26 results about "Rivaroxaban" patented technology

The invention discloses a construction method of a rivaroxaban population pharmacokinetic model and application of the rivaroxaban population pharmacokinetic model in an individualized medication prediction model, and relates to the field of biological information. According to the invention, a high performance liquid chromatography-tandem mass spectrometry method is adopted to determine the blood concentration of a rivaroxaban taking person, and a DNA sequencing method is adopted to determine the gene polymorphism of related metabolic enzymes CYP3A4 and CYP3A5 and transporters ABCB1 and ABCG2 of the rivaroxaban taking person; collecting data to establish a rivaroxaban group pharmacokinetic model, performing internal verification, and evaluating the stability and prediction performance of the model; in the final PPK model, the influence of the creatinine clearance rate, the ABCB1rs1045642 and the health condition on the clearance rate is the greatest; the experimental verification result shows that the model has good predictability and is accurate and reliable; the method can be applied to an individualized medication prediction model.

The invention discloses a rivaroxaban tablet. A tablet core is prepared from the following components in parts by weight: 10 parts of rivaroxaban, 15-25 parts of meglumine, 50-80 parts of a filling agent, 20-40 parts of a disintegrating agent and 0.5-1.5 parts of a lubricating agent; wherein the particle size D90 of the rivaroxaban is 50-100 [mu] m, and the invention discloses a preparation method of the rivaroxaban tablet, and the meglumine and the rivaroxaban are adopted to form a stable clathrate compound to prepare the preparation, so that the dissolution rate and the stability of the rivaroxaban tablet can be improved.

The invention belongs to the technical field of medicine synthesis, and particularly relates to a preparation method of a rivaroxaban intermediate. 4-(3-oxomorpholinyl) phenyl isocyanate, namely a compound 1, and (2s)-3-chloro-2-hydroxy propyl carbamic acid tert-butyl ester, namely a compound 2 are subjected to a reaction, and an intermediate (S)-tert-butyl-(2-oxo-3-(4-(3-carbonyl morpholine) phenyl) oxazoline-5-methylene) carbamate, namely a compound 3, is obtained. The reaction conditions are mild and stable, the intermediate can be prepared with high yield and high purity, the problems of long reaction time, high-temperature reaction and the like are avoided, and the method is suitable for industrial production.

This document discloses rivaroxaban tablets for oral suspension formulation for oral administration. Also disclosed is a method for preparing rivaroxaban tablets for oral suspension and a method of treating diseases.

The invention belongs to the technical field of medicine, and particularly discloses a rivaroxaban tablet and a preparation method and application thereof, the rivaroxaban tablet is composed of rivaroxaban and a ternary composite carrier; the ternary composite carrier is composed of vitamin E polyethylene glycol succinate, a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol grafted copolymer and a crystal inhibitor; wherein the mass ratio of the rivaroxaban to the ternary composite carrier is 1: (3-7); the mass ratio of the vitamin E polyethylene glycol succinate to the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol grafted copolymer to the crystal inhibitor in the ternary composite carrier is 1: 2: 3. According to the rivaroxaban tablet and the preparation method and application thereof, the preparation method is simple in process, good in production continuity, high in mechanization degree and suitable for industrial production, the rivaroxaban tablet prepared through the preparation method is high in dissolution rate, and the bioavailability of the rivaroxaban tablet is remarkably improved compared with that of a preparation on the market.

An oral liquid formulation of anticoagulant drugs comprising rivaroxaban, a salt or prodrug thereof; one or more viscosifying agents; at least one wetting agent; at least one vehicle, and one or more

The invention belongs to the technical field of pharmaceutical preparations, and discloses a rivaroxaban tablet preparation and a preparation process thereof. The preparation process comprises the following steps: (1) pretreating raw materials; (2) preparing a PBS solution; (3) preparing a nano-liposome; (4) synthesizing nanogel; (5) mixing the nano-liposome with the pH / enzyme double-response type nano-gel solution; (6) electrostatic spinning; (7) freeze drying; (8) total mixing; and (9) tabletting and forming. According to the invention, the problems of low solubility, high burst release property and poor targeting property of rivaroxaban are systematically solved through microfluidic homogenization, dual-response gel design and a nano-carrier composite process; the prepared rivaroxaban tablet preparation is remarkably superior to a traditional process in drug loading efficiency, release accuracy and stability, and has definite innovativeness and clinical application value.

The present invention relates to an orodispersible tablet of rivaroxaban having overall improved characteristics. its process of manufacturing and its use as anticoagulant.

The application discloses a rivaroxaban concentration determination method based on anti-Xa factor activity, a determination reagent and a preparation method thereof, and relates to the technical field of biology, and comprises reagent R1, reagent R2 and a sample diluent.The reagent R1 comprises Xa factor, a buffer, a stabilizer and inorganic salt.The reagent R2 comprises a chromogenic substrate, a buffer, polyethylene glycol and inorganic salt.The sample diluent comprises a buffer, a stabilizer and inorganic salt and is used for diluting samples with a concentration higher than a preset threshold value.The application remarkably reduces the cost by adopting an optimized formula of bovine factor and domestic raw materials, ensures the detection accuracy of high-concentration samples, and has excellent sensitivity, specificity and stability, realizes a detection performance highly related to a gold standard method, and thus successfully overcomes the technical bottlenecks of high detection cost, limited linear range, inaccurate detection of high-value samples and lack of high-quality domestic reagents in the prior art.

