104 results about "Apixaban" patented technology

The invention discloses an Apixaban tablet, which comprises the following components in parts: 1 part of Apixaban, 10-20 parts of water-soluble carrier material, 30-60 parts of filling agent, 5-10 parts of disintegrating agent and 5-10 parts of glidant. The Apixaban tablet provided by the invention improves the deficiencies in the prior art that the extracorporeal dissolution rate and the bioavailability is low. The preparation method of the Apixaban tablet disclosed by the invention is simple to operate, has good reproducibility, and is suitable for large-scale production. The Apixaban tablet is mainly used for the anti-thrombosis purpose.

Compositions comprising crystalline apixaban particles having a D₉₀ equal to or less than 89 μm, and a pharmaceutically acceptable carrier, are substantially bioequivalent and can be used to for the treatment and/or prophylaxis of thromboembolic disorders.

The present invention provides a synthetic method for an Apixaban drug intermediate. According to the invention, the reduction reaction of nitro groups in a compound 2 is conducted by sodium sulphide and amino groups in the compound 2 are protected by 5-chloro-pentanoyl. Therefore, the synthesis of Apixaban can be realized more simply and more directly. A novel one-pot synthesis method is provided by the invention and the method is mild in reaction conditions, high in safety coefficient, strong in maneuverability, simple in process and easy to industrialize. Meanwhile, a high-purity intermediate compound 14-1 can be obtained, so that the Apixaban of high purity and super-low impurity content can be obtained more easily. At the same time, the invention provides an effective and novel synthetic method for the preparation of an Apixaban key intermediate. By means of the method, the reaction efficiency is improved, and the production cost is lowered. The adoption of expensive reagents and severe reaction conditions can be avoided.

The invention relates to the field of chemical pharmacy and particularly relates to a method for preparing apixaban. The method comprises the following steps: (1) synthetic method of apixaban crude product: performing ammonolysis by an ammonia-accessing method; (2) refining method of apixaban: the refining method includes ethyl alcohol refining and isopropanol refining. The purity of the compounded apixaban is more than 97%, the byproducts are few, the operation method is simple and the reaction process is easy to control, at the same time, the yield of the ammonolysis is more than 91%; after two refining processes, the purity of the apixaban is greatly increased to more than 99.6%, and the single impurity is less than 0.1% and the yield is more than 90%. The solvent used in the refining process is low in toxicity, high in safety, cheap and easy to obtain. The refining process is simple in operation, mild in reaction condition, low in cost and is suitable for industrial production.

The invention relates to a method for preparing apixaban tablets. The method comprises the following steps: (1) uniformly mixing apixaban, an excipient, a disintegrating agent, a surfactant and a lubricating agent, performing wet granulation, screening the prepared soft material by using a 20-mesh sieve, granulating, drying and finishing the obtained particles, and collecting the dried particles with the particle size being between 20 meshes and 80 meshes; and (2) mixing the prepared particles with the lubricating agent for 30 minutes and tabletting, wherein the hardness of the tablets is 50-60N. In order to improve the dissolubility, a method for adding the surfactant into the prescription is adopted. According to the method, the dissolubility of the apixaban can be improved, and the problem is well solved, so that the bioavailability of the medicine is improved, and an excellent treatment effect is achieved.

The invention discloses a method for detecting an initial material II in apixaban through reversed-phase high performance liquid chromatography. The method comprises the following steps: 1, preparing a sample solution; 2, detecting the sample through reversed-phase high performance liquid chromatography; and 3, calculating the content of every impurity and the content of total impurities in the sample through an area normalization technique. The method for detecting initial material II related substances in apixaban through reversed-phase high performance liquid chromatography realizes complete separation of the chromatographic peaks of the initial material II and all the impurities through a simple mobile phase component; and the detection result of the method is accurate and reliable, so the method makes control of the quality of the initial material in the apixaban synthesis process possible.

