30 results about "FLUPIRTINE MALEATE" patented technology

The invention relates to a preparation method of flupirtine maleate, which takes flupirtine as a raw material, and obtains flupirtine maleate pure products through salification and fine purification steps. By strictly controlling the use level and the reaction condition of maleic acid, the method greatly improves the yield of crude products, adopts a fine purification method integrating ultrafiltration and recrystallization, avoids product loss caused by adopting activated carbon, and greatly improves the purity and the yield of the flupirtine maleate pure products.

The invention discloses a flupirtine maleate sustained release tablet which is composed of the following ingredients of: by weight, 90-110 parts of flupirtine maleate intermediate-release particles, 290-310 parts of flupirtine maleate sustained release particles, 25-35 parts of sodium carboxymethyl starch, 20-30 parts of aerosol, 3-8 parts of magnesium stearate and 15-25 parts of microcrystalline cellulose. Weight proportions of the flupirtine maleate intermediate-release particles and the flupirtine maleate sustained release particles are both weighed according to the weight of flupirtine maleate.

The invention discloses a preparation method of flupirtine maleate capsules, comprising the following steps: A, taking the prescribed amount of calcium hydrogen phosphate, cross-linked polyvinylpyrrolidone, sodium lauryl sulfate, magnesium stearate, and micropowder silica gel , pass through 100 mesh sieves respectively; B, take the prescribed amount of flupirtine maleate raw material and carry out ultrafine pulverization treatment to 10-25um, then mix it with the auxiliary materials in step A according to the equal amount incremental method; C, take 80-100ml 50% ethanol solution is used as a binder to make soft materials, and granulated through a 20-mesh sieve; D. Dry the wet granules prepared in step C at a temperature of 55-65°C for 2-4 hours, and granulate through a 20-mesh sieve E. Add magnesium stearate and micropowder silica gel in the prescribed amount, mix well, and fill to obtain the required flupirtine maleate capsules. The invention has ingenious concept and simple process, and the prepared flupirtine maleate capsule has high blood drug concentration, small drug dose, high bioavailability and obvious pain treatment effect.

The invention discloses a method for synthesizing flupirtine maleate by use of a one-pot process. The method comprises the steps of taking 2,6-dichloro-3-nitropyridine as a starting material and performing ammonolysis to obtain a key intermediate 2,6-diamino-3-nitropyridine, and then condensing the key intermediate with p-fluorobenzaldehyde and performing Pd / C catalytic hydrogenation reduction, ethyl chloroformate acylation and maleic acid salifying to obtain the flupirtine maleate; the selected process route is simple and convenient to operate; the various steps are not separated and one-pot process production is realized; as a result, the production cost is effectively reduced, and the yield and the product purity are improved; in short, the method is suitable for industrial large-scale production.

The invention relates to a preparation method of a flupirtine derivative and a preparation of inorganic acid salts of the flupirtine derivative. The flupirtine derivative is shown in a chemical formula 1, wherein the flupirtine derivative is an important impurity produced in a flupirtine maleate synthesizing and / or storage process. By adopting the preparation methods, the flupirtine derivative andthe inorganic acid salts thereof can be prepared with high yields, and the reaction yield of each step can reach 55% or above.

The invention provides a flupirtine maleate capsule composition. The flupirtine maleate capsule composition contains flupirtine maleate and a solubilizer. The solubilizer is copovidone S630. The invention also provides a flupirtine maleate capsule preparation method having simple processes and quality controllability. a flupirtine maleate raw material and calcium hydrophosphate are mixed and sieved by a sieve of 60 meshes so that raw material and auxiliary material uniform mixing is guaranteed, a yield is improved and a production cost is reduced. The preparation method utilizes a dry granulation technology so that granule bulk density is large, and compared with the existing granules having small bulk density, the same weight of the granules obtained by the preparation method can be put into a small-volume capsule. The products obtained by the preparation method and the formula have qualified quality and stable drug effects and are conducive to large-scale production realization.

The invention relates to a preparation method of flupirtine maleate, which takes flupirtine as a raw material, and obtains flupirtine maleate pure products through salification and fine purification steps. By strictly controlling the use level and the reaction condition of maleic acid, the method greatly improves the yield of crude products, adopts a fine purification method integrating ultrafiltration and recrystallization, avoids product loss caused by adopting activated carbon, and greatly improves the purity and the yield of the flupirtine maleate pure products.

The invention discloses a method for preparing flupirtine maleate with crystal form A and high bulk density, specifically dissolving flupirtine in a mixed solvent containing DMSO and solvent X, and then adding the maleic acid solution into the flupirtine solution , stirred, and after the crystals are fully separated, filtered, washed, and dried to obtain the high bulk density crystal A flupirtine maleate product. The flupirtine maleate prepared by the method of the invention has high bulk density, stable crystal form content, can meet the requirements of high-quality preparation production, has strong process repeatability, simple process condition requirements, low cost, and is more suitable for industrial production.

The invention relates to a preparation method of flupirtine maleate. The method comprises the following steps of: 1, synthesizing 2-amino-3-nitro-6-chloropyridine; 2, synthesizing 2-amino-3-nitro-6-[(4-luorobenzyl)amino] pyridine; 3, synthesizing 2,3-diamino-6-[(4-luorobenzyl)amino] pyridine; 4, synthesizing 2-amino-3-nitro-ethyl carbamate-6-[(4-luorobenzyl)amino] pyridine; 5, synthesizing 2-amino-6-[(4-luorobenzyl)amino] pyridine-3-ethyl carbamate maleate; and 6, refining flupirtine maleate.

The invention discloses a method for preparing flupirtine maleate by a one-pot method. The method is characterized in that 2-amino-3-nitro-6-pyridine and 4-fluorobenzylamine serve as starting materials, and condensation, raney nickel reduction, ethyl chloroformate acylation and maleic acid salification are accomplished in a reactor without intermediate separation. The total yield of flupirtine maleate is increased from below 40% of a step-by-step method to above 70%, and the purity of a crude product is greater than 99%. According to the method, the technical flow is shortened, equipment is decreased, and the problem of high oxidation stain possibility of aminopyridine intermediates in a separation process is effectively solved. The feasibility and controllability of the one-pot method is proven by small-scale and pilot-scale studies, and the method is a handleable and environment-friendly manner to prepare flupirtine maleate, and is suitable for industrial production.

The invention belongs to the technical field of medicine and relates to impurity compounds A, B, C, D and E for flupirtine maleate analysis and a use of the impurity compounds in flupirtine maleate drug analysis.

The invention provides a synthesis method of flupirtine maleate. Recrystallization by use of methanol is carried out in the refining step of the crude product of the flupirtine maleate so that the product is white in appearance and high in purity, and the crystal form of the product is pure A crystal and same as the crystal form of the commercial products. The optimal reaction solvent, reaction time and reaction temperature are explored and found out by use of a simplified process flow, and a method for preparing the flupirtine maleate in the pure A crystal form, which is high in yield, low in cost and simple to operate, uses easily available raw materials and is applicable to the industrial production is found.

The present invention is concerned with new polymorphic forms of flupirtine maleate, processes for preparing the new polymorphic forms, pharmaceutical compositions containing them, therapeutic uses thereof and methods of treatment employing them.

The invention discloses a synthesis method for a flupirtine maleate compound. The method comprises the steps that 2-amino-3-nitro-6-chloropyridine (a first compound) is used as a starting material to react with fluorobenzylamine (a second compound) to generate 2-amino-3-nitro-6-p-fluorobenzylamine pyridine (a third compound), the third compound is processed through di-tert-butyl dicarbonate ester protection to obtain 2-amino-3-nitro-6-p-fluorobenzylamine pyridine-3-based-tert-butyl acetate (a fourth compound), the fourth compound is processed through hydrogenation reduction and then react with ethyl chloroformate, after reacting is finished, deprotection is performed to obtain flupirtine hydrochloride (a fifth compound), and the fifth compound is salified with maleic acid to obtain flupirtine maleate (the sixth compound). According to the synthesis method, the starting material is cheap and easy to obtain, byproduct generation is avoided through amino protection, therefore, the impurity content is decreased, and the product quality is improved; catalytic reduction is performed by adopting palladium chloride, the reaction condition is mild, the reaction process is easy to operate, and the method is suitable for industrial production.