This document discloses rivaroxaban tablets for oral suspension formulation for oral administration. Also disclosed is a method for preparing rivaroxaban tablets for oral suspension and a method of treating diseases.

Provided are an oral dissolving film composition of rivaroxaban, a method for preparing same, and use thereof. The oral dissolving film composition comprises one or more of rivaroxaban and a pharmaceutically acceptable salt, hydrate, and solvate thereof as an active ingredient, and a film-forming material. Also, the present invention features a simple process, no sedimentation during the preparation of film solutions, qualified content uniformity, high drug loading capacity, and improved patient compliance, and is particularly suitable for patients with dysphagia.

This invention provides an orally soluble film composition for rivaroxaban, its preparation method, and its applications. The rivaroxaban orally soluble film composition comprises an active pharmaceutical ingredient and a film-forming material; the active pharmaceutical ingredient is one or more of the following: 5-chloro-nitro-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholino)phenyl]-1,3-azolidin-5-yl}methyl)-2-thiophene-carboxamide, a pharmaceutically acceptable salt, hydrate, and solvate thereof, as shown in Formula I. The rivaroxaban orally soluble film composition provided by this invention has the advantages of good taste, stable properties, high dissolution, and immediate dissolution in the oral cavity without the need for drinking water, without a gritty feeling after dissolution in the oral cavity, and rapid oral absorption. Furthermore, the process of this invention is simple, no sedimentation occurs during the preparation of the film solution, the content uniformity meets requirements, the drug loading is high, and clinical patient compliance is improved, making it particularly suitable for patients with swallowing difficulties, and it has good market prospects.

Disclosed is a method for preparing a rivaroxaban dry powder inhalation composition, the method comprising the steps of: (S1) placing rivaroxaban or a pharmaceutically acceptable salt thereof and beads into a ball mill device and milling same to obtain bead-milled rivaroxaban dry powder; and (S2) placing the obtained bead-milled rivaroxaban dry powder into an air jet mill device and pulverizing same. Also, disclosed are: a rivaroxaban dry powder inhalation composition comprising rivaroxaban dry powder having a Dv50 diameter of 5 μm or less; and a dry powder inhaler comprising the composition.

Disclosed herein relates to an oral liquid formulation of rivaroxaban. The present invention is specifically related to an oral liquid suspension of rivaroxaban comprising therapeutically effective amount of rivaroxaban, a salt or prodrug thereof; one or more viscosifying agents; one or more buffering agents; at least one wetting agent; at least one vehicle, and one or more pharmaceutically acceptable excipients. Also disclosed herein relates to process of preparation of an oral liquid formulation of rivaroxaban and a method of using the same.

The application belongs to the technical field of pharmaceutical preparations, and particularly relates to a rivaroxaban tablet, a preparation method and use. The rivaroxaban tablet comprises a rivaroxaban inclusion compound, lactose, starch, low-substitution hydroxypropyl cellulose and magnesium stearate. The rivaroxaban is packaged by using trimethylamine modified methyl cellulose as a packaging material, and the preparation process is optimized. The problem of low drug loading and low encapsulation efficiency of the rivaroxaban inclusion compound in the prior art is solved. The rivaroxaban tablet with a rivaroxaban inclusion compound with high drug loading and high encapsulation efficiency is provided, and the delivery efficiency of the rivaroxaban inclusion compound is improved. Through verification, the rivaroxaban tablet provided by the application has high dissolution rate, few impurities and stability.

This application discloses a method for detecting related substances in rivaroxaban tablets and its application, belonging to the field of pharmaceutical analysis technology. The method employs high-performance liquid chromatography (HPLC) with a column packed with octadecylsilane-bonded silica gel. The column is 150 mm long, 34.0 mm in inner diameter, and has a particle size of 23 μm. Mobile phase A is a 0.095%-0.105% phosphoric acid aqueous solution, and mobile phase B is acetonitrile. Gradient elution is used. The flow rate is 0.95-1.05 ml / min. The column temperature is 3337℃. The detection wavelength is 230-250 nm. The injection volume is 1020 μl. This method is highly specific, sensitive, and accurate, and can simultaneously detect known and unknown impurities, including LFSB1 to LFSB13, in rivaroxaban tablets, making it suitable for the quality control of this formulation.

The application discloses a model for predicting the risk of rivaroxaban anticoagulation bleeding and application thereof, and belongs to the technical field of biological detection. The model comprises a data input unit of two independent risk factors of a CYP3A4 genotype and clinical bleeding history of a subject, an assignment unit, an efficacy prediction unit and a report output unit, a C&B scoring system is formed according to the units, the total score is 3 points, if the C&B score is less than or equal to 1 point, rivaroxaban can be used as a coagulation factor X inhibitor for anticoagulant therapy, and if the C&B score is greater than or equal to 2 points, warfarin can be selected for anticoagulant therapy. The model can be used for guiding a clinician to accurately select a coagulation factor X inhibitor, the result of predicting the risk of rivaroxaban bleeding is accurate and reliable, and balance between anticoagulation benefits and bleeding risks can be achieved.

