37 results about "Lamotrigine" patented technology

The present disclosure relates to novel lamotrigine salts, co-crystals, and compositions. In some embodiments, the lamotrigine salt is a lamotrigine dicarboxylic acid salt or hydrate or solvate thereof. In some embodiments, the lamotrigine co-crystal is a co-crystal of lamotrigine and a dicarboxylic acid, or a hydrate or solvate thereof. In some embodiments, the compositions comprise lamotrigine or a salt or co-crystal thereof, or a hydrate or solvate thereof. In some embodiments, the composition is in the form of a powder. In some embodiments, the composition is in the form of a liquid. The present disclosure also relates to methods of preparation and use in medical therapy, for example, for the treatment of a subject with epilepsy or bipolar disorder.

Disclosed are ready to use non-aqueous solutions of lamotrigine. The lamotrigine is dissolved in a solvent, wherein the solvent comprises propylene glycol and optionally at least one co-solvent, and wherein if water is present in the ready to use non-aqueous solution, the water is not at least one co-solvent. Also disclosed are methods for treating a neurological disorder or a mental disorder by administering the ready to use non-aqueous solutions of lamotrigine, processes for preparing ready to use non-aqueous solutions of lamotrigine, and kits containing lamotrigine to prepare ready to use non-aqueous solutions of lamotrigine.

The invention relates to the technical field of drug analysis and detection, and particularly discloses a method for detecting genotoxic impurities in lamotrigine. According to the method for detecting the genotoxic impurities in the lamotrigine, a Venusil XBP C18 (L) (150mm * 4.6 mm, 5mu m) chromatographic column is adopted, a mixed solution of a monopotassium phosphate solution-triethylamine and a mixed solution of acetonitrile are used as a mobile phase, and the genotoxic impurities (impurities K) in the lamotrigine are accurately detected in a gradient elution mode through a high performance liquid chromatography method. The detection limit of the impurity K is 0.0013 mu g / mL, the quantification limit is 0.0025 mu g / mL, and the detection requirements of the guiding principle of ICH M7 are met. The method provided by the invention has the advantages of strong specificity, high sensitivity, good linear relationship, good precision and durability, and can be used as a basis for monitoring the quality of lamotrigine drugs.

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 application relates to the technical field of medicine, in particular to a kind of preparation and application of self-microemulsifying composition containing lamotrigine.The self-microemulsifying composition includes lamotrigine and self-microemulsifying drug delivery system (SMEDDS) carrier;The SMEDDS carrier includes: by lamotrigine, oil phase, emulsifier and co-emulsifier;The self-microemulsifying composition, by mass ratio, lamotrigine is 0.1% to 18.7%, oil phase is 20% to 33%, milk phase is 67% to 80%, the milk phase is by emulsifier and co-emulsifier, and the mass ratio of emulsifier and co-emulsifier is 25.7 to 32.9%:67.1% to 74.3%, and the mass concentration of lamotrigine reaches 18.7%.The particle size of microemulsion formed by the self-microemulsifying composition dispersed in aqueous medium is less than 50nm or even smaller.The self-microemulsifying composition is prepared into soft capsule, hard capsule, tablet, granule, temperature-sensitive gel and other dosage forms, and is applied in the preparation of antiepileptic drugs.

Disclosed are ready to use non-aqueous solutions of lamotrigine. The lamotrigine is dissolved in a solvent, wherein the solvent comprises propylene glycol and optionally at least one co-solvent, and wherein if water is present in the ready to use non-aqueous solution, the water is not at least one co-solvent. Also disclosed are methods for treating a neurological disorder or a mental disorder by administering the ready to use non-aqueous solutions of lamotrigine, processes for preparing ready to use non-aqueous solutions of lamotrigine, and kits containing lamotrigine to prepare ready to use non-aqueous solutions of lamotrigine.

The invention discloses a method for detecting the content of benzyl chloride in a lamotrigine key intermediate. The detection method based on gas chromatography is good in specificity, precision and repeatability, and the sensitivity meets the control requirements of the impurities. When the method is used for detecting multiple batches of test products, benzyl chloride is not detected.

