31 results about "Bbb permeability" patented technology

Provided are a CAR-T cell having good blood-brain barrier permeability, a product, and a use. On the basis of the research on CAR-T cell therapy for central nervous system diseases, provided are a CAR-T cell having good blood-brain barrier permeability and a corresponding drug, for use in treating or relieving central nervous system diseases. Such a CAR-T cell uses a B cell maturation antigen as a target, and highly expresses a CXCR3 chemokine receptor and CCL1, CCL3 and CCL4 chemokines. Also provided is a product for testing and determining the blood-brain barrier permeability of the CAR-T cell, e.g., a probe, a reagent, and a kit, thereby accurately testing and determining the blood-brain barrier permeability of a certain CAR-T cell.

The invention discloses a black phosphorus-methylene blue nano composition for improving blood brain permeability and a synthesis method thereof. The synthesis method comprises the following steps: step 1, mixing black phosphorus nanosheets with polyethylene glycol for reaction; step 2, carrying out centrifugal cleaning on the reaction liquid in the step 1, and collecting a lower-layer reactant; step 3, adding aminated superparamagnetic nanoparticles and methylene blue into the lower reactant obtained in the step 2 for reaction; and 4, carrying out centrifugal cleaning on the reaction liquid obtained in the step 3, and collecting a lower-layer reactant. The invention also discloses the black phosphorus-methylene blue nano composition synthesized by the synthesis method, the drug loading rate of methylene blue in the composition exceeds 60%, and the composition has good biological safety, is non-toxic to cells and mice, is very simple and convenient in preparation process, and has a wide application prospect in the aspect of improving the blood-brain barrier permeability.

By applying an alternating electric field to the brain for a period of time, certain substances (e.g., macromolecules) that would normally be unable to cross the blood-brain barrier can be introduced into the brain, where the frequency of the alternating electric field is chosen such that application of the alternating electric field increases the permeability of the blood-brain barrier. In some embodiments, the frequency of the alternating electric field is less than 190 kHz (e.g., 100 kHz). Once the permeability of the blood-brain barrier is increased, the substance is able to cross the blood-brain barrier.

The present application relates to a kind of hyperbranched polymer, nano preparation and its preparation method and application, belong to functional medical material and nanotechnology field.The hyperbranched polymer of the present application can be broken in ROS environment Release dihydrolipoic acid, play the role of antioxidant, be reduced to lipoic acid in vivo, and then play its role as coenzyme, participate in mitochondrial tricarboxylic acid cycle, restore mitochondrial function, thereby play the role of antioxidant and play the role of treating ischemic stroke.The nano preparation provided by the present application can be quickly distributed to brain in a short time, temporarily increase the paracellular permeability of BBB by inhibiting the expression of multi-drug resistance protein P-gp and ATP-dependent drug efflux protein on BBB, and the process of opening BBB by borneol is physiological and reversible, without destroying the structural integrity of blood-brain barrier.

A system for noninvasive regulation and control of blood brain barrier permeability through a transcranial pulsed electric field comprises a high-voltage pulse generator and a plurality of treatment electrodes. The connection tightness of endothelial cells is adjusted through a high-voltage short-pulse electric field, local regulation and control of the brain area are achieved in combination with electrode design, pulse parameters are flexibly adjusted to balance the effect and damage, and a new non-invasive physical treatment means is provided for assisting drug cross-blood-brain-barrier delivery. Compared with focused ultrasound, the multi-mechanism synergistic effect (electroporation effect and bioelectrochemical effect) is utilized instead of depending on the mechanical effect of exogenous microbubbles, so that the safety risk is remarkably reduced. The method has the advantages of noninvasiveness, high efficiency and safety, and can achieve a multi-mechanism synergistic effect. The non-invasive electrode is used for delivering instantaneous high-voltage electric pulses, which is different from conventional low-voltage long-time electric stimulation.

