29 results about "Valproate Sodium" patented technology

The invention belongs to the technical field of separation of drug intermediates, and particularly relates to a control method for a process impurity 2-ethyl valeric acid (EP-B) in preparation of valproic acid or sodium valproate by a diethyl malonate method. According to the method disclosed by the invention, the content of 2-ethyl-2-propylmalonic acid process impurities in dipropylmalonic acid is controlled, so that the content of 2-ethylvaleric acid (EP-B) which is a process impurity in valproic acid or sodium valproate is accurately controlled; adding a polar solvent into the dipropylmalonic acid crude product, heating, pulping for a certain time, cooling, filtering and drying to obtain a high-purity dipropylmalonic acid refined product; high-purity valproic acid (RRT is equal to 1.00) is prepared through decarboxylation of the dipropyl malonic acid fine product, and the purity is 99.779%; 0.020% of 2-ethyl valeric acid (RRT is equal to 0.90); and valeric acid (RRT = 0.77), 0.039%. The valproic acid product quality meets the requirements of European Pharmacopoeia. According to the method, the problems of quality control and process evaluation of valproic acid or sodium valproate prepared by a diethyl malonate method are solved.

The invention belongs to the technical field of separation of drug intermediates, and particularly relates to a method for preparing a high-purity dipropylmalonic acid refined product by adding a polar solvent into a dipropylmalonic acid crude product, heating, pulping for a certain time, cooling, filtering and drying. Decarboxylating the refined dipropylmalonic acid product to obtain high-purity valproic acid; distilling the filtrate to recover the polar solvent to obtain 2-methyl-2-propylmalonic acid, and carrying out decarboxylation on the 2-methyl-2-propylmalonic acid to obtain 2-methylpentanoic acid; 2-methylvaleric acid is used as a perfume additive. According to the method disclosed by the invention, the process impurity 2-methyl-2-propylmalonic acid in dipropylmalonic acid is separated, and the process impurity 2-methylvaleric acid (EP-L) in valproic acid or sodium valproate is precisely separated; the quality of the valproic acid product prepared by the method disclosed by the invention meets the requirements of European Pharmacopoeia EP-11 (2023). According to the invention, the problems of quality control and process evaluation of valproic acid or sodium valproate prepared by a dimethyl malonate method are solved.

Described herein, inter alia, are compositions comprising and methods of making and using endothelial cells (ECs) comprising one or more mitophagy-inducing agents (e.g., rapamycin, SKF-96365, lithium, carbamazepine, latrepirdine, spermidine, resveratrol, sodium valproate, trehalose, kaempferol, metformin, AICAR, nilotinib, ambroxol, curcumin, and VL-004). Also described herein, inter alia, are methods vascular cell therapy, promoting blood vessel formation, and increasing vascular development, angiogenesis, and cell junction via administration of a population of ECs comprising a mitophagy-inducing agent (MIA-ECs).

The invention discloses an ingredient mixing device and method for sodium valproate sustained release tablet production, and relates to the field of pharmaceutical equipment.The ingredient mixing device comprises a mixing main body, the top of the mixing main body is connected with a top cover through a plurality of bolts, the bottom of the top cover penetrates through the bottom and is fixedly connected with a feeding cylinder, and a main shaft is arranged in the center of the interior of the mixing main body; four outer plates are fixedly connected to the outer surface of the main shaft at equal intervals, and a mixed discharging switching structure is arranged in the mixing main body. By arranging the mixing and discharging switching structure, rapid switching between a mixing mode and a discharging mode is achieved, and the structure allows a channel to be opened in the mixing stage so that materials can be subjected to sufficient convection, and allows the channel to be closed in the discharging stage so that the materials can be guided to an outlet; due to the integrated design, the tedious step that materials need to be transferred to another device for discharging after mixing in a traditional technology is avoided, the risks of procedure interruption, material loss and cross contamination are remarkably reduced, and the continuity and the overall efficiency of the production process are greatly improved.

The invention belongs to the technical field of medicine detection, and particularly relates to a high performance liquid chromatography detection method for dipropylmalonic acid and impurities thereof. The method comprises the following steps: preparing a to-be-detected sample into a test solution; the to-be-detected sample is dipropyl malonic acid prepared by adopting a diethyl malonate method and impurities of the dipropyl malonic acid; and detecting the test solution by adopting a high performance liquid chromatography method to obtain a detection result of dipropylmalonic acid and impurities thereof in the sample to be detected. According to the detection method provided by the invention, the detection of dipropylmalonic acid prepared by adopting a diethyl malonate method and impurities thereof is realized through high performance liquid chromatography (HPLC) for the first time, and the problems of quality control and process evaluation of the dipropylmalonic acid prepared by adopting the diethyl malonate method, which is an intermediate of a sodium valproate raw material medicine, are solved; therefore, detection and control of impurities (including 2-ethyl valeric acid) in the sodium valproate raw material medicine are realized.

