64 results about "Barrier permeability" patented technology

Permeability of the blood-brain barrier and other physiological barriers can be modulated by the degree of tyrosine phosphorylation of proteins. Agents which promote tyrosine protein dephosphorylation reduce the permeability of the blood-brain barrier and those which promote phosphorylation increase permeability. Increasing blood-brain barrier permeability is useful in delivering drugs having a desired effect upon the central nervous system; decreasing blood-brain barrier permeability and other physiological barrier permeability is useful in preventing undesired compounds reaching the CNS and in certain clinical conditions.

The present invention refers to compounds that, in addition to enhancing the sensitivity to acetylcholine and choline, and their exogenous agonists, of neuronal cholinergic receptors and / or acting as cholinesterase inhibitors and / or neuroprotective agents, have enhanced blood-brain barrier permeability in comparison to their parent compounds. The compounds are derived (either formally by their chemical structure or directly by chemical synthesis) from natural compounds belonging to the class of amaryllidaceae alkaloids e.g., galantamine, narwedine and lycoramine, or from metabolites of said compounds. The compounds of the present invention can either interact as such with their target molecules, or they can act as “pro-drugs”, in the sense that after reaching their target regions in the body they are converted by hydrolysis or enzymatic attack to the original parent compound and react as such with their target molecules, or both. The compounds of this invention may be used as medicaments.

The invention discloses endomorphin-derived peptides with blood-brain barrier permeability. The endomorphin-derived peptides are formed by connecting cell-penetrating peptide SynB3 with the carbon terminal of EM1 (Endomorphin1) and analogue (D-A1a2) EM1 through a disulfide bond; good BBB (Blood-Brain Barrier) permeability of the SynB3 is used to mediate the EM1 and the analogue (D-A1a2) EM1 to permeate the blood-brain barrier to reach the center by means of adsorption effect; and the characteristics that the disulfide bond is stable in blood and is easily reduced to break in meninx are utilized, the disulfide bond is broken under the action of a meningeal reductase to release free endomorphin-derived peptide so that the pain killing effect of the endomorphin-derived peptide can be exerted. A pharmacodynamic experiment proves that the endomorphin-derived peptides can be peripherally administrated besides the obviously improved pain killing activity to provide a wide prospect for developing clinical application of a neuropeptide medicine.

The invention provides a combination of polyethylene glycol and tamsulosin and a pharmaceutical compound comprising the combination which is as shown in a general formula (II). In the combination, a P and a P' are H or polyethylene glycol, and the P and the P' cannot be the H at the same time. The tamsulosin structurally contains a sulfamide group, the low-molecular-weight polyethylene glycol is introduced through an alkylation reaction, and therefore hydrophobicity of the tamsulosin is lowered, hydrophilism of the tamsulosin is increased, and the blood-brain barrier permeability of the tamsulosin is lowered. Therefore, the toxicity of the tamsulosin is lowered.

The invention discloses a polysubstituted quinazoline compound and an application thereof, and belongs to the field of chemical medicines. The substituted quinazoline compound represented by the general formula (I) and the pharmaceutically acceptable salt thereof have excellent brain barrier permeability, enhanced metabolic stability and longer metabolic half-life period, show higher inhibitory activity on an activated or drug-resistant mutant form EGFR than a wild type EGFR, and can effectively reduce side effects.

The invention is suitable for the technical field of control, and provides a blood-brain barrier permeability regulation and control device, and a method and a storage medium. The device comprises anultrasonic radiation module, and a vagus nerve positioning module and a signal excitation module which are connected with the ultrasonic radiation module; the vagus nerve positioning module is used for acquiring position information of the vagus nerve and determining a radiation position according to the position information of the vagus nerve; the signal excitation module is used for sending an excitation signal to the ultrasonic radiation module when the ultrasonic radiation module is located at the radiation position, and the excitation signal is used for controlling the ultrasonic radiation module to radiate ultrasonic waves to the vagus nerves so as to regulate and control the blood-brain barrier permeability. By regulating and controlling the permeability of the blood-brain barrier,the obstruction of the blood-brain barrier to macromolecular substances can be improved, so that the macromolecular substances can be smoothly transferred into the brain.

