136 results about "Imatinib mesylate" patented technology

This invention features a method of treatment for vascular stenosis or restenosis using a combination of N-phenyl-2-pyrimidine derivatives such as imatinib mesylate and PI3K inhibitors, such as rapamycin.

Provided is a process for preparing crystalline imatinib mesylate in substantially pure α-form, which preferably includes crystallizing imatinib mesylate from an organic solvent containing imatinib and methanesulfonic acid, and seed crystals of imatinib mesylate α-form, wherein the seed crystals are added before imatinib mesylate begins to precipitate from the mixture. Also provided are stable, free-flowing imatinib mesylate crystals in substantially pure α-form, and a pharmaceutical composition containing the stable, free-flowing imatinib mesylate crystals.

Implantable medical devices having an anti-restenotic coatings are disclosed. Specifically, implantable medical devices having coatings of proteintyrosine kinase inhibitors are disclosed. The anti-restenotic protein-tyrosine kinase inhibitor is 4+4-Methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridinyl)-2pyrimidinyl]amino]-phenyl]benzamide methanesulfonate and pharmaceutically acceptable derivatives thereof (imatinib mesylate). The anti-restenotic medial devices include stents, catheters, micro-particles, probes and vascular grafts. The medical devices can be coated using any method known in the art including compounding the protein-tyrosine kinase inhibitor with a biocompatible polymer prior to applying the coating. Moreover, medical devices composed entirely of biocompatible polymer-protein-tyrosine kinase inhibitor blends are disclosed. Additionally, medical devices having a coating comprising at least one proteintyrosine kinase inhibitor in combination with at least one additional therapeutic agent are also disclosed. Furthermore, related methods of using and making the antirestenotic implantable devices are also disclosed.

The invention relates to a stable, non hygroscopic alpha crystalline form of methane sulfonic acid addition salt of 4-(4-methyl piperazin-1yl methyl)-N-[4-methyl-3-(4-pyridin-3-yl) pyrimidin-2-yl amino)phenyl]-benzamide (imatinib mesylate). A process for the preparation of the crystalline form is also described.

Provided is a process for producing imatinib and salts thereof, e.g., imatinib mesylate. The process includes reacting4-(4-methyl-piperazin-1-ylmethyl)-benzoic acid with N-(5-amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidine-amine in the presence of a carboxylic acid coupling reagent, to produce imatinib, and optionally converting the imatinib into a salt.

The invention provides an imatinib mesylate composition and a preparation method thereof. The imatinib mesylate composition is prepared from imatinib mesylate used as an active ingredient through a dry granulation process, and the dissolution rate of imatinib mesylate is effectively improved.

The invention relates to the technical field of pharmaceutical preparation, in particular to an effervescent tablet containing imatinib mesylate and a method for preparing the same. The effervescent tablet comprises 25 to 500 milligrams of the imatinib mesylate and an acid base pair which is acceptable in pharmacy; furthermore, a filling agent, an adhesive, a disintegrating agent, a lubricating agent, a sweetening agent and a flavour modifying agent which are acceptable in pharmacy can be added in the effervescent tablet. The effervescent tablet containing the imatinib mesylate has the advantages of faster action speed compared with the tablets and capsulated drugs in the market, has convenient use and good taste in taking, and is more suitable for children, the elderly, and patients who can not swallow solid medicines.

The present invention provides methods and compositions for treating graft failure resulting from neointimal hyperplasia. These methods and compositions feature the use of platelet derived growth factor receptor (PDGFR) inhibitor compounds, such as N-phenyl-2-pyrimidine compounds (e.g., imatinib mesylate) to inhibit the biological activity of the PDGFR.

The invention relates to the technical field of pharmaceutical preparation, in particular to an orally disintegrating tablet containing imatinib mesylate and a method for preparing the same, wherein the orally disintegrating tablet comprises effective amount of the imatinib mesylate and a pharmaceutic adjuvant which is acceptable in pharmacy and can rapidly collapse and release drugs in an oral cavity. The orally disintegrating tablet containing the imatinib mesylate has the advantages of faster action speed compared with the prior tablets and capsulated drugs, has convenient use and good taste in taking, and is more suitable for children, the elderly, and patients who can not swallow solid medicines.