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.

This invention, entitled "A Method and Product for Pretreatment of Mesenchymal Stem Cells and Its Application in Stroke Drugs," belongs to the field of biotechnology. The technical problem to be solved is to improve the function and therapeutic effect of mesenchymal stem cells. The key technical solution is a method for pretreatment of mesenchymal stem cells, including: culturing cells using an activation medium, culturing cells using a directional medium, and culturing cells under hypoxic conditions using an adaptation medium; the activation medium contains complete medium, IFN-γ, TNF-α, and IL-1β; the directional medium contains complete medium, sodium valproate, 5-azacytidine, and all-trans retinoic acid; the adaptation medium is a complete medium containing basal medium and free of animal serum. The pretreatment method of this invention enhances the anti-inflammatory, neuroprotective, and angiogenic capabilities of mesenchymal stem cells, showing significant therapeutic effects on stroke, and since it does not use animal serum, it meets clinical requirements.

The present application relates to a method for detecting impurities in valproic acid or sodium valproate prepared by methyl cyanoacetate method by gas chromatography, characterized in that the impurities in valproic acid or sodium valproate prepared by methyl cyanoacetate method are detected by gas chromatography; the impurities are selected from valeric acid (A), 2-methyl valeric acid (L), 2-isopropyl valeric acid (C), valproic amide (F) or 2-propyl hexanoic acid (X):

The invention relates to a pharmaceutical composition for oral administration. The pharmaceutical composition comprises: a) immediate release particles comprising i. An active ingredient selected from the group consisting of valproic acid, semi-sodium valproate, sodium valproate and magnesium valproate, and ii. A filler, b) sustained release pellets comprising: i. A pellet core comprising (1) an active ingredient selected from the group consisting of valproic acid, semi-sodium valproate, sodium valproate and magnesium valproate, and (2) a filler, ii. A sub-coating disposed on the pellet core, the content of the sub-coating layer is 10-20 wt% based on the weight of the pellet core and the sub-coating layer comprises a film-forming agent, and iii. A slow-release coating layer disposed on the sub-coating layer, the content of the slow-release coating layer is 25-100 wt% based on the weight of the pellet core coated with the sub-coating layer and the slow-release coating layer comprises a film-forming agent, and the content of the slow-release coating layer is 25-100 wt% based on the weight of the pellet core coated with the sub-coating layer. Wherein the amount of the active ingredients in the quick-release particles accounts for 70-80 wt% of the total weight of the active ingredients in the pharmaceutical composition, and the amount of the active ingredients in the slow-release pellets accounts for 20-30 wt% of the total weight of the active ingredients in the pharmaceutical composition. In further aspects, the present invention relates to methods of preparing pharmaceutical compositions and pharmaceutical compositions for use in methods of pre-treating cancer.

The present invention belongs to the technical field of impurity removal of fine chemicals, and specifically relates to a method for removing valeric acid, an impurity of valproic acid, in a sodium valproate synthesis process. The method for removing valeric acid as an impurity of the present invention comprises the following steps: adding toluene and water to a decarboxylation mother liquor, and filtering with suction; allowing the filtrate to stand for separation, and removing the lower aqueous phase; adjusting the pH of the toluene layer to >10; standing for separation, retaining the aqueous phase, adding toluene, and adjusting the pH to <2; standing for separation, performing a first alkaline extraction operation on the toluene layer, standing for separation, until the residual valeric acid in the toluene layer is less than 0.1%, adding hydrochloric acid and toluene to the remaining aqueous phase, separating, retaining the toluene layer, and performing a second alkaline extraction operation until the residual valeric acid is less than 0.1%; after the two alkaline extractions, the toluene layers are mixed, and then an alkaline solution is added dropwise to adjust the pH, and the crude sodium valproate is obtained. The method for removing valeric acid as an impurity of valproic acid in a sodium valproate synthesis process provided by the present invention has a low valeric acid content in the crude sodium valproate, and the prepared sodium valproate has high purity.

