117 results about "Blood brain barrier permeability" patented technology

Glucocorticoid blockers, including glucocorticoid receptor antagonists, are effective to prevent glucocorticoid-induced decrease in permeability of the blood-brain barrier and to increase the permeability of the blood-brain barrier. Administration of glucocorticoid blockers, including glucocorticoid receptor antagonists, concomitant with administration of drugs for treating diseases of the central nervous system increases delivery of such drugs into the central nervous system.

Disclosed are methods and systems for optimized deep or superficial deep-brain stimulation using multiple therapeutic modalities impacting one or multiple points in a neural circuit to produce Long-Term Potentiation (LTP) or Long-Term Depression (LTD). Also disclosed are methods for treatment of clinical conditions and obtaining physiological impacts. Also disclosed are: methods and systems for Guided Feedback control of non-invasive deep brain or superficial neuromodulation; patterned neuromodulation, ancillary stimulation, treatment planning, focused shaped or steered ultrasound; methods and systems using intersecting ultrasound beams; non-invasive ultrasound-neuromodulation techniques to control the permeability of the blood-brain barrier; non-invasive neuromodulation of the spinal cord by ultrasound energy; methods and systems for non-invasive neuromodulation using ultrasound for evaluating the feasibility of neuromodulation treatment using non-ultrasound / ultrasound modalities; neuromodulation of the whole head, treatment of multiple conditions, and method and systems for neuromodulation using ultrasound delivered in sessions.

Disclosed are methods and systems for optimized deep or superficial deep-brain stimulation using multiple therapeutic modalities impacting one or multiple points in a neural circuit to produce Long-Term Potentiation (LTP) or Long-Term Depression (LTD). Also disclosed are methods for treatment of clinical conditions and obtaining physiological impacts. Also disclosed are: methods and systems for Guided Feedback control of non-invasive deep brain or superficial neuromodulation; patterned neuromodulation, ancillary stimulation, treatment planning, focused shaped or steered ultrasound; methods and systems using intersecting ultrasound beams; non-invasive ultrasound-neuromodulation techniques to control the permeability of the blood-brain barrier; non-invasive neuromodulation of the spinal cord by ultrasound energy; methods and systems for non-invasive neuromodulation using ultrasound for evaluating the feasibility of neuromodulation treatment using non-ultrasound / ultrasound modalities; neuromodulation of the whole head, treatment of multiple conditions, and method and systems for neuromodulation using ultrasound delivered in sessions.

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 relates generally to a peripheral marker or marker of blood brain barrier integrity and methods of using them in the diagnosis, prognosis, and treatment of a variety of diseases. The preferred embodiments of the present invention relate to methods, compositions, kits, and assays useful in determining the integrity or permeability of a blood brain barrier. The various embodiments of the present invention can be used to identify subjects at risk for developing a disease associated with increased permeability of the blood brain barrier, as well as to provide insight on the ability of an agent or agents to pass the blood brain barrier. Preferably, increased levels of S100β protein are used alone or in combination with other markers of diseased state in order to diagnose and prognosticate permeability of the BBB.

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 relates to a micro-fluidic chip, which is applicable to researches on blood brain barrier drug permeability and high-throughput screening. The chip is prepared from elastic polydimethylsiloxane by virtue of a molding method. The chip, which is of a three-layer structure, comprises an array of nine groups of parallel micro-reaction units, wherein each of the micro-reaction units is composed of an upper cell culture chamber layer, a lower cell culture chamber layer and a microporous membrane layer, and each of the micro-reaction units comprises a chip micro-electrode and a fluid circulating pipeline. By continuously injecting a culture solution to the cell culture chambers, a fluid state in blood vessels can be simulated, so that a fluid environment is closer to a real internal environment of human body. By virtue of the chip micro-electrodes, electrical impedance signals are collected, and the physiological activity situations of the cell layers in the chip are monitored in real time. Drug molecules, which penetrate through the microporous membranes and the cell layers, deposit in the fluid circulating pipeline on the lower part of the chip and are eluted by virtue of the pipeline, and then membrane-permeable drugs can be collected for subsequent analysis. The micro-fluidic chip disclosed by the invention, compared with an existing method, can reflect blood brain barrier permeability of drugs, and the micro-fluidic chip can conduct high-throughput screening on nine drugs in a targeted mode in one time.

