56 results about "Brivaracetam" patented technology

The imine reductase mutant provided by the invention can catalyze asymmetric reductive amination of ethyl 3-formylhexanoate and (S)-2-aminobutanamide to synthesize brivaracetam, two chiral centers of brivaracetam are constructed in one step, and the problems of poor environmental protection property, low atom utilization rate, long route and the like in the existing industrial synthesis route are solved. Wide application prospects are realized.

The present invention designs a method for preparing a key intermediate of synthetic boceprevir, namely a chiral pyrrolidone derivative, through catalytic hydrogenation. Specifically, it involves the use of substrate chiral induction by adjusting and modifying the substituents of the substrate to achieve the asymmetric catalytic hydrogenation of dihydropyrrolidone by a metal catalyst. The advantages of the present invention are that the process route is simple and feasible, the yield is high, the cost is low, and it is easy to industrialize production, etc.

The present invention relates to a modified release tablet formulation comprises brivaracetam and at least one pharmaceutically acceptable excipient wherein the amount of brivaracetam is 20.0% to 55.0% by weight in the total composition and at least one matrix agent. Furthermore, the tablet is also obtained by using an effective process which is simple, rapid, cost effective, time-saving and industrially convenient process.

The present invention relates to a modified release tablet formulation comprises brivaracetam and at least one pharmaceutically acceptable excipient wherein the amount of brivaracetam is 20.0% to 55.0% by weight in the total composition and at least one matrix agent. Furthermore, the tablet is also obtained by using an effective process which is simple, rapid, cost effective, time-saving and industrially convenient process.

The invention relates to the technical field of medicines, in particular to a briracetam oral solution and a preparation method thereof. According to the present invention, by adjusting the formula and the preparation process of the oral solution of the briracetam, the stability of the briracetam is effectively improved, the antibacterial effect is effectively improved without adding the preservative, the taste of the oral solution is adjusted, and the medication compatibility of children patients is improved.

The present invention relates to a dual-release tri-layer tablet for brivaracetam, which is composed of three layers: an immediate-release layer, a barrier layer, and a sustained-release layer, wherein the barrier layer is drug-free and located in the center, and at least 75% of the area of ​​each of the immediate-release layer and sustained-release layer is covered by the barrier layer, and the sustained-release material in the barrier layer comprises a wax-like sustained-release material. The tablet has the following properties: after administration of the tablet, the drug substance dissolves at a rate of 25% or more within 30 minutes, 30-65% within 2 hours, 65% or more within 6 hours, and 80% or more but less than 100% within 14 hours, when measured by the paddle method at a rotation speed of 50 rpm in test solutions of pH 1.2, pH 4.5, pH 6.8, or water; and the tablet also shows zero-order release 30 minutes after administration, thereby significantly improving the release profile of the drug brivaracetam, enhancing compliance and safety, and optimizing the therapeutic effect of the drug. The present invention also relates to a dual-release tri-layer tablet for brivaracetam, and a method for preparing the same, which belong to the pharmaceutical technology.

The present application discloses a method for preparing a brivaracetam solution and the brivaracetam solution thereof, belonging to the field of medical technology. The method for preparing the brivaracetam solution comprises the following steps: (1) preparing solution 1: mixing a mixture including sodium carboxymethylcellulose and glycerol with purified water and stirring to obtain solution 1; (2) preparing solution 2: mixing purified water, methylparaben, sodium malate, malic acid, sucralose, crystalline sorbitol solution, brivaracetam, and glycerol and stirring to obtain an intermediate solution, mixing the intermediate solution with essence and stirring to obtain solution 2; (3) mixing solution 1, solution 2 and purified water, stirring, and filtering to obtain a brivaracetam solution. The method improves the clarity of the solution by controlling the order and temperature of addition of each auxiliary material, and the obtained brivaracetam solution has good stability and is free of precipitation and degradation impurities.

