44 results about "Bbb permeability" patented technology

This relates to a discovery of a cell surface protein, namely NgR2, that is implicated in regulation of blood-brain barrier (BBB). In addition, the invention relates methods for identifying agents that modulate BBB permeability. Furthermore, the invention relates to methods of delivering therapeutic agents to the central nervous system by increasing BBB permeability.

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

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

The present invention relates to a method of increasing blood brain barrier (“BBB”) permeability in a subject. This method involves administering to the subject an agent or agents which activate both of the A1 and A2A adenosine receptors. Also disclosed is a method to decrease BBB permeability in a subject. This method includes administering to the subject an agent which inhibits or blocks the A2A adenosine receptor signaling. Compositions relating to the same are also disclosed.

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 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.

Macromolecule intracellular transduction technology based on improved cell-permeable Parkin recombinant protein (iCP-Parkin) has been developed as a protein-based anti-neurodegenerative agent for efficient BBB-penetration to effectively deliver the recombinant protein into the brain. Parkin protein, a dopaminergic neuronal cell death inhibitor, has been fused with a newly developed advanced macromolecule transduction domain (aMTD) and solubilization domain (SD) to increase the solubility/yield and cell-/tissue-permeability of the recombinant protein. In addition, our newly developed aMTD/SD-fused recombinant iCP-Parkin protein has shown BBB-permeability. Both in vitro and in vivo, our iCP-Parkin recombinant protein improved motor skills, a typical phenotype of Parkinson's disease, by increasing dopamine level in the brain by suppressing apoptosis of dopaminergic neuron cells. In conclusion, iCP-Parkin could be applicable in clinical studies as a protein-based anti-neurodegenerative agent to treat Parkinson's disease by protecting dopaminergic neuron cells and regulating the secretion of dopamine.

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 relates to the field of biological pharmacy, and discloses a preparation method and application of a cyclosporine A-loaded efficient brain-targeted drug delivery system. The drug delivery system is composed of CsA and Fn; by utilizing the characteristic that ferritin is denatured in acetone and can be renatured in water, the CsA is wrapped in a cage structure (CsA(at)Fn) of the Fn through a solvent evaporation method; the CsA(at)Fn can be mediated by transferrin receptors on the surfaces of brain capillary endothelial cells to penetrate through a blood brain barrier and be accumulated in an ischemic area; on one hand, the CsA(at)Fn van protect the integrity of the blood brain barrier and reduce accumulation of inflammatory factors in a cerebral ischemic area; and on the other hand, the CsA(at)Fn taken by neuronal cells can inhibit the opening of mitochondrial permeability conversion pores of the neuronal cells, reduce the release of mitochondrial ROS and cytochrome C, inhibit the apoptosis of the neuronal cells and play a role in neuroprotection.

The invention discloses a method for regulating and controlling blood brain barrier permeability and application of the method for the regulating and controlling blood brain barrier permeability. Through specific knockout of a fifth exon, a sixth exon and a seventh exon of a PTEN gene in a mouse cerebrovascular endothelial cell, increase of the blood brain barrier permeability and blood brain barrier leakage of a mouse can be observed; recombinant adeno-associated viruses expressing NEDD4-2 protein are constructed and injected into the mouse, it is found that the number of vesicles in cerebral vascular endothelial cells of the mouse is increased, the increase of the vesicles also leads to increase of the blood brain barrier permeability and the blood brain barrier leakage of the mouse. it is proved that PTEN deletion can cause blood brain barrier leakage caused by overexpression of NEDD4-2-Mfsd2a, therefore, the blood brain barrier permeability can be regulated and controlled by regulating and controlling the content or activity of the PTEN protein or the NEDD4-2 protein, and the PTEN protein or the NEDD4-2 protein can be applied to clinical preparation or development of related medicines for regulating and controlling the blood brain barrier permeability or cerebrovascular related medicines.

The invention belongs to the technical field of biology and relates to agitation micelle for treatment of cerebral arterial thrombosis as well as a preparation method and an application thereof. A drug delivery system comprises a functional group across BBB (blood brain barrier), a neuroprotection drug and a nano drug delivery system, wherein the functional group is an adenosine A2A receptor agitation group capable of reversibly regulating BBB permeability, and a micromolecular agonist is linked with a PEG end of the outer surface of a micelle drug carrier system in a chemical bond connectionmanner. The nano drug delivery system can enters the stroke area safely and initiatively across BBB, and the long-term neuroprotection function is provided through sustained and controlled release ofthe neuroprotection drug. The drug delivery system has great clinical significance in improving the treatment efficacy of patients suffering from cerebral arterial thrombosis and reducing the toxic and side effects of drugs used currently.

The invention discloses an application of butylphthalide or derivatives thereof in preparation of medicaments for treating or preventing radiation brain damage. The mechanism of action for treating the radiation brain damage by using the butylphthalide is that oxygen free radical balance in brain tissues subjected to radiation damage can be improved and the damage effect of oxygen free radicals can be relieved by the butylphthalide; the permeability of blood-brain barrier of a rat with radioactive brain damage can be reduced by reducing the number of circulating endothelial cells of the rat after whole brain irradiation, and the radioactive brain damage is protected, i.e., acting target cells of the butylphthalide are mainly vascular endothelial cells; and the AQP4 (Aquaporin 4) effect can be adjusted so as to protect the blood-brain barrier.

The invention provides a drug combination for analgesia, anesthesia or drug rehabilitation. The drug combination is composed of a tetrodotoxin injection and an opioid medical injection which are packaged separately. The tetrodotoxin injection is composed of tetrodotoxin containing a buffer agent and a high penetrating agent for opening of the blood-brain barrier (BBB) or a BBB carrier. The opioid medical injection is a commercially available injection containing an opioid receptor stimulant. In the drug combination for analgesia, anesthesia or drug rehabilitation, the BBB-opening high penetrating agent or the BBB carrier can raise BBB permeability and bioavailability of tetrodotoxin and the opioid medicine, and tetrodotoxin has a synergistic effect of de-addiction and synergism. Through cooperation of the three drugs, the drug therapeutic effect can be enhanced, duration of drug effect is prolonged, dosage of the opioid medicine is reduced, and tolerance and dependency of the opioid medicine are decreased or eliminated.

The present invention features novel peripherally-restricted non-benzodiazipene analogs with reduced blood brain barrier permeability and methods of use thereof for reducing tactile dysfunction, social impairment, and anxiety in a subject diagnosed with Autism Spectrum Disorder, Rett syndrome, Phelan McDermid syndrome, or Fragile X syndrome, or for treating touch over-reactivity, pain, or mechanical allodynia.

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 provides an application of a midazolam nanocrystal and a composition thereof in medicines for improving blood-brain barrier permeability. According to the midazolam nanocrystal, the solubility problem is solved, the bioavailability is improved, the problem that the treatment effect is poor when tablets and injection are used as anticonvulsant and antiepileptic drugs is solved, and the midazolam nanocrystal can effectively penetrate through a blood brain barrier and is used for treating epilepsy. In addition, the invention provides a technical platform, and the blood-brain barrierpermeability of the brain medicine is improved by the nanocrystalline preparation in the presence of a space protective agent and a charge stabilizer.

Compositions and methods of using ILC2 to reduce microglial activation or to reduce blood-brain barrier (BBB) permeability are described. Also described are methods and compositions that use an agent that increases the number of activated ILC2 to reduce microglial activation or BBB permeability.