Novel compounds and methods for the inhibition of biological barrier permeability and for the inhibition of peptide translocation across biological barriers are identified. Assays for determining modulators of biological barrier permeability and for peptide translocation across biological barriers are provided. Methods for treating diseases relating to aberrant biological barrier permeability and peptide translocation across biological barriers are provided. Such diseases include celiac disease, necrotizing enterocolitis, diabetes, cancer, inflammatory bowel diseases, asthma, COPD, excessive or undesirable immune response, gluten sensitivity, gluten allergy, food allergy, rheumatoid arthritis, multiple sclerosis, immune-mediated or type 1 diabetes mellitus, systemic lupus erythematosus, psoriasis, scleroderma and autoimmune thyroid diseases.

The invention relates to a new strain of Lactobacillus mucosae which is able to decrease intestinal barrier permeability. This strain is useful in particular for alleviating intestinal barrier dysfunctions.

Tricyclic pyrone compounds having high oral bioavailability, excellent blood-brain barrier permeability, and low toxicity are presented. Administration of the compounds to Alzheimer's Disease transgenic models resulted in substantially reduced soluble and insoluble Aβ species in the brain without affecting general behavior and motor coordination. Furthermore, in addition to blocking the toxicity and formation of both intraneuronal and extracellular Aβ aggregates, the compounds also increase cellular cholesterol efflux, restore axonal trafficking, and enhance hippocampal synaptic plasticity.

The invention provides the application of nanogold in preparation of a reagent for measuring blood-brain barrier permeability. The nanogold is formed by the following nanogold particles with the particle sizes by weight percent: 1 part of nanogold particles with the particle size range of 9-15nm and the average particle size of 11+ / -0.5nm, 1 part of nanogold particles with the particle size range of 18-31nm and the average particle size of 27.5+ / -0.5nm, 1 part of nanogold particles with the particle size range of 41-63nm and the average particle size of 48.5+ / -0.5nm, 1 part of nanogold particles with the particle size range of 50-76nm and the average particle size of 68+ / -0.5nm, 1 part of nanogold particles with the particle size range of 93-114nm and the average particle size of 104+ / -0.5nm, 1 part of nanogold particles with the particle size range of 134-156nm and the average particle size of 145.5+ / -0.5nm and 1 part of nanogold particles with the particle size range of 151-176nm and the average particle size of 166+ / -0.5nm. According to the application, the quantitative measurement for the blood-brain barrier permeability of animals with cerebral trauma can be completed by the nanogold particles with different particle sizes; the number of nanogold permeating into the blood-brain barrier can be measured, and the largest pore of the opening of the blood-brain barrier can be estimated according to the particle sizes of the nanogold permeating into the blood-brain barrier; therefore, a quantitative measurement standard is provided for various blood-brain barrier damage models in animal experiments.

The invention discloses application of ferroptosis inhibitor Liproxstatin-1 to preparation of medicine for treating traumatic brain injury, and belongs to the technical field of biomedicines. The system of the ferroptosis inhibitor Liproxstatin-1 illustrates a time-course changing process (from 6h to 14d) of ferroptosis-related protein expression and occurrence of iron deposits after traumatic brain injury; meanwhile, the Liproxstatin-1 is dosed through an abdominal cavity after a person suffers from traumatic brain injury for 1 hour, which proves that the Liproxstatin-1 can alleviate cerebraledema and blood-brain barrier permeability caused by the traumatic brain injury; the findings proves that the Liproxstatin-1 has an improvement effect on exercise and learning memory impairment caused by the traumatic brain injury; the confirmation shows that the Liproxstatin-1 can obviously improve anxiety and cognitive functions caused by TB1; and in addition, revelation shows that a protectioneffect of the Liproxstatin-1 is related with up-regulation of FTH1 and Nrf2 and down-regulation of expression of NOX2 caused by reversion of TB1. An evidence is provided for using of the Liproxstatin-1 as a novel medicine for treating the traumatic brain injury.