The application discloses a kind of compound screening method and system for regulating blood-brain barrier permeability, it is related to medical screening technical field, the specific steps of the method are as follows: S100, collect blood-brain barrier related cell multi-omics data to form original set;S200, data is preprocessed and standardized;S300, molecular network is constructed by cross-omics analysis, and key target is screened;S400, target information is integrated to establish structured target pool;S500, effective compound for regulating blood-brain barrier permeability is screened out by molecular docking and primary cell verification, the application constructs gene-protein-metabolite network by multi-omics integration and cross-omics analysis, accurately identifies blood-brain barrier key target, provides high credibility target pool;Combined with molecular docking and primary cell mixed culture verification, realize efficient screening and functional safety evaluation of candidate compound, significantly reduce research and development cost, provide efficient technical path for drug research and development.

The present invention relates to the technical field of compound synthesis, and in particular, to a compound capable of enhancing the permeability of the blood-brain barrier, a preparation method thereof, and an application thereof. The compound capable of enhancing the permeability of the blood-brain barrier has the following structural formula: wherein X represents a halogen, R1 represents a C1-C5 alkyl, and R represents a substituted or unsubstituted alkyl and a substituted or unsubstituted phenyl. The compound has a high blood-brain barrier permeability, and can then enter the brain more quickly, which is beneficial for the compound to exert its pharmacological effect. At the same time, the compound can simultaneously inhibit ALK and EGFR, and can serve as a dual inhibitor of ALK and EGFR, and has a good therapeutic effect on cancers such as non-small cell lung cancer, anaplastic lymphoma, lung adenocarcinoma, and glioma.

The invention relates to a multi-mode eye-brain collaborative maintenance intelligent device, and belongs to the technical field of eye-brain nursing equipment.The device is provided with an impression stimulation module, the impression stimulation module stimulates mild energy of an impression acupoint, the mild energy can be directly conducted to a paranasal sinus olfactory bulb in the deep part of a nasal cavity, the area is the starting end of paranasal sinus nerves, the paranasal sinus nerves are branches of cranial nerves, and therefore the paranasal sinus acupoint can be stimulated; the neural pathway directly extends to brain hippocampus, brain marginal tissue, pituitary gland and other core structures related to neuronutrition and brain metabolism; after stimulation, the paranasal sinus olfactory bulb and paranasal sinus nerves are activated to form a neural pathway for targeted delivery of the atomized liquid, so that the atomized particles of the brain care liquid are adsorbed on the surface of the paranasal sinus olfactory bulb and permeate into the brain along the activated neural pathway, and meanwhile, the permeability of the blood brain barrier is improved, so that the delivery resistance of the atomized liquid to related functional areas of the brain is further reduced, and the targeted delivery of the atomized liquid is realized. Precise nutrition for cranial nerves is achieved, and the problem that brain maintenance is invalid due to the fact that conventional nasal cavity atomized liquid enters the lung is thoroughly solved.

Many drugs and other molecules cannot ordinarily traverse the blood brain barrier (BBB). However, when alternating electric fields at certain optimum frequencies (e.g., 100 kHz) are applied to the brain, the BBB becomes permeable to those molecules. When the alternating electric fields are discontinued, the BBB eventually recovers to its original impermeable state. Subsequently, re-application of alternating electric fields at the optimum frequencies will re-open the BBB. Ordinarily, many frequencies (e.g., 200 kHz) of alternating electric fields are either ineffective or less effective at inducing permeability than the optimum frequencies. But once the BBB has been opened by applying alternating electric fields at the optimum frequencies, alternating electric fields at non-optimum frequencies can maintain the permeability of a previously-opened BBB.

The invention belongs to the field of treatment of inflammatory diseases, and provides application of an EED inhibitor in preparation of a medicine for preventing and treating blood-brain barrier permeability injury caused by endotoxemia. Experiments show that the EED inhibitor significantly reduces blood brain barrier permeability, inhibits neuroinflammation and improves disease behaviors. The invention provides a new medicine and a new way for treating secondary diseases related to endotoxemia.

