889 results about "Central nerve system" patented technology

The present disclosure relates generally to compounds, their methods of synthesis, and their use in the treatment of mental illness or central nervous system disorders.

The invention provides a ziconotide nasal-brain delivery preparation which is high in brain targeting, safe and noninvasive and directly enters the brain through nasal administration. The nasal-brain delivery preparation comprises an active component ziconotide and an absorption enhancer, wherein the absorption enhancer is selected from one or more of dodecyl-beta-D-maltoside (DDM), menthol, hydroxypropyl-beta-cyclodextrin (HP-beta-CD), sodium glycocholate (SGC) and related derivatives thereof. The absorption enhancer with a specific type and content and the ziconotide cooperate and act together, so that the ziconotide bypasses a blood brain barrier, enters the brain through a nasal olfactory mucous membrane, forms a medicine storage bank in an olfactory bulb, is slowly released to the brain and keeps a long-term medicine effect, and therefore, a traditional ziconotide intrathecal administration mode is abandoned; the ziconotide nasal-brain administration mode is created, and the ziconotide nasal-brain administration method is a new-generation therapy for pain diseases related to the central nervous system.

The invention discloses an individualized pain prediction method and system based on a mixing effect. The method comprises the following steps: acquiring pain scores and corresponding central nervous system data when a plurality of healthy individuals receive pain stimulation; performing data processing on the obtained central nervous system data to obtain central nervous system physiological signals of pain stimulation received by corresponding individuals; combining the obtained physiological signals of the central nervous system and the corresponding pain scores to construct a mixed effect model; predicting the pain state of the individual by using the constructed mixed effect model; the system comprises a pain stimulation device, a central nervous detection system, a data acquisition module, a data analysis module, a prediction model construction module and a pain recognition module. The constructed mixed effect model gives consideration to the characteristics of an individualized model and a group model, not only can new individuals be migrated, but also individual differences are considered, the hierarchical characteristics of data are fully utilized, and the pain score prediction effectiveness can be effectively improved.

The present invention relates to a branched-chain fatty acid composition and its use in helping to regulate brain neuroimmunity, and belongs to the field of nutrient research. The branched-chain fatty acid composition provided by the present invention comprises C15:0 and C17:0, and more specifically comprises iso-C15:0, anteiso-C15:0, anteiso-C17:0 and iso-C17:0. The branched-chain fatty acid composition promotes the trend of LPS-induced microglia differentiation into M2 phenotype microglia, which is higher than the trend of promoting LPS-induced microglia differentiation into M1 phenotype microglia, and it also promotes the secretion of anti-inflammatory factors such as IL-4 and IL-10, and inhibits the secretion of pro-inflammatory factors such as NO, TNF-a, and IL-1β. Each branched-chain fatty acid in the branched-chain fatty acid composition has a synergistic effect, which can play a role in regulating brain neuroimmunity and maintaining the health of the central nervous system.

According to the LLM-based multi-agent collaborative decision-making system and the decision-making method thereof, each agent of the decision-making system is configured with a schedulable path, and the agents are scheduled according to the schedulable paths without root routers. The decision-making method comprises the following steps of: 1, configuring a human prompt word, a schedulable path and a decision-making mechanism of each agent, and binding functions of the agents; 2, in the interaction process, when the question and answer service receives the user input content, the personal setting, the decision-making mechanism, the tool function description, the interaction context and the user input content are transmitted to the LLM together, so that the LLM becomes a central nervous system of an intelligent agent; and step 3, making one decision of scheduling, executing, replying / questioning by the intelligent agent. According to the invention, each agent can autonomously decide and dispatch without a root router, and the agent can be ensured to complete a specific task according to an artificially formulated execution process.

Intranasal dry powder epinephrine compositions are described herein. The compositions include epinephrine or a pharmaceutically acceptable salt thereof, as well as a stabilizing agent and a carrier. The stabilizing agent is operable to include citric acid, or a pharmaceutically acceptable salt derived therefrom. Such intranasal compositions as described herein are useful in the treatment of health conditions which threaten the central nervous system (CNS) and impede the actions of alpha and beta-adrenergic receptors. Such health conditions include anaphylaxis, bronchospasms, respiratory impairment, organophosphate poisoning, and major adverse cardiac events (MACE).

The invention discloses a brain-targeted active oxygen responsive hydrogen sulfide donor liposome, a preparation method and an application, and belongs to the technical field of pharmaceutical preparations, the structure of the brain-targeted active oxygen responsive hydrogen sulfide donor liposome comprises a lipid material and a hydrogen sulfide donor encapsulated in the lipid material, the lipid material comprises phospholipid, cholesterol, active oxygen sensitive lipid and brain-targeted lipid, and the lipid material comprises phospholipid, cholesterol, active oxygen sensitive lipid and brain-targeted lipid. The active oxygen sensitive lipid comprises a phospholipid lipophilic part, a polyethylene glycol hydrophilic part and an active oxygen sensitive bond, and the brain-targeted lipid comprises a phospholipid lipophilic part, a polyethylene glycol hydrophilic part and brain-targeted peptide. The hydrogen sulfide donor lipidosome can penetrate through a blood brain barrier, target neuronal cells, respond to an active oxygen environment of a focus part and sensitively release a hydrogen sulfide donor, so that hydrogen sulfide is distributed in the focus neuronal cells, active oxygen and active nitrogen substances are effectively removed, oxidation and nitration stress are inhibited, and damage and death of the neuronal cells are reduced; the growth and functional recovery of neuronal cells are promoted, and the application prospect in the aspect of treating central nervous system injury diseases is good.

The invention relates to the technical field of medicines, in particular to novel application of orifice-opening and deafness-removing pills in preparation of anti-dizziness medicines. Experiments prove that the administration group can remarkably shorten the standing time consumption of a vertigo mouse caused by movement on the horizontal rod and reduce the vertigo response index, so that the movement vertigo model mouse can stand stably on the horizontal rod more quickly; abnormal changes of indexes such as ACTH, NE and CREB in mouse serum and BDNF, CREB, 5-HT and DA in brain caused by motion vertigo can be remarkably reversed. Therefore, the orifice-opening and deafness-removing pill has an obvious anti-dizziness effect, can be used as an active ingredient for preparing the anti-dizziness medicine, and is an effective treatment medicine especially for dizziness induced by movement. According to the invention, new indications of the orifice-opening and deafness-removing pill except deafness, tinnitus and otitis media are expanded. In anti-dizziness treatment, compared with dizziness stop, the traditional Chinese medicine composition can avoid digestive system reaction, cardiovascular reaction, central nervous system reaction and other side effects caused by dizziness stop.

Provided herein are compositions including brain, brain microvascular endothelial cell-targeting peptides and / or blood-brain barrier crossing (BBB) tissue-targeting peptides linked thereto or inserted in a targeting protein of a recombinant vector having at least one exogenous peptide comprising Xn – n-mer – Xm. Compositions providing such conjugates, targeting peptides, or recombinant vectors having an engineered capsid or envelope protein are provided as are uses thereof.

Methods of treating a nerve injury are disclosed. The methods include administering to a target site of the nerve injury a thermally stable preparation having a purified amphiphilic peptide in an aqueous biocompatible solution, being configured to self-assemble into a hydrogel, and administering to the target site a buffer having an effective amount of an ionic salt and a biological buffering agent to form the hydrogel. The methods include administering to the target site a biological material suspension in an amount effective to treat the nerve injury. The methods include administering to the target site an anti-scarring agent in an amount effective to treat the nerve injury. The target site is associated with central nervous system tissue or peripheral nervous system tissue. The nerve injury includes spinal cord injury and peripheral nerve injury.

The invention relates to the technical field of biological medicines, in particular to a recombinant rabies virus nano-antibody fused with a solubilizing oligopeptide and a cell penetrating peptide and application of the recombinant rabies virus nano-antibody in preparation of rabies prevention and treatment products. The recombinant rabies virus nano-antibody fused with the solubilizing oligopeptide and the cell penetrating peptide comprises a humanized rabies virus nano-antibody, and the C end of the humanized rabies virus nano-antibody is fused with a solubilizing tag peptide P17 and the cell penetrating peptide. The recombinant rabies virus nano antibody utilizes a prokaryotic expression system, is low in cost, has excellent cell membrane and BBB penetrating ability, can enter a central nervous system from veins for virus neutralization treatment, and has an efficient passive immune effect.

The present letter invention provides an engineered AAV capsid in which at least one protein on the capsid is modified to include an n-mer motif that promotes transduction of the capsid into the central nervous system (CNS) by interaction with a transferrin receptor. Further embodiments provide a carrier system comprising one or more carriers encoding an AAV capsid and a method of delivering a cargo to a CNS. The methods comprise administering an AAV capsid according to embodiments described herein in vivo or in vitro, and the AVV capsid comprises one or more carrier molecules.

Provided is a compound represented by formula (I), or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof. The compound represented by formula (I) is contained within a nucleotide or at the 5' end and / or 3' end, and is used for delivering double-stranded RNA to extrahepatic tissues, such as the central nervous system or eyes. Further provided are an oligonucleotide comprising the compound represented by formula (I), a double-stranded RNA, a vector, a cell, a pharmaceutical composition and a kit.

The invention provides an application of a pentacyclic triterpenoid compound targeting hydroxyl steroid 17-beta dehydrogenase 4. The pentacyclic triterpenoid compound can effectively relieve or treat central nervous system diseases (inflammatory diseases), including central nervous system degenerative diseases or chronic central inflammatory diseases. The pentacyclic triterpenoid compound can maintain the structural stability or activity of hydroxysteroid 17-beta dehydrogenase and maintain the stability or activity of peroxisome, thereby relieving or treating central nervous inflammation. The pentacyclic triterpenoid compound can target hydroxysteroid 17-beta dehydrogenase 4, inhibit neuroglial cell excessive activation related neuroinflammation, relieve neuron damage or death speed and improve a central nervous system cell metabolism microenvironment.

The present disclosure provides a compound of formula H having excellent PDE4B inhibitory activity, and a pharmaceutical composition thereof and a use thereof. The compound provided by the present disclosure can be used for effectively treating PDE4-related diseases and disorders, including but not limited to inflammatory respiratory diseases, inflammatory bowel diseases, inflammatory joint diseases, inflammatory skin diseases, inflammatory eye diseases, and diseases or cancers of the peripheral or central nervous system.

There are disclosed deuterated 2C—X phenethylamine compounds. the use of such compounds in the treatment of diseases associated with a serotonin 5-HIT2 receptor, pharmaceutical compositions such as tablet compositions and kits containing the compounds. methods of delivering the compounds in a mist via inhalation, and methods of treating diseases or disorders associated with a serotonin 5-HT2 receptor, such as central nervous system (CNS) disorders or psychological disorders with the compounds of the invention.

The present application is directed to a cochleate composition including one or more cochleates and at least two anti-fungal compounds selected from amphotericin B, 5-flucytosine, fluconazole, ketoconazole, ravuconazole, albaconazole, itraconazole, posaconazole, isavuconazole and / or voriconazole. Methods of using the antifungal cochleate formulations are also disclosed.

The invention relates to the technical field of biology, in particular to a variant AAV capsid protein and a recombinant adeno-associated virus rAAV. The variant AAV capsid protein provided by the invention comprises: 1) an amino acid sequence having at least 80%, 83%, 85%, 88%, 90%, 93%, 95% and 98% of identity with an amino acid sequence as shown in SEQ ID NO.1; and 2) an amino acid sequence shown as SEQ ID NO.1, wherein the amino acid sequence comprises amino acid substituted A587D, Q588G, A589N and Q590P, and an amino acid sequence TLAVPFK is inserted after the 588th site and before the 589th site; related products constructed by the variant AAV capsid protein can be used for cross-blood-brain-barrier efficient transduction to realize drug delivery to a central nervous system to treat related diseases of the central nervous system, and meanwhile, the related products have the characteristic of remarkably reducing liver transduction.

The invention relates to a branched chain fatty acid composition and application thereof in regulating brain immune balance, and belongs to the field of nutrient substance research. The branched chain fatty acid composition provided by the invention comprises C15: 0, C17: 0 and C16: 0, and more specifically comprises iso-C15: 0, anteiso-C15: 0, anteiso-C17: 0 and iso-C16: 0. The branched chain fatty acid composition promotes the tendency of LPS-induced microglial cells to be differentiated into M2 phenotype microglial cells which is higher than the tendency of the branched chain fatty acid composition to promote the LPS-induced microglial cells to be differentiated into M1 phenotype microglial cells, meanwhile, the branched chain fatty acid composition also promotes secretion of IL-4, IL-10 and other anti-inflammatory factors, and inhibits secretion of NO, TNF-a, IL-1beta and other proinflammatory factors. The branched-chain fatty acids in the branched-chain fatty acid composition have a synergistic effect, so that the effects of regulating the immune balance of the brain and maintaining the health of the central nervous system can be achieved.

Provided herein are engineered nucleic acids (e.g., expression vectors, including viral vectors, such as lentiviral vectors, adenoviral vectors, AAV vectors, herpes viral vectors, and retroviral vectors) that encode OCT4; KLF4; SOX2; or any combination thereof that are useful, for example, in inducing cellular reprogramming, tissue repair, tissue regeneration, organ regeneration, reversing aging, or any combination thereof in the central nervous system or ex vivo. Also provided herein are recombinant viruses (e.g., lentiviruses, alphaviruses, vaccinia viruses, adenoviruses, herpes viruses, retroviruses, or AAVs) comprising the engineered nucleic acids (e.g., engineered nucleic acids), engineered cells, compositions comprising the engineered nucleic acids, the recombinant viruses, engineered cells, engineered proteins, chemical agents that are capable of activating expression of OCT4; KLF4; SOX2; or any combination thereof, an engineered protein selected from the group consisting of OCT4; KLF4; SOX2; or any combination thereof, an antibody capable of activating expression of OCT4; KLF4; SOX2; or any combination thereof, and methods of treating a disease (e.g., a neurological disease), preventing a disease (e.g., neurological disease), regulating (e.g., inducing or inducing and then stopping) cellular reprogramming, regulating tissue repair, regulating tissue regeneration, or any combination thereof.

The present invention relates to antibodies or antibody fragments that bind to human and non-human primate transferrin receptors. The antibodies described herein can be used as agents to deliver pharmaceutical compounds into or through cells during receptor-mediated endocytosis and / or transendocytosis processes. As transferrin receptors are also present in the blood brain barrier endothelial cells, one aspect of the invention provides means and methods to increase delivery of pharmaceutical compounds to the central nervous system.

The present application relates to single-stranded or double-stranded interfering RNA molecules (e.g., siRNAs) that target the alpha synuclein (SNCA) gene. The interfering RNA molecule may contain a specific pattern of nucleoside modification and inter-nucleoside linkage modification as a pharmaceutical composition comprising the interfering RNA molecule. The siRNA molecule may be a branched siRNA molecule, such as a two-branched, three-branched or four-branched siRNA molecule. The disclosed siRNA molecules may also be characterized by a 5 '-phosphorus stabilizing moiety and / or a hydrophobic moiety. In addition, the present disclosure provides methods for delivering siRNA molecules of the present disclosure to a subject, such as the central nervous system of a subject identified as having synucleinopathies.

The present disclosure relates generally to compounds, their methods of synthesis, and their use in the treatment of mental illness or central nervous system disorders.

Described herein are shock wave catheters and methods of use thereof for delivering an active agent of a drug to the CNS via a body lumen or cavity, such as sinonasal cavity, which can bypass the blood-brain barrier (BBB). The catheters described herein can be advanced through an intranasal passage to the nasal cavity such that at least a portion of the enclosure is disposed in the nasal cavity. The enclosure can be coated with a drug coating. The method can include filling the enclosure with a conductive fluid. At least one shock wave can be generated at a shock wave emitter of the catheter disposed within the enclosure. The at least one shock wave can cause a therapeutically effective amount of the active agent of the drug coating to be delivered to the CNS via tissue of the nasal cavity, in turn, treating central nervous system diseases.

A chimeric autoantibody receptor (CAAR) that enables targeting of an immune cell to autoantibody producing B cells. The CAAR includes an autoantigen or fragment thereof that is bound by autoantibodies associated with neurological autoimmune disease primarily targeting the central nervous system. Also disclosed is a nucleic acid molecule encoding a chimeric autoantibody receptor (CAAR), the nucleic acid sequence encoding an autoantigen or fragment thereof that is bound by autoantibodies associated with a neurological autoimmune disease primarily targeting the central nervous system, a transmembrane domain, and an intracellular signaling domain, a vector comprising a nucleic acid molecule encoding a chimeric autoantibody receptor (CAAR), a genetically modified immune cell comprising the nucleic acid molecule encoding the CAAR and use of the immune cell in the treatment or prevention of a neurological autoimmune disease primarily targeting the central nervous system, such as an autoimmune encephalopathy or encephalomyelopathy, preferably anti-NMDAR encephalitis.

The invention discloses an aza-four-membered ring connected pyrazolopyridine compound or pharmaceutically acceptable salt and application thereof, and the compound with the structure can be used as a novel high-selectivity PDE10A inhibitor for treating peripheral tissue diseases such as cardiac hypertrophy and cardiac dysfunction (heart failure), diabetes, hypertension, renal function impairment and renal fibrosis. Lung inflammation and pulmonary fibrosis, immune regulation disorder and cancers (colon cancer, ovarian cancer and lung cancer). Through strategies in two aspects, the inhibition effect of the compound on a PDE10A high-selectivity inhibitor is reduced while the inhibition effect of the compound on a central nervous system is reduced. Firstly, in the aspect of molecular structure modification, the structure of the pyrazolopyridine compound connected with the aza-four-membered ring is optimized, for example, the polar surface area of molecules is increased by increasing the proportion of the number of N, O and S atoms in the molecular structure, and the fat solubility is reduced; and hydrophilic groups are introduced to increase water solubility and the like, so that the permeability of the compound to the blood brain barrier BBB is reduced. And 2, targeted drug delivery of lung tissues is realized by means of a pharmaceutical preparation.

A method for predicting a development level difference of language and communication capability normality of a healthy infant or toddler. The method comprises obtaining electroencephalogram (EEG) or magnetoencephalogram (MEG) waveform data of a healthy infant or toddler caused by external auditory stimulus; obtaining, from the EEG or MEG waveform data, quantitative data that represents measurement index data of a central nervous system caused by the external auditory stimulus; and using a data set to train a machine learning classifier, so as to obtain a prediction result. Further provided are a relevant tool and an integrated system.

The present disclosure provides a compound of formula H having excellent PDE4B inhibitory activity, and a pharmaceutical composition and use thereof. The compounds provided by the present disclosure are useful for the effective treatment of PDE4-related diseases and disorders, including but not limited to respiratory tract inflammatory diseases, inflammatory bowel diseases, arthritis diseases, skin inflammatory diseases, eye inflammatory diseases, and diseases or cancers of the peripheral or central nervous system. # imgabs0 #

The present disclosure provides oligonucleotides comprising at least one radical of a central nervous system receptor ligand at a nucleobase, the 2' position of a nucleoside, or the 3' position of a nucleoside. The present disclosure also provides pharmaceutical compositions and kits comprising said oligonucleotides, methods of delivering said oligonucleotides, methods of modulating the activity of a protein using such oligonucleotides, and methods of treating, preventing, or diagnosing diseases (e.g., central nervous system diseases, neurodegenerative diseases, and neurocognitive diseases) in a. subject in need thereof using said oligonucleotides or pharmaceutical compositions thereof. The present disclosure also provides oligonucleosides that may be useful for making the oligonucleotides.

The present invention relates to a branched fatty acid composition and its use in assisting the maintenance of nervous system health, and belongs to the field of nutrient research. The branched fatty acid composition provided by the present invention comprises C14:0, C15:0, C16:0 and C17:0. After LPS-induced microglia are treated with the branched fatty acid composition, the trend that the microglia can be promoted to differentiate into M2 phenotype microglia is higher than the trend that the microglia are promoted to differentiate into M1 phenotype microglia, while promoting the secretion of anti-inflammatory factors such as IL-4 and IL-10, and inhibiting the secretion of pro-inflammatory factors such as NO, TNF-a, and IL-1β. C14:0, C15:0, C16:0 and C17:0 in the branched fatty acid composition have a good synergistic effect, which plays a role in regulating brain immunity and maintaining the health of the central nervous system.