments, there are methods and compositions directed to antagonists of TRPM4, including at least for therapeutic treatment of traumatic brain injury, cerebral ischemia, central nervous system (CNS) damage, peripheral nervous system (PNS) damage, cerebral hypoxia, or edema, for example.

Novel blood-brain barrier permeant amyloid-targeting peptides and peptide conjugates are described. The peptide conjugates include a radioisotope or other label in a stable complex that translocates across brain capillary endothelial cell monolayers. The labeled peptide conjugate binds to amyloid plaques (Aβ) associated with Alzheimer's disease, and is useful for the targeted delivery of therapeutic and diagnostic molecules into the brain.

The invention which belongs to the biotechnical field concretely relates to a brain targeted AmB polymer micelle administration system. The brain targeted AmB polymer micelle administration system is prepared by utilizing brain targeted head base Angiopep-2 modified polymer micelles extremely having a clinical application potential, and entrapping micromolecular hydrophobic drugs. The prepared brain targeted AmB polymer micelle administration system can effectively improve the uptaking of the hydrophobic drugs on brain capillary endothelial cells, and can effectively improve the accumulation amount of the drugs in the brain and the brain entrance efficiency of the drugs especially in a noninvasive intravenous injection mode; compared with present clinical preparations of the drugs, such as AmB for injection, the system of the invention has a substantially improved brain targeting efficiency; and the constructed polymer micelle administration system can obviously reduce the hemolyticity and the cytotoxicity of the AmB. The Angiopep-2 modified brain targeted AmB polymer micelle administration system of the invention can be used to promote the accumulation of hydrophobic drugs with low brain entrance efficiencies in the brain.

It is intended to provide a screening system for a centrally acting drug transported across the blood-brain barrier, a drug acting on the blood-brain barrier itself, or a drug transferred into the brain without being expected to centrally act. Moreover, another object of the present invention is to achieve pathogenesis analysis study or the screening in a diseased state by applying various diseased environments to this screening system. The present invention provides an in-vitro model of blood-brain barrier obtained by using a three-dimensional culture apparatus comprising: a culture solution; a plate holding the culture solution; and a filter immersed in the culture solution and placed in no contact with the inside bottom of the plate, the filter having plural pores of 0.35 to 0.45 μm in diameter, and by comprising: seeding primary cultured brain capillary endothelial cells onto the upper surface of the filter; seeding primary cultured brain pericytes onto the under surface of the filter; seeding primary cultured astrocytes onto the inside surface of the plate; and coculturing these cells in a normal culture solution.

The invention belongs to the field of pharmacy, and relates to a multi-purpose targeting molecule, and applications of a compound and a drug delivery system modified by the multi-purpose targeting molecule in brain tumor diagnosis and treatment. According to the invention, the multi-purpose targeting molecule RGD-pHA being compatible to brain capillary endothelial cells and crossing the blood-brain barrier, being highly compatible to integrin and crossing the blood-brain tumor barrier, and targeting to the brain tumor cells is prepared by adopting a molecule splicing method; the invention further relates to preparation of fluorescein and a medicine modified by RGD-pHA, and a macromolecular carrier material, and applications of RGD-pHA in construction of the drug delivery system. The experimental result shows that the RGD-pHA can be specifically taken by brain capillary endothelial cells expressing the dopamine receptor for mediating the model drug or the nanometer drug delivery system to enter the brain, so that the model drug or the nanometer drug delivery system is specifically taken by the positive cells and the tumor sphere tissue expressing the integrin, the good brain tumor targeting effect is shown in vitro and vivo, and the efficiency in resisting brain tumor is obviously improved.

The present invention belongs to the field of biotechnology, and is one kind of brain targeting gene transfer and release system and its preparation process. Lactoferrin is first used to modify cationic polymer by means of hydrophilic polymer, and the modified cationic polymer is then compounded with plasmid DNA by means of electrostatic effect to form the gene transfer and release system. The present invention can raise the transfection efficiency and expression efficiency of gene on brain capillary endothelial cell effectively, and raise the brain targeting property of gene transfer and release system and the expression of the gene in brain obviously after the non-invasive administration via intravenous injection. Compared with available technology, the present invention has obviously raised brain targeting effect.

