26 results about "Etiracetam" patented technology

The invention relates to a levetiracetam sustained-release micro-tablet and a preparation method thereof. The levetiracetam sustained-release micro-tablet is composed of a tablet core and a coating layer, and the mass ratio of the tablet core to the coating layer is (100-105): (25-30); the tablet core is prepared from the following raw materials in parts by mass: 45-65 parts of levetiracetam, 1-5 parts of a foaming retardant, 5-15 parts of a retardant reinforcing agent, 20-40 parts of a filling agent and 0.5-3 parts of a flow aid; the coating layer is prepared from the following raw materials in parts by mass: 15-25 parts of a coating material and 2-8 parts of a pore-foaming agent. According to the preparation method, magnesium stearate or analogues thereof are excessively used during preparation of the levetiracetam sustained-release micro-tablets for the first time, an organic foaming agent is added, the path length and complexity of drug release are increased, the speed of drugs passing through hydrophobic pore channels is slowed down due to the hydrophobicity of a retarding enhancer, the sustained-release effect is achieved, and the sustained-release effect is achieved. The levetiracetam sustained-release micro-tablet can uniformly release the effective component levetiracetam within 24 hours, and the sustained-release time of the levetiracetam sustained-release micro-tablet is effectively prolonged.

The invention discloses a levetiracetam sustained-release granule and a preparation process thereof, and relates to the technical field of pharmaceutical preparations. The preparation method specifically comprises the following steps: S1, preparing levetiracetam active particles; s2, preparing a transition coating solution and a slow-release coating solution; and S3, coating the levetiracetam active particles with a transition layer and a sustained-release layer in sequence to obtain the levetiracetam sustained-release particles. Wherein the transition coating liquid is prepared by mixing the following raw material components in parts by weight: 3-5 parts of sodium alginate, 1-1.5 parts of a plasticizer and 100 parts of purified water; wherein the molecular weight of the sodium alginate is 50000 to 100000; the slow-release coating solution is prepared by mixing the following raw material components in parts by weight: 5-8 parts of silicon dioxide modified chitosan, 3-5 parts of sodium alginate, 1.5-3 parts of a plasticizer and 200 parts of purified water; wherein the molecular weight of the sodium alginate is 150000 to 200000.

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 present invention relates to the technical field of pharmaceutical preparations, and discloses a levetiracetam oral solution and a preparation method thereof, the levetiracetam oral solution comprises the following raw material components by mass concentration: 80-120 mg / ml of an active component levetiracetam, a pH value regulator, 2.50-2.90 mg / ml of a bacteriostatic agent, 180-220 mg / ml of a cosolvent and 280-350 mg / ml of a flavoring agent, and the pH value of the levetiracetam oral solution is 5.0-5.6. The preparation method is carried out according to the following charging sequence: purified water and glycerol, methylparaben, propylparaben, mono-ammonium glycyrrhizinate S, acesulfame potassium, sodium acetate, liquid maltitol, levetiracetam, 1% acetic acid solution and essence. Compared with the prior art, the levetiracetam oral solution prepared by the preparation method disclosed by the invention is better in mouth feel and higher in stability; the adjustment of the preparation process greatly shortens the time required for preparation.

The present application relates to a levetiracetam oral solution. Specifically, the present application provides a levetiracetam oral solution comprising levetiracetam, sucralose, polyethylene glycol 400, glycerol, lactose, mannitol, sorbitol, hydroxyethyl cellulose, citric acid, disodium hydrogen phosphate, sodium bisulfite and water. The levetiracetam oral solution of the present application can effectively mask the bitter taste of levetiracetam and its residues, thereby having excellent oral compliance, and the levetiracetam oral solution has excellent stability to light, high temperature and high humidity, can be divided and packed in transparent containers, is convenient for storage and transportation, ensures quality safety, and guarantees medication safety.