The invention discloses a method for determining the content and the impurity limit of imatinib mesylate based on a HPLC-DAD (High performance liquid chromatography-diode array detection) method. A C18 chromatographic column is used; a methanol-triethylamine water solution is used as a flowing phase; the volume percentage concentration of the triethylamine water solution is 0.5-1 percent; the pH value of the triethylamine water solution is 7.5-11; the flowing speed is 0.8-1.2 ml / min and the detection wavelength is 200-400 nm during a gradient elution process; the process of the gradient elution lasts for 0-55 minutes and the volume percentage concentration of the triethylamine water solution is 65-15 percent. Under the chromatographic condition, the separation degrees among all components are greater than 2.0; the linear range ranges from 9.09 to 90.92 microgram.ml<-1> (r=0.9998); the detection limit is 0.3ng. The method is simple, accurate, high in sensitivity and good in repeatability, and avoids the influence on agents and the service life of the chromatographic column due to octane sulfonic acid sodium ions.

The invention relates to an imatinib-containing composition and a preparation method thereof, belonging to the technical field of pharmaceutical preparations. The imatinib-containing composition disclosed by the invention is composed of imatinib, a diluent, a disintegrating agent, an adhesive and a lubricant, wherein the imatinib is imatinib mesylate alpha crystal; the diluent is a mixture of microcrystalline cellulose and lactose; the disintegrating agent is cross-linked polyvidone; the adhesive is polyvidone K30; and the lubricant is a mixture of magnesium stearate, talc powder and silica micropowder. The preparation method is simple and efficient in process, and can be used for industrial mass production, and the problem that the imatinib mesylate alpha crystal has strong hydroscopicityis and is not easy to form preparation is completely solved.

The invention discloses a preparation method of alpha-crystal form imatinib mesylate. The preparation method comprises the following steps that 1, 4-[(4-methyl piperazine-1-yl)methyl]benzoic acid dihydrochloride shown in the formula II is converted into an acyl chloride shown in the formula III by an acylating chlorination reagent; 2, the acyl chloride shown in the formula III and N-(5-amino-2-methylphenyl)-4-(3-pyridyl)-2-aminopyrimidin undergo a condensation reaction in the presence of an alkali to produce a compound shown in the formula IV; and 3, the compound shown in the formula IV and methylsulfonic acid undergo a salt forming reaction in the presence of an organic solvent to produce a compound shown in the formula I. The preparation method can realize preparation of stable alpha-crystal form imatinib mesylate and allows mild process conditions. The stable alpha-crystal form imatinib mesylate can be after-treated simply and has high purity. The preparation method has a low reaction cost and is suitable for industrial production.

The invention discloses an imatinib mesylate pellet tablet and a preparation method thereof. The preparation method comprises the following steps: firstly, preparing a main drug, namely imatinib mesylate, into a gastric-soluble coating pellet by a fluidized bed coating process, and then mixing the coating pellet with a filling agent, a disintegrating agent, an adhesive, a plasticizing agent, a lubricating agent and the like to prepare the gastric-soluble tablet by a compressing dry granulation technology. The tablet can be directly swallowed and can be quickly disintegrated into pellets in water so as to be convenient for patients with dysphagia and especially children to take. The accurate dose of the tablet can be ensured, and the tablet can be taken safely and conveniently.

The invention discloses a medicinal preparation containing crystal form a imatinib mesylate. The medicinal preparation comprises crystal form a imatinib mesylate, a disintegrating agent, a diluent, a lubricating agent and a flow aid, wherein the using amount of the imatinib mesylate accounts for 50-80 percent of the total weight of the medicinal preparation; the using amount of the disintegrating agent is 15-30 percent of the total weight of a tablet; the using amount of the diluent is 0-20 percent of the total weight of the tablet; the using amount of the lubricating agent is 0.1-2 percent of the total weight of the tablet; and the using amount of the flow aid is 0.1-2 percent of the total weight of the tablet. Due to the adoption of the medicinal preparation prepared in the invention, the defects of poor flowability of a crystal form a and difficulty in preparing a solid preparation can be well overcome, the prepared medicinal preparation is dissolved quickly, and the crystal form does not change in preparing and storing processes.