The invention discloses a construction method and an application of a transgenic mouse with blood-brain barrier permeability enhanced. The construction method of the transgenic mouse with blood-brain barrier permeability enhanced comprises the step of modifying genes of a mouse, so that expression quantity of slit protein is increased, and a transgenic animal model with blood-brain barrier permeability enhanced is obtained; Study shows that overexpression of slit protein can cause that a tricorn of the mouse is enlarged, a choroid plexus structure is seriously destroyed, and tight junction of epithelium cells is lost; observation on a vascular structure of the brain of a Slit-Tg mouse by virtue of immunofluorescent staining shows that bifurcation of blood vessels of the brain of the Slit-Tg mouse is less, more microvessels exist, the shapes of vessels are incomplete and the distribution of the vessels is irregular; a transmission electron microscope map also shows that endothelial cells of the Slit-Tg mouse are damaged and highly irregular and basement membranes of vessels are incomplete. Evansblueassay detects that the permeability of the mouse is enhanced, i.e., the detection result shows that the blood-brain barrier permeability of the Slit-Tg mouse is enhanced, the Slit-Tg mouse can be applied to an animal experiment of central nervous system drugs and the Slit-Tg mouse can be used for screening, research and development as well as therapeutic effect evaluation on nervous system drugs.

The invention belongs to the field of detection of nano-drugs and in particular relates to a method for evaluating blood-brain barrier permeability of the nano-drug. The method comprises the followingsteps: (1) establishing a transwell in-vitro blood-brain barrier model; (2) adding suspension liquid containing a fluorescence nano-drug and / or a fluorescence dyed nano-drug into an upper tank of themodel established in step (1) and standing; (3) after finishing standing, taking out a membrane in a small chamber; carrying out fluorescence dyeing on cells on the membrane to obtain a sample to bedetected, wherein a dyed fluorescence color can be distinguished from a fluorescence color in step (2); (4) carrying out layer-by-layer scanning and photographing on the sample to be detected in step(3) along the thickness direction by adopting a laser co-focusing microscope; (5) superimposing pictures obtained by step (4) according to a scanning or photographing sequence and then taking a lateral view; evaluating the blood-brain barrier permeability of the nano-drug through observing the lateral view. The method provided by the invention can be used for accurately and rapidly evaluating theblood-brain barrier permeability of the nano-drug in vitro.

The invention discloses a sulfhydryl compound serving as a histone deacetylase inhibitor, and an application thereof. Pharmacological experiment results show that the composition has high anti-proliferative activity on various tumor cells, shows a protective effect on glutamic acid-induced neuronal cell damage on a cell model, has low toxicity to normal cells, low potential cardiotoxicity, ideal pharmacokinetic characteristics and high blood-brain barrier permeability, and has a development prospect as a high-efficiency low-toxicity antitumor or neurodegenerative disease treatment agent. The sulfhydryl compound is a compound with a structural general formula represented by formula (I) shown in the description, or a pharmaceutically acceptable salt, an ester or a prodrug thereof.

The invention discloses a drug-loaded ZIF-8 nanoparticle covered with a TF-PEG-PLGA coating and a preparation method and application thereof.The preparation method comprises the steps that a target drug, 2-methylimidazole and zinc nitrate are added into a methanol solution to be mixed for a first reaction, then the target drug, 2-methylimidazole and zinc nitrate are purified and dissolved in methanol, and a drug-loaded ZIF-8 nanoparticle solution is obtained; activating COOH-PEG-PLGA, uniformly mixing the activated COOH-PEG-PLGA with transferrin in the PBS to carry out a second reaction, purifying and dissolving in the PBS to obtain a transferrin modified PEG-PLGA solution; and uniformly mixing the drug-loaded ZIF-8 nanoparticle solution with the transferrin modified PEG-PLGA solution, so as to obtain the drug-loaded ZIF-8 nanoparticles covered with the TF-PEG-PLGA coating. The nanoparticle has blood-brain barrier permeability and tumor targeting property, realizes targeted drug delivery for craniocerebral tumors, and provides an ideal carrier for efficient and targeted drug delivery of intracranial tumors.

The invention provides a novel small-molecule inhibitor of an insulin-like growth factor 1 receptor and application of the novel small-molecule inhibitor. The novel small-molecule inhibitor is a derivative of picropodophyllotoxin; fluorine atoms are used for replacing hydrogen atoms at two positions of the left side of picropodophyllotoxin, so that the capacity of molecules penetrating through a blood-brain barrier is improved; meanwhile, deuterium atoms are used for replacing hydrogen atoms, so that the half-life period of the molecules in an organism can be effectively prolonged. The small-molecule inhibitor can be used for preparing drugs for preventing and treating cancers. Compared with picropodophyllotoxin in the clinical test stage at present, the small-molecule inhibitor has higherblood-brain barrier permeability and longer in-vivo half-life while maintaining the action mechanism and biochemical characteristics of picropodophyllotoxin. When used alone, the small-molecule inhibitor can effectively inhibit proliferation and brain metastasis of various tumors, and can be synergistically combined with other anti-cancer drugs, so that proliferation of tumor cells is efficientlyinhibited, and the lifetime is remarkably prolonged.