The present invention relates to novel blood-brain barrier (BBB) ​​permeable substituted bicyclic derivatives capable of selectively inhibiting myosin light chain phosphate phosphorylation mediated by ROCK2 and / or Rho kinase, compositions comprising such derivatives, methods for preparing such derivatives and / or compositions, and methods for using such derivatives and / or compositions.

The invention discloses application of electroshock therapy in improvement of depression by regulating blood brain barrier and inflammatory factors, and relates to the technical field of nerve regulation. The invention discloses application of an electroshock treatment device in preparation of a medicine or a medical preparation for improving depression. The medicine or the medical preparation is used for improving depression by adjusting blood-brain barrier permeability of a subject. The regulation of the permeability of the blood-brain barrier comprises a close connection structure for repairing the blood-brain barrier; the repair is realized by up-regulating the expression of a tight junction protein, and the tight junction protein is selected from at least one of ZO-1, occuldin or claudin-5. The invention systematically discloses a brand new mechanism for treating and improving depression by electroshock, namely, a continuous path for reversing peripheral immune activation, repairing blood-brain barrier injury and relieving central nervous inflammation plays a role; the mechanism chain is clear, and innovative explanation is provided for the curative effect of ECT.

To provide a pharmaceutical composition that permeabilizes the blood brain barrier, for use in the treatment of cancer in the central nervous system of a mammal.SOLUTION: A pharmaceutical composition includes a treatment agent and a monoterpene. The monoterpene is perillyl alcohol. The treatment agent is an antibody or antibody fragment.SELECTED DRAWING: Figure 1

The invention discloses a compound screening method and system for regulating and controlling permeability of a blood brain barrier, and relates to the technical field of medicine screening, and the method comprises the following specific steps: S100, collecting multi-omics data of blood brain barrier related cells to form an original set; s200, preprocessing the data and standardizing the data; s300, constructing a molecular network through cross-omics analysis, and screening key targets; s400, integrating target spot information to establish a structured target pool; s500, molecular docking and primary cell verification are carried out, and compounds capable of effectively regulating and controlling the permeability of the blood brain barrier are screened out. Through multi-omics integration and cross-omics analysis, a gene-protein-metabolite network is constructed, key targets of the blood brain barrier are accurately recognized, and a high-credibility target pool is provided; molecular docking and primary cell mixed culture verification are combined, efficient screening and functional safety evaluation of candidate compounds are achieved, the research and development cost is remarkably reduced, and an efficient technical path is provided for drug research and development.

Described herein are methods for stimulating specific groups of neurons in the brain, e.g. the ventral tegmental area (VTA) or its axons, wherein the stimulation can open the blood-brain barrier (BBB) with sub-millimeter and / or sub-second specificity. Stimulation of the VTA can result in opening of the BBB for drug delivery, and / or opening the BBB for clearance of “junk” and / or waste. Also described herein, are non-invasive methods to provide control to BBB permeability.

The present disclosure relates to a blood-brain barrier permeable fusion protein and uses thereof, and provides a blood-brain barrier permeable fusion protein, a polynucleotide encoding the fusion protein, a vector including the polynucleotide, a transfection cell line transfected with the vector, and a pharmaceutical composition for preventing or treating diseases associated with brain dysfunction, including the fusion protein as an active ingredient.

By applying an alternating electric field to the brain for a period of time, certain substances (e.g., macromolecules) that would normally be unable to cross the blood-brain barrier can be introduced into the brain, where the frequency of the alternating electric field is chosen such that application of the alternating electric field increases the permeability of the blood-brain barrier. In some embodiments, the frequency of the alternating electric field is less than 190 kHz (e.g., 100 kHz). Once the permeability of the blood-brain barrier is increased, the substance is able to cross the blood-brain barrier.