The invention discloses a dry pharmaceutical composition, which comprises one or more lamotrigine hydrate crystals with a therapeutically effective amount and one or more pharmaceutically acceptable auxiliary materials, and the auxiliary materials comprise a thickening agent; the dry pharmaceutical composition is preferably a dry suspension, which can be formulated as a suspension for administration, which can be stably used for at least 1-3 months. The invention also discloses a preparation method of the dry pharmaceutical composition and the dry suspension and application of the dry pharmaceutical composition and the dry suspension to treatment of nervous system diseases.

The invention discloses a method for detecting the contents of lamotrigine and preservative in a lamotrigine dry suspension. The method adopts a high performance liquid chromatography method for separation and determination. A chromatographic column of the high performance liquid chromatography method uses octadecylsilane bonded silica gel as a filler, and gradient elution is performed using a mobile phase A and a mobile phase B. The mobile phase A is an acetate buffer solution, and the mobile phase B is an acetonitrile-methanol mixed solution with a volume ratio of 40-60:60-40. The total volume of the mobile phase is 100%, and the gradient elution program is as follows: 0-3 min, 80%→60% mobile phase A, 20%→40% mobile phase B; 3-12 min, 60%→40% mobile phase A, 40%→60% mobile phase B; 12-15 min, 40%→80% mobile phase A, 60%→20% mobile phase B; 15-20 min, 80% mobile phase A, 20% mobile phase B. The method for detecting the contents of lamotrigine and preservatives in the lamotrigine dry suspension of the present invention has strong specificity, the separation degrees between impurities and the raw material medicine and the preservative are all greater than 2, other auxiliary materials and the raw material medicine and the preservative do not interfere with each other, and the contents of lamotrigine and preservatives can be accurately determined.

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.

The invention discloses a pharmaceutical salt of lamotrigine, a pharmaceutical composition, a preparation method and application. Through a medicine-medicine combination strategy, lamotrigine and lipoic acid are combined in a salifying or mixture form, in epilepsy treatment, lamotrigine fragments can inhibit abnormal discharge and nerve over-excitation in the brain, and lipoic acid fragments can enhance the resistance of the brain to epileptic seizure, so that the epilepsy treatment effect is improved, and the epilepsy treatment effect is improved. The damage to the brain after the epileptic seizure is relieved, a multi-channel treatment effect with a synergistic effect is exerted, and the disease development is delayed. Meanwhile, the formed salt also has better physical and chemical stability, dissolution, pharmacokinetics and pharmacodynamic properties, is more beneficial to medicine formation on the whole, and provides an effective medicine for treating epilepsy.

The invention relates to the technical field of drug impurity detection, in particular to a method for detecting the content of dicyandiamide in a lamotrigine key intermediate. Respectively dissolving the test sample and the reference substance in a detection solvent to obtain a test sample solution and a reference substance solution; respectively separating the test solution and the reference solution by adopting a liquid chromatography technology, detecting by adopting a mass spectrometry detector, and calculating the content of dicyandiamide by adopting an external standard method according to a peak area; the liquid chromatography conditions are as follows: a C8 chromatographic column is adopted, and the flow rate is 0.45-0.55 ml / min; the column temperature is 30-40 DEG C; the mobile phase is A: 0.1% formic acid aqueous solution; b: acetonitrile; 8%-12% of A and 92%-88% of B are used for isocratic elution; the mass spectrometry conditions are as follows: in an ESI + positive ion mode, the taper hole voltage is 52V, the parent ion m / z is 85.2, the quantitative ion pair m / z is 85.2 / 68.4, the quantitative ion collision energy is 16V, the qualitative ion pair m / z is 85.2 / 43.5, and the qualitative ion collision energy is 14V. The methodology verifies that the method can be used for quantitatively detecting the content of dicyandiamide in the lamotrigine key intermediate.

The invention discloses a preparation method of lamidipine succinate intermediate 2-amino-6-(1-methylpiperidine-4-yl acyl)-pyridine dihydrochloride, Boc anhydride is introduced in the reaction process, the preparation method is simple in preparation process and low in cost, and the obtained product is high in purity, high in yield and suitable for industrial mass production.