The present application relates to a co-crystal of rivaroxaban and a preparation method thereof, and also relates to a pharmaceutical composition containing the co-crystal, and also relates to application of the co-crystal in preparation of a medicine for anticoagulation.

The present application relates to a kind of rivaroxaban tablets and its preparation method, the rivaroxaban tablet includes 5-15 parts rivaroxaban, 2-10 parts disintegrating agent, 0.1-1 part binder, 0.1-1 part surfactant, 55-80 parts filling agent and 0.2-1.2 parts lubricant by weight fraction.The rivaroxaban tablet used in the present application is greater than 85% at 15min under different pH and different medium conditions Cumulative dissolution, dissolution behavior is fast, batch stability.The preparation method is simple, and the content of the obtained tablet is uniform, the dissolution rate of the tablet is fast, the impurity has no obvious increasing trend, the content and dissolution degree are basically unchanged, and the preparation stability is good.

The invention discloses a rivaroxaban key intermediate synthesis method, and relates to the technical field of organic synthesis.The rivaroxaban key intermediate 4-(4-aminophenyl) morpholine-3-ketone is synthesized through a substitution reaction, a nitration reaction and a hydrogenation reduction reaction with N-hydroxyethyl aniline and chloroacetyl chloride as reaction raw materials. The synthesis method has the advantages that the reaction raw materials are easy to obtain, the reaction conditions are mild, dangerous reagents and high-pollution reagents are avoided, the operation is simple and convenient, the process environmental protection property is strong, and the synthesis method is suitable for industrial production of the 4-(4-aminophenyl) morpholine-3-ketone.

According to the present invention, by selecting an appropriate range of rivaroxaban particle size and hydrophilic polymer content, it is possible to provide a rivaroxaban composition having bioavailability independent of food while using microscale rivaroxaban particles.

According to the rivaroxaban-containing tablet and the preparation method thereof, specific auxiliary materials are screened out, the ratio of the auxiliary materials is controlled, a lactose microcrystalline cellulose co-treatment substance is used as a filling agent, a microcrystalline cellulose-sodium carboxymethyl cellulose compound is used as a dispersing agent, sucrose stearate is used as a wetting agent, and the rivaroxaban-containing tablet is prepared. The rivaroxaban tablet solves the problems of hygroscopicity, poor compressibility, stickiness, poor content uniformity, slow disintegration, poorer dissolution rate and the like of tablet materials, the whole tablet is simple in auxiliary materials and only comprises three auxiliary materials, in the preparation process of the tablet, a microcrystalline cellulose-sodium carboxymethyl cellulose compound, sucrose stearate, rivaroxaban and purified water are prepared into a suspension, and the suspension is added into the tablet to prepare the rivaroxaban tablet. According to the present invention, the prepared tablet has the advantages of smooth tablet surface, good compressibility, good content uniformity, rapid disintegration, rapid dissolution, good stability and the like, and the whole preparation method is simple, and is suitable for large-scale industrial production.

This invention relates to a solid dispersion and its formulation, wherein the solid dispersion contains the active ingredient rivaroxaban and a carrier, and the solid dispersion exhibits good stability, rapid dissolution rate, and the ability to improve the solubility of the active ingredient. The carrier is defined as described in the specification.

This document discloses rivaroxaban tablets for oral suspension formulation for oral administration. Also disclosed is a method for preparing rivaroxaban tablets for oral suspension and a method of treating diseases.

The present invention provides a sodium humate preparation and its composition for treating venous thrombosis, belonging to the technical field of cardiovascular treatment. Through experiments, the present invention discovers that when sodium humate is used to treat venous thrombosis, it can effectively reduce the thrombus formation rate and thrombus length of venous thrombosis. Therefore, sodium humate can be used to prepare drugs for treating venous thrombosis. Secondly, the present invention discovers that when sodium humate and rivaroxaban are used in combination, they can produce a synergistic effect on the inhibition of venous thrombosis. Therefore, sodium humate can be used to prepare an enhancer of rivaroxaban to better exert the effect of rivaroxaban.

The present invention belongs to the field of pharmaceutical synthesis technology and specifically discloses a method for preparing rivaroxaban, comprising eight steps: 1) preparing a compound of formula II; 2) preparing a compound of formula III; 3) preparing a compound of formula IV; 4) preparing a compound of formula V; 5) preparing a compound of formula VI; 6) preparing a compound of formula VII; 7) preparing a compound of formula VIII; and 8) preparing a compound of formula IX. The present invention simplifies the post-processing process of rivaroxaban, eliminating the need for cumbersome operating procedures, significantly saving production time and improving production efficiency. The synthetic reaction is milder, avoiding the difficulty of production operations caused by harsh reaction conditions, increasing rivaroxaban production, facilitating purification of intermediates in each step, improving yield and economic benefits, and ensuring the operability and safety of rivaroxaban preparation, thereby making the preparation method suitable for industrial-scale production.