The invention relates to application of a black phosphorus nanosheet in preparation of a medicine for treating the Parkinson's disease. The black phosphorus nanosheet is a black phosphorus nanosheet of which the surface is modified with polyethylene glycol. The black phosphorus nanosheet has photothermal conversion performance, can improve blood-brain barrier permeability through a photothermal effect, and can improve the brain-targeted delivery efficiency of the black phosphorus nanosheet. In addition, the black phosphorus nanosheet also has oxidation resistance, can remove excessive active oxygen in the Parkinson's disease pathological state, has a nano biological effect of resisting the Parkinson's disease, and has a wide application prospect in future clinical practice.

The invention relates to a substituted quinazoline compound, a pharmaceutical composition containing the compound, and applications of the compound, wherein the substituted quinazoline compound with ageneral formula (I) and the pharmaceutically acceptable salt thereof have excellent brain barrier permeability, enhanced metabolic stability and long metabolic half-life period, show high inhibitoryactivity on activated or drug-resistant mutant form EGFR compared with wild type EGFR, and can effectively reduce side effects.

The invention discloses a polysubstituted quinazoline compound and application thereof, and belongs to the field of chemical medicines. The substituted quinazoline compound shown in the general formula (I) and the pharmaceutically acceptable salt thereof have excellent brain barrier permeability, enhanced metabolic stability and longer metabolic half-life period, show higher inhibitory activity on activated or drug-resistant mutant form EGFR than wild type EGFR, and can effectively reduce side effects.

The invention belongs to the technical field of hypoxic blood-testis-barrier permeability action mechanisms, and discloses a method for constructing a mouse model of an action mechanism in hypoxic blood-testis-barrier permeability. The method comprises the following steps: establishing a hypoxic induced C57BL / 6 and testicular mTOR single-gene knockout mouse hypoxic blood-testis-barrier permeability model, separating and collecting mTOR gene knockout mouse and C57BL / 6 mouse seminiferous tubule primary support cell lines and mouse support cell strains, and applying technologies like western blot, immunocytochemistry and qPCR in vitro to prove a potential molecular mechanism of the regulating effect of mTOR on JAM-B. According to the invention, the protective effect of a hypoxic inhibitory activated metabolic balance marker molecule, namely the mTOR in hypoxic blood-testis-barrier permeability and the molecular mechanism of the mTOR on expression of activated JAM-B are defined; and a theoretical basis and a treatment strategy are provided for treatment of the hypoxic blood-testis-barrier permeability.

The present invention refers to compounds that, in addition to enhancing the sensitivity to acetylcholine and choline, and their exogenous agonists, of neuronal cholinergic receptors and / or acting as cholinesterase inhibitors and / or neuroprotective agents, have enhanced blood-brain barrier permeability in comparison to their parent compounds. The compounds are derived (either formally by their chemical structure or directly by chemical synthesis) from natural compounds belonging to the class of amaryllidaceae alkaloids e.g. galanthamine, narwedine and lycoramine, or from metabolites of said compounds. The compounds of the present invention can either interact as such with their target molecules, or they can act as ''pro-drugs'', in the sense that after reaching their target regions in the body they are converted by hydrolysis or enzymatic attack to the original parent compound and react as such with their target molecules, or both. Compounds of this invention may be used as medicaments.

The invention relates to an application of mouse umbilical cord mesenchymal stem cells to protection of a blood-brain barrier function from being damaged after skin is scaled, and relates to a methodfor preparing medicines for protection of a blood-brain barrier function from being damaged after skin is scaled. Experiments prove that the mouse umbilical cord mesenchymal stem cells can effectivelyimprove the change of blood-brain barrier permeability after the mice are scaled.