The invention relates to the field of pharmacy, and discloses a levetiracetam derivative, and the levetiracetam derivative is a boron dipyrromethene levetiracetam derivative. The structural formula of the BODIPY-L-Racetam derivative is as shown in formula (I), wherein the BODIPY-L-Racetam derivative contains two substituent groups, namely R1 and R2; wherein R1 is any one of straight chain alkyl groups or branched chain alkyl groups of-C6H5,-(4-Me) C6H4,-(4-Cl) C6H5,-(4-Br) C6H4,-(4-F) C6H4,-(3-F) C6H4,-(3-Br) C6H4 and C4-C10; r2 is any one of-H,-Cl,-OCH3,-OCH2CH3,-OC6H5,-O (4-OMe-C6H4),-O (4-Me-C6H4),-O (4-ClC6H4),-O (4-BrC6H4),-O (4-CF3C6H4),-C6H5,-(4-Me) C6H4,-(4-Cl) C6H5,-(4-Br) C6H4,-(4-F) C6H4, CH (CO2CH2CH3) 2 and CH (CO2CH2CH3) 2, and a synthesis method and application thereof. According to the invention, synthesis of the levetiracetam derivative is realized, the characteristic that levetiracetam can treat epilepsy is reserved, and the levetiracetam has a bright color, so that the levetiracetam derivative is favorably applied to research of levetiracetam drug delivery and drug effect monitoring.

Provided is use of levetiracetam or a pharmaceutically acceptable salt thereof in the preparation of an anti-obesity drug. The pharmaceutically acceptable salt is an acid addition salt formed by levetiracetam and the following acid: hydrochloric acid, hydrobromic acid, sulfuric acid, lactic acid, citric acid, phosphoric acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, naphthalene sulfonic acid, tartaric acid, pyruvic acid, acetic acid, maleic acid or succinic acid, fumaric acid, salicylic acid, phenylacetic acid, or mandelic acid. Levetiracetam can significantly inhibit OA-induced obesity in Caenorhabditis elegans and significantly reduce the body weight of C56BL / 6J mice with DIO. Levetiracetam has a significant anti-obesity effect and can be used as an anti-obesity drug.

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.

This invention relates to the preparation of high-purity levetiracetam (S)-2-(2-oxo-1-pyrrolidine)butyramide. The preparation of the high-purity levetiracetam begins with 2-(2-oxopyrrolidine-1-yl)butyric acid as the starting material. Through esterification and ammonolysis, a racemic levetiracetam is obtained, which is then resolved by R-mandelic acid to yield high-purity levetiracetam with a chiral content of over 99.9%, a chiral isomer content of less than 0.05%, and no chloride detected. The chiral isomer (R)-2-(2-oxo-1-pyrrolidine)butyramide recovered after resolution can be racemed and further resolved by R-mandelic acid for the preparation of levetiracetam, achieving a total yield of over 90%. The recovered R-mandelic acid can be reused repeatedly, significantly reducing the consumption of resolving agent. This reaction has a short procedure, is easy to operate, and has a stable yield, which significantly reduces the cost of preparing levetiracetam. In addition, it has a very high chiral content, making it suitable for large-scale industrial production.

This invention relates to the field of pharmaceutical analysis technology, specifically to a method for determining the content of L-2-aminobutyric acid (GABA), a degradation impurity, in a concentrated solution of levetiracetam for injection. The method includes the following steps: diluting the concentrated levetiracetam for injection with a 50% acetonitrile aqueous solution, and then determining the content using high-performance liquid chromatography (HPLC) with a UV detector. C0.05 is also used. 18 The chromatographic column uses an aqueous solution of ammonium dihydrogen phosphate and acetonitrile as the mobile phase. This invention provides an accurate method for determining the degradation impurity L-2-aminobutyric acid in levetiracetam, which is highly specific, sensitive, accurate, and easy to operate, effectively controlling the quality of concentrated levetiracetam injection solutions.

