22 results about "Antiepileptic Agents" patented technology

The invention relates to the technical field of antiepileptic drugs, in particular to a 2-methyloxazole derivative as well as a preparation method and application thereof. The structural general formula of the 2-methyloxazole derivative is shown in the specification. The 2-methyloxazole derivative provided by the invention has remarkable histamine H3 receptor antagonistic activity and shows an anti-convulsion characteristic, so that the 2-methyloxazole derivative can be used as an anti-epileptic compound. Compared with a compound 1 of the patent application CN115784983B, the 2-methyloxazole derivative provided by the invention has a better anti-epileptic effect under the dosage of 30mg / kg, can completely resist convulsion of a tested mouse, and solves the problem that the existing compound is still insufficient to completely resist convulsion attack. # imgabs0 #

The invention relates to an ultrasonic response bionic piezoelectric nano-drug for treating epilepsy as well as a preparation method and application of the ultrasonic response bionic piezoelectric nano-drug. The ultrasonic response bionic piezoelectric nano-drug comprises hafnium-based piezoelectric nano-particles UIO-66-NH2 etched by sulfuric acid, an anti-epileptic drug, a microglial cell membrane and transferrin receptor targeting peptide, wherein the anti-epileptic drug is loaded in hafnium-based piezoelectric nanoparticles etched by sulfuric acid to form a drug loading core; the microcolloid cell membrane coats the outer surface of the drug loading core; the transferrin receptor targeting peptide is connected to a microglial cell membrane. The ultrasonic response bionic piezoelectric nano-drug is high in brain entering efficiency, stable in drug release amount and clear in preparation method path, is suitable for targeted delivery of various anti-epileptic drugs and treatment and research of nervous system diseases such as epilepsy, can adopt an intravenous injection administration mode and non-invasive administration, can avoid injury caused by an operation, and has a good application prospect. The electrical stimulation is generated in vivo without implanting and taking out the electrode, so that secondary injury and infection are avoided.

The invention relates to the technical field of biological detection, and particularly discloses a method for simultaneously determining serum concentrations of an anti-epileptic drug and active metabolites thereof based on an LC-MS / MS (Liquid Chromatography-Mass Spectrometry / Mass Spectrometry) method. According to the method, the C18 chromatographic column with the filler particle size of 3.0 microns is selected for the first time, efficient separation of lamotrigine, levetiracetam, oxcarbazepine and active metabolites thereof is achieved, and the separation efficiency is equivalent to that of a small-particle-size column; a pretreatment process is simplified by precipitating protein through a single organic solvent, and accurate quantification of four components is completed by only using two isotope internal standard oxcarbazep-d4 and levetiracetam-d6, so that the cost is reduced. In the aspect of the detection range, the lower quantification limit of oxcarbazepine is broken through to 0.04 [mu] g.mL <-1 >, and the technical contradiction between oxcarbazepine and the upper quantification limit (as high as 50 [mu] g.mL <-1 >) of LEV across three orders of magnitude is overcome. According to the scheme, hardware requirements and reagent cost are reduced, and meanwhile, high sensitivity and a wide linear range are achieved.

The invention relates to (i) the prevention or treatment of a sleep disturbance, preferably in a patient having neuropathic pain; and / or (ii) the prevention or treatment of neuropathic pain in a patient having a sleep disturbance; and / or (iii) the prevention or treatment of neuropathic pain in a patient having been treated previously and / or being treated concomitantly with an analgesic medication for relief of neuropathic pain, preferably selected from antiepileptics, antidepressants and opioid analgesics, wherein the patient preferably has a sleep disturbance; in either cases by means of one or more high-concentration capsaicin and / or capsaicinoid topical dose units, preferably pharmaceutical patches, comprising capsaicin and / or capsaicinoid at a concentration of at least 2.5 wt.-%, relative to the total weight of dose unit.

The present invention provides a method for preparing a refractory epilepsy animal model and its application. Specifically, the present invention provides a method for preparing a refractory epilepsy animal model of a non-human mammal, wherein the preparation method comprises the following steps: (1) providing a non-human mammal A and a non-human mammal B expressing neuron cell-specific Cre recombinase of the same species; wherein the genome of the non-human mammal A has: (E1) an endogenous Cdkl5 gene, and (E2) a conditional knockout element operably linked to the Cdkl5 gene for conditional knockout of the Cdkl5 gene, wherein, in the presence of the Cre recombinase, the conditional knockout element conditionally knocks out the Cdkl5 gene in the genome of neuron cells, thereby inactivating the Cdkl5 gene; (2) mating and breeding the animal A with the animal B to obtain a progeny non-human mammal C with neuron cell-specific knockout of the Cdkl5 gene; (3) culturing the progeny non-human mammal C to obtain the refractory epilepsy animal model. The present invention can also preliminarily evaluate the efficacy of anti-epileptic drugs according to the changes in the spontaneous epilepsy phenotype of the animals.