The invention provides application of combination of resolvin D1 and sodium valproate in preparation of a medicine for treating epilepsy and the medicine for treating epilepsy, and relates to the technical field of biomedicine. Research of the inventor finds that RvD1 and sodium valproate have a synergistic promotion effect on treatment of epilepsy, through synergistic cooperation of RvD1 and sodium valproate, epilepsy symptoms can be remarkably relieved, chronic epilepsy can be prevented, damage of epilepsy to nerves can be reduced, and RvD1 and sodium valproate can be used for preparing the medicine for treating epilepsy. According to the medicine for treating epilepsy provided by the invention, the active ingredients are RvD1 and sodium valproate, and the epilepsy can be effectively treated through the synergistic cooperation of RvD1 and sodium valproate.

The invention provides a sodium valproate oral solution and a preparation method thereof, and belongs to the technical field of pharmaceutical preparations. The sodium valproate oral solution provided by the invention comprises sodium valproate, sorbitol, sucralose, a preservative, a thickening agent, a pH regulator, essence and water, and a coloring agent is not added. According to the sodium valproate oral solution provided by the invention, sucralose is used for replacing saccharin sodium in an original prescription, and carmine is removed, so that the safety of the sodium valproate oral solution to children can be effectively ensured, and the sodium valproate oral solution is good in taste and suitable for being taken by the children; the preparation method is simple, the preparation efficiency is high, and the oral solution is stable in quality and suitable for industrial production through stability tests.

The present invention relates to a histone deacetylase (HDAC) inhibitor for use in the pretreatment of relapsing cancer prior to treatment of the relapsing cancer, wherein the HDAC inhibitor is selected from the group consisting of valproic acid, valproate semisodium, sodium valproate, magnesium valproate or mixtures thereof, and wherein the HDAC inhibitor is administered to a subject suffering from the relapsing cancer.

The invention discloses a neural stem cell culture medium which is composed of an Rho kinase inhibitor Y-27632, an HDAC inhibitor sodium valproate, an E-cadherin regulator 8-bromocyclic adenylate, a Wnt signal channel regulator CHIR99021, an anti-aggregation agent polyether F-68, heparin and an NSC complete culture medium. The neural stem cell culture medium is applied to passive control of the size of the neural stem cell aggregate. The invention further discloses a passive control method for the size of the neural stem cell aggregate. The neural stem cell culture medium provided by the invention can effectively and accurately control the size of the cell aggregate, improves the consistency and the cell viability of the cell aggregate under the condition of not influencing the physiological characteristics of cells, avoids the center necrosis problem of the aggregate, provides a more economical and efficient scheme for large-scale culture of neural stem cells, and has wide application prospects. And the application prospects in the fields of cell therapy, drug screening and the like are expanded.

The invention discloses a method for detecting acetaldehyde in ethyl cellulose and sodium valproate tablets, which comprises the following steps: step 1, pre-treating a sample to obtain a test solution; 2, preparing an acetaldehyde contrast solution; and step 3, injecting the test solution into gas chromatography, and detecting. According to the method disclosed by the invention, the acetaldehyde in the ethyl cellulose and sodium valproate tablets is quantitatively detected by adopting the gas chromatography for the first time. A detailed method verifies that the gas chromatography detection method is suitable for quantitative analysis of acetaldehyde in ethyl cellulose and sodium valproate tablets under the laboratory condition.

A stable pharmaceutical composition in the form of orally administrable prolonged release tablet comprising sodium valproate and valprioic acid with no granulating solvent is disclosed, further comprising low viscosity polymer, high viscosity polymer, binder, adsorbent and glidant. A process for the preparation of said orally administrable prolonged release tablet is also disclosed.

The present invention provides a method for administering a γ-hydroxybutyrate composition together with divalproex sodium. [Solution] An oral pharmaceutically acceptable composition of gamma-hydroxybutyrate (GHB) is provided that is suitable for concomitant administration with divalproex sodium (DVP) without substantially altering the dosage of any of the drugs. The therapeutic use of the composition for the treatment of one or more symptoms of narcolepsy is also provided. One of the main treatments for narcolepsy is sodium oxibate, a neuroactive agent with various central nervous system (CNS) pharmacological properties.