The invention provides an apixaban/carboxylic acid eutectic crystal which comprises an apixaban/malonic acid eutectic crystal, an apixaban/D-malic acid eutectic crystal, an apixaban/maleic acid eutectic crystal, an apixaban/L-proline eutectic crystal and an apixaban/L-tartaric acid eutectic crystal. According to the apixaban/carboxylic acid eutectic crystal, the dissolution rate of apixaban is improved while safe medication is met, the defects of low solution rate and low dissolution rate of apixaban are overcome and the bioavailability of apixaban is improved.

The invention discloses a method for preparing an antithrombotic drug apixaban. The method is characterized in that a compound IV is used as a raw material to perform a hydrolysis reaction for 5-60 minutes at 10-100 DEG C in a polar organic solvent under an alkaline condition, and is transformed into a compound antithrombotic drug apixaban; the antithrombotic drug apixaban is prepared by re-crystallizing, sizing and column chromatography purification. The method has the advantage of high yield, is simple and convenient in the subsequent treatment due to extraction, drying, sizing, filtering, crystallizing, recrystallizing and other operation methods, and large-scale production is easily realized.

The present disclosure relates to a stable, reproducible and bioequivalent apixaban compositions, wherein the composition comprising apixaban having a D₉₀ particle size of more than 100 microns, preferably between 300 and 1000 microns, and more preferably between 350 and 800 microns, and further comprising one or more pharmaceutically acceptable excipients. The present disclosure further provides a process for preparation of a pharmaceutical composition comprising apixaban by wet granulation.

The invention relates to oral dosage forms for modified release of apixaban. The invention also relates to methods of preparing said dosage forms and to an agglomerated mixture of matrix former and filler for preparing an oral dosage form for use in the treatment of venous thromboembolism.

The present application relate to amorphous form of Apixaban useful in making pharmaceutically acceptable dosage forms, and to processes for their preparation.

The invention discloses an apixaban tablet comprising the raw materials including apixaban, an excipient, a disintegrating agent, a surfactant and a lubricant in a weight ratio of (5-20):(0.5-2.5):(0.1-0.3):(0.1-2.0). In order to improve the dissolution degree of the apixaban tablet disclosed by the invention, a method for adding the surfactant into the formula is adopted, and the method can increase the dissolution degree of apixaban, so that the problem is well solved, the bioavailability of the medicament is improved, and a very good curative effect is achieved.

The invention relates to an apixaban pellet and a preparation method thereof. The apixaban pellet is composed of, from interior to exterior, a blank pellet core, a drug-containing layer and a coating layer, wherein the drug-containing layer is composed of micronized apixaban, a binder and a disintegrating agent. The apixaban pellet comprises, by weight, 60 to 84 parts of the blank pellet core, 2 to 7 parts of the micronized apixaban, 3 to 10 parts of the binder, 5 to 20 parts of the disintegrating agent and 2 to 8 parts of the coating layer. Thus, the apixaban pellet obtained in the invention has a rough and regular shape and uniform particle size; and compared with commercially available tablets, the apixaban pellet provided by the invention has better stability, faster dissolving-out rate and higher bioavailability.

An injectable Factor Xa inhibitor formulation is provided which includes the Factor Xa inhibitor razaxaban or apixaban, a solubilizing agent which is a substituted β-cyclodextrin, preferably, sulfobutyl ether β-cyclodextrin (SBE-CD) or hydroxypropyl-β-cyclodextrin (HPB-CD), and water. A method for preventing or treating venous thrombosis, deep venous thrombosis and acute coronary syndrome employing the above formulation is also provided.

The invention relates to a method for determining apixaban cleaning residues by high performance liquid chromatography, and belongs to the field of chemical pharmaceutical detection. The invention aims at providing a method for determining the apixaban cleaning residues. The method is easy and quick to operate and accurate and reliable in determination results to evaluate a cleaning effect so as to ensure medicine quality and medication safety. The high performance liquid chromatography for determining the apixaban cleaning residues, which is disclosed by the invention, is easy and quick to operate, and accurate and reliable in the determination results, so that the cleaning effect of the equipment can be evaluated effectively. According to the high performance liquid chromatography, a 280 nm flow phase is selected, so that the detection limit is reduced effectively. A chromatographic column temperature selects 40 DEG C, so that the peak type can be improved effectively, and minimal residues can be effectively detected; methanol is selected to serve as a solvent, and is not absorbed in the wavelength, so that the interference on the detection caused by the solvent is avoided, and the reliability of the detection method is improved.