A genetically-modified rat having a PKHD1L1 gene with a point or other mutation and a construction method thereof are disclosed. A CRISPR / Cas9 system knocks the PKHD1L1 gene into a rat source, and a codon changes from TTA to TCA to construct the mutant PKHD1L1 gene. The genetically-modified rat can be applied to epilepsy pathogenesis studies and design and testing of new anti-epileptic drugs. Methods for detecting abnormal cortical excitability and detecting an epileptic phenotype of an animal can use the genetically-modified rat. A somatosensory evoked potential is used to detect whether the genetically-modified rat has an abnormal cortical excitability phenotype, so as to confirm whether the rat can be a successful model for testing anti-epileptic drugs. The method can detect abnormal cortical excitability and verify the effectiveness of anti-epileptic drugs or treatments.

This invention discloses a glutamate-responsive nanoliposome, its preparation method, and its application in antiepileptic treatment. The glutamate-responsive nanoliposome comprises liposomes, glutamate oxidase, DSPE-TK-mPEG, and an antiepileptic drug. The glutamate oxidase is encapsulated in the hydrophilic region at the center of the liposome, the antiepileptic drug is loaded in the hydrophobic region of the liposome bilayer, and DSPE-TK-mPEG is modified onto the liposome bilayer membrane. The preparation method includes: first preparing a lipid solution, adding an antiepileptic drug solution and glutamate oxidase, and obtaining drug-loaded nanoliposomes through repeated extrusion. The glutamate-responsive drug-releasing nanoliposomes of this invention can significantly improve the stability and bioavailability of antiepileptic drugs, overcoming the shortcomings of traditional antiepileptic drugs in the treatment process. By optimizing the preparation of liposomes, a good drug delivery platform for antiepileptic drugs is provided.

The invention relates to a method for detecting antiepileptic drugs in serum based on polarity conversion UPLC-MS / MS. The antiepileptic drugs (AEDs) are respectively levetiracetam, pregabalin, gabapentin, lamotrigine, phenobarbital, oxcarbazepine, phenytoin sodium, carbamazepine, clonazepam, diazepam and sodium valproate. Simplifying sample pretreatment by adopting a methanol (containing formic acid) one-step extraction method; in the chromatographic analysis, C18 is used as a chromatographic column and a pre-column, a 5% methanol aqueous solution (containing formic acid)-95% methanol aqueous solution (containing formic acid) is used as a mobile phase, gradient elution is carried out, and the mass spectrum adopts an MRM mode. The method has the advantages of being high in sensitivity, good in precision and accuracy, easy to operate, free of matrix interference and the like, can be used for measuring serum AEDs of different species, and provides technical support for the prevention and treatment mechanism of epilepsy drugs, clinical AEDs blood concentration monitoring, individualized drug delivery scheme formulation and pharmacokinetic research.

Disclosed is a method of administering a Kv7 channel activator, or a pharmaceutically acceptable salt thereof, to a human without developing adverse events typically associated with antiepileptic drugs in the human. Also disclosed is a method of treating a medical condition in a patient without developing an adverse event typically associated with an antiepileptic drug, the method comprising administering to the patient in need of such treatment a therapeutically effective amount of a Kv7 channel activator or a pharmaceutically acceptable salt thereof.

The invention relates to the technical field of treatment drug monitoring, in particular to a method for simultaneously determining the concentration of multiple antiepileptic drugs in plasma. Comprising the following steps: S1, preparing a standard working solution; s2, preparing an internal standard solution; s3, mixing the standard working solution with blank plasma, adding an internal standard solution, centrifuging, and detecting to obtain a chromatogram of a standard solution; s4, based on the chromatogram, taking the ratio of the peak area of the anti-epileptic drug to the peak area of the corresponding internal standard substance as a vertical coordinate Y, taking the ratio of the concentration of the anti-epileptic drug to the concentration of the corresponding internal standard substance as a horizontal coordinate X, and fitting to obtain a standard curve equation; s5, preparing a plurality of groups of quality control working solutions, and verifying the standard curve equation obtained in the step S4; and S6, uniformly mixing the blood to be detected with the internal standard solution, centrifuging, detecting the supernate, and calculating the concentration of the antiepileptic drug in the plasma. The method can realize simultaneous, accurate and quantitative detection of multiple antiepileptic drugs in blood.