Disclosed is a method for enzymatic synthesis of a brivaracetam chiral intermediate, i.e., a method for synthesizing a brivaracetam chiral intermediate (R)-3-cyanohexanoic acid by catalyzing the hydrolysis of 3-cyanohexanitile using an enzyme with nitile hydrolysis activity, and the enzyme with nitrile hydrolysis activity is obtained by carrying out a single mutation or a double mutation on an amino acid at position 140 or an amino acid at position 175 in an amino acid sequence as set forth in SEQ ID NO.2. Compared with a wild type, the nitrilase mutant of the present invention has the activity increased by 10 times, an ee value increased to 300 or more from 39, a substrate conversion rate of 45%, and a product ee which can reach 98.5%, and the yield of (R)-3-aminomethyl-hexanoic acid by catalytic hydrogenation synthesis using (R)-3-cyanohexanoic acid reaches 85% or more. The present invention features a short synthesis route, mild reaction conditions, and high atom economy, and can be applied to the industrial synthesis of the brivaracetam intermediate.

The present disclosure relates to a preparation method of brivaracetam or a pharmaceutically acceptable salt thereof, which has short reaction time, good yield and high purity, and is suitable for industrial production.

The key intermediate of brivaracetam was synthesized by the ruthenium-catalyzed asymmetric hydrogenation of unsaturated cyclobutanone esters, which features high yield, high ee value, mild reaction conditions, low catalyst dosage, and can be scaled up to gram scale, showing great potential application value.

A brivaracetam pharmaceutical composition contains an active pharmaceutical ingredient, a matrix forming agent, and a swelling agent. It has a sustained release effect and has a more flat release curve compared with a common gel skeleton sustained-release preparation, and thus achieves the purposes of reducing the release rate of the medicament, controlling the in vivo effective dosage of the medicament, stabilizing the blood concentration, reducing toxic and side effects and reducing the times of daily administration.

The present disclosure relates to transdermal drug delivery compositions for delivering brivaracetam, and uses, processes, methods of preparation and delivery thereof. The present disclosure also relates to iontophoresis drug delivery devices and systems, and methods of treatment comprising such compositions.

The present application relates to a kind of high stability's bexontan solution, with 0.1-10% bexontan, 20-50% high molecular material and buffer solution in bexontan solution with mass volume percentage, wherein, the high molecular material is selected from any one or combination of polymethyl methacrylate, cyclodextrin, hydroxypropyl methyl cellulose, sodium carboxymethyl cellulose, the buffer solution is selected from any one of citric acid buffer solution, phosphate buffer solution, malic acid buffer solution, succinic acid buffer solution, tartaric acid buffer solution, lactic acid buffer solution, acetic acid buffer solution, bexontan solution pH4-7.5.The bexontan solution of the present application significantly delays the diffusion of drug bitter taste in oral cavity and realizes taste masking, and has excellent stability, more optimal cost, quality controllable, good taste and the like advantages.

The present application provides a polymer of a compound shown in formula I, or a copolymer of the compound shown in formula I as a monomer and a monomer containing a carbon-carbon double bond as an adhesive of a gel patch adhesive ointment layer. The gel patch adhesive ointment prepared by the present application has excellent adhesion, good compatibility with the active drug brivaracetam, and good drug release behavior, and has a wide application prospect.

The invention discloses a liquid chromatographic analysis method for isomer impurities in a briracetam intermediate, which comprises the following steps: step 1, mixing a briracetam intermediate (compound 1) sample with a diluent to prepare a sample solution; and 2, detecting the sample solution by using high performance liquid chromatography so as to determine the content of isomer impurities in the sample of the compound 1. According to the method, normal-phase high-performance liquid chromatography is adopted, and normal hexane and isopropanol are used as mobile phases, so that the elution strength is improved, and the separation capacity is improved. By adopting gradient elution, the separation capacity is improved, the peak shape is improved, and the sensitivity is increased.

The invention discloses an imine reductase which is derived from Jianggellauris, Streptomyces aureococcus, Streptomyces alboflavus, Sandaracinus amylolyticus, Phyllobacterium SYSU D60010, Mesorhizobium, Labitorixococcus or a metagenome, the imine reductase is used as a biocatalyst for preparing the anti-epileptic drug brivaracetam and a diastereoisomer of the brivaracetam, the problems that an existing industrial synthesis route is poor in environmental protection property, low in atom utilization rate, long in route and the like are solved, and the imine reductase has a wide application prospect.

