30 results about "FLUPIRTINE MALEATE" patented technology

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 provides a novel preparation method of flupirtine maleate; the method mainly comprises steps of substitution reaction, reduction reaction, acylation reaction, salt forming reaction and refining. It is proved by small and medium scale tests that a novel process route and reaction process are achievable, technical parameters are stable, reproducibility is good and product quality is stable.

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 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.

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 discloses a flupirtine maleate sustained release tablet. The flupirtine maleate sustained release tablet is prepared from, by weight, 0.2 parts of flupirtine maleate, 70 to 190 parts of a sustained-release matrix material, and 10 to 20 parts of a lubricant. A preparation method of the flupirtine maleate sustained release tablet comprises following steps: material preparation, total blending, granulating, total blending, performing, and aluminum plastic packaging. The flupirtine maleate sustained release tablet is capable of relieving pain, relaxing muscle, and protecting nerve. According to the preparation method, novel sustained release preparations are adopted. According to the sustained release preparations, medicine releasing rate of medicines from the preparations is slowed, and absorption rate of the medicines in body is reduced, so that more stable treatment effects are achieved. Compared with oral liquid, the flupirtine maleate sustained release tablet is high in drug stability, and is convenient for packaging, transportation, and storing; and the preparation method is simple and convenient, and is suitable for industrial production.

The invention discloses a method for preparing a flupirtine maleate capsule. The method comprises the following steps of: (A) weighting calcium hydrophosphate, crosslinking polyvinylpyrrolidone, lauryl sodium sulfate, magnesium stearate and superfine silica powder according to a formula and sieving through a sieve of 100 meshes; (B) performing superfine grinding on a flupirtine maleate raw material according to the formula until the particle size is 10 to 25 mu m, and uniformly mixing the treated flupirtine maleate raw material with the auxiliary materials in the step (A) according to an equivalent adding method; (C) granulating 50 percent of ethanol solution with the volume of 80 to 100 ml serving as an adhesive preparation soft material after sieving through a sieve of 20 meshes; (D) drying the wet particles prepared in the step (C) at the temperature of 55 to 65 DEG C for 2 to 4 hours, and arranging the particles after sieving through the sieve of 20 meshes; and (E) uniformly mixing the magnesium stearate and the superfine silica powder according to the formula, and filling to obtain the flupirtine maleate capsule. The method is ingenious in concept and simple in flow; the flupirtine maleate capsule is high in blood concentration, small in medicine amount and high in bioavailability; and the pain treating effect is obvious.

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 microcrystallinecellulose. 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 provides a high efficient synthesis method of flupirtine maleate, and relates to the technical field of drug preparation. According to the synthesis method, flupirtine maleate is taken as the raw material; flupirtine maleate is obtained after steps of condensation reactions, reduction reactions (in the presence of a reducing agent), ethyl chloroformate acylation reaction, and maleic acid salt forming reactions; during the synthesis process, the yield of product can reach 93%, the product purity is high, the generation of byproducts is avoided, moreover, the technology route is simple, the reaction conditions are easy to control, better reaction conditions are provided for industrial production, the equipment requirements are largely reduced, and the synthesis method can be better applied to the industrial production.

New polymorphic forms of flupirtine maleate are described.

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 the technical field of medicinal chemistry production, in particular to a rivastigmine hydrogen tartrate preparation method and an application thereof. To be specific, rivastigmine hydrogen tartrate is prepared from 2-amino-3-nitro-6-chloropyridine and p-fluorobenzylamine used as raw materials, the reaction condition is mild, the production cost is low, and the method is simple to operate, adopts a preparation process with high controllability, has the low requirement for production equipment and is suitable for industrial production.

The invention relates to composition containing flupirtine maleate and a preparation method of the composition. The composition is prepared from raw materials in percentage by weight as follows: 25%-35% of flupirtine maleate, 50%-70% of a diluent, 1.5%-4.5% of a disintegrating agent, 1.5%-4.5% of a flow aid, 0.5%-1.5% of a cosolvent and 0.5%-1.5% of a lubricant. The problem that the raw materials are unstable under illumination and high-humidity conditions is solved. The composition is stable in quality, the content of flupirtine maleate, related impurities and dissolution rate have no remarkable change, the in-vitro dissolution behavior is consistent with that of flupirtine maleate capsules from the German AWD company, the risk of clinical effect difference is reduced, the process is simple, and realization of industrial production is facilitated.