The invention discloses a method and a device for detecting antiepileptic drugs in serum based on liquid chromatography-tandem mass spectrometry. The method comprises the following steps: preparing a basic solution; preparing each standard stock solution; respectively diluting all the standard stock solutions into a first mixed solution and a second mixed solution, and respectively diluting again to correspondingly obtain a plurality of calibration product working solutions and quality control product working solutions; preparing a calibration product and a quality control product; preparing an internal standard solution from methanol, eight isotope internal standard standard substances and an internal standard diluent; the method comprises the following steps: respectively pre-treating a serum sample, a calibration product and a quality control product by adopting an internal standard solution to form corresponding to-be-detected solutions; detecting each to-be-detected solution by using liquid chromatography-tandem mass spectrometry, and establishing a standard curve of each analyte according to the detected data to obtain the concentration of the anti-epileptic drug in the serum sample. The method can realize efficient and sensitive detection of 11 antiepileptic drugs, is high in precision and accuracy, ensures a wide linear range and a low sample size, reduces the use variety and use amount of the internal standard, and is low in cost.

A genetically-modified rat having a PKHD1L1 gene with a point or other mutation and a construction method thereof are disclosed. A CRISPR / Cas9 system knocks the PKHD1L1 gene into a rat source, and a codon changes from TTA to TCA to construct the mutant PKHD1L1 gene. The genetically-modified rat can be applied to epilepsy pathogenesis studies and design and testing of new anti-epileptic drugs. Methods for detecting abnormal cortical excitability and detecting an epileptic phenotype of an animal can use the genetically-modified rat. A somatosensory evoked potential is used to detect whether the genetically-modified rat has an abnormal cortical excitability phenotype, so as to confirm whether the rat can be a successful model for testing anti-epileptic drugs. The method can detect abnormal cortical excitability and verify the effectiveness of anti-epileptic drugs or treatments.

This application relates to the field of analytical detection technology, specifically to sample pretreatment methods, kits, and detection methods for the detection of antiepileptic drugs. The sample pretreatment method for the detection of antiepileptic drugs in this application includes one or more of the following antiepileptic drugs: valproic acid, carbamazepine, phenytoin, levetiracetam, lamotrigine, and phenobarbital. The sample pretreatment method includes the following steps: mixing magnetic beads with an activation solution to prepare a magnetic bead suspension; mixing the sample to be tested, the magnetic bead suspension, and an internal standard solution, and separating the supernatant and the magnetic bead complex after magnetic adsorption treatment; adding an eluent to the magnetic bead complex, and collecting the magnetic bead-target complex after elution treatment; adding an elution buffer to the magnetic bead-target complex, and collecting the supernatant after elution treatment for detection. The above sample pretreatment method is simple to operate, time-saving, and low-cost, providing key technical support for the efficient quantitative detection of antiepileptic drugs.

The invention relates to the technical field of analysis and detection, in particular to a sample pretreatment method for anti-epileptic drug detection, a kit and a detection method. According to the sample pretreatment method for anti-epileptic drug detection, an anti-epileptic drug comprises one or more of valproic acid, carbamazepine, phenytoin, levetiracetam, lamotrigine and phenobarbital; the sample pretreatment method comprises the following steps: mixing magnetic beads with an activating solution to prepare a magnetic bead suspension; mixing a to-be-detected sample, the magnetic bead suspension and the internal standard solution, performing magnetic attraction treatment, and separating supernate and a magnetic bead compound; leacheate is added into the magnetic bead compound, and after leaching treatment, a magnetic bead-target compound is collected; and adding an eluent into the magnetic bead-target compound, carrying out elution treatment, and collecting a supernatant for detection. The sample pretreatment method is simple to operate, short in time consumption and low in cost, and can provide key technical support for efficient quantitative detection of the anti-epileptic drugs.

The invention provides application of XBP1 protein in preparation of a medicine for treating epilepsy, and relates to the technical field of biological medicine. In the pathophysiological process of epilepsy, X-box binding protein 1 (XBP1) serves as a key regulatory factor of endoplasmic reticulum stress and plays an important role, the XBP1 can regulate expression of endoplasmic reticulum stress related genes and inhibit neuronal apoptosis so as to influence the pathologic process of epilepsy, epilepsy is a chronic brain disease caused by multiple etiological factors, and the epilepsy is a chronic brain disease caused by multiple etiological factors. The invention develops an anti-epileptic drug based on a non-ionic channel as a target, and XBP1 is used as a beneficial supplement of the existing anti-epileptic drug and is beneficial to improving the effective rate of epileptic drug treatment on the whole.