The invention discloses an application of apolipoprotein E receptor mimetic peptide 6KApoEp in preparation of a medicine for treating secondary brain injury after cerebral hemorrhage, and discloses a protein sequence of the apolipoprotein E receptor mimetic peptide 6KApoEp, a construction method of the protein sequence of the apolipoprotein E receptor mimetic peptide 6KApoEp and preparation of an application mixed solution; after the 6KApoEp is applied, the expression of CypA can be reduced; by inhibiting activation of a / MMP-9 pathway, cerebral edema and blood-brain barrier damage after cerebral hemorrhage and generation of proinflammatory factors are relieved; the brain water content is reduced, the BBB permeability is improved, the increase of blood-brain barrier related proteins such as claudin-5, occludin and ZO-1 is promoted, the inflammatory response after cerebral hemorrhage is regulated and controlled by inhibiting CypA / NF-KB / MMP-9, the water content of brain tissues is reduced, and the blood-brain barrier permeability is improved, so that the secondary brain injury after cerebral hemorrhage is relieved, and the neuroprotective effect on cerebral hemorrhage is achieved; the inflammatory response after cerebral hemorrhage is reduced, and the blood-brain barrier permeability is improved.

The invention relates to a synthetic fasudil-lipoic acid dyad. The concrete structural formula of the synthetic fasudil-lipoic acid dyad is shown in the formula (I). The invention further provides a synthesis route of the synthetic fasudil-lipoic acid dyad. The synthetic fasudil-lipoic acid dyad can improve the blood-brain barrier permeability and neuroprotective effect of fasudil to a certain extent and enable fasudil to achieve the effect of multiple-targeted resistance to neurodegenerative diseases.

The invention relates to a nano-fiber heating plate. The nano-fiber heating plate comprises a heating plate body, and metal electrode sheets, which are fixedly connected with the two opposite side edges of the heating plate body, and are connected with an external power supply. The heating plate body is formed by an upper insulation wear-resistant layer, a lower insulation wear-resistant layer, and a nano-fiber heating film layer disposed between the above mentioned two layers. The two side edges of the nano-fiber heating film layer are contacted with the metal electrode sheets The nano-fiber heating plate is advantageous in that the inner interlayer of the heating plate body is the thin nano-fiber heating film layer, and the heating plate body is a surface-shaped heating body, and has a high-quality far-infrared radiation capability and a high electric energy-heat energy conversion rate, and the corresponding cost is reduced by 60-70% by comparing with the conventional heating body; the upper layer and the lower layer of the heating plate body are the insulation wear-resistant layers made of PET, has good heat permeability, and is capable of insulating water vapor and air, and has a good protection function for the interlayer, namely the nano-fiber heating film, and at the same time, the heat-resistant performance and the mechanical performance of the PET are good, and the PET is used as the surface layer, and then the heating plate has insulation, wear-resistant, and impact-resistant characteristics.

The invention discloses a prediction method for the blood brain barrier permeability of a medicine, which is characterized in that a non-linear model for predicting the blood brain barrier permeability of a medicine is established by utilizing a group contribution method and an artificial neural network. According to the method, a prediction model is established by adopting an artificial neural network, a nonlinear model for predicting the blood brain barrier permeability of a medicine is established, a nonlinear method which better conforms to the relationship between the structure and the property of a medicine is provided for prediction and evaluation of the blood brain barrier permeability of the medicine, and the method is a novel method for predicting the blood brain barrier permeability of a medicine. Based on the group contribution method and the artificial neural network, the nonlinear prediction model for predicting the blood-brain barrier permeability of a medicine is established, the molecular structure of a medicine is utilized to predict the blood brain barrier permeability of the medicine, the defects that traditional experiments are large in difficulty, time-consuming, expensive and the like are overcome, and a prediction method which is more in line with the nonlinear relationship between the molecular structure and the blood brain barrier permeability of a medicine, and is high in accuracy and strong in applicability is provided for predicting the blood-brain barrier permeability of a medicine.

The present invention relates to a substituted pyrimidine compound, its pharmaceutical composition and the use of the compound. It has excellent inhibitory activity on mutant EGFR and mutant HER2, and the substituted pyrimidine compounds with general formula (I) and pharmaceutically acceptable salts thereof have excellent pharmacodynamic properties, metabolic stability and / or better Blood-brain barrier permeability.