The invention discloses a method for preparing alpha-imatinib mesylate, and belongs to the field of medicines. The method comprises the following steps of: suspending imatinib base in a mixed solvent of water and an organic solvent, stirring, and adjusting the temperature to be 20-30DEG C; dissolving methanesulfonic acid, and dripping into reaction liquid; after the dripping is finished, standingfor clarifying the liquid, heating to the temperature of between 50 and 60DEG C, and keeping the temperature to react for 0.5 to 1 hour; and reducing the temperature to 32-40DEG C, adding alpha-imatinib mesylate seed crystals, dripping the organic solvent, continuously reducing the temperature to 20-30DEG C, separating out crystals, filtering, and drying to obtain a product. The preparation method has the advantages of simple operation, short reaction time, high yield, high purity of alpha-imatinib mesylate, low production cost, and suitability for industrial production.

The invention relates to the technical field of pharmaceutical preparation, in particular to a chewable tablet containing imatinib mesylate and a method for preparing the same. The chewable tablet containing the imatinib mesylate consists of the principal imatinib mesylate, a filling agent, a flavour modifying agent, a glidant, an odor modifying agent, and an adhesive. The chewable tablet containing the imatinib mesylate can be applied to patients having difficulty in orally taking the common tablets, has good drug compliance, can be dissolved in saliva after chewing and being absorbed by oral or esophageal mucosa, and has high bioavailability. The chewable tablet not only has sweet taste and good mouthfeel, but also modifies penetrating odors and has flavor; the chewable tablet is convenient to take and carry around; and the chewable tablet is prepared by a direct tabletting method, and has good drug stability, simple production process, and low cost.

The invention discloses an imatinib mesylate tablet and a preparation method thereof. The imatinib mesylate tablet comprises 8-30% of crospovidone and 8 to 40% of silica. The preparation method comprises the following steps of carrying out granulation of imatinib mesylate and a waterless organic solvent, drying the granules, uniformly mixing the granules, crospovidone, silica, a filler and a lubricant, and carrying out tabletting. The preparation method solves the problem of a slow dissolution rate of a preparation obtained by the prior art.

The invention discloses an imatinib mesylate tablet. The imatinib mesylate tablet comprises the following components in percentage by weight: 40-60% of alpha-crystal imatinib mesylate, 5-20% of antisticking agent, 20-50% of disintegrating agent and 0.2-1% of lubricating agent, wherein the sum of the weight percent of each component is 100%. According to the invention, through adding the antisticking agent, the defects of poor mobility, poor compressibility, poor stickness, static electricity and the like of alpha-crystal imatinib mesylate are avoided effectively; and the imatinib mesylate tablet prepared by alpha-crystal imatinib mesylate has consistent hardness, disintegration, dissolution and other quality standards with original tablet prepared by beta-crystal imatinib mesylate, and the detect that only beta-crystal imatinib mesylate is required as the raw material for preparing the imatinib mesylate tablet in the existing industry is solved.

The invention discloses a polymouphous substance II of imatinib mesylate, and also discloses a preparation method for the polymouphous substance and a medicinal composition of the polymouphous substance.

The invention relates to a method for determining trace imatinib in a blood sample and application to zero phase clinical trial, in particular, the invention relates to a method for determining imatinib or pharmaceutical salts of the imatinib in a biological sample. The method adopts the high performance liquid chromatography-tandem mass spectrum for determination and comprises the following steps and the testing conditions: treatment of a tested sample, determination of the sample, and determining a liquid chromatogram condition and a mass spectrum condition and the like. The invention also relates to application of imatinib or pharmaceutical salts of the imatinib to zero phase clinical trial and application of the method to pharmacokinetics experimental study of imatinib or pharmaceutical salts. The result shows that the detection method with the above characteristics can be beneficially used for detecting the concentration of imatinib or pharmaceutical salts of the imatinib such as mesylate in the biological sample such as blood plasma in the medicine zero phase clinical trial. The chemical structure of imatinib mesylate is shown in the description.

