41 results about "Barrier 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.

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 purpose of the present invention is to provide a novel blood-brain barrier permeability regulator.　The present invention pertains to a blood-brain barrier permeability regulator containing a compound represented by formula (I) (Symbols in the formula (I) are as defined in the present specification.) or an isomer thereof, or a salt thereof. The present invention also pertains to a medicine for preventing and / or treating various brain diseases, severe infections, or sepsis by using the compound or an isomer thereof, or a salt thereof alone or in combination with a drug for preventing and / or treating a brain disease.

The invention discloses ICA1L derived peptide and application thereof in relieving Alzheimer disease A beta pathology. The amino acid sequence of the ICA1L derived peptide is shown as SEQ ID NO.01. The invention further discloses a preparation method of the ICA1L derived peptide. The compound can be combined with low-density lipoprotein receptor associated protein 1 (LRP1), inhibit K48 connection type ubiquitination of the LRP1 and prevent degradation through a proteasome pathway, so that the protein level of the LRP1 is stabilized, and the expression of beta-site APP lyase 1 is reduced to reduce the generation and deposition of beta-amyloid protein. In vitro, the peptide shows good biocompatibility and cell uptake ability; in vivo, the peptide has blood-brain barrier permeability, can be positioned in neurons, can significantly reduce hippocampus and cortex A beta plaque deposition in a 5xFAD mouse model through caudal vein injection, reduces BACE1 and beta-CTF levels, and improves the cognitive function. The invention further discloses an ICA1L-LRP1 regulatory axis, and a new strategy is provided for treatment of the Alzheimer's disease.

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 invention belongs to the technical field of cerebral apoplexy treatment, and discloses a traditional Chinese medicine composition for blood brain barrier permeability after cerebral apoplexy and a preparation method thereof, and the traditional Chinese medicine composition comprises the following raw materials: angelica sinensis, radix paeoniae alba, astragalus membranaceus, elecampane, pinellia ternate, mangnolia officinalis, caulis bambusae in taeniam, immature bitter orange, pericarpium citri reticulatae, bighead atractylodes rhizome, ligusticum wallichii, lumbricus, codonopsis pilosula and liquidambar formosana hance. The traditional Chinese medicine is used for treating cerebral arterial thrombosis with symptoms of turbid phlegm, blood stasis, brain collaterals and deficiency of healthy qi. The traditional Chinese medicine composition has the effects of reducing phlegm, activating blood, tonifying qi and strengthening the body resistance, and has a treatment effect on the pathological characteristics of cerebral arterial thrombosis such as blockage of brain collaterals due to turbid phlegm and blood stasis and deficiency of healthy qi.

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.

This invention relates to a midazolam nanocrystal suspension, which, by weight-volume percentage, comprises 5%–45% midazolam, 1%–10% Tween, and 0.1%–10% sodium deoxycholate (SDC). The midazolam nanocrystal suspension of this invention exhibits superior blood-brain barrier permeability and bioavailability, making it suitable for needle-free injection administration.

The present application relates to a kind of cytidine choline dextrohydrotalcid derivatives and its preparation method and application, belong to biological medicine technical field.The present application is aimed at solving the technical problems of low blood-brain barrier penetration rate and limited treatment effect of existing edaravone dextrohydrotalcid compound preparation.The present application prepares a dextrohydrotalcid derivative (C-B) with boronic acid structure, then it is compounded with cytidine choline in specific pH buffer system, and forms cytidine choline dextrohydrotalcid derivative (C-D-B).The present application can effectively improve the efficiency of drug crossing blood-brain barrier by using the dynamic covalent characteristics of boronic ester bond and free radical responsiveness.The experimental results show that, compared with existing combination drug, the derivative of the present application can significantly reduce the infarction area of cerebral ischemia model animal, reduce cell damage and active oxygen level, and promote vascular regeneration, and show better treatment effect on ischemic brain injury.

The application belongs to the technical field of biological medicine, and particularly relates to an N-carbonyl-substituted sulfur-containing fused pyrimidinone derivative based on XAV939 as well as a synthesis method and application thereof. The application provides a compound structure with a sulfur-containing fused pyrimidinone skeleton. The application introduces a carbonyl substituent at a specific nitrogen site of a parent nucleus, effectively improves pharmacokinetic properties of the compound XAV939, improves blood-brain barrier permeability, and realizes systemic administration. In addition, the application has a high bioavailability, and can be used for treating autism spectrum disorders. Shank3b In mutant autism model mice, the N-carbonyl-substituted sulfur-containing fused pyrimidinone derivative based on XAV939 first proposed by the application can significantly inhibit Wnt-glycolysis signals, improve social barriers, and has no obvious cytotoxicity, thereby providing a new drug selection for treating autism spectrum disorders.

