56 results about "Blonanserin" patented technology

The invention relates to a novel dispersible tablet which is prepared from a certain amount of antipsychotic medicines or pharmaceutically acceptable salt or ester thereof or mixture thereof, a certain amount of selective serotonin reuptake inhibitors (SSRIs) and at least one of pharmaceutically acceptable carriers, wherein the antipsychotic medicines are aripiprazole, fluvoxamine, escitalopram, olanzapine, mirtazapine, clozapine, ziprasidone, mianserin, agomelatine, lurasidone, iloperidone, blonanserin, moclobemide, timiperone, palipeddone, trimipramine, carpipramine, lofepramine or mosapramine. The novel dispersible tablet is used for preventing, delaying or treating depression or schizophrenia of patients. Compared with common tablets or capsules, the novel dispersible tablet has the characteristics of quick and uniform dispersion, short disintegration time, quick medicine absorption, high bioavailability and good stability, and is convenient to take.

The invention discloses a blonanserin-containing medicinal composition, which consists of the following components in percentage by weight: 3.3 to 20 percent of blonanserin, 60 to 85 percent of filler, 5 to 25 percent of disintegrating agent, 2 to 6 percent of adhesive, 0.25 to 5 percent of lubricant and 0.5 to 2 percent of fluidizer. The medicinal composition has the dissolution rate of over 75 percent in a dissolution medium with the pH of 4.0 to 6.0 so as to effectively solve the problem of dissolution rate of blonanserin medicaments.

The invention discloses a method for preparing a Blonanserin intermediate. The method comprises the following two steps in sequence: (a) carrying out catalytic hydrolysis on 3-(4-fluorophenyl)-3-oxopropanenitrile by utilizing sulfuric acids so as to generate 3-(4-fluorophenyl)-3-oxopropionamide; and (b) carrying out catalytic reaction on the 3-(4-fluorophenyl)-3-oxopropionamide and cyclooctanone by utilizing anhydrous p-toluenesulfonic acids so as to generate 4-(4-fluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta[b] pyridine-2(1H)-ketone. According to the method provided by the invention, the yield coefficient of the prepared 4-(4-fluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta[b] pyridine-2 (1H)-ketone is increased from 63.5 percent to 75 percent.

The invention discloses a preparation method of a Blonanserin intermediate. In the method, 4-fluorobenzoylacetonitrile reacts with cyclooctanone to generate 4-(4-fluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta pyridine-2(1H)-ketone at a high yield in the presence of a catalyst.

The invention discloses a [2-(4-ethyl-1-piperazinyl)-4-(4-fluorophenyl)-5, 6, 7, 8, 9, 10- hexahydro-cycloocta-(b) pyridine), a composition of salts thereof for medical purposes and a preparation method thereof. The pharmaceutical composition has such a stabilizing agent as alkaline substance with a weight not less than 10 percent. The composition has good stability and can block a 5-hydroxytryptamine-2 acceptor and a dopamine-2 acceptor and be applied to the treatment of schizophrenia.

An oral controlled release pharmaceutical composition comprising Blonanserin and release controlling agent(s) and optionally pharmaceutically acceptable excipients is provided. The present invention further relates to a controlled release pharmaceutical composition comprising Blonanserin and release controlling agent(s) such that the composition releases not less than about 80% of Blonanserin within 20 hours, when dissolution is carried out in 900 ml, 0.1 N HCl, USP apparatus Type II (Paddle) at 50 rpm for 20 hrs. The controlled release pharmaceutical composition of the invention releases 50% of Blonanserin between about 4 to 14 hours, when dissolution is carried out in 900 ml, 0.1 N HCl, USP apparatus Type II (Paddle) at 50 rpm.

The invention provides a Blonanserin tablet and a preparation method thereof. The tablet contains Blonanserin, lactose and microcrystalline cellulose. Compared with present products and their preparation technologies, as the loss of active components during the direct compression process is very small, the Blonanserin tablet of the invention has a higher active component content and improved hardness, thus meeting the demands of commercial production and clinical medication.

The invention relates to a method for preparing a compound blonanserin in a formula (I), which comprises a step of transforming a compound in a formula (II) and N-ethylpiperazine under the catalysis of base into the compound blonanserin in the formula (I). The blonanserin has extremely valuable pharmacodynamic and treatment properties in the aspect of treating schizophrenia.