The invention relates to the technical field of medicine synthesis, in particular to a preparation method of high-purity levetiracetam. According to the method, (S)-2-aminobutanamide hydrochloride and 4-chlorobutyryl chloride are used as raw materials, and high-purity levetiracetam is prepared through an acylation reaction, a cyclization reaction and a specific crystallization process. The preparation method of the levetiracetam is simple and convenient, simple to operate and low in cost, and also effectively avoids the risk of introducing a toxic impurity tetrabutylammonium bromide. By utilizing the method disclosed by the invention, the problems of low purity and yield of a product and high cost caused by the fact that tetrabutylammonium bromide is required to be added in a method for synthesizing levetiracetam in the prior art are effectively solved.

Methods, compositions and kits are disclosed directed at levetiracetam derivatives, immunogens, signal generating moieties, antibodies that bind levetiracetam and immunoassays for detection of levetiracetam.

Disclosed is a method for preparing levetiracetam and intermediates from a compound of formula (I), wherein CR is selected from cyano, carboxylic acid, carboxamide, alkali metal carboxylate, alkaline earth metal carboxylate, alkyl carboxylate and mixtures thereof.

The application provides a synthesis method of levetiracetam, wherein starting material I is reacted with SOCl2 under the action of a solvent A to generate an intermediate I; the intermediate I is reacted with starting material II under the action of a solvent B to generate an intermediate II; and the intermediate II is reacted with 4-chlorobutyryl chloride under the action of a solvent C to generate levetiracetam. The method is simple in operation, mild in reaction condition, high in yield, low in cost, friendly to the environment and suitable for industrialized mass production of levetiracetam.

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.

There is disclosed an improved process for the racemization of (R)-α-ethyl-2-oxo-1-pyrrolidineacetic acid in a solution of alkali hydroxide. The process comprises heating a crystalline suspension of the racemic (RS)-α-ethyl-2-oxo-1-pyrrolidineacetic acid at a temperature from 100° C. to 250° C. to increase the yield and purity. The racemic (RS)-α-ethyl-2-oxo-1-pyrrolidineacetic acid is optically resolved into(S)-α-ethyl-2-oxo-1-pyrrolidineacetic acid and converted to levetiracetam.

The application discloses a preparation method of levetiracetam, which comprises the following steps: after (S)-alpha-ethyl-2-oxo-1-pyrrolidine acetate is ammoniated in water, excessive ammonia gas in a reaction system is removed, part of water is removed through distillation, and inorganic salt is added before extraction, so that the yield and quality of levetiracetam are improved.

The utility model discloses a preparation system of a levetiracetam injection. A mixing device comprises a first mixing unit and a second mixing unit which are communicated with each other, the first mixing unit comprises a shell, and a liquid flowing plate is arranged in the shell and used for receiving liquid flowing out of the main liquid pipe and the auxiliary material tank and enabling the liquid to be mixed in a flowing and dripping manner; the second mixing unit comprises a cylinder body, and the interior of the cylinder body is divided into a plurality of separated cavity spaces by the partition plates. The utility model relates to the technical field of pharmaceutical equipment, and the system not only improves the mixing efficiency and shortens the preparation time, but also ensures the uniformity and stability of liquid medicine, and provides a powerful guarantee for producing high-quality medicaments. And multi-stage and multi-mode mixing in the online liquid conveying process is also realized. The multi-stage mixing strategy ensures that each step from preliminary mixing to final uniform mixing can be effectively controlled, so that the mixing efficiency and the liquid medicine quality are improved.

An orodispersible tablet of levetiracetam, comprising: 55-85 %w / w levetiracetam or pharmaceutically acceptable salts thereof; a diluent at 2-35 %w / w (e.g. microcrystalline cellulose (MCC) (1-20 %w / w),

The invention discloses a levetiracetam sustained-release micro-tablet and an application of the levetiracetam sustained-release micro-tablet. The levetiracetam sustained-release micro-tablet core disclosed by the invention has good friability and tabletability, is easy to form in a tabletting processing process, and solves the difficult problems of tabletting formability of the micro-tablet core and friability of the micro-tablet core in a subsequent coating process in the prior art; the successful preparation of the levetiracetam sustained-release micro-tablet core and the sustained-release coated micro-tablet is realized. Compared with an original sustained-release tablet, the levetiracetam sustained-release micro-tablet disclosed by the invention has the advantages that the size and the volume are greatly reduced, the levetiracetam sustained-release micro-tablet is easier to swallow by a patient, and the medication compliance of the patient is greatly improved. And the sustained-release layer coating is coated on the outer layer of the tablet core, so that the levetiracetam sustained-release micro-tablet realizes stable release of a membrane control mechanism, and the long-acting and stable release effect of the sustained-release micro-tablet is achieved.