The invention provides a preparation method of a composition for relieving tinnitus symptoms, which comprises the following steps: stirring and mixing a ginkgo leaf extract, an organic solvent and soya bean lecithin to obtain a component primary solution; adding gamma-aminobutyric acid and alpha-lipoic acid into the component primary liquid, uniformly mixing, and concentrating and purifying to obtain a phospholipidized complex; uniformly mixing soybean lecithin, sitosterol and an organic solvent, concentrating, adding a buffer solution to prepare a liposome mixed solution, carrying out ultrasonic dispersion, adding the phospholipid complex, stirring to obtain a core-shell structure mixed solution, filtering, and freeze-drying to obtain core-shell structure powder; the composition for relieving the tinnitus symptom is obtained by adding the active components and the auxiliaries into the core-shell structure powder, granulating and filling into capsules, a stable core-shell structure is formed by the prepared phosphatidylated complex and lipidosome, the fat solubility and stability of the composition are improved, and the blood-brain barrier transmittance is also improved.

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.

The application belongs to the technical field of medicine, and relates to a monoamine oxidase B inhibitor and a pharmaceutical application thereof. The monoamine oxidase B is a coumarin compound, and has the characteristics of high activity, high selectivity, high blood-brain barrier permeability and low neurocyte toxicity. The monoamine oxidase B can be clinically used for treating Parkinson's disease, Alzheimer's disease, neurodegenerative disease and depression.

The present invention discloses pyridazinone compounds represented by formula (I), as well as their preparation methods, pharmaceutical compositions, and uses. These compounds have potential advantages as PARP inhibitors in terms of blood-brain barrier permeability, and their inhibitory activity against PARP enzyme reaches nanomolar concentrations. They can be used to prepare drugs for preventing and / or treating stroke. In addition, the preparation method of such PARP inhibitors is simple and easy to operate. [C40] TIFF2026505719000064.tif26168

The application discloses a composition based on synergistic effect of SOD-LF covalent conjugate and nerve regulation and application thereof in preparation of medicine for relieving anxiety insomnia and improving sleep quality, and belongs to the technical field of biotechnology.The present application prepares SOD-LF covalent conjugate by using lactoferrin and SOD; the SOD-LF covalent conjugate is uniformly dispersed in a sodium alginate solution, then sprayed into a calcium chloride solution, and then placed, filtered to obtain SOD-LF covalent conjugate coated with sodium alginate; the SOD-LF covalent conjugate coated with sodium alginate, fucoidan and sodium tripolyphosphate are dispersed in a chitosan solution, stirred, reacted, centrifuged and collected to obtain the composition based on synergistic effect of SOD-LF covalent conjugate and nerve regulation.The composition can enhance the blood-brain barrier permeability through SOD-LF covalent conjugate, regulate the intestinal flora-gut-brain axis in combination with fucoidan, and synergistically inhibit nerve inflammation and oxidative stress, so as to improve anxiety insomnia.

A machine learning system and method for predicting blood-brain barrier permeability is provided. The system obtains samples of data associated with molecules from various data sources, converts the samples into structural representations, and generates a plurality of features from the structural representations, such as fingerprint representations. Tests are executed on the features to determine blood-brain barrier permeability dependency, The system analyzes the ratio of permeable to non-permeable samples in the samples of data and augments the samples with synthetic data to create a balanced dataset if an imbalance between the types of samples is detected. The system reduces the features utilized for training the machine learning utilizing a technique, such as logistic regression, to create a selected set of features for the balanced dataset. The system trains a machine learning model using the balanced dataset and utilizing the machine learning model to predict blood-brain barrier permeability for the candidate molecule.

The present invention relates to a composition for preventing, ameliorating or treating cognitive dysfunction or Alzheimer's disease comprising, as an active ingredient, Lactobacillus fermentum SRK414 strain which has accession number KCTC13687BP. The strain of the present invention is excellent in reducing barrier permeability and reducing amyloid beta and tau proteins and has an excellent effect in improving cognitive function, and accordingly, the strain can be useful for a food and therapeutic agent for same purposes.

The invention discloses a nicardipine delivery system and application of the nicardipine delivery system in resisting post-traumatic stress disorder. According to the present invention, the functional modification is performed on the PLGA-PEG to develop the brain enrichment type PLGA-PEG-MANNOse molecule, the nicardipine is subjected to nanometer modification, the blood brain barrier permeability is enhanced, and the fear memory disorder of the post-traumatic stress disorder model animal can be effectively relieved; research finds that when PPM-N is used for treating mice related to electric shock complicated post-traumatic stress disorder, indexes of multiple experimental results are equivalent to serotonin reuptake inhibitor medicine sertraline. Related experiments show that PPM-N has the effect of treating and / or relieving post-traumatic stress disorder and has a good clinical application prospect.

This invention relates to the field of pharmaceutical technology, specifically to a 6-(6-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)quinazoline-4-amine derivative, its preparation method, and its applications. This invention utilizes a "conformation-locking" and "drug-likeness optimization" strategy to optimize the 4-position side chain of quinazoline into conformationally defined structures such as dihydroindanol and fluoropiperidine, thereby reducing P-gp recognition through conformational rigidity. Simultaneously, the introduction of groups such as cyclopropylformyl groups reduces off-target toxicity, thus broadening the therapeutic window. The 6-(1H-pyrrolo[2,3-b]pyridin-3-yl)quinazoline-4-amine derivative provided by this invention simultaneously achieves potent DYRK1A inhibition, high kinase selectivity, low microglial cytotoxicity, significant anti-neuroinflammatory effects, good blood-brain barrier permeability, and oral bioavailability. Furthermore, it is a novel small-molecule inhibitor that can be validated for cognitive improvement in AD animal models, possessing significant clinical value and urgent application needs.