The invention relates to the technical field of drug impurity detection, in particular to a method for detecting the content of cyanamide in a lamotrigine key intermediate. Respectively dissolving the test sample and the reference substance in a detection solvent to obtain a test sample solution and a reference substance solution; respectively separating the test solution and the reference substance solution by adopting a liquid chromatography technology, detecting by adopting a mass spectrometry detector, and calculating the content of hydrazine by adopting an external standard method according to a peak area; the liquid chromatography conditions are as follows: a C18 chromatographic column is adopted, and the flow rate is 0.5-0.7 ml / min; the column temperature is 30-40 DEG C; the mobile phase is A: 0.1% formic acid aqueous solution; b: acetonitrile; 3%-7% of A and 97%-93% of B are used for isocratic elution; the mass spectrometry conditions are as follows: in an ESI-anion mode, the taper hole voltage is 52V, the parent ion m / z is 274.2, the quantitative ion pair m / z is 274.2 / 257.9, the quantitative ion collision energy is 31V, the qualitative ion pair m / z is 274.2 / 194.0, and the qualitative ion collision energy is 39V. The methodology verifies that the method can be used for quantitatively detecting the content of cyanamide in the lamotrigine key intermediate.

The invention relates to the technical field of drug impurity detection, in particular to a method for detecting the content of aminoguanidine in a lamotrigine key intermediate. Respectively dissolving the test sample and the reference substance in a detection solvent to obtain a test sample solution and a reference substance solution; respectively separating the test solution and the reference solution by adopting a liquid chromatography technology, detecting by adopting a mass spectrometry detector, and calculating the content of aminoguanidine by adopting an external standard method according to a peak area; the liquid chromatography conditions are as follows: a C8 chromatographic column is adopted, and the flow rate is 0.95-1.05 ml / min; the column temperature is 30-40 DEG C; the mobile phase is A: 0.1% formic acid aqueous solution; b: acetonitrile; gradient elution is carried out for 0.0 to 0.8 min, and 90 percent of A is obtained; when the time is 0.8-2.0 min, 90%-10% of A is added; in 2.0-4.0 min, 10% of A is taken; the mass spectrometry conditions are as follows: in an ESI + positive ion mode, the taper hole voltage is 38V, the parent ion m / z is 75.2, the quantitative ion pair m / z is 75.2 / 58.4, the quantitative ion collision energy is 11V, the qualitative ion pair m / z is 75.2 / 43.5, and the qualitative ion collision energy is 36V. The methodology verifies that the method can be used for quantitatively detecting the content of aminoguanidine in the lamotrigine key intermediate.

The invention discloses a lamotrigine oral suspension and a preparation method thereof, the lamotrigine oral suspension is composed of lamotrigine and other pharmaceutic adjuvants, the pharmaceutic adjuvants are composed of a suspending aid, a wetting agent, a bacteriostatic agent, a flavoring agent, a defoaming agent, a pH regulator and a solvent, and the wetting agent is hydroxypropyl methylcellulose, glycerin, Tween 80 and the like. According to the invention, the suspending aid is adopted to increase the liquid viscosity and improve the stability of the suspension, and the wetting agent is adopted to improve the hydrophobicity of API, so that the stability and redispersibility of the suspension are improved, and the preparation process is simple and suitable for industrial mass production.

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.

Disclosed are ready to use non-aqueous solutions of lamotrigine. The lamotrigine is dissolved in a solvent, wherein the solvent comprises propylene glycol and optionally at least one co-solvent, and wherein if water is present in the ready to use non-aqueous solution, the water is not at least one co-solvent. Also disclosed are methods for treating a neurological disorder or a mental disorder by administering the ready to use non-aqueous solutions of lamotrigine, processes for preparing ready to use non-aqueous solutions of lamotrigine, and kits containing lamotrigine to prepare ready to use non-aqueous solutions of lamotrigine.