The present invention relates to a pharmaceutical composition comprising apixaban, in particular to a pharmaceutical composition comprising apixaban and a polymer having low viscosity as binder, and to a process for its preparation. The pharmaceutical composition is particularly useful as a medicament, especially for the treatment or prevention of a thromboembolic disorder.

The invention relates to apixaban sustained-release tablets. The apixaban sustained-release tablets are prepared from the raw materials in parts by weight: 5 parts of apixaban, 50-95 parts of sustained-release framework material and 3-20 parts of lubricant. A preparation method of the apixaban succinate sustained-release tablets comprises the steps of preparing materials, mixing, granulating, mixing, tabletting and carrying out aluminum-plastic packaging. According to the apixaban sustained-release tablets, postprandial hyperglycemia related symptoms of type 2 diabetes patients (only limited to the patients, of which blood sugar cannot be effectively controlled by dietotherapy and kinesitherapy, or the patients, of which the blood sugar cannot be effectively controlled yet after an alpha-glucosidase inhibitor is applied based on the dietotherapy and the kinesitherapy) can be effectively improved, novel sustained-release preparations are adopted, and sustained release means delaying the drug release rate of a drug from a dosage form, lowering the organism entering absorption rate of the drug and thus exerting a more stable treatment effect; the apixaban sustained-release tablets have the advantages of good drug stability, convenience in packaging, transportation and storage and the like; the preparation method of the apixaban sustained-release tablets is simple and easy and is applicable to industrial production.

The invention belongs to the field of analysis detection, and relates to a method for detecting an Apixaban intermediate II through a reversed-phase high-performance liquid chromatogram. The method includes the following steps of firstly, preparing a test solution; secondly, detecting the test solution through the reversed-phase high-performance liquid chromatogram; thirdly, calculating the content of each single impurity and all the impurities in the test solution according to an area normalization method. By means of the method, through simple mobile-phase components, the intermediate II can be completely separated from chromatographic peaks of all the impurities; meanwhile, the method is accurate and reliable in detection result and provides possibility for controlling the quality of the intermediate product in the Apixaban synthesis process.

The invention discloses apixaban tablets and a preparation method thereof. The apixaban tablets are prepared from the following raw materials: 20-30 parts of apixaban, 20-60 parts of HS-15, 10-30 parts of PVP-K30, 500-550 parts of lactose, 280-320 parts of microcrystalline cellulose, 45-55 parts of polyvinylpolypyrrolidone (PVPP) and 20-40 parts of coating premix, wherein the mass ratio of the HS-15 to the PVP-K30 is equal to (4 to 1)-(1 to 3). The preparation method comprises the following steps: (1) dissolving the apixaban, the HS-15 and the PVP-K30 in ethanol to obtain a transparent solution; then, spray-drying to obtain a solid dispersion; (2) evenly mixing the solid dispersion with the lactose, the microcrystalline cellulose and the PVPP and directly tabletting to obtain plain tablets; (3) coating the plain tablets to obtain the apixaban tablets. The tablets can significantly improve the dissolution rate of the medicine, increase medicine absorption, and improve the bioavailability, so that the therapeutic effect of the medicine can be fully exerted.

The invention discloses a method for determining the impurity content of apixaban by virtue of a high performance liquid chromatography. The method is specifically characterized in that an Agilent 1200 series high performance liquid chromatograph is matched with a DAD detector and an automatic feeder, an Inertsil ODS-3V, 5-micron, 250*4.6mm chromatographic column is adopted for work for 32 minutesin a gradient manner, and the working conditions are as follows: the column temperature is 40 DEG C, the feeding amount is 10 microliters, the detection wavelength is 230nm, and the flow speed is 1.5ml/min. The analysis method is good in specificity, and an impurity BMS-591455 has good linearity in the range of 0.5microg/ml-1.5microg/ml. The method has the advantages of simplicity and rapidness in operation, reliable determination result and the like, the impurity content can be effectively controlled, and the quality of an apixaban drug can be controlled.