20 results about "Brexpiprazole" patented technology

The invention provides a preparation method of blenocateb, which comprises the following steps: condensing a new intermediate compound 4 and an intermediate compound 5 by using a condensing agent to obtain an intermediate compound 6, and then completing a reaction of converting an amide group into a cyano group by using a dehydration reagent to obtain an intermediate compound 7. And finally, removing Boc from the intermediate compound 7, dissociating the intermediate compound 7, and then crystallizing to obtain the target product Brensocateon hydrate compound 8 in a hydrate form. The preparation process has the advantages of simple route and low cost, is beneficial to synthesis of high-purity products, and is suitable for industrial production.

The invention discloses an efficient synthesis method of brexpiprazole, which comprises the following steps: taking 4-bromo-benzothiophene and N-Boc-piperazine as initial raw materials, under the protection of nitrogen, carrying out reaction by using a supported catalyst to prepare 4-Boc piperazine benzothiophene, and then carrying out acidolysis to obtain 4-piperazine benzothiophene hydrochloride; the method comprises the following steps: reacting 3, 4-dihydro-7-hydroxy-2 (1H) quinolinone with 1-bromo-4-chloro-butane to generate 3, 4-dihydro-7-(4-chlorobutoxy)-2 (1H)-quinolinone, and then converting the 3, 4-dihydro-7-(4-chlorobutoxy)-2 (1H)-quinolinone into 7-(4-chlorobutoxy)-2 (1H)-quinolinone; then condensing with 4-piperazine benzothiophene hydrochloride to obtain a crude product of brexpiprazole; and finally, crystallizing and purifying for multiple times to obtain high-purity brexpiprazole. According to the preparation method disclosed by the invention, 4-bromo-benzothiophene and N-Boc-piperazine are taken as starting raw materials, and high-purity brexpiprazole is prepared by optimizing selection of a catalyst and conditions of each step and through an excellent purification process.

The invention belongs to the technical field of medicine synthesis, and particularly relates to a preparation method of brexpiprazole. The preparation method comprises the following steps: by taking a compound 4-amino benzo [b] thiophene and chloroacetaldehyde as starting materials, carrying out substitution reaction to prepare an intermediate 2, 2 '-(benzo [b] thiophene-4-yl azane diyl) diacetaldehyde, and then carrying out reductive amination reaction on the intermediate 2, 2'-(benzo [b] thiophene-4-yl azane diyl) diacetaldehyde and 7-(4-amino butoxy) quinoline-2 (1H)-ketone to construct a piperazine ring, thereby preparing the target product bupremizole I, the product obtained by the process has high yield and purity, and is suitable for industrial production.

The invention provides a long-acting brexpiprazole in-situ gel injection and a preparation method thereof. The long-acting brexpiprazole in-situ gel injection is an injectable sustained-release preparation prepared by taking a polylactic acid-glycolic acid copolymer (PLGA) and poloxamer as gel matrixes, dissolving brexpiprazole in an amphiphilic solvent and adding an additive. The long-acting brexpiprazole in-situ gel injection prepared by the invention has good mechanical properties, and the drug release time can be maintained for 1 month. The preparation is simple in preparation process, low in equipment requirement and suitable for industrial production.

The invention belongs to the technical field of medicine synthesis, and particularly relates to a synthesis method of brexpiprazole. The preparation method comprises the following steps: taking compounds 4-amino benzo [b] thiophene and chloroacetaldehyde as starting materials, firstly carrying out reductive amination disubstitution reaction to prepare an intermediate N, N-bis (2-chloroethyl) benzo [b] thiophene-4-amine, then carrying out substitution reaction on the intermediate N, N-bis (2-chloroethyl) benzo [b] thiophene-4-amine and 7-(4-amino butoxy) quinoline-2 (1H)-ketone to construct a piperazine ring to prepare the target product brexpiprazole. The product obtained by the process has high yield and purity, and is suitable for industrial production.

The invention relates to a brexpiprazole oral soluble film and a preparation method thereof, the film agent does not use a thickening agent, and comprises 2%-10% of brexpiprazole, 60%-90% of a polymer film-forming material and 5%-30% of a plasticizer; the polymer film-forming material is a composition of hydroxypropyl methylcellulose and hydroxy propyl cellulose. The prepared brexpiprazole oral soluble film is flat in appearance, free of curl, uniform and smooth, free of visible particles, capable of being disintegrated rapidly and good in tensile strength and stability.

The invention belongs to the technical field of medicine synthesis, and particularly relates to a novel method for synthesizing brexpiprazole. 4-piperazinyl benzothiophene and 4-bromobutyraldehyde are used as starting materials, a brominated intermediate compound with high activity is prepared through a reductive amination reaction, the brominated intermediate compound and 7-hydroxy-2H-benzopyran-2-ketone are subjected to a substitution reaction to prepare the target product burepidazole, and the product obtained through the process has high yield and purity and is suitable for industrial production.

The invention relates to a brexpiprazole orally disintegrating tablet and a preparation method thereof. The invention provides the brexpiprazole-containing orally disintegrating tablet. The tablet has the advantages of excellent disintegrating property, good taste, no hard core and excellent storage stability; specifically, the orally disintegrating tablet provided by the invention comprises the following raw materials in addition to mannitol, low-substituted hydroxypropyl cellulose, hydroxypropyl methyl cellulose, microcrystalline cellulose, corn starch, sucralose, sodium stearyl fumarate and magnesium stearate, good friability (less than or equal to 0.3%) of the tablet under low hardness is ensured; moreover, the use amount of L-HPC is reduced (less than 5%), and L-HPC is supplemented into mannitol, so that the taste advantage of mannitol is more prominent on the basis of ensuring excellent disintegration; in addition, a small amount of corn starch is added, so that the problem of low content of the raw materials in the mixing process is solved. In addition, the invention further provides a preparation method which is simple in preparation process and high in production efficiency, and the problems that the brexpiprazole is low in proportion, poor in content uniformity and unqualified in dissolution curve are effectively solved.

The application belongs to the technical field of chemical medicines, and particularly relates to 4,5-dichloro-3-hydroxy-6-({4-[(2-oxo-1H-quinolin-7-yl)oxy]butyl}oxy)benzene-1,2-dicarbonitrile, a preparation method and application thereof. H The 4,5-dichloro-3-hydroxy-6-({4-[(2-oxo-1H-quinolin-7-yl)oxy]butyl}oxy)benzene-1,2-dicarbonitrile has a structure shown in formula I: formula I. The impurity in brexpiprazole contains the structure shown in formula I, the content of the impurity in brexpiprazole can be effectively detected by using the novel compound provided by the application as a standard sample, and the drug quality stability and drug safety can be effectively ensured.

The invention provides a brexpiprazole tablet pharmaceutical composition and a preparation method thereof, and belongs to the technical field of medicines. The invention provides a brexpiprazole tablet pharmaceutical composition. The brexpiprazole tablet pharmaceutical composition comprises a tablet core and a coating layer, by controlling the content of the disintegrating agent, the concentration of the adhesive and the adding process, on one hand, the flowability of particles is improved, the particles can be smoothly granulated and tableted, and the quality of the obtained tablets is stable and controllable; on the other hand, the high-brexpiprazole-content tablet with better consistency in solubility compared with a reference is obtained.

The invention relates to the technical field of pharmaceutical preparations, and particularly provides a brexpiprazole sustained-release injection based on in-situ phase change gel as well as a preparation method and application of the brexpiprazole sustained-release injