53 results about "Brain Thrombus" patented technology

The invention belongs to the technical field of biological medicines, and particularly relates to application of a targeted liposome as an active component in preparation of a medicine for treating ischemic brain injury. The targeted lipidosome for treating cerebral arterial thrombosis is prepared by fusing the lipidosome and the platelet-neutrophil aggregate membrane, realizes efficient and specific targeting of an ischemic brain region, effectively reduces brain tissue infarction and damage of a new region, relieves brain inflammation through multi-channel regulation and control, and improves the cerebral arterial thrombosis treatment effect. The compound can be used as an active ingredient for preparing a medicine for treating ischemic brain injury. And after the target liposome is further coated with a rutin drug, the synergistic treatment effect is realized. The liposome medicine can be used as an active component and has a good application prospect in treatment of ischemic brain injury diseases.

The invention relates to the technical field of biological medicine, in particular to a cerium oxide nano-enzyme delivery system based on carried neutrophil, and the system comprises cerium oxide nano-particles; the surfaces of the cerium oxide nanoparticles are coated with the lipoic acid zwitterionic polymer layers; the sialic acid molecules and the protocatechuic aldehyde molecules are modified on the surface of the lipoic acid zwitterionic polymer layer; wherein the system realizes breakthrough of a blood brain barrier and precise delivery of ischemic lesions through mediation targeting delivery of L-selectin on the surface of neutrophile granulocyte, and based on a cerium oxide nano-enzyme delivery system carrying neutrophile granulocyte, a'antioxidation-anti-inflammation-angiogenesis promotion-neural restoration 'quadruple synergistic mechanism is integrated, so that the system has the advantages that the system is simple in structure and convenient to use, and the application prospect is wide. And a new strategy of multi-target intervention is provided for cerebral arterial thrombosis treatment.

Disclosed in the present invention is the use of a mesenchymal-stem-cell-derived intracellular nanovesicle in neuroprotection. Compared to a small extracellular vesicle with exosomes as the main component, the small intracellular nanovesicle of the present invention has a smaller particle size, a narrower particle size distribution range, and greater stability at different temperatures, and has good tissue compatibility. The small intracellular nanovesicle of the present invention can better ameliorate nerve injury or neurodegenerative diseases such as optic nerve injury, ischemic stroke and Alzheimer's disease, and has very good application and research value in the field of pharmaceuticals.

The invention relates to the technical field of medicines, in particular to application of DP-b99 and a derivative thereof in preparation of a medicine for treating cerebral ischemia mechanical thrombus extraction reperfusion injury. On the basis of mechanical thrombus extraction and reperfusion of cerebral ischemia, DP-b99 is combined to reduce mechanical thrombus extraction and reperfusion injury of cerebral arterial thrombosis, so that the inflammation level of brain tissues can be reduced, the volume of cerebral infarction can be reduced, the injury of the brain tissues can be effectively reduced, and the treatment effect is remarkable.

The invention belongs to the technical field of biological medicines, and particularly discloses a self-assembled nano preparation coated with a macrophage membrane as well as a preparation method and application of the self-assembled nano preparation. According to the nano preparation, nano particles formed by self-assembly of epigallocatechin gallate (EGCG), ferric chloride (FeCl3) and edaravone (EDV) serve as a core, and the outer layer of the nano preparation is coated with a macrophage membrane. The preparation method is a one-pot method and comprises the following steps: mixing and self-assembling EGCG, FeCl3 and EDV in a phosphate buffer solution, carrying out centrifugal purification, and carrying out ultrasonic fusion with a macrophage membrane. The nano preparation is uniform in particle size, has excellent free radical scavenging capacity and antioxidant activity, can effectively pass through a blood-brain barrier and target a cerebral ischemia reperfusion injury area, and shows a remarkable effect in preparation of drugs for treating cerebral arterial thrombosis.

The invention relates to the technical field of fusion membrane nano preparations, and provides a nano preparation capable of being used for cerebral arterial thrombosis gene drug targeted delivery, which comprises lipid-calcium phosphate nanoparticles, which are composed of DOPA modified calcium phosphate cores and lipidosome and are used for providing positive charges to obtain efficient gene loading efficiency and proton sponge effect, the intracellular efficient delivery and release of the gene are realized; and the exosome membrane is prepared from a cell culture solution extracted from bone marrow-derived mesenchymal stem cells and is used for improving the transfection efficiency of the carried medicine. According to the present invention, by using the process characteristic that the inner layer phospholipid and the outer layer phospholipid are not synchronously prepared during the LCP preparation process, the biological membrane of the exosome and the LCP outer layer phospholipid are fused during the LCP preparation of the outer layer phospholipid so as to construct the fusion membrane preparation having the characteristics of the biological membrane and capable of carrying out AMD3100 targeting modification, such that the advantages of the biological membrane and the AMD3100 in the targeting delivery system are combined so as to achieve the target delivery effect; and the bottleneck of drug delivery for brain diseases is solved.

The invention provides a method for quantifying a water content ratio, which comprises the following steps of: scanning a brain by using first energy and second energy through dual-energy CT (Computed Tomography) equipment to generate plain scanning data of each voxel; setting the three substances of the dual-energy tomography three-substance separation mathematical model as water, grey matter and white matter; processing the plain scanning data of each voxel by using the dual-energy tomography three-substance separation mathematical model to obtain enhanced data of each voxel; and calculating the water content percentage of each voxel according to the enhancement data of each voxel. The method for quantifying the water content can quantify the water content of the encephaledema tissue of the acute stroke patient, and further quantify the edema proportion of the encephaledema tissue. The invention further provides a water content ratio quantifying device, a tomography system and a storage medium which relate to the method.

The invention provides a selective KCNQ channel opener and application of the selective KCNQ channel opener in pharmacy. According to the invention, a series of KCNQ channel openers with high selectivity are obtained by carrying out structural modification and activity and selectivity evaluation on a KCNQ2 agonist 124-A10 (CAS number: 1173735-00-6) obtained by screening. Compared with common KCNQ channel openers, such as retigabine, ICA27243 and the like, the subtype selectivity of the compounds is enhanced, so that some toxic and side effects generated in the application of pharmaceutical preparations due to poor selectivity can be effectively avoided. The invention also provides applications of the compounds in preparation of anti-epileptic drugs, anti-schizophrenia drugs, anti-depression drugs and drugs for treating cerebral arterial thrombosis diseases, and provides more effective choices for treatment of related diseases.

The invention relates to application of peroxidase reductase 1 as a target spot in preparation of an IS treatment medicine, and belongs to the technical field of biological medicine. The method comprises the steps of high-sensitivity blood immune proteome map construction, large-scale independent queue longitudinal correlation verification, cross-racial and multi-tissue causal correlation verification, targeted experiment verification and mechanism exploration, target druggability evaluation, treatment potential confirmation and the like, and selects immune response proteins with significant differences between patients and controls. The immune response protein strongly related to the onset risk of the cerebral arterial thrombosis (IS) is further screened from plasma, cerebrospinal fluid and brain tissue samples, and finally the cerebral arterial thrombosis traditional Chinese medicine target peroxide reductase 1 (PRDX1) is found. A drug, such as a PRDX1 agonist or overexpression PRDX1, designed aiming at the drug target can effectively improve the progress of the IS disease.

The invention belongs to the technical field of gene drugs, and particularly relates to application of lncRNA-AU020206 in preparation of drugs for treating cerebral arterial thrombosis, the key effect of the lncRNA-AU020206 in occurrence and development of the cerebral arterial thrombosis is disclosed for the first time, and it is clear that the lncRNA-AU020206 activates ferroptosis signal channels through negative regulation of SLC7A11 expression, so that cerebral ischemia reperfusion injury is aggravated. In-vivo and in-vitro experiments prove that the levels of MDA, ROS and Fe < 2 + > can be remarkably reduced by silencing the lncRNA-AU020206, the expression of GPX4 and SLC7A11 can be up-regulated, the cerebral infarction volume and neurological dysfunction can be reduced, and cerebral edema and apoptosis can be improved. Therefore, the lncRNA-AU020206 not only can be used as a new target for treating the cerebral arterial thrombosis, but also can be used for developing a related diagnostic kit, and has remarkable clinical application prospect and market value.

The invention discloses application of Nrsn1 in preparation of a medicine for differentiating neural stem cells into neuronal cells, and belongs to the technical field of neurobiology. The invention provides application of Nrsn1 in preparation of a medicine for differentiating neural stem cells into neuronal cells. The invention relates to application of Nrsn1 in preparation of drugs for preventing and / or treating cerebral arterial thrombosis or neurodegenerative diseases. It is found that the Nrsn1 gene can promote the neural stem cells to be differentiated into neurons, and the efficiency of differentiating the neural stem cells into the neurons is improved.

The invention discloses an application of an Mbtps1 gene and a protein SKI-1 coded by the Mbtps1 gene in screening or preparing a medicine for treating cerebral arterial thrombosis, and particularly discloses an application of the Mbtps1 gene / protein SKI-1 as a medicine target of cerebral arterial thrombosis. A tMCAO mouse model is constructed by specifically knocking out a microglial cell Mbtps1 gene / protein SKI-1 of a tMCAO mouse to verify that the Mbtps1 gene and the protein SKI-1 can be used as drug targets for screening or preparing drugs for treating cerebral arterial thrombosis; the compound PF429242 is screened out and has the functions of repairing brain injury nerves caused by cerebral arterial thrombosis, inhibiting neuroinflammation and repairing fragmentation of a mitochondrial network, namely, the feasibility of the Mbtps1 gene and the protein SKI-1 serving as targets in screening or preparing medicines for preventing or treating cerebral arterial thrombosis is verified.

The invention discloses application of Ptbp2 in diagnosis and prognosis of cerebral arterial thrombosis. It is found for the first time that Ptbp2 can be used for early diagnosis of cerebral arterial thrombosis, and the Ptbp2 also has a good prediction effect on prognosis of cerebral arterial thrombosis patients. According to the present invention, the verification results of the collected real clinical samples show that the Ptbp2 has good effects of cerebral arterial thrombosis diagnosis and prognosis prediction, and has high accuracy, high sensitivity and high specificity. The invention provides a new thought and strategy for the technical field of cerebral arterial thrombosis diagnosis and prognosis prediction, and has important scientific significance and clinical application value.

This invention discloses a brain-targeting neutrophil membrane-encapsulated tanshinone IIa PLGA nanoparticle formulation, its preparation method, and its uses. The brain-targeting tanshinone IIa nanoparticle formulation, Neu-Tan-IIa@PLGA, is characterized by comprising a PLGA-loaded tanshinone IIa nanoparticle core (Tan-IIa@PLGA) and an outer neutrophil membrane coating. This invention effectively overcomes the problems of poor water solubility, low oral bioavailability, and difficulty in crossing the blood-brain barrier associated with tanshinone IIa. This invention provides a tanshinone IIa with strong targeting and high drug stability, enabling delivery to lesions in ischemic brain regions and improving the safety and efficacy of stroke treatment.

The invention discloses a kit for screening cerebral arterial thrombosis risk and a screening method, and belongs to the technical field of biological detection. The kit for screening the cerebral arterial thrombosis risk is a kit for detecting gene mutation of a C677T site of an MTHFR gene and comprises a forward primer and a reverse primer, the sequence of the forward primer is shown as SEQ ID NO.1, and the sequence of the reverse primer is shown as SEQ ID NO.2. The kit for screening the cerebral arterial thrombosis risk is a kit for detecting gene mutation of the C677T site of the MTHFR gene. The invention creatively finds that the gene polymorphism of the C677T site of the MTHFR gene has certain relevance with the disease of the cerebral arterial thrombosis, the site mutation is one of high-risk factors of the cerebral arterial thrombosis, and the A1298C site mutation of the MTHFR gene is not obviously associated with the susceptibility of the cerebral arterial thrombosis. The risk of the cerebral arterial thrombosis is evaluated by screening a susceptibility gene locus, the operation is simple, the cost is reduced, the prevention of the cerebral arterial thrombosis is enhanced, and the incidence rate of the cerebral arterial thrombosis is further reduced.

The invention discloses application of lncRNA-DCST1-AS1 in preparation of a medicine for treating cerebral arterial thrombosis, and relates to the technical field of biomedicine. The invention finds that after expression of lncRNA-DCST1-AS1 is up-regulated, the activity of neurons subjected to hypoglycemia and hypoxia reperfusion can be further inhibited, and neuronal injury and apoptosis are promoted. By down-regulating and intervening the lncRNA-DCST1-AS1, the occurrence of cerebral ischemia / reperfusion injury can be avoided, and the lncRNA-DCST1-AS1 has an obvious protection effect on neuronal injury caused by sugar deficiency and hypoxia reperfusion, can obviously improve the cell activity and reduce the cell apoptosis caused by the neuronal injury, can be applied to preparation of the medicine for treating cerebral arterial thrombosis, and has a very good application prospect.

The invention belongs to the technical field of cerebral apoplexy treatment medicine research, and particularly relates to a nano delivery system and application thereof. The nano delivery system is prepared according to the following steps: modifying cationic starch spheres with mitochondrial targeting peptide, loading PDK4-IN-1, and carrying out self-assembly to obtain an inner core; the preparation method comprises the following steps: modifying aminated anionic starch with homing peptide, and loading carfilzomib to form a starch spiral shell; and mixing the inner core with the starch spiral shell, and self-assembling to form the nano drug delivery system. According to the invention, a three-targeting, double-controlled-release and double-drug nano drug delivery system is constructed and is accurately delivered to a matrix action site in cytoplasm or mitochondria, so that double-channel synergistic enhancement of IS mitochondrial autophagy and toxicity attenuation and synergistic treatment of IS are realized.

The present invention relates to the technical field of cell therapy. Specifically disclosed are a mesenchymal stromal cell-based drug and a use thereof in the treatment of acute cerebral infarction. The present invention provides a cell-based drug, comprising mesenchymal stromal cells and a pharmaceutically acceptable excipient. Compared with stem cells, the mesenchymal stromal cells have a negative expression level of mRNA encoding self-renewal and differentiation in the mesenchymal stromal cells. The mesenchymal stromal cells account for 90% or more of the cell-based drug. The cell-based drug exhibits the characteristics and mechanism of action of stromal cells, homes to the neovasculature formed by endothelial cells at the injury site within an effective time window, plays a role in promoting / maintaining the neovasculature and remodeling the microenvironment of the injury site, fully ensures the safety and effectiveness of disease treatment, and provides a novel method for the diagnosis and treatment of related diseases.

The invention discloses a targeted delivery preparation as well as a preparation method and application thereof, and belongs to the technical field of biology and new medicine. The targeted delivery preparation comprises an agent A and an agent B in a ratio of (0.1-0.3) g: (2-5) mL; the agent A comprises nasal brain targeting peptide modified stem cell factor liposome freeze-dried powder and gel dry powder, the amino acid sequence of the nasal brain targeting peptide is as shown in SEQ ID NO.1, and the gel dry powder is formed by self-crosslinking mangiferin and rutin; and the agent B is a normal saline solution containing carboxymethyl chitosan. The targeted delivery preparation not only can meet long-time stable storage, but also can enhance the nasal-brain delivery efficiency of stem cell drugs. Besides, the targeted delivery preparation can be used independently or in combination with other treatment drugs, and is used for treating ischemic cerebral diseases, especially cerebral arterial thrombosis.

The invention discloses an engineered brain-targeted delivery cell as well as a preparation method and application thereof. The engineered brain-targeted delivery cell is prepared by carrying out modification treatment on the surface of the cell by using a modifier, wherein the modifier comprises a cationic material, alkaloid and / or polysaccharide. The method provided by the invention aims to overcome the problem that the cells are difficult to efficiently pass through the blood brain barrier (BBB) or effectively target the brain lesion site in the existing cell therapy. Through the above surface modification strategy, the tropism and retention ability of the modified cells to the brain microenvironment are significantly enhanced, so that the enrichment efficiency of the cells in the brain is improved. The modified cells obtained on the basis of the method are suitable for preparing drugs or cell preparations for treating various brain diseases. The brain diseases include but are not limited to cerebral apoplexy, Alzheimer's disease (AD), Parkinson's disease, brain tumor and the like. The method provides an important technical means for developing a novel and efficient brain disease cell treatment strategy, and has potential clinical application value.

The invention discloses an application of polygonatum odoratum-derived extracellular vesicle-like particles in preparation of cerebral ischemia reperfusion nerve injury protection drugs. The polygonatum odoratum-derived extracellular vesicle-like particle disclosed by the invention has the effects of promoting the cell viability of HT22 cells after OGD / R and reducing the apoptosis of the HT22 cells after OGD / R. In-vivo experiments show that the polygonatum odoratum-derived extracellular vesicle-like particles can reduce apoptosis of ischemic side brain cells after cerebral ischemia reperfusion of rats, reduce the cerebral infarction area and improve neuromotor dysfunction, and a new thought and basis are provided for developing drugs to treat cerebral apoplexy.

This application relates to the fields of biomedical engineering and neuromodulation, disclosing the application of ultrashortwave in the fabrication of devices for modulating brain neural activity. The modulation of brain neural activity is achieved through the non-thermal effects of ultrashortwave, which refers to ultrashortwave with a frequency of 27.12MHz ± 0.6%, a wavelength of 11.06 nm, and a power of 1.6 ± 0.72 W. This application breaks through the traditional technical prejudice that high-frequency electric fields are unsuitable for the central nervous system, proving that non-thermal ultrashortwave can be safely used for brain neural modulation, opening up a completely new technical direction for neural modulation. With "ultrashortwave + application scenario" as its core protection element, it provides fundamental patent support for research on the treatment of various central nervous system diseases such as Parkinson's disease, stroke, depression, and Alzheimer's disease, possessing extremely high core patent value and broad clinical translation prospects.

The application relates to the field of biological medicine, and particularly discloses a fusion protein and application thereof. The fusion protein is composed of a polypeptide and six histidines, the polypeptide has sequence consistency of at least 9 / 10, 14 / 15 or 29 / 30 with the amino acid sequence shown in SEQ ID NO:1, and the six histidines are located at the C-terminal of the polypeptide. The fusion protein designed in the application is derived from a human body protein, the metabolic product is an amino acid, and therefore the safety is better than that of other therapeutic drugs. Moreover, the fusion protein can significantly reduce the infarction volume of the brain of a tMCAO model mouse, has a significant treatment on ischemic stroke, and has a longer treatment time window than that of an existing thrombolytic drug. Compared with the existing ischemic stroke treatment drug, the human sTREM2-6His fusion protein has a brand-new treatment mechanism and target.

The invention discloses a composition, a culture medium composition and a method for efficiently and stably inducing differentiation of cortical brain organoid. The composition is prepared from lithium calcium silicate, Y-27632, SB431542, LDN193189, FGF2, EGF, BDNF, NT-3 and Matrigel. According to the invention, lithium calcium silicate (LCS) is innovatively introduced as a novel bioactive material, and the cortex purity, the structural polarity, the progenitor cell maintenance and the functional maturity of the organoid can be remarkably improved through the slow-release ion effect (such as Li, Ca and SiO) of the LCS in a culture system in cooperation with a stage-specific signal channel regulation and control and a serum-free culture system. According to the invention, the brain organ with high-purity cortical characteristics, good structural texture and functional maturity can be obtained, and a new technical solution is provided for transplantation materials for cerebral arterial thrombosis disease mechanism research, drug screening evaluation and nerve regeneration treatment.

The invention discloses a calculation method and system for conduction and scattering processes of low-frequency electromagnetic waves in the brain, and relates to the technical field of brain detection.The method has the advantages that brain tissues are simplified into homogeneous isotropic sphere models, accordingly, the calculation complexity can be obviously reduced, and foundations can be laid for efficient solution; an electromagnetic wave propagation and scattering physical model based on Maxwell equations is constructed, and the movement law of electromagnetic waves in brain tissue is accurately described; the physical model is deeply integrated into a deep learning algorithm, and three-dimensional intracerebral electromagnetic field distribution is efficiently solved; finally, the propagation path, energy distribution and scattered field characteristics of electromagnetic waves are analyzed, positioning and qualitative diagnosis of lesions such as encephaledema and tumors are achieved, key support is provided for brain tissue health assessment, the efficiency bottleneck of a traditional numerical method in brain electromagnetic calculation is overcome, the timeliness and accuracy of brain disease diagnosis are improved, and the method is suitable for popularization and application. And reliable technical support is provided for rapid bedside diagnosis of stroke and other emergencies.