To provide therapeutic approaches for treating epileptogenesis associated with a brain insult, e.g., traumatic brain injury (TBI), stroke, or brain infection.SOLUTION: Provided are liquid pharmaceutical compositions including topiramate or a pharmaceutically acceptable salt thereof, meglumine, and a pharmaceutically acceptable excipient, the liquid pharmaceutical compositions optionally further including, e.g., levetiracetam or brivaracetam and / or atorvastatin or a pharmaceutically acceptable salt thereof (e.g., atorvastatin sodium).SELECTED DRAWING: Figure 1

The invention discloses a briracetam orally disintegrating tablet and a preparation method thereof, and belongs to the technical field of biological medicines. The briracetam orally disintegrating tablet is prepared from the following components in parts by mass: 10 to 50 parts of a briracetam cyclodextrin inclusion compound, 10 to 87 parts of a filling agent, 1 to 20 parts of a disintegrating agent, 1 to 10 parts of a lubricating agent and 1 to 10 parts of a flavoring agent. According to the preparation method disclosed by the invention, the defect of poor flowability of the briracetam is effectively improved by a process of firstly preparing the cyclodextrin inclusion compound of the briracetam and then pressing the inclusion compound into the tablet; performance inspection on the tablets shows that the tablets have the characteristic of rapid disintegration accidentally, and the stability is remarkably improved.

The present invention relates to a telescoping process for the preparation of brivaracetam. The process according to the present invention is a cost effective process in that it avoids isolation of intermediates at every step (Formula (I)).

The invention discloses an olefin reductase SeER mutant and application thereof in synthesis of chiral drugs, and provides a series of novel olefin reductase SeER mutants capable of efficiently and asymmetrically reducing beta-alkyl / aryl-beta-cyanoacrylate compounds, and the olefin reductase SeER mutants have high conversion rate (gt; 99% conversion rate), good enantioselectivity (gt; 99% ee), the substrate range is wide (gt; according to the present invention, the screened olefin reductase SeER mutant can be successfully synthesized into the chiral GABA derivative drugs such as pregabalin and brivaracetam through the chemical-enzyme coupling method, such that the overall reaction yield is improved, and the route is simple;

The present invention relates to a modified release tablet composition comprises brivaracetam and at least one diluent wherein the amount of diluents is 32.0% to 55.0% by weight in the total composition and further comprising a release rate-controlling membrane coating. Furthermore, the tablet is also obtained by using an effective process which is simple, rapid, cost effective, time-saving and industrially convenient process.

The application discloses a kind of brivaracetam injection pharmaceutical equipment, pharmaceutical method and its medicine, specifically related to pharmaceutical technical field, the rolling plate of the rolling assembly of the present application, the ball on the surface of rolling plate, the solid medicinal materials on the bottom of placing barrel are rolled at multiple angles, so that the drug liquid in solid medicinal materials is fully rolled out, then better complete the separation between drug liquid and solid medicinal materials.In addition, the present application also includes pharmaceutical equipment, wherein the medicine manufactured by the brivaracetam injection pharmaceutical equipment, brivaracetam is a levetiracetam analogue, and the affinity for SV2A is 13 times that of levetiracetam, the dosage is about one tenth of levetiracetam, the side effects are lower than levetiracetam, and the dosage is usually 25-100mg / day.The brivaracetam injection of the present application is stable in nature, safe and effective.

The present invention relates to an effervescent tablet formulation comprising brivaracetam or a pharmaceutically acceptable salt thereof, and at least one acid source and at least one gas generating agent, wherein the amount of brivaracetam is between 0.1% and 6.0% by weight in the total formulation. The present invention also relates to a simple, rapid, cost effective, time-saving and industrially convenient process of preparing the effervescent tablet.

