69 results about "Barrier permeability" patented technology

The invention belongs to the technical field of medical nano-materials, and particularly relates to a lactoferrin nano-material for sonodynamic regulation and control of blood-brain barrier permeability as well as a preparation method and application of the lactoferrin nano-material. The nanomaterial is nanoparticles LCe6 formed by self-assembly of lactoferrin and chlorin e6, can target brain microvascular endothelial cells, and can temporarily, reversibly and targeting open BBB by using the sonodynamic effect of the LCe6 in combination with transcranial ultrasonic stimulation, so that the accumulation of the nanoparticles LCe6 at a focus part is improved; in addition, the nanoparticle LCe6 also has a targeting property on brain tumor cells, the tumor cells can be accurately killed by utilizing the sonodynamic effect of the nanoparticle under secondary transcranial ultrasound, and the effect of sonodynamic treatment on brain glioma is exerted to the maximum extent; the nanoparticles LCe6 have excellent biocompatibility and low toxicity; according to the invention, the intracerebral delivery efficiency of the drug can be obviously improved, and a novel method for targeting open brain disease BBB is provided.

The invention discloses a macrophage-polymer lipid nanoparticle composite drug delivery system, a preparation method thereof and application of the macrophage-polymer lipid nanoparticle composite drug delivery system in cryptococcus infection resistance. According to the drug delivery system, alpha-linolenic acid (ALA), high molecular weight chitosan oligosaccharide (HCOS) and amphotericin B (AmB) are used as raw materials to construct nanoparticles AmB-PLHNs, the nanoparticles are loaded in macrophages through the phagocytosis of the macrophages, and the AmB-PLHNs (at) M1 is constructed. AmB is a common medicine for clinically treating Cn infection, but has the problems of toxic and side effects on kidney and incapability of being transferred into the center. The AmB-PLHNs (at) M1 carries AmB-PLHNs to be transferred into the brain according to the blood-brain barrier penetrating characteristic of M1 type macrophages, and the brain entering efficiency of the medicine is improved. By combining the phagocytosis of macrophages on cryptococcus, the inflammation immune regulation function of the macrophages and the bacteriostatic action of the drug-loaded nanoparticles, the drug-loaded nano-particles are used for treating Cn central infection, and the toxic and side effects of AmB are reduced.

The invention relates to a brain-targeted stilbene glucoside and tanshinone IIA loaded combined liposome for treating Alzheimer's disease and improving learning and memory ability disorders and a preparation method thereof. The composition comprises a modification factor Angiopep-2, a liposome carrier, stilbene glucoside and tanshinone IIA. Angiopep-2 is used as a target head, and a film dispersion and ammonium sulfate gradient method is adopted to prepare the liposome. According to the present invention, the problems of poor solubility and low bioavailability of stilbene glucoside and tanshinone IIA are solved, and the Angiopep-2 and the blood brain barrier (BBB) surface LRP-1 are subjected to specific recognition and are combined to enter the brain, such that the blood brain barrier transmittance of the drug is increased, and the targeting ability of the drug is improved. The traditional Chinese medicine composition has a good application prospect in the aspects of treating the Alzheimer's disease and improving learning and memory dysfunction.

The invention discloses a composition based on the synergistic effect of an SOD-LF covalent conjugate and neuromodulation and application of the composition in preparation of drugs for relieving anxiety and insomnia and improving sleep quality, and belongs to the technical field of biology. The preparation method comprises the following steps: preparing an SOD-LF covalent conjugate from lactoferrin and SOD; uniformly dispersing the SOD-LF covalent conjugate in a sodium alginate solution, spraying into a calcium chloride solution, standing, and filtering to obtain a sodium alginate coated SOD-LF covalent conjugate; and dispersing the sodium alginate coated SOD-LF covalent conjugate and fucoidin in a chitosan solution, adding sodium tripolyphosphate, stirring for reaction, and centrifugally collecting to obtain the composition based on the synergistic effect of the SOD-LF covalent conjugate and nerve regulation. According to the composition disclosed by the invention, the blood brain barrier transmittance is enhanced through the SOD-LF covalent conjugate, and the fucoidin is combined to regulate the intestinal flora-enteric brain axis to synergistically inhibit neuroinflammation and oxidative stress, so that anxiety and insomnia are improved.

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.

This invention belongs to the field of drug carrier technology and discloses a brain-targeted nanocarrier, its preparation method, and application. The primary raw materials for preparing the brain-targeted nanocarrier include PLGA-PEG-NHS, D-mannosamine, and a sulfide donor. This brain-targeted nanocarrier utilizes the dual targeting effects of mannose and sulfide to not only target the brain but also effectively improve blood-brain barrier permeability. With its high targeting and high permeability, it can be used as a carrier to effectively deliver therapeutic drugs to the brain to exert therapeutic effects, and has promising application prospects.