The invention relates to a method for detecting impurities in a process for preparing valproic acid, sodium valproate or magnesium valproate by atom economy reaction, which comprises the following steps of: selecting a gas chromatograph with the model of Agilent 8890, and detecting valproic acid prepared by atom economy reaction and process impurities thereof by gas chromatography; the detection conditions of the gas chromatography are as follows: a chromatographic column is DB-FFAP, and the specification is 0.32 mm * 60 m, 0.5 [mu] m; the carrier gas is nitrogen; the detector is an FID (Flame Ionization Detector); the flow rate is 2ml / min; the sample injection volume is 2 microliters; the temperature of a sample inlet is 220 DEG C; the column temperature is 100 DEG C; in the heating procedure, the initial temperature is 100 DEG C and kept for 5 min, then the temperature is increased to 140 DEG C at the speed of 4 DEG C / min and kept for 5 min, and then the temperature is increased to 200 DEG C at the speed of 4 DEG C / min and kept for 15 min; the operation time is 50 min; the temperature of a detector is 220 DEG C; the method comprises the following steps of: injecting 2 microliters of diluent dichloromethane, 2 microliters of reference solution and 2 microliters of test solution into a gas chromatograph, and recording a chromatogram; a test article is selected from a valproic acid crude product prepared by atom economy reaction; the impurities are selected from 2-propyl-4-pentenoic acid, valeric acid, 2-methyl valeric acid, 2-ethyl valeric acid, methyl valproate, ethyl valproate or propyl valproate; the solvent is a solvent; according to the detection result of the gas chromatography, the variety and the content of the process impurities in the valproic acid, the sodium valproate or the magnesium valproate are judged through a control sample.

The present application relates to a kind of sodium valproate nasal mucosa administration preparation and its preparation and application, belong to medical technical field.A kind of sodium valproate nasal mucosa administration preparation, the preparation includes gastrodin and as medicinal component sodium valproate.The weight ratio of sodium valproate and gastrodin is 1:0.0025~2.The administration preparation of the present application is a kind of sodium valproate nasal mucosa administration preparation, can be delivered to brain by bypassing blood-brain barrier through nasal administration, improve brain bioavailability, prolong the effective action time of drug in brain, avoid first pass effect, reduce the risk of peripheral toxic side effect.The present application uses gastrodin as absorption promoter, by optimizing the ratio of gastrodin and sodium valproate, can reach the effect of increasing the absorption of sodium valproate in whole body and brain, further improve its brain bioavailability, enhance its therapeutic potential.

The utility model discloses a sodium valproate oral liquid extraction device, which belongs to the technical field of sodium valproate oral liquid preparation and comprises a bottom frame, a shock absorber is arranged at the top of the bottom frame, a support frame is arranged at the top end of the shock absorber, and a support component is arranged between the support frame and the bottom frame. The sodium valproate oral liquid extraction device has the beneficial effects that according to the sodium valproate oral liquid extraction device, through the arrangement of the shock absorber, vibration generated when a structure works can be relieved, the stability of the structure during working can be guaranteed, through the arrangement of the supporting assembly, the stability of the structure is improved, and the service life of the structure is prolonged. The supporting frame can be limited and supported, the stability and safety of the supporting frame are guaranteed, the driven gear, the rotating shaft, the adjusting frame and the extraction tank can be driven to rotate through work of the driving assembly, the extraction tank can be assisted in extraction work, and the extraction efficiency is improved.

Provided is a method for preparing valproamide represented by chemical structural formula I and sodium valproate represented by formula II. The method is characterized in that cyanoacetate and 1-chlor

Oral pharmaceutical compositions of gamma-hydroxybutyrate (GHB) suitable for concomitant administration with a dose of divalproex sodium (DVP) without materially altering the dosage amount of either drug are provided. Also provided are therapeutic uses of the compositions for the treatment of one or more symptoms of narcolepsy.

The present application relates to the technical field of crystal preparation, and particularly relates to sodium valproate crystal and a preparation method and application thereof. The sodium valproate crystal provided by the present application has diffraction peaks at least at the following diffraction angles 2theta in the X-ray powder diffraction pattern: 5.67°+ / -0.2°, 6.73°+ / -0.2°, 16.94°+ / -0.2°, 18.18°+ / -0.2°, 18.67°+ / -0.2°, 20.16°+ / -0.2°, 20.92°+ / -0.2°, 21.13°+ / -0.2°, 22.55°+ / -0.2° and 24.45°+ / -0.2°. The sodium valproate crystal provided by the present application has good stability, good water solubility, significantly reduced hygroscopicity, ensures the quality stability within the effective period of the medicine, and significantly shortens the dissolution time of the product, and the product has good redissolution.