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.

The invention discloses a composition containing gamma-aminobutyric acid for promoting growth and development of children and a preparation method thereof, the composition comprises gamma-aminobutyric acid and two newly designed modified compounds N-(4-trifluoromethylbenzyl)-gamma-aminobutyric acid amide and a gamma-aminobutyric acid-zinc complex, and functional components such as animal bifidobacterium subsp.lactis, hydrolyzed yolk powder, casein phosphopeptides, minerals and theanine are supplemented. The preparation process comprises the following steps: respectively dissolving and homogenizing the components, mixing step by step in a protective atmosphere, and finally degassing, filling and performing low-temperature irradiation sterilization. The two modified compounds are prepared through activation amidation and complex reaction respectively, and the blood-brain barrier transmittance, stability and bioavailability of original components are remarkably improved. The composition can effectively promote secretion of growth hormones, improve bone growth and improve sleep quality through a multi-target synergistic effect, and is suitable for promoting growth and development of children.

The technology described herein is directed to compositions comprising antibodies and antibody reagent that binds specifically to Mfsd2A and method of using such compositions, e.g., to increase blood-brain barrier permeability in therapeutic methods.

The invention discloses a sesquiterpene compound, a preparation method and application of the sesquiterpene compound as an acetylcholin esterase inhibitor. According to the invention, a compound physochlatone A with a novel structure is obtained through separation, molecular docking is carried out on the compound and acetylcholin esterase, the binding activity of the compound and acetylcholin esterase is simulated, and the binding energy is-9.6 kcal / mol; a blood-brain barrier permeability prediction result shows that the compound can pass through a blood-brain barrier; an acetylcholin esterase inhibitory activity evaluation result shows that the compound has obvious acetylcholin esterase inhibitory activity. Technicians in the field know that significant decline of the acetylcholine level is one of the important causes causing various neurodegenerative diseases, and the decline of the acetylcholine level can be inhibited by inhibiting the activity of acetylcholin esterase, so that the effect of resisting the neurodegenerative diseases is achieved. Therefore, the physochlatone A has the prospect of being developed into the medicine for resisting the neurodegenerative diseases (such as the Alzheimer's disease).

Provided is use of anisodine hydrobromide in the preparation of a therapeutic drug for stroke patients after tPA thrombolysis, which can improve various clinical indexes of the patient after thrombolysis for ischemic stroke, repair blood-brain barrier permeability, inhibit leukocyte infiltration, regulate the expression levels of related proteins, etc.

Disclosed is a CAR-T cell with good blood-brain barrier permeability, a product, and use thereof, relating to the technical field of treatment of central nervous system diseases. Based on the study on CAR-T cell immunotherapy for central nervous system diseases, this disclosure provides a CAR-T cell with good blood-brain barrier permeability and a corresponding drug for treating or improving the central nervous system diseases. The CAR-T cell targets B-cell maturation antigens and highly expresses a chemokine receptor CXCR3 and chemokines CCL1, CCL3, and CCL4. This disclosure further provides a product for detecting and judging the blood-brain barrier permeability of the CAR-T cell, such as probes, reagents, and kits, which can accurately detect and judge the blood-brain barrier permeability of a specific CAR-T cell.

The invention discloses a hetero-diad compound taking indanone-tetrahydrothieno [3, 2-c] pyridine as a parent body and a preparation method and application thereof, the hetero-diad compound taking indanone-tetrahydrothieno [3, 2-c] pyridine as the parent body is selected from the compounds shown in the following general formulas (I), (II) and (III), the compound takes indanone of donepezil as a parent nucleus, and the compound is selected from the compounds shown in the general formulas (I), (II) and (III). And the compound is combined with an anti-platelet functional group tetrahydrothieno [3, 2-c] pyridine through a linking group. The compound has multiple action mechanisms (inhibiting AChE, resisting Abeta aggregation, resisting platelet aggregation and improving learning and memory impairment) and high blood-brain barrier permeability, and is suitable for preventing and treating vascular dementia.

This invention discloses a m-sulfamylbenzamide compound, its preparation method, pharmaceutical composition, and applications. The compound has the structure of Formula I and includes its stereoisomers, pharmaceutically acceptable salts, or mixtures thereof. This class of compounds and its pharmaceutical compositions can specifically inhibit butyrylcholinesterase activity, optimally achieving nanomolar concentrations; they also possess excellent blood-brain barrier permeability, enabling effective delivery to the lesion, and are virtually non-toxic at effective inhibitory doses; furthermore, they exhibit good neuroprotective effects and significantly improve memory and cognitive function, achieving therapeutic efficacy for Alzheimer's disease through multiple mechanisms of action.

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 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.