The present invention addresses the problem of providing: a blood-brain barrier model that can be produced in a relatively simple manner and in which a physiological barrier function and selective permeability are reproduced; and a method for producing the blood-brain barrier model.　A blood-brain barrier model in which a physiological barrier function and selective permeability are reproduced can be produced in a relatively simple manner in a blood-brain barrier model having three cell layers of perisites, astrocytes, and vascular endothelial cells by culturing vascular endothelial cells so as to form a sheet structure on the surface of a porous membrane and so that perisites are present in an internal structure layer of the porous membrane.

This application relates to the field of intelligent healthcare, specifically to a method, device, and program product for assessing vascular occlusion reperfusion therapy based on thrombus permeability. It includes acquiring brain images of patients with acute ischemic stroke; classifying the responsible vessel in the brain images to determine whether it is large vessel occlusion, medium vessel occlusion, or distal small vessel occlusion; when the determination result is medium vessel occlusion, thrombus region localization and measurement are performed on the brain images, thrombus permeability is calculated, and reperfusion therapy is assessed based on the thrombus permeability to obtain an assessment result for intravenous thrombolysis or endovascular therapy. This application has significant clinical application value.

Examples are directed to devices, methods, and systems for determining opening or increased permeability of a blood-brain barrier (BBB) of a patient. An example device comprises memory circuitry that stores a set of non-transitory instructions, and processor circuitry coupled to the memory circuitry and configured to execute the instructions to determine opening or increased permeability of a BBB of a patient during an ultrasound-based BBB opening procedure using physiologic signals obtained from the patient.

When the composition of the present invention is used, it is possible to provide accurate basic information on the regulation of blood-brain barrier permeability, which limits future drug delivery, by predicting the permeability of the blood-brain barrier. In addition, when the pharmaceutical composition of the present invention is used, it is possible to effectively prevent, ameliorate or treat neuroinflammation by reducing blood-brain barrier permeability.

The invention discloses an application of a small molecule compound Nec-1s in preparation of a medicine for treating meningitis, and finds that the Nec-1s can limit enhancement of BBB permeability and invasion of RS218 in brain tissues by inhibiting RIPK1 kinase, so as to obviously relieve E.coli meningitis symptoms. The innovative treatment scheme of the targeted host cell provided by the invention can be used as a potential medicine for treating E.coli meningitis.

The invention discloses a bionic nano-carrier capable of reversibly regulating and controlling a blood brain barrier and application of the bionic nano-carrier. The bionic nano-carrier is of a core-shell structure, a lecithin surface modified inorganic nano-material serves as a core, a cell membrane of brain metastatic cancer cells coats the surface of the core to serve as a shell, and an A2A adenosine receptor agonist is loaded in a cell membrane coating layer. The blood brain barrier crossing efficiency is further improved; wherein the lecithin surface modified inorganic nano-material is obtained by using an oleic acid modified inorganic nano-material as a matrix and carrying out surface modification through amphiphilic ligand lecithin. The bionic nano-carrier regulates and controls the blood-brain barrier permeability in a reversible mode, the problems that the brain transfer efficiency of a brain metastatic cell membrane bionic carrier through a cell bypass path is limited, potential safety hazards exist in a traditional blood-brain barrier permeability regulation and control open means and the like are solved, and a new strategy is provided for efficient brain delivery.

A method of inducing blood-brain barrier (BBB) opening for delivery of a non-BBB permeable substance to a brain of a subject includes the steps of: administering an ethyl alcohol at 0.01%-5% v / v and the non-BBB permeable substance via microcatheter to a target area of the brain leading from an intracerebral artery and inducing a homogeneous distribution of the non-BBB permeable substance in the target area. The ethyl alcohol reaches the target area to induce a transient and reversible BBB opening for about 120 minutes so that the non-BBB permeable substance can penetrate the BBB to reach the target area. The non-BBB substance includes a therapeutic agent, a diagnostic agent, or a prophylactic agent. The use of low concentrations of ethyl alcohol allows the BBB to be restored to normal without causing significant harmful effects.