The invention provides a leucine dehydrogenase mutant and application thereof, and belongs to the technical field of bioengineering. The leucine dehydrogenase mutant provided by the invention can maintain higher catalytic stability in a wider pH value and temperature range, and the adaptability and durability of the leucine dehydrogenase mutant in an industrial reaction environment are remarkably improved. The improvement directly improves the efficiency and reliability of the process for catalytically synthesizing L-2-aminobutyric acid by using the enzyme, so that the reaction process is easier to control, and the cost loss caused by enzyme inactivation is potentially reduced. Finally, the mutant provides a catalyst with excellent performance for green, efficient and large-scale production of L-2-aminobutyric acid with high optical purity, so that a preparation process of chiral amino acid is simplified; and moreover, the method has important significance in reducing the production cost of key intermediates of downstream chiral drugs (such as certain antiepileptic drugs and antituberculosis drugs) and improving the product quality, and shows a good industrial application prospect.

The invention relates to the technical field of antiepileptic drugs, in particular to a sulfur-containing piperidine ether aryl derivative as well as a preparation method and application thereof, and the structural general formula of the sulfur-containing piperidine ether aryl derivative is as shown in formula (I), in the formula (I), R is selected from H, 2-Cl, 3-Cl and 4-Cl; n = 1 or 2. The sulfur-containing piperidine ether aryl derivative provided by the invention has remarkable histamine H3 receptor antagonistic activity and shows an anti-convulsion characteristic, so that the sulfur-containing piperidine ether aryl derivative can be used as an anti-epileptic compound.

The application relates to the field of animal model construction, in particular to an animal model construction method. The application provides application of an NF-kappa B inhibitor in animal model construction. The NF-kappa B inhibitor PDTC provided by the application is mainly concentrated in the inflammation field in previous research, and has not been applied in epilepsy model construction. The method for constructing an animal model by using PDTC provided by the application can construct an ideal epilepsy model which is low in price, simple in operation, stable in onset and clear in the epileptogenic process, and is helpful to further expand new mechanisms of epilepsy onset and evaluate effects of antiepileptic drugs, and is a new application of the pharmacological tool drug PDTC.

The invention belongs to the technical field of biological medicine, and particularly relates to preparation of a novel high-selectivity KV7.2 opener and application of the novel high-selectivity KV7.2 opener in antiepileptic drugs. A series of KV7.2-targeted small-molecule inhibitors are designed and synthesized, and the small-molecule inhibitors can enhance the current of a potassium ion channel KV7.2, accelerate channel activation and delay the inactivation process of the channel. The small molecule has a remarkable potential for treating epilepsy, shows efficient anti-epileptic activity in three classic epilepsy models for simulating human comprehensive attack and drug-refractory focal attack, is remarkably superior to positive control RTG, can be used for preparing anti-epileptic drugs and has a wide application prospect.

Provided herein are alpha? nicotinic receptor specific activators as anti-epileptogenic agents effective against epilepsy or epileptogenesis and associated comorbidities in a subject after a traumatic brain injury. Provided herein are methods for treating epilepsy in a subject, preventing seizures in a subject at risk for the same and preventing epileptogenesis in a traumatic brain injured subject and associated comorbidities. a7-nAChR activators are administered to the subject alone or in combination with established anti-epileptic or anti- epileptogenic drugs.

Provided herein are alpha? nicotinic receptor specific activators as anti-epileptogenic agents effective against epilepsy or epileptogenesis and associated comorbidities in a subject after a traumatic brain injury. Provided herein are methods for treating epilepsy in a subject, preventing seizures in a subject at risk for the same and preventing epileptogenesis in a traumatic brain injured subject and associated comorbidities. a7-nAChR activators are administered to the subject alone or in combination with established anti-epileptic or anti- epileptogenic drugs.

The invention provides a concentration determination kit for five anti-epileptic drugs, the kit is used for detecting the anti-epileptic drugs in a serum sample by liquid chromatography-tandem mass spectrometry, the kit comprises a diluent, an internal standard solution IS, a plurality of calibration products and a plurality of quality control products, and the calibration products and the quality control products are freeze-dried preparations. The kit provided by the invention can be used for detecting that the linearity range of clonazepam is 4-200ng / mL, the linearity range of valproic acid is 3-150mu g / mL, the linearity range of 10, 11-dihydro-10-hydroxycarbamazepine is 0.8-40mu g / mL, the linearity range of levetiracetam is 1.0-50mu g / mL, the linearity range of topiramate is 0.5-25mu g / mL, the correlation coefficient r is not less than 0.9900, and the detection result is accurate and reliable. The in-batch variation coefficient CV is not greater than 15.0%, the inter-batch variation coefficient CV is not greater than 15.0%, and the kit is good in consistency and high in stability. The accurate recovery rate is in a range of 85.0%-115.0%, and the detection result is accurate. The quantitative limit CV is smaller than or equal to 20%, the relative deviation is within the range of + / -15%, and the kit is high in sensitivity and has high repeatability and reliability. The product can be stably stored for 12 months at 2-8 DEG C, and the shelf life is long.