The present disclosure provides intermediates used for preparing Brivaracetam, a preparation method and a use thereof, including an intermediate compound A and an intermediate compound B and a preparation method thereof, as well as a synthetic route for using the intermediate compound B to prepare Brivaracetam. The present technical solution can obtain high-quality and high-optical purity Brivaracetam and intermediates thereof, the proportion of Brivaracetam among the four optical isomers being greater than 99.5%. In addition, neither silica gel column for separation and purification nor expensive chiral high performance liquid chromatography for resolution is required, thereby avoiding cumbersome separation and purification steps, also avoiding waste of raw materials, reducing the production cost and making it more suitable for industrial production.

The invention relates to a brivaracetam intermediate and a novel preparation method of brivaracetam, and belongs to the field of pharmaceutical chemicals. Specifically, the invention provides a novel preparation method of a brivaracetam key intermediate compound shown as a formula V-a, and R is a straight chain or branched chain alkyl group with the carbon atom number of 1-6; the method has the technical advantages of high product chiral purity, mild reaction and the like.

The invention discloses a method for preparing brivaracetam by converting an intermediate shown in # imgabs0 # into an intermediate shown in # imgabs1 #. Wherein R1 and R2 are independently selected from hydrogen, alkali metal, alkaline earth metal, alkyl or a mixture thereof.

The present invention relates to the technical field of pharmaceutical preparation, and specifically discloses a brivaracetam sustained-release dry suspension and a preparation method thereof. The brivaracetam sustained-release dry suspension of the present invention is composed of a sustained-release drug-loaded resin, a suspending agent and a flavoring agent. The brivaracetam dry suspension prepared by the present invention through ion exchange resin drug loading and then sustained-release coating has a sustained-release effect, can reduce the daily dosing frequency, and can also overcome the problems of difficult administration of tablets, inconvenient carrying of oral solutions, and troublesome administration methods of injections.

The present invention belongs to the field of biocatalyst technology and discloses an alkene reductase mutant and its use in catalyzing the preparation of a brivaracetam synthetic intermediate. The amino acid sequence of the alkene reductase mutant of the present invention is shown in SEQ ID NO.1. The mutant, carbonyl reductase K1, and glucose dehydrogenase form a composite enzyme that can use the compound 5-hydroxy-4-n-propyl-2-furanone as a substrate, reduce double bonds and remove hydroxyl groups to obtain the compound (R)-4-propyldihydrofuran-2(3H)-one. The catalytically obtained (R)-4-propyldihydrofuran-2(3H)-one has an ee value of 93.0%, and can further obtain (R)-4-propyldihydrofuran-2(3H)-one with an ee value greater than 99.8% through diastereoisomer crystallization. The complex enzyme can be used for the efficient and green preparation of (R)-4-propyldihydrofuran-2(3H)-one, a key intermediate of brivaracetam.

The application belongs to the field of chemical medicine preparation and relates to a preparation method of brivaracetam. The brivaracetam is prepared from 3-alkenyl pyrrolidone through an asymmetric Michael addition reaction, a substitution reaction, an aminolysis reaction and the like. The method has high stereoselectivity, does not need to purchase chiral raw materials, and can obtain the brivaracetam with high yield and high purity by using common raw materials.

A method for synthesizing a brivaracetam chiral intermediate (R)-3-cyanohexanoic acid by catalyzing the hydrolysis of 3-cyanohexanitile using an enzyme with nitile hydrolysis activity, and the enzyme with nitrile hydrolysis activity is obtained by carrying out a single mutation or a double mutation on an amino acid at position 140 or an amino acid at position 175 in an amino acid sequence as set forth in SEQ ID NO.2. Compared with a wild type, the nitrilase mutant has the activity increased by 10 times, an ee value increased to 300 or more from 39, a substrate conversion rate of 45%, and a product ee which can reach 98.5%, and the yield of (R)-3-aminomethyl-hexanoic acid by catalytic hydrogenation synthesis using (R)-3-cyanohexanoic acid reaches 85% or more. This features a short synthesis route, mild reaction conditions, and high atom economy, and can be applied to the industrial synthesis of the brivaracetam intermediate.