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 a flavone derivative delivery system of targeted EGFR (Epidermal Growth Factor Receptor) protein as well as a preparation method and application of the flavone derivative delivery system, and belongs to the technical field of medicinal chemistry. The flavonoid derivative HT11 with anti-A beta and antioxidant activity is synthesized firstly, the depolymerization effect of the flavonoid derivative HT11 on A beta 1-42 reaches up to 92.40%, and the flavonoid derivative HT11 has good blood-brain barrier permeability. Then, the HT11 is loaded by taking the graphene oxide quantum dot as a carrier to obtain the HT11 coated GOQDs, so that the defect of low solubility of the HT11 is effectively overcome, and the targeting property and the curative effect of the HT11 coated GOQDs can be enhanced. Experimental results show that the HT11-coated GOQDs effectively solve the problem of reduction of AD animal space learning and memory ability, and possibility is provided for application of the HT11-coated GOQDs in the field of biological medicine.

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 invention relates to a fusion protein comprising GLP-1, immunoglobulin Fc region, and IGF-1, and use thereof. The fusion protein of the present invention has excellent efficiency in blood-brain barrier permeability, and thus can be widely used for the effective treatment of neurological diseases.

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 present invention provides the use of α-asarone in the preparation of a drug for preventing or treating hemorrhagic stroke. The structure of α-asarone is shown in Formula I. It can significantly improve short-term neurological deficits and long-term learning and memory function in model rats, reduce cerebral edema, improve blood-brain barrier permeability, and prevent or alleviate brain tissue atrophy during the recovery period. It has a definite therapeutic effect on animal models of hemorrhagic stroke without significant toxic side effects, and is expected to become a promising drug for the prevention and treatment of hemorrhagic stroke. #imgabs0#

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 belongs to the technical field of liposome pharmaceutical preparations, and particularly relates to a liposome and application thereof, a liposome preparation and a preparation method and application thereof. The invention provides a liposome. A glutathione group and an indole residue are modified on a liposome membrane. The lipidosome provided by the invention has excellent transmembrane transport capacity, can efficiently penetrate through a blood-brain barrier and can be taken by glioma cells, and also shows excellent endosome escape characteristic, so that the technical problem of low blood-brain barrier transmittance in the glioma treatment process of temozolomide is effectively solved. Meanwhile, the invention provides a liposome preparation, the delivery efficiency and the anti-tumor curative effect are improved, the liposome preparation has an inhibiting effect on human / mouse glioma cells, the wide clinical application potential is shown, and an efficient and low-toxicity novel treatment scheme is provided for glioma patients.

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 present invention belongs to the technical field of liposome pharmaceutical preparations, and specifically relates to a liposome and its application, a liposome preparation and its preparation method and application. The present invention provides a liposome, wherein the liposome membrane is modified with a glutathione group and an indole residue. The liposome provided by the present invention has excellent transmembrane transport ability, efficiently penetrates the blood-brain barrier and can be taken up by glioma cells, while exhibiting excellent endosomal escape properties, thereby effectively solving the technical problem of low blood-brain barrier permeability during the treatment of gliomas with temozolomide. At the same time, the present invention provides a liposome preparation that improves delivery efficiency and anti-tumor efficacy, has an inhibitory effect on both human and mouse glioma cells, shows a wide range of clinical application potential, and provides a new treatment plan for glioma patients with high efficiency and low toxicity.

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

Application of total flavonoid extract of Ziziphora clinopodioides Lam. in the preparation of drugs for treating cerebral ischemia-reperfusion injury. The present invention belongs to the field of cerebrovascular diseases, and particularly relates to the application of total flavonoid extract of Ziziphora clinopodioides Lam. (ZCF) in the preparation of drugs for treating cerebral ischemia-reperfusion injury. The present invention has studied the effects of different doses of ZCF against cerebral ischemia-reperfusion injury. The research shows that ZCF has a significant therapeutic effect on Sprague-Dawley rats with a middle cerebral artery occlusion-reperfusion (MCAO / R) model prepared by the suture method, significantly reduces the cerebral infarction area (Figure 1), reduces the blood-brain barrier permeability, and can effectively improve cognitive and motor dysfunction. The present invention also provides a drug that effectively resists cerebral ischemia-reperfusion injury, and can provide a reliable experimental basis and theoretical basis for the development of drugs for treating cerebral ischemia-reperfusion injury using Ziziphora clinopodioides Lam.

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 discloses arylpyrimidine compounds which are selective inhibitors of histone deacetylase 6 (HDAC6), and their use in the preparation of drugs for treating HDAC6-related diseases; specifically, compounds of formula (I) and their pharmaceutically acceptable salts are disclosed. The compounds of the present invention have high inhibitory activity against HDAC6 and high selectivity for HDAC enzyme subtypes, and at the same time have ideal pharmacokinetic characteristics, high blood-brain barrier permeability and good safety.

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.