The present invention is directed to a nanoparticulate compositions of imatinib mesylate, or a salt or derivative thereof, having improved pharmacokinetic profiles and reduced fed / fasted variability. The nanoparticulate imatinib mesylate particles of the composition have an effective average particle size of less than about 2000 nm and are useful in the treatment of chronic myeloid leukemia, gastrointestinal stromal tumors and related diseases.

The invention discloses an application of imatinib mesylate in preparation of drugs for resisting Parkinson's disease (PD). The application of imatinib mesylate (STI571) in preparation of drugs for treating neurodegenerative diseases belongs to the protective range of the invention, and the neurodegenerative diseases can be PD. An experiment proves that by continuous administration of the STI571, the dyskinesia induced by MPTP can be obviously improved, and the cognitive dysfunction of mice can be improved. The STI571 can obviously improve the dopaminergic neuron loss induced by the MPTP, can inhibit the rat CA1 and DG (diacylglycerol) region nerve cell apoptosis reaction induced by rotenone, can obviously inhibit the primary substantia nigra neuron apoptosis and Lewy protein expression induced by rotenone, and can inhibit the phosphorylation activation of PKC (Protein Kinase C) and Akt. The STI571 used as a specific inhibitor of c-Ab1 can resist the formation of PD, can improve the behavioral abnormity and cognitive dysfunction of PD, can be used as a new candidate drug for resisting neurodegenerative diseases such as PD and the like, and has favorable application prospects; and the clinical indications of the STI571 are greatly expanded.

The invention relates to an imatinib mesylate preparation, in particular to an imatinib mesylate liposome preparation. Imatinib mesylate liposome comprises blank liposome and imatinib mesylate liposome original medicines, the blank liposome comprises phospholipid, cholesterol, hydrophilic polymer lipid derivatives, citric acid-sodium citrate solution and alkaline substances, the mass ratio of imatinib mesylate to the phospholipid ranges from 1:8 to 1:30, the mass ratio of the cholesterol to the phospholipid ranges from 1:1 to 1:8, and the mole ratio of the hydrophilic polymer lipid derivatives to the phospholipid ranges from 1:30 to 1:10. A preparation process includes the steps of blank liposome preparation, liposome grading, medicine loading and the like. The imatinib mesylate liposome preparation is high in liposome embedding ratio, uniform in particle size, low in cost and good in process repeatability.

The invention relates to substituted tetrahydronaphthalene amide compound as shown in a general formula I (in the Specification), pharmaceutically acceptable salt thereof, and a preparation method and application. The substituted tetrahydronaphthalene amide compound can be used as an antitumor drug, the invention also provides a preparation method of compounds similar to the substituted tetrahydronaphthalene amide compound and pharmaceutical compositions containing the compounds, and in vitro and in vivo anti-tumor effect research results and acute toxicity research results. The substituted benzo-cyclic amide compound as the antitumor drug, has better antitumor activity and safety, particularly resists imatinib mesylate resistance tumors, can be applied to curing tumors, such as leukemia, gastrointestinal stromal tumor, lung cancer, colon cancer, ovarian cancer and kidney cancer, is wide in therapeutic window, and as antitumor agent, the compound has high application value in the field of medicine.

The invention discloses a method and a detection reagent for detecting plasma concentration of imatinib mesylate in blood plasma with LC-MS / MS (liquid chromatography-tandem mass spectrometry). The method comprises steps as follows: (i), preparing a standard solution; (ii), preparing an internal standard solution; (iii), pre-processing samples; (iv), drawing a standard curve; (v), measuring the plasma concentration of imatinib mesylate in blood plasma. The detection reagent comprises a moving phase A, a moving phase B, the standard solution and the internal standard solution. The method for detecting the plasma concentration of imatinib mesylate in blood plasma with LC-MS / MS is provided, imatinib and carbamazepine as an internal standard substance can be completely separated with the method, besides, the method is slightly affected by an endogenous substance impurity peak, and recovery rate and precision are high.

The present invention belongs to the field of medicine and pharmaceutical chemistry, specifically relates to novel antitumor pharmaceutical combinations, and particularly relates to pharmaceutical combinations of bisbenzylisoquinoline alkaloids (e.g. berbamine and tetrandrine) and imatinib mesylates and their use in treating tumors.