The invention belongs to the technical field of impurity removal of fine chemicals, and particularly relates to a method for removing impurity valeric acid in valproic acid in a sodium valproate synthesis process. The method for removing the impurity valeric acid comprises the following steps: adding methylbenzene and water into decarboxylated mother liquor, and carrying out suction filtration; standing and layering the filtrate, and removing a lower-layer water phase; adjusting the pH gt by a toluene layer; 10; standing for layering, keeping a water phase, adding methylbenzene, and adjusting the pH to be 1t; 2; adding hydrochloric acid and toluene into the residual water phase, standing for layering, reserving a toluene layer, carrying out first alkali extraction operation, standing for layering until the residual valeric acid in the toluene layer is lower than 0.1%, adding hydrochloric acid and toluene into the residual water phase, layering, reserving the toluene layer, and carrying out second alkali extraction operation until the residual valeric acid is lower than 0.1%; mixing toluene layers after two times of alkali extraction, then dropwise adding an alkali solution, adjusting the pH value, and treating to obtain a sodium valproate crude product; according to the method for removing the impurity valeric acid in the valproic acid in the sodium valproate synthesis process provided by the invention, the content of the valeric acid in the sodium valproate crude product is low, and the purity of the prepared sodium valproate is high.

The invention discloses a kit for predicting sodium valproate treatment response based on TPH2 gene polymorphism and a method and application thereof, and belongs to the technical field of individualized medication for children epilepsy treatment. The method comprises the following steps: S01, collecting a biological sample of a child epilepsy patient, and extracting genome DNA; s02, detecting the genotype of the rs4570625 site of the TPH2 gene in the genome DNA (Deoxyribose Nucleic Acid); s03, people suitable for sodium valproate treatment are selected according to the genotypes, and the GG genotype patients are suitable for sodium valproate standard dosage maintenance treatment; a non-GG genotype patient adopts an adjusted sodium valproate scheme or a sodium valproate substitute medicine. The invention further provides a corresponding kit and application. According to the invention, the TPH2 gene polymorphism is introduced into the prediction of the VPA treatment response of the child epilepsy, and the individualized medication of the VPA treatment of the child epilepsy is accurately guided.

The present invention relates to the field of biomedicine, and particularly to perampanel microspheres based on a double emulsion process, a preparation method thereof, and an application. The preparation method uses water-in-oil-in-water double emulsion droplets as templates, and prepares the long-acting controlled release perampanel microspheres by a microfluidic emulsion templating method. Based on microfluidic technology, the present invention introduces an inner aqueous phase containing an amphiphilic polymer material sustained release regulator, which can not only prepare perampanel microspheres with a porous structure, but also achieve simultaneous encapsulation of multiple components (i.e., compound microsphere drugs), increase the drug release channels, weaken the hysteresis effect, and achieve precise controlled release of perampanel and / or sodium valproate.

The present invention provides an improved process for manufacturing of Valproic acid, intermediates, and sodium salt of valproic acid (Divalproex sodium). The present invention provides sequential additions of reactants and / or catalyst or reagents and / or solvent(s) which is most effective to achieve maximum conversion efficiency, less or no impurity formation, which overall results in increased yield as well as purity not less than 99%. Furthermore, it involves use of green solvents (recover and / or recycle easily); mild & cheaper catalyst or reagent; reduced reaction time and steps to be performed. In the present invention, synthesis of valproic acid is carried out without isolating any intermediate compound; and divalproex sodium is synthesised by heating valproic acid without use of solvent at about 60°C to about 110°C. The obtained compound of formula (Divalproex sodium) is substantially free of impurities.

A process for preparing valpromide of formula I and sodium valproate of formula II which comprises: cyanoacetate and 1-chloropropane are subjected to composite catalytic dipropylation in the presence of alkali to obtain 2-cyano-2-valproate of formula III; 2-cyano-2-valproate is hydrolyzed and deacidified to give propylvaleronitrile of formula V; propylvaleronitrile is alcoholized in the presence of acid to give valpromide of formula I and valproate ester of formula VI; and valproate ester is hydrolyzed in a sodium hydroxide solution to afford sodium valproate of formula II.

Oral pharmaceutical compositions of gamma-hydroxybutyrate (GHB) suitable for concomitant administration with a dose of divalproex sodium (DVP) without materially altering the dosage amount of either drug are provided. Also provided are therapeutic uses of the compositions for the treatment of one or more symptoms of narcolepsy.