The present invention relates generally to a peripheral marker or markers of blood barrier integrity and methods of using same in the diagnosis, prognosis, and treatment of a variety of diseases. The peripheral marker(s) of the present invention are particularly useful in the differential diagnosis of diseased states. The preferred embodiments of the present invention relate to methods, compositions, kits, and assays useful in determining the integrity or permeability of either a blood CSF barrier or a blood brain barrier. The various embodiments of the present invention can be used to identify subjects at risk for developing a disease associated with increased permeability of the blood brain barrier, as well as to provide insight on the ability of an agent or agents to pass through the blood brain barrier. Embodiments of the present invention preferably involve the use of subject derived blood samples to determine the occurrence and level of circulating proteins indicative of blood brain barrier permeability or integrity. The embodiments of the present invention also provides screening methods for diagnosis, prognosis, susceptibility, or degree of permeability of penetration of the blood brain barrier by detecting the presence of serum Transthyretin either directly or through the use of antibodies.

The invention discloses a functional platelet bionic intelligent carrier and application thereof in anti-ischemic cerebral apoplexy. The bionic carrier is composed of polymer nanoparticles of a platelet membrane coated neuroprotectant ZL006e, a Tat cell-penetrating peptide as well as substrate peptide fragments and fibrinolytic protein conjugates capable of being cut by thrombin. The carrier system has the characteristics of excellent biocompatibility, capacity of effectively prolonging in-vivo cycle time and the like, and is capable of targeting micro-thrombus in lesions of ischemic cerebralapoplexy and releasing thrombolytic drugs. Meanwhile, the exposed Tat cell-penetrating peptide mediated neuroprotectant is capable of increasing blood-brain barrier permeability, the pH serves as an intelligent drug release switch, and the pH-mediated degradation at the lesions is responded, so that the drug is quickly released at lesions of cerebral ischemia, the curative effects are improved tothe greatest degree, and toxic and side effects are reduced.

The invention discloses a lipoprotein nanometer drug delivery system containing a solid phase core, and a preparation method thereof, and applications of the lipoprotein nanometer drug delivery systemin preparation of drugs. According to the present invention, the drug-loading solid phase core is coated with the recombinant lipoprotein, such that the limitation that the drug coating method is limited by the physical and chemical properties of the drug is solved, and the loading ability and the stability of the hydrophilic drug are improved; the nanometer drug delivery system has performancesof lysosome escape, high Ras expression or activated tumor cell targeting property, blood-brain barrier permeability and the like; and the preparation method is simple, and is suitable for large-scaleproduction.

The invention discloses a black phosphorus nano material for treating Alzheimer's disease, wherein a black phosphorus nanosheet is prepared from black phosphorus powder by an ultrasonic liquid peeling process. Moreover, the invention also discloses a preparation method and application of the nano material. According to the invention, the black phosphorus nanosheet for treating Alzheimer's disease can be used as a nano acquirer for effectively and selectively acquiring Cu<2+>, so as to reduce generation of active oxygen in cells and protect the cells from the toxicity related to non-dynamic balance of the Cu<2+>. According to the black phosphorus nanosheet medicine for treating Alzheimer's disease disclosed by the invention, the blood-brain barrier permeability can be improved through a photothermal effect, the shortcomings that a small-molecule compound or polypeptide cannot pass through blood-brain barrier and is unstable are overcome, and the efficacy is improved. The nanomaterial has the advantages of simple preparation process, no additional drug load, high stability and high biocompatibility, and thus has excellent biosecurity when used for treating Alzheimer's disease.