The invention discloses a method for detecting the hydrazine content in a lamotrigine key intermediate. The method comprises the following steps: respectively dissolving a test sample and a reference substance in a detection solvent to obtain a test sample solution and a reference substance solution; respectively separating the test solution and the reference substance solution by adopting a liquid chromatography technology, detecting by adopting a mass spectrometry detector, and calculating the content of hydrazine by adopting an external standard method according to a peak area; the liquid chromatography conditions are as follows: a C18 chromatographic column is adopted, and the flow rate is 0.5-0.7 ml / min; the column temperature is 30-40 DEG C; the sample size is 10 microliters; the mobile phase is A: 0.1% formic acid aqueous solution; b: acetonitrile; 8%-12% of A and 92%-88% of B are used for isocratic elution; the mass spectrometry conditions are as follows: in an ESI + positive ion mode, the taper hole voltage is 52V, the parent ion m / z is 113.3, the quantitative ion pair m / z is 113.3 / 56.4, the quantitative ion collision energy is 14V, the qualitative ion pair m / z is 113.3 / 58.4, and the qualitative ion collision energy is 15V. The methodology verifies that the method is suitable for quantitative detection of the hydrazine content in the lamotrigine key intermediate.

The present invention relates to a crystalline form of a lamotrigine hydrate, a method for preparing the same and a composition comprising the same, and in particular, to a lamotrigine hydrate form A, a method for preparing the lamotrigine hydrate form A and a composition comprising the lamotrigine hydrate form A.

The present invention relates to the field of pharmaceutical technology, specifically to a self-microemulsifying composition containing lamotrigine, its preparation, and application. The self-microemulsifying composition comprises lamotrigine, an oil phase, an emulsifier, and a co-emulsifier. The oil phase comprises monolinolein and medium-chain triglycerides, the emulsifier is polyoxyethylene 40 hydrogenated castor oil, and the co-emulsifiers are PEG400 and diethylene glycol monoethyl ether. Calculated by weight, the composition contains less than or equal to 18.7% lamotrigine, and the oil phase: emulsifier: co-emulsifier ratio is (2.8-3.0): (1.7-2.0): (5.0-5.4). When the self-microemulsifying composition is dispersed in an aqueous medium, the microemulsion formed has a particle size of less than 50 nm or even smaller. The self-microemulsifying composition can be prepared into dosage forms such as capsules, tablets, granules, and thermosensitive gels, and its application in the preparation of anti-epileptic drugs is also discussed.

The present invention discloses a complete lamotrigine antigen and its use in the preparation of lamotrigine antibodies and immunoassay detection. The structure of the complete lamotrigine antigen is shown in Formula 1. The present invention also discloses anti-lamotrigine monoclonal antibodies prepared using the complete antigen, hybridoma cells producing the monoclonal antibodies, and detection cards and kits for detecting lamotrigine analogs. The present invention discloses an ELISA method and a fluorescent immunochromatographic method for detecting lamotrigine analogs. The fluorescent immunochromatographic method is simple to operate, has a short detection time, low cost, high specificity, and good reproducibility.

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 present disclosure relates to novel lamotrigine salts, co-crystals, and compositions. In some embodiments, the lamotrigine salt is a lamotrigine dicarboxylic acid salt or hydrate or solvate thereof. In some embodiments, the lamotrigine co-crystal is a co-crystal of lamotrigine and a dicarboxylic acid, or a hydrate or solvate thereof. In some embodiments, the compositions comprise lamotrigine or a salt or co-crystal thereof, or a hydrate or solvate thereof. In some embodiments, the composition is in the form of a powder. In some embodiments, the composition is in the form of a liquid. The present disclosure also relates to methods of preparation and use in medical therapy, for example, for the treatment of a subject with epilepsy or bipolar disorder.

The invention discloses a lamotrigine composition and a preparation process thereof. The lamotrigine composition is prepared from the following raw materials in mass concentration: 20-40% of lamotrigine, 30-40% of lactose monohydrate, 30-40% of microcrystalline cellulose, 1-4% of a disintegrating agent and 0.3-1% of magnesium stearate, and the total amount is 100%. The disintegrating agent is polyvinylpolypyrrolidone or sodium carboxymethyl starch. According to the lamotrigine composition provided by the invention, novel direct-mixing type auxiliary materials are adopted, the formula composition is simplified under the condition that the same in-vitro release target as a reference preparation is achieved, and the qualification of a product is further improved. According to the invention, a direct-mixing tabletting process is adopted, so that the production process is greatly simplified, and the production cost is reduced; water vapor and high temperature are avoided in the production process, and the stability of the product is ensured; the lamotrigine tablet prepared by the process has the advantages of uniform weight, complete appearance, no sticking and top cracking and the like, and is suitable for industrial production.