The invention provides a method for preparing crystal form A of medicament 2-ethylpiperazine-4-(4-fluorobenzene)-5,6,7,8,9,10-hexahydro cyclooctane pyridine for treating atypical psychosis. The method is characterized by comprising the following steps of: ensuring that the 2-ethylpiperazine-4-(4-fluorobenzene)-5,6,7,8,9,10-hexahydro cyclooctane pyridine is dissolved in acetone, isopropanol or ethyl acetate by heating, and then obtaining the crystal form A through recrystallization. The total relevant material (PHLC determination) of the crystal form A of the 2-ethylpiperazine-4-(4-fluorobenzene)-5,6,7,8,9,10-hexahydro cyclooctane pyridine prepared through the method can reach lower than 0.3 percent, and single impurity is lower than 0.1 percent.

The invention relates to a crystal of 2-(4-ethyl-1-piperazinyl)-4-(4-fluorophenyl)-5,6,7,8,9,10-hexahydro-cycloocta[b]pyridine (blonanserin, Blonanserin) and a preparation method thereof. The invention also relates to a blonanserin pharmaceutical composition containing the crystal and an application of the new crystal to the manufacture of medicines for curing schizophrenia.

The present invention discloses a method for preparing a blonanserin micron drug through solvent method. According to the method, under an ultrasonic wave condition, a certain amount of blonanserin is dissolved in an organic solvent, and the obtained solution is slowly added to a water stabilizer with a certain concentration in a dropwise manner; the affinity of the organic phase on the water is more than the affinity of the organic phase on the blonanserin, such that the blonanserin is slowly diffused into the water along with the organic phase; and the concentration of the blonanserin in the solution is increased, such that the crystal nucleus is formed and precipitated so as to obtain the blonanserin micron particles with a particle size of 1-10 [mu]m, wherein the particle size is uniform, the specific surface area is increased, and the bioavailability of the blonanserin drug is easily improved. According to the present invention, the operation is simple, other drug adjuvants are not introduced, the equipment investment is low, and the yield is high.

The invention relates to Blonanserin and a preparation method thereof. The preparation method comprises the following specific steps that firstly, the compound shown in the formula III is reacted with a chlorinating agent, namely phosphenylic oxychloride, and the compound shown in the formula II is obtained; secondly, in the presence of potassium iodide, the compound shown in the formula II is reacted with N-ethylpiperazine, and the compound shown in the formula I, namely Blonanserin, is obtained. The preparation method has the advantages shown in the description.

The invention provides a Blonanserin intermediate 4-fluorobenzoylacetonitrile synthesis method. The method comprises the following steps: (1) mixing acetonitrile, t-butanol, p-fluorobenzonitrile and organic solvent A into mixed solution; (2) adding potassium tert-butoxide and the organic solvent A to a reactor, then adding the mixed solution obtained in the step (1), and stirring for reaction to obtain 3-amino-3-p-fluorophenyl acrylonitrile; (3) hydrolyzing the 3-amino-3-p-fluorophenyl acrylonitrile with hydrochloric acid solution to obtain the 4-fluorobenzoylacetonitrile, wherein the organic solvent A is isopropyl ether and/or tetrahydrofuran. According to the method, the potassium tert-butoxide is used as a condensing agent, which greatly improves the safety of the process. The potassium t-butoxide is mild in nature, has hygroscopicity but is nonflammable, and can be used in wider temperature and humidity ranges, and is more conducive to industrial production. And meanwhile, the method is stable in yield and high in obtained product purity.

The invention provides a crystal form B of medicament 2-ethylpiperazine-4-(4-fluorobenzene)-5,6,7,8,9,10-hexahydro cyclooctane pyridine, which is characterized in that powder diffraction occurs in the positions of approximately 7.74+/-0.2, 15.6+/-0.2, 19.1+/-0.2 and 31.64+/-0.2 of a reflecting angle 2 theta through X-ray. The invention also provides a preparing method of the crystal form B, which is characterized by comprising the following steps of: ensuring that the medicament 2-ethylpiperazine-4-(4-fluorobenzene)-5,6,7,8,9,10-hexahydro cyclooctane pyridine is dissolved in ethanol by heating, and then obtaining the crystal form B through recrystallization.