The utility model discloses reaction equipment for levetiracetam. The reaction equipment comprises a support, a reaction tank is arranged on the support, a sealing cover is fixedly connected to the top end of the reaction tank, a straight rod is arranged on the sealing cover, a motor is arranged at one end of the straight rod, and a flushing nozzle is arranged on the straight rod. When regular cleaning or cleaning after use is needed, the water tank and the water passing opening can be connected through the connecting pipe, a water source is conveyed through the interior of the straight rod, the straight rod is continuously driven by the motor to rotate, and the washing spray head is driven by the rotating stirring blade to rotate, so that the interior of the reaction tank is washed, and subsequent use in preparation of levetiracetam is guaranteed; compared with the prior art with complicated operation and structure, the reaction equipment can be washed in a simple and convenient manner and structure, so that the subsequent or next levetiracetam preparation can be smoothly executed, the consumed labor is reduced, the consumed time can be reduced, and the use efficiency of the reaction equipment can be improved.

The invention relates to a crystal form B of (S)-2-aminobutanamide hydrochloride, a preparation method of the crystal form B and a method for preparing levetiracetam by using the novel crystal form. The novel crystal form can improve the reaction yield and product purity of subsequent levetiracetam.

There is disclosed a method for preparing levetiracetam and intermediates from a compound of the formula:wherein CR is selected from the group consisting of cyano, carboxylic acid, carboxamide, alkali carboxylate, alkaline earth metal carboxylate, alkyl carboxylate, and a mixture thereof.

The invention belongs to the technical field of medicines, and particularly relates to an application of levetiracetam in preparation of an anti-fatigue medicine, and the levetiracetam is proved to be capable of remarkably prolonging running time and swimming time of a mouse through systematic mouse experiments. Therefore, the levetiracetam has a remarkable effect on enhancing the exercise tolerance of the body. The levetiracetam becomes an effective anti-fatigue medicine for people who need to do physical activities or exercises for a long time, such as athletes, soldiers and workers, and helps the people to improve the athletic performance and the working efficiency. In an in-vitro muscle endurance test, it is clear that levetiracetam significantly improves the fatigue index of mouse muscles. The result shows that levetiracetam can directly act on muscular tissues to improve the fatigue state of the muscular tissues. For people who often do high-intensity physical activities, levetiracetam is helpful for relieving muscle fatigue and injury.

The application discloses a levetiracetam sustained-release granule and a preparation process thereof, and relates to the technical field of pharmaceutical preparations. Specifically, the preparation process comprises the following steps: S1, preparing levetiracetam active granules; S2, preparing a transition coating liquid and a sustained-release coating liquid; and S3, sequentially performing transition layer and sustained-release layer coating on the levetiracetam active granules to obtain the levetiracetam sustained-release granules. The transition coating liquid is prepared by mixing the following raw material components in parts by weight: 3-5 parts of sodium alginate, 1-1.5 parts of a plasticizer and 100 parts of purified water; the molecular weight of the sodium alginate is 50000-100000; the sustained-release coating liquid is prepared by mixing the following raw material components in parts by weight: 5-8 parts of silicon dioxide modified chitosan, 3-5 parts of sodium alginate, 1.5-3 parts of a plasticizer and 200 parts of purified water; and the molecular weight of the sodium alginate is 150000-200000.

There is disclosed a process for the production of levetiracetam by crystallizing levetiracetam in an aqueous solution, optionally in the presence of a water-soluble solvent. The product of levetiracetam contains no residual organic solvent.