The present application relates to a fusion protein capable of permeating the blood-brain barrier and uses thereof, and provides a fusion protein capable of permeating the blood-brain barrier, a polynucleotide encoding the fusion protein, a vector containing the polynucleotide, a cell line transfected with the vector, and a pharmaceutical composition for preventing or treating diseases associated with brain dysfunction, comprising the fusion protein as an active ingredient.

When treating a subject using alternating electric fields (e.g., using TTFields to treat a tumor, or using alternating electric fields to increase the permeability of the blood brain barrier), some subjects experience an unpleasant electrosensation effect. This electrosensation can be reduced or eliminated by increasing the area of the transducer arrays that is active during certain times in the treatment. In some embodiments, this is accomplished by applying an AC signal between two pairs of transducer arrays at certain times (as opposed to the prior art approach of applying an AC signal between two individual transducer arrays).

Certain substances (e.g., large molecules) that ordinarily cannot traverse the blood brain barrier can be introduced into the brain by applying an alternating electric field to the brain for a period of time, wherein the frequency of the alternating electric field is selected so that application of the alternating electric field increases permeability of the blood brain barrier. In some embodiments, the frequency of the alternating electric field is less than 190 kHz (e.g., 100 kHz). Once the permeability of the blood brain barrier has been increased, the substance is able to cross the blood brain barrier.

When treating a subject using alternating electric fields (e.g., using TTFields to treat a tumor, or using alternating electric fields to increase the permeability of the blood brain barrier), some subjects experience an unpleasant electrosensation effect. This electrosensation can be reduced or eliminated by increasing the area of the transducer arrays that is active during certain times in the treatment. In some embodiments, this is accomplished by applying an AC signal between two pairs of transducer arrays at certain times (as opposed to the prior art approach of applying an AC signal between two individual transducer arrays).

The present invention relates to use of SC79 or an analogue thereof in the preparation of a blood-brain barrier permeability regulator. The blood-brain barrier permeability regulator comprises SC79 or an analogue thereof as an active ingredient, which down-regulates expression of tight junction proteins Claudin-5 and Occludin by activating Claudin-5 and Occludin signaling pathway downstream the protein kinase B, and thereby increases the blood-brain barrier permeability, and enhances the efficiency of transportation of a brain targeting drug delivery system, especially, an Angiopep-2-modified glycolipid nano-delivery system, into the brain. The present invention also relates to a kit comprising the blood-brain barrier permeability regulator and a brain targeting drug delivery system. According to the present invention, use of the blood-brain barrier permeability regulator in combination with a brain targeting drug delivery system can enhance the efficiency of transportation of a brain targeting drug delivery system into the brain, and thereby improve the therapeutic efficacy of the brain targeting drug delivery system.

The present invention relates to the measurement of changes in the glymphatic system of a dementia patient, and more specifically, to a low-intensity ultrasound irradiation device for measuring changes in the glymphatic system of a dementia patient. To this end, at least one of a first and second transducer (100, 110) is attached to the forehead region of the patient's head (10), oriented toward the external occipital protuberance (EOP) in the occipital region, and irradiates low-intensity ultrasound (50); at least one of a third and fourth transducer (120, 130) is attached to the temple regions of both sides of the patient's head (10), oriented toward each other, and irradiates low-intensity ultrasound (50); and a fixing band (300) that fixes the first, second, third, and fourth transducers (100, 110, 120, 130) to the head (10). By including first, second, third, and fourth driving units (140, 150, 160, 165) that each drive first, second, third, and fourth transducers (100, 110, 120, 130) to generate low-intensity ultrasound (50); and a control unit (180) that controls the first, second, third, and fourth driving units (140, 150, 160, 165), changes in the glymphatic system and changes in the permeability of the blood-brain barrier are measured through continuous venous contrast-enhanced T1 mapping and dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) together with irradiation of low-intensity ultrasound (50).