The invention discloses a chemical reprogramming multifunctional mesenchymal stromal cell based on a glycyrrhizic acid solubilizing technology and application thereof. According to the invention, a specific chemical small molecule combination is adopted, and human fibroblasts are reprogrammed into multifunctional mesenchymal stromal cells (CiMFSCs) with high expression of NSMF / NAV2 / BMP4 / LAMA2 and other genes. The key advantage of the CiMFSCs is that the CiMFSCs can target a plurality of key links of cerebral arterial thrombosis treatment at the same time, including promotion of neurogenesis, angiogenesis, repair of blood brain barrier (BBB) and exertion of paracrine function, so that effective neural function recovery is finally realized. Compared with umbilical cord mesenchymal stem cells, neural stem cells differentiated by iPSC, vascular endothelial cells differentiated by iPSC and pericytes differentiated by iPSC, the CiMFSCs show a remarkable and superior treatment effect in a stroke model mouse: the CiMFSCs can remarkably reduce the cerebral infarction volume, improve the survival rate of the model mouse, improve the neurobehavioral score and realize comprehensive repair of nerve and blood vessel units.

The invention discloses a double-fibroin gel platform for co-delivery of traditional Chinese medicine components and mesenchymal stem cells and a preparation method and application of the double-fibroin gel platform. The double-fibroin gel platform comprises active oxygen response type fibroin gel and single fibroin gel, the active oxygen response type fibroin gel is mainly formed by loading traditional Chinese medicine components on methacrylated silk fibroin modified by active oxygen response groups, and the single fibroin gel is mainly formed by loading mesenchymal stem cells on unmodified methacrylated silk fibroin. The co-delivery gel platform prepared by the invention has the performance of hierarchical functionalization, sequential release of neuroprotective traditional Chinese medicine components and neural repair of mesenchymal stem cells. According to the platform, the reservation of the brain mesenchymal stem cells is improved through a time-space synergistic sequential delivery mechanism, the dual treatment effect of'protection first and repair second 'is realized, and a novel strategy with higher pertinence and high efficiency is provided for precise treatment of cerebral arterial thrombosis.

The invention relates to a phosphorus-containing dendrimer co-loaded fibronectin / melatonin nano-drug as well as a preparation method and application thereof. The nano-drug comprises a phosphorus-containing dendrimer ZY-135 at a hydroxyl terminal, fibronectin FN and melatonin MT. The nano-drug provided by the invention can penetrate through a blood brain barrier, accurately target a diseased region, cooperatively regulate and control microglial cells, nerve cells and vascular endothelial cells, and can realize combined treatment of oxidative stress and inflammation level alleviation, neuroprotection and vascular regeneration of cerebral arterial thrombosis, so that nerve cell apoptosis is reduced, and cerebral arterial thrombosis is reduced. Good clinical transformation prospects and application values are realized.

The application provides a method for constructing a local inflammation model of an experimental animal brain, which comprises the following steps: anesthetizing the experimental animal and fixing the experimental animal on a positioning device; injecting an immunomodulator into a target region according to the coordinates of the target region by using a puncture tool; controlling the injection speed and dose of the immunomodulator by using a micro-infusion device; keeping the puncture needle in the body for a period of time after injection to reduce the backflow of the liquid medicine; verifying the local immune activation by quantitatively detecting the expression change of an inflammation marker in the target region, and synchronously detecting the expression level of the inflammation marker in a peripheral medium to exclude a systemic immune response. The application can effectively solve the problem that the peripheral inflammation effect is difficult to distinguish in the research of brain diseases caused by systemic administration in the prior art, and can be applied to the research of the local immune activation effect of diseases such as Alzheimer's disease, ischemic stroke and glioblastoma, and the evaluation of the efficacy and mechanism of STING agonists in these diseases.