Disclosed are methods for delivering an enzyme to a subject's brain or bone. The methods include administering a hyaluronidase to the subject and administering the enzyme to the subject. The hyaluronidase and the enzyme are administered to the subject under conditions effective to deliver the enzyme to the subject's brain or bone. Compositions and kits which include hyaluronidase and an enzyme are also disclosed, as are methods for increasing blood-brain barrier permeability in a subject. Also disclosed are methods, compositions, and kits for delivering genes or other nucleic acid molecules to a subject's brain or bone, as well as methods, compositions, and kits for delivering enzymes to a subject's tissues. The methods, compositions, and kits are disclosed as being useful in treating or preventing a variety of enzyme deficiency diseases, such as those affecting brain and / or bone, e.g., as Canavan's disease, Fabry disease, Gaucher's disease, various forms of mucopolysaccharidosis (e.g., Hurler's syndrome, Scheie syndrome, Hurler-Scheie syndrome, Sanfillippo A syndrome, Morquio A syndrome, Morquio B syndrome, etc.), Niemann-Pick disease, Schindler disease, and Pompe disease.

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 invented inositol and trehalose derivatives, prepared by introducing multiple units of the guanidine group to the backbone molecules, show excellent blood-brain barrier permeability, and accordingly, it can be easily transported to the brain tissues and utilized for the treatment of neurodegenerative diseases such as Alzheimer's disease and Huntington's disease.

The invention discloses the application for regulating double-side blood-brain barrier permeability through medical diagnosis ultrasonic wave stimulation microbubbles. According to the method, the double-side blood-brain barrier permeability is effectively, reversibly and briefly regulated based on the biological effect generated by ultrasonic wave stimulation microbubble contrast media under the synergistic effect of different biological effects, and the effect of promoting conveying of medicine crossing micro-vessels is achieved; brief regulating of the blood-brain barrier permeability is characterized in that three layers of the micro-vessels are connected and opened closely, and therefore the concentration of the medicine crossing the micro-vessels and entering the brain tissue is improved, and the effects of the medicine can be developed. The application for regulating the double-side blood-brain barrier permeability through the medical diagnosis ultrasonic wave stimulation microbubbles is firstly proposed, the biological effect of the medical diagnosis ultrasonic wave stimulation microbubble contrast media of the application can be developed to the maximum on the basis of safety and economy, and more conveying ways are provided for the diagnosis of dispersing growing, infiltrating growing and even diffusing growing type brain tissue structure diseases in the cranium and the treatment by the medicine crossing the micro-vessels.

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 relates to a method for improving blood-brain barrier permeability by regulating Swiprosin-1 expression, and specifically provides an application of Swiprosin-1 and a regulator thereof in preparing a drug. The drug is used for regulating the blood-brain barrier permeability, or preparing an animal model with increased or reduced blood-brain barrier permeability. The invention further provides a specific Swiprosin-1 overexpression vector, siRNA and shRNA. The method proves that a mouse with Swiprosin-1 overexpression has increased blood-brain barrier permeability, while a mouse with Swiprosin-1 genes knocked out after MCAO operation has decreased blood-brain barrier permeability, therefore, Swiprosin-1 and the regulator thereof can be used for treating diseases related to blood-brain barrier permeability, and establishing an animal model with increased or decreased blood-brain barrier permeability.

The invention belongs to medical preparations and relates to a new phenytoin targeting nanopreparation and a preparation method thereof. The nanopreparation for targeting therapy of drug-resistant epilepsy is prepared by taking phenytoin as an active ingredient, a P-glycoprotein monoclonal antibody as a targeting head group and a macromolecular polymer as a carrier. The loading rate and the releasing speed of the phenytoin are controlled by changing the proportion of polyethylene glycol to polycaprolactone in the macromolecular polymer; the problems of poor blood brain barrier permeability, low drug concentration at an epilepsy lesion area, poor treatment effect and serious adverse reaction in the conventional treatment of the drug-resistant epilepsy by the phenytoin are solved by using slow release and active targeting technologies; and the safety of the phenytoin is obviously improved. The preparation can be targeted to the lesion area of the drug-resistant epilepsy, so that the phenytoin content of the lesion area is greatly improved and the seizure of the epilepsy is suppressed.