The invention discloses a method for constructing a blood capillary model and a microsystem chip thereof. The invention utilizes microsystem processing technology to design and manufacture a microchip system for ordered arrangement and culture of endothelial cells of a blood capillary. The method constructs the blood capillary model with normal physiological functions by the following three main steps: design and manufacture of the microsystem chip, transfer, arrangement, fixation and culture of the endothelial cells of the blood capillary, and measurement of the functions of the blood capillary model. The blood capillary model can be used for culturing and observing the endothelial cells of the blood capillary, can perform real-time measurement on the concentration of vasodilative factors NO excreted by the endothelial cells, can make the permeability of the tube wall changed along with different additional stimuli, approximately simulate the functions of the blood capillary under normal physiological conditions, and can be used for sieving active ingredients of cardiovascular drugs.

The invention discloses a method for establishing an in-vitro model capable of simulating barrier functions of pulmonary epithelial cells and capillary endothelial cells during acute lung injury. Themethod comprises the following steps: (1) inoculating endotoxin-infected mouse C3H/10T1/2 microvascular endothelial cell strains into lower culture of a cell by using a Transwell co-culture system; inoculating mouse-derived TC-1 pulmonary epithelial cells into the upper layer of the cell, co-culturing for a period of time, and collecting the cell culture supernatant; and (2) detecting conditions of barrier synthesis of pulmonary epithelial cells/capillary endothelial cells in the cell culture supernatant and expressions of inflammatory factor and inflammatory cell infiltration associated proteins, and establishing a pulmonary epithelial cell/capillary endothelial cell co-culture model applicable to endotoxic acute lung injury study. The model established by the method disclosed by the invention is close to a cell barrier function during in-vivo endotoxic acute lung injury, and can provide a reliable model basis for clinical acute lung injury study.

The invention discloses application of transthyretin (TTR) to the inhibition of ocular neovascularization and belongs to the field of biochemistry, molecular biology and medical science. The application finds out that mammal TTR is given and ocular new blood vessels in STZ (Streptozocin)-induced diabetes mellitus rat and mouse models are obviously reduced. An in-vivo experiment model of ocular neovascularization and brain neovascularization verifies that the TTR has the effect of inhibiting the neovascularization and a result shows that the TTR acts on ocular capillary endothelial cells and can be used for effectively inhibiting the formation of 90 percent of the blood vessels; and when the TTR acts in the rat and mouse models, high up to 90% of neovascularization can be effectively inhibited.

The invention discloses a primary homologous three-cell four-dimensional model of the pharmaceutical research on a central nervous system, and a construction method. The primary homologous three-cell four-dimensional model of the pharmaceutical research on the central nervous system is characterized in that neuron cell cultures and a neuron cell culture medium are contained in a 24-mesh culture plate; a Transwell Insert is inserted into the neuron cell culture medium; the inner chamber surface of a filter membrane of the Transwell Insert is coated with collagen IV; capillary endothelial cell cultures are contained in the inner chamber surface of the Transwell Insert; astroglia cell cultures are contained in the outer chamber surface of the Transwell Insert; protrusions of astroglia cell cultures penetrate into the capillary endothelial cell cultures through filter membrane pore size of the Transwell Insert; and the neuron cell culture medium comprises components in percentage by volume as follows: 98% of the cell culture medium, 1% of a double-antibody and 1% of L-glutamine.

The invention belongs to the field of pharmaceutical preparations, and relates to a gene delivery system of a targeting brain capillary endothelial cell mediated by a short peptide. The gene delivery system comprises a targeting functional group, a gene medicament and a carrier, wherein the targeting functional group is a short peptide; the carrier is poly beta-amino ester and polyethylene glycol-poly beta-amino ester; the short peptide is in covalent connection with the polyethylene glycol; and the gene medicament and the carrier form the nano gene delivery system in an entrapment or adsorption manner. By using the gene delivery system, a gene is delivered into a brain capillary endothelial cell in an active targeting manner, so that the brain capillary endothelial cell expresses the required secretion type medicament protein and further secretes and delivers the protein into the brain, thereby realizing treatment of neurodegenerative diseases of the brain.