The application discloses a pharmaceutical salt of lamotrigine, a pharmaceutical composition, a preparation method and application. Through a drug-drug combination strategy, lamotrigine and thioctic acid are combined in the form of a salt or a mixture. In the treatment of epilepsy, the lamotrigine fragment can inhibit abnormal discharge and excessive excitement of the brain, and the thioctic acid fragment can enhance the resistance of the brain to seizures, reduce the damage to the brain after seizures, and play a synergistic multi-pathway treatment effect to delay the development of the disease. Meanwhile, the formed salt has better physical and chemical stability, dissolution, pharmacokinetics and pharmacodynamics, and is more beneficial to the preparation of a medicine, and an effective epilepsy treatment drug is provided.

The present disclosure relates to novel lamotrigine salts, co-crystals, and compositions. In some embodiments, the lamotrigine salt is a lamotrigine dicarboxylic acid salt or hydrate or solvate thereof. In some embodiments, the lamotrigine co-crystal is a co-crystal of lamotrigine and a dicarboxylic acid, or a hydrate or solvate thereof. In some embodiments, the compositions comprise lamotrigine or a salt or co-crystal thereof, or a hydrate or solvate thereof. In some embodiments, the composition is in the form of a powder. In some embodiments, the composition is in the form of a liquid. The present disclosure also relates to methods of preparation and use in medical therapy, for example, for the treatment of a subject with epilepsy or bipolar disorder.

The invention belongs to the technical field of medical artificial intelligence, and particularly relates to a method for searching a target spot of a drug for treating diseases through network pharmacology and computer-aided drug design and application of the target spot. Epidemiological studies show that the treatment of depression is mainly psychological guidance and drug therapy, however, different patients have different reactions to drugs, and unexpected adverse reactions are generated. Through network pharmacology, molecular docking and Mendel randomization technologies, the application of lamotrigine in preparation of the anti-depression medicine through acting on one or more target spots in GABRA1, GABRB2, GABRA6, GABRD, GABRG2, GABRG1, GABRA5, GABRA4, GABRB3 and GABRA2 is found and verified. The lamotrigine provides new dawn for safely, economically and effectively improving clinical treatment of depression patients based on the safe and economical'old medicine 'characteristics and the potential effective targeting activation effect of the lamotrigine on GABA receptors.

The invention relates to the technical field of medicines, in particular to a preparation and application of a self-microemulsion composition containing lamotrigine. Comprising lamotrigine and a self-microemulsion (SMEDDS) carrier, the SMEDDS carrier is prepared from lamotrigine, an oil phase, an emulsifier and a co-emulsifier; the self-microemulsion composition comprises, by mass, 0.1%-18.7% of lamotrigine, 20%-33% of an oil phase and 67%-80% of an emulsion phase, the emulsion phase is composed of an emulsifier and a co-emulsifier, the mass ratio of the emulsifier to the co-emulsifier is 25.7%-32.9%: 67.1%-74.3%, and the mass concentration of the lamotrigine reaches 18.7%. The particle size of the microemulsion formed by dispersing the self-microemulsion composition into an aqueous medium is less than 50 nm or even less. The self-microemulsion composition can be prepared into soft capsules, hard capsules, tablets, granules, temperature-sensitive gels and other dosage forms to be applied to preparation of anti-epileptic drugs.

The present disclosure provides a dry pharmaceutical composition, including a therapeutically effective amount of one or more lamotrigine hydrate crystals and one or more pharmaceutically acceptable excipients. The excipients include a thickener. The dry pharmaceutical composition is preferably a dry suspending agent. The dry pharmaceutical composition can be formulated into a suspension available for administration, which is stable for use for at least 1-3 months. The present disclosure further discloses methods for preparing the dry pharmaceutical composition and the dry suspending agent and use of the dry pharmaceutical composition and the dry suspending agent in the treatment of a neurological disease.