The invention provides a preparation method of a blonanserin intermediate. The preparation method comprises the following steps: reacting 4-(4-fluorophenyl)-3-5,6,7,8,9,10-hexahydro cyclooctane pyridine-2(1H)-ketone with a chloro agent under a certain condition, pouring a reactant after the reaction into ice water, adjusting the pH value by using ammonia water, and performing stirring, filtration or centrifugation to obtain a crude product of 2-chloro-4-(4-fluorophenyl)-5,6,7,8,9,10-hexahydro cyclooctane [b] pyridine (compound I); and dissolving, decoloring and recrystallizing the compound I by using hot ethanol to obtain a refined product of the compound I. Compared with the prior art, the method avoids multiple times of extraction during refining, reduces solvent loss in a middle process, is simple and easy to operate, improves the purity and yield of the product, and is suitable for process scaling and industrial production.

The invention discloses a blonanserin dropping pill which comprises a mixture of blonanserin and a water-soluble substrate with a weight ratio of 1:2-1:50, wherein each dropping pill contains 0.1 mg-20 mg of blonanserin, and the weight of the dropping pill is 5 mg-150 mg; the water-soluble substrate is polyethylene glycol, poloxamer, polyoxyethylene monostearate (S-40), polyoxyethylene dehydratedsorbitol fatty acid ester, or a mixture of two or more than two compounds. The dropping pill related to by the invention solves the problem of dissolution rate of a hard-soluble drug, and has an in-vitro dissolution rate which fits well with that of commercial preparations in Japan; the dropping pill is easy to swallow, is convenient for dose fractionation, is reasonable for clinical application,and improves the compliance of patients; meanwhile, the preparation method has simple process and no dust, facilitates labor protection, has low production cost, and has good industrial practicality.

A bonanserin pharmaceutical composition with improved oral absorptivity is characterized by comprising the components by weight: a first part: 4 g of bonanserin and 25 g of alpha cyclodextrin; and a second part: 20 g of cospovidone, 50 g of microcrystalline cellulose, 60 g of lactose, 20 g of pregelatinized starch, 1 g of powdered steatile, 1 g of magnesium stearate and proper amount of a povidone anhydrous-alcohol solution with a ratio of 5%.

The invention relates to a sustained release preparation of blonanserin and a preparation method of the sustained release preparation of the blonanserin. A blonanserin tablet is prepared by mixing slow release particles prepared by slow release components and common components according to the prescription proportion; the mass ratio of the slow release components to the common components ranges from 75:25 to 80:20; the slow release components of the blonanserin tablet mainly comprise, by mass, 8.00%-12.0% of the blonanserin, 15.0%-20.0% of hydroxypropyl methylcellulose, 15.0%-25.0% of sodium carboxymethylcellulose and the like; the common components mainly comprise, by mass, 8.00%-12.0% of the blonanserin, 30.0%-50.0% of lactose and the like. By means of the tablet prepared from the sustained release preparation, the number of medicine taking can be decreased, the stable blood concentration can be maintained, and side effects can be reduced.

The invention relates to a blonanserin tablet composition and a preparation method thereof. Particularly, the blonanserin tablet composition comprises, by weight, 4 parts of blonanserin, 60-200 parts of diluting agents, 5-20 parts of disintegrating agents, 1-5 parts of adhesives, 0.1-2 parts of flow aids and 0.1-1 part of lubricants. The blonanserin tablet composition has excellent properties such as tablet dissolution performance stated in the specification.

The invention discloses a preparation process of blonanserin tablets. The tablet contains blonanserin, hydroxypropyl cellulose (low substitution), lactose, hydroxypropyl cellulose, microcrystalline cellulose, magnesium stearate, silicon dioxide, and the preparation of the blonanserin tablet The process includes the following steps: 1) blonanserin raw material micropowder is premixed with silicon dioxide; 2) the premix is ​​mixed with hydroxypropyl cellulose (low substitution) and lactose; 3) hydroxypropyl cellulose aqueous solution Make soft materials for binders, granulate, dry, and granulate; 4) Add silicon dioxide, microcrystalline cellulose and magnesium stearate, mix well, and compress into tablets. The blonanserin tablet prepared by the invention has the advantages of simple process operation, easy industrialization, good stability, good dissolution rate and the like.

The invention discloses a separation method of a blonanserin intermediate IV and other intermediates by high performance liquid chromatography. The separation method selects octylsilane chemically bonded and silica as a chromatographic column of a filling agent (250mm multiplied by 4.6mm, 5mum), adopts a buffer solution and an organic modifier with different proportions as flowing phase, and the blonanserin intermediate IV and other intermediates which has the similar polarity with the blonanserin intermediate IV can be separated under the normal temperature by gradient elution, so that the accurate control of the quality of blonanserin can be realized.