39 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 field of organic synthesis, and in particular to a method for preparing high-purity rivaroxaban. In the existing process for synthesizing rivaroxaban, there are many types of solvents, large environmental pressure, difficult centrifugation of intermediates, and large impurity quality problems. It is urgent to solve these problems in industry to improve the industrialization capacity of rivaroxaban. In order to solve the above problems, the present invention provides a method for industrial production of high-purity rivaroxaban. The present invention only uses a single solvent of acetonitrile to synthesize from starting material 4-(4-aminophenyl)-3-morpholinone to rivaroxaban crude product, greatly reducing the reaction solvent type, economic and environmental protection, while improving the crystallization particle size of each step intermediate, solving the problem that the product is sticky, difficult to centrifuge, and the impurity content is high, improving product quality and production efficiency, and being suitable for industrial production.

A computer implemented method for determining a dosage of rivaroxaban for administering to a patient, the method comprising: receiving patient data relating to a patient, wherein the patient data includes a kidney function metric; processing the patient data with a dosage calculator to determine the dosage of rivaroxaban for administering to the patient, wherein the dosage calculator is derived from a plasma level prediction model; and indicating the dosage.

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.

Provided in the present invention is a method for synthesizing rivaroxaban. The method comprises: reacting an intermediate I with an intermediate II in an organic solvent in the presence of an alkali to obtain rivaroxaban, wherein the synthesis route is shown as follows, R in formula I is phenyl or substituted phenyl, and in substitution, the substituent is selected from nitro, halogen and C1-C6 alkyl; and X in formula II is bromine or chlorine. The method for synthesizing rivaroxaban provided in the present invention is short in terms of route, mild in terms of reaction conditions, simple in terms of post-treatment, high in terms of reaction yield and very suitable for industrial production

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.

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

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.

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.

The invention belongs to the field of pharmaceutical preparations, and particularly relates to a rivaroxaban orally disintegrating tablet and a preparation method thereof. The orally disintegrating tablet provided by the invention is rapidly disintegrated when being placed in the mouth or water, has enough hardness and excellent storage stability in general production, transportation and use, and is simple in preparation method and suitable for modern industrial mass production.

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.

1. Name of the product of this design: pharmaceutical packaging box (rivaroxaban tablets). 2. Purpose of this design product: This design product is used for packaging of medicines. 3. The design key points of this appearance design product are: the combination of shape, pattern and color. 4. The picture or photo that best illustrates the design points: three-dimensional picture. 5. The design for which protection is sought includes color.

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 invention relates to a pharmaceutical composition comprising an amorphous solid solution of rivaroxaban and copovidone, povidone or crospovidone, wherein the weight ratio of rivaroxaban to copovidone, povidone or crospovidone is 1:4.1 to 1:7; to the use of said pharmaceutical composition in the treatment of a subject suffering from at least one of deep vein thrombosis and pulmonary embolism; and to a hot melt extrusion method for preparing such pharmaceutical composition.

The invention relates to a stable rivaroxaban content detection kit with strong anti-interference capability. The kit comprises a chromogenic substrate reagent and an Xa factor reagent, the chromophoric substrate reagent comprises an Xa factor sensitive substrate, a buffer solution, a surfactant and a preservative; the Xa factor reagent comprises an Xa factor, a buffering agent, inorganic salt, a complexing agent and a preservative. The kit is high in accuracy and good in repeatability, and the stability and the anti-interference capability of the detection reagent can be guaranteed at the same time. The kit disclosed by the invention can be suitable for different types of blood coagulation analyzers, and provides a reliable detection means for quantitatively detecting the content of rivaroxaban in vitro.

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 invention relates to the field of biomedicine, and particularly to an oligocyclodextrin and its application in an antidote. The raw materials for preparing the oligocyclodextrin include β-cyclodextrin and a crosslinking agent; the molar ratio of the β-cyclodextrin to the crosslinking agent is 1:(8-30); the crosslinking agent is epichlorohydrin. The present invention prepares an oligocyclodextrin by reacting the crosslinking agent epichlorohydrin with β-cyclodextrin. It has both the characteristics of a monomeric cyclodextrin molecule and the characteristics of a polymer, and can detach the drug from the binding site on the FXa factor through the inclusion effect of the hydrophobic cavity, reversing its anticoagulant effect, so as to promote the recovery of normal blood coagulation function in a timely manner when the use of rivaroxaban is excessive. The oligocyclodextrin of the present invention has a reversing effect on a variety of oral anticoagulants, has a simple synthesis route, low raw material cost, and good biosafety when used in large doses, and can fill the gap in the lack of corresponding antidotes for oral anticoagulants.

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.