The invention belongs to the technical field of biological medicines and in particular relates to an acute brain and spinal ischemia/reperfusion injury cellular network model as well as a construction method and application thereof. The cellular network model comprises primary isogenous central nervous system capillary endothelial cells, astrocytes and neurons, wherein the endothelial cells, astrocytes and neurons are three-dimensionally co-cultured according to the relative spatial position and quantity relations of the endothelial cells, astrocytes and neurons in vivo; the environment of oxygen and glucose deprivation/reoxygenation and recovery of glucose in a central nervous system during acute brain/spinal ischemia/reperfusion injury in vivo is simulated by utilizing a low oxygen regulation system/ordinary cell culture system and glucose-free cell culture fluid/normal cell culture fluid. The cellular network model has the beneficial effects that a medicine research mode of adopting the central nervous system capillary endothelial cell culture fluid in lumens of inserts for administration is put forward for the first time, so that the cellular network model further conforms to the organism pharmacokinetics; the cellular network model is used for further research of acute brain/spinal ischemia/reperfusion injury emergence and development mechanisms; the new cellular network model is provided for research and evaluation of clinical diagnostic markers and medicines.

The invention relates to the field of biological pharmacy, and discloses a preparation method and application of a cyclosporine A-loaded efficient brain-targeted drug delivery system. The drug delivery system is composed of CsA and Fn; by utilizing the characteristic that ferritin is denatured in acetone and can be renatured in water, the CsA is wrapped in a cage structure (CsA(at)Fn) of the Fn through a solvent evaporation method; the CsA(at)Fn can be mediated by transferrin receptors on the surfaces of brain capillary endothelial cells to penetrate through a blood brain barrier and be accumulated in an ischemic area; on one hand, the CsA(at)Fn van protect the integrity of the blood brain barrier and reduce accumulation of inflammatory factors in a cerebral ischemic area; and on the other hand, the CsA(at)Fn taken by neuronal cells can inhibit the opening of mitochondrial permeability conversion pores of the neuronal cells, reduce the release of mitochondrial ROS and cytochrome C, inhibit the apoptosis of the neuronal cells and play a role in neuroprotection.

The invention belongs to the technical field of biological medicines and particularly relates to an intracranial and spinal excitotoxic injury cell network model and a building method and application thereof. The cell network model comprises primary homologous central nervous system capillary endothelial cells, astrocytes and nerve cells, stereoscopic coculture is carried out according to in vivo relative space position and quantity relationship of the primary homologous central nervous system capillary endothelial cells, the astrocytes and the nerve cells, and the environment of the central nervous system in a body in the case of intracranial and spinal excitotoxic injury is simulated by using a common cell culture system and glutamic acid-glycine cell culture fluid/normal cell culture fluid. The invention puts forwards a pharmaceutical research mode of drug administration through plug-in central nervous system capillary endothelial cell culture liquid for the first time, is different from a conventional in vitro pharmaceutical research mode in which drug directly acts on a target cell(s) in the central nervous system and is more according with the pharmacokinetics of a living body. Therefore, the intracranial and spinal excitotoxic injury cell network model and the building method thereof can be used for deep research on generation and development of excitotoxic injury; and moreover, a new cell network model can be provided for clinical diagnosis markers and medicine research and evaluation.

The invention belongs to the field of pharmacy, and relates to an AMP complex and an application thereof in preparation of a tumor targeting nano-drug delivery system. The invention provides a drug and a polymer carrier material modified by adenosine monophosphate (AMP) and an application thereof in construction of a drug delivery system for tumor imaging and targeting therapy. Experimental results show that the AMP complex can cross brain capillary endothelial cells, are specifically absorbed by tumor tissues and have good intracerebral delivery and tumor targeting and imaging functions. Thenano-drug delivery system constructed by the AMP-modified polymer carrier material, such as liposomes, polymer micelles, polymer discs and nanoparticles, can cross a blood-brain barrier to enter the brain and target to tumors, and significantly enhances antitumor effects. The AMP-modified drug and the nano-drug delivery system have remarkable advantages in targeting brain tumors, and have good application prospects in targeting diagnosis and treatment of tumors.

The invention relates to a multi-component combined solution. The multi-component combined solution is characterized by comprising the following components in percentage by weight of 1 to 10 percent of collagen, 1 to 10 percent of thiotaurine, 10 to 50 percent of thermal spring water and 30 to 88 percent of deionized water. Deionized water and thermal spring water are used as solvents, collagen and thiotaurine are added, and a multi-component combined solution is formed. Experimental results show that the composition has an obvious effect on tissue structure and loricrin/involucrin expression of an epidermis model, has a positive regulation effect on dermal capillary endothelial cells, and has a correct response to a capillary permeability control regulation factor; and meanwhile, the multi-component combined solution has obvious effects on resisting lipid peroxidation and inflammation of skin keratinocytes.