The invention relates to a series of compounds represented as the formula (I), or pharmaceutically acceptable salts thereof, which can be used as new-generation Wee1 selective inhibitor. Compared withexisting Wee1 inhibitor, the compound has a higher selectivity on Wee1 kinase, so that the compound is safer and is higher in treatment index, and also has higher blood brain barrier permeability. The compound has better safety and a larger applicable range, and can be applied to treatment on various tumors, including brain tumor.

The invention discloses application of coumarin-dithiocarbamate derivatives to pharmacy. The derivatives to which the invention relates are synthesized according to the following steps of: 1, by usingconcentrated sulfuric acid as a catalyst, taking resorcinol and ethyl acetoacetate and place same in a first organic solvent to perform a reaction so as to obtain an intermediate 2; 2, taking the intermediate 2 and dibromo alkane and place same in a second organic solvent, and performing a reaction under the condition that pH is greater than or equal to 8 so as to obtain an intermediate 3; 3, taking the intermediate 3, carbon disulfide and secondary amine in a third organic solvent, and performing a reaction under the condition that pH is greater than or equal to 8 so as to obtain a corresponding target compound. Experiments of an applicant show that the coumarin-dithiocarbamate derivatives show excellent selective acetylcholin esterase inhibitory activity, Abeta1 to 42 resistant self-gathering activity and blood-brain barrier permeability; part of the compounds are low in toxicity for nerve cells, and can penetrate blood-brain barriers and show ideal low-toxicity or non-toxicity effect; the coumarin-dithiocarbamate derivatives have excellent application prospect in the aspect of treating diseases such as the AD (Alzheimer's disease).

The invention discloses a monosialotetrahexosyl ganglioside sodium liposome injection and its preparation method. The liposome injection is made from monosialotetrahexosyl ganglioside sodium, hydrogenated egg yolk lecithin, soybean derived sterol, sodium deoxycholate, poloxamer 188, sodium bisulfite and other auxiliary materials. The liposome injection provided by the invention has good stability; the liposome will not break due to fusion and ice crystals during the freezing process and will also maintain good entrapment rate after stored for a long time. According to the invention, the quality of the preparation product is improved, toxic and side effects are minimized, retention time of the medicament in systematic circulation is increased, bioavailability and blood-brain barrier permeability of the medicament are raised and the curative effect is obviously enhanced. In addition, the preparation method is simple and is suitable for industrial production.

The invention relates to a 4-methoxyphenyl substituted tetrahydro-beta-carboline piperazine dione derivative and uses thereof, and specifically discloses a compound represented by a formula I, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein each group is defined in the specification. According to the present invention, the compound has dual inhibitory activity onacetylcholinesterase and phosphodiesterase 5, and has good blood-brain barrier permeability, such that the compound can be used for preparing drugs for treatment and / or prevention of Alzheimer's diseases. The formula I is defined in the specification.

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.

The present invention relates to a kind of bornyl benzoate and its preparation method and application, its chemical structure is shown in following formula (I), and chemical name is (+)-4-methoxybornyl benzoate. The synthetic method of bornyl benzoate of the present invention is that (+)-borneol, 0.75 times of borneol quality 4-methoxybenzoic acid, 0.025 times of borneol quality p-toluenesulfonic acid are added in toluene, It was obtained by reacting at 120°C for 8 hours. The (+)-4-methoxybornyl benzoate of the present invention has low cytotoxicity and the effect of penetrating the blood-brain barrier, and can promote medicines to penetrate the blood-brain barrier.

The invention relates to a functional curcumin nano-drug for diagnosis and treatment of cerebral diseases and application of the nano-drug. An amphipathic curcumin derivative is synthesized through a chemical method, and the nano-drug with curative activity and a drug loading function can be formed in an aqueous medium through self-assembling. The nano-drug has pharmacological activity aiming at treatment of the cerebral diseases and can achieve the effects of increasing blood-brain barrier permeability and promoting cerebral targeted drug delivery, so that the nano-drug achieves excellent effects of diagnosing and treating the cerebral diseases and has wide application prospects.