25 results about "Barrier permeability" patented technology

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.

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.

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 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 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 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.

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.

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.

A compound used as a BTK inhibitor or HER2 inhibitor, its preparation method, and its uses are disclosed. The compound has the structure shown in Formula II or its tautomers, mesosomes, racemates, enantiomers, diastereomers, or mixtures thereof, as well as pharmaceutically acceptable hydrates, solvates, or salts. The BTK protein kinase inhibitors of this invention exhibit strong inhibitory activity against both wild-type BTK and mutant BTK (C481S), with some compounds showing high brain penetration rates. The HER2 inhibitors of this invention exhibit good HER2 kinase inhibitory activity and high blood-brain barrier permeability. Furthermore, the compounds of this invention possess favorable pharmacokinetic properties and show promising application prospects.

The invention belongs to the technical field of medicine preparation, and particularly relates to application of hypoglycosylated apolipoprotein D in preparation of a medicine for repairing a blood brain barrier. Experiments in the invention show that in the molecular level, the binding affinity of low glycosylated apolipoprotein D (ApoD) and CD36 is increased by about 9 times compared with that of high glycosylated apolipoprotein D, and a key mechanism foundation is laid for function exertion; in an MCAO (middle cerebral artery occlusion) stroke model (middle cerebral artery occlusion model), the hypoglycosylated apolipoprotein D can remarkably repair a capillary structure, reduce an infarct area, improve neurological dysfunction, reduce blood-brain barrier permeability and enhance capillary perfusion, and the treatment efficiency is far superior to that of the hyperglycosylated apolipoprotein D; aiming at an elderly stroke model, the hypoglycosylated ApoD can improve the survival rate of mice, repair disordered and expanded capillaries, inhibit pathological endothelial cell proliferation and strengthen the integrity of a blood-brain barrier, and the hypoglycosylated ApoD can still continuously improve neurological functions and vascular phenotypes 30 days after stroke.

The application discloses a kind of aromatic amino acid compounds and preparation method, pharmaceutical composition and application thereof.The compound structure is as shown in formula I, which includes isomers, pharmaceutically acceptable salts or mixtures thereof.The aromatic amino acid compound and the pharmaceutical composition thereof can effectively and selectively inhibit butyrylcholinesterase, optimally reach nanomolar concentration level;It also has excellent blood-brain barrier permeability, and in addition, it is almost non-toxic.The prepared drug can effectively treat Alzheimer's disease through neuroprotective effect, memory and cognitive function improvement and various effects.

A machine learning system and method for predicting blood-brain barrier permeability are provided. The system acquires samples of molecular-related data from various data sources, converts the samples into structural representations, and generates multiple features from the structural representations, such as fingerprint representations. Tests are performed on the features to determine the dependence on blood-brain barrier permeability. The system analyzes the ratio of permeable to impermeable samples in the data samples and, if an imbalance between sample types is detected, augments the samples with synthetic data to create a balanced dataset. The system reduces the features used to train the machine learning model using techniques 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 uses the machine learning model to predict the blood-brain barrier permeability of candidate molecules.

The application discloses an amino thiazole compound and use thereof as a brain-permeable histamine H2 receptor agonist, and belongs to the field of medicines. The amino thiazole compound provided by the application has a structural general formula as shown in formula (I) and includes pharmaceutically acceptable salts. The amino thiazole compound has histamine H2 receptor agonistic activity and excellent blood-brain barrier permeability. Therefore, the amino thiazole compound can be applied to preparation of a medicine for treating diseases such as schizophrenia, mania, attention deficit hyperactivity disorder, binge eating or bulimia nervosa, autism, Parkinson's disease, ischemic brain injury and the like.

The application discloses flavonoid compounds with neuroprotective activity, and a preparation method and application thereof, and particularly relates to four specific ester derivatives of formononetin, namely, an allyl carbonate derivative (compound A), a 2-chlorobenzoic acid ester derivative (compound B), a cinnamic acid ester derivative (compound C), and a propionic acid ester derivative (compound D). The application significantly improves the defects of the parent compound, such as poor liposolubility, low blood-brain barrier permeability and low bioavailability, through specific ester group modification. Experiments show that the lipid-water partition coefficients and bioavailability of the four types of derivatives are significantly improved compared with the parent compound. In addition, the four types of derivatives show better neuroprotective activity than the parent compound and a positive control drug in Alzheimer's disease and Parkinson's disease models, and show a synergistic effect between the parent compound and the modification group. The application further provides a preparation method of the above compounds and application of the above compounds in preparation of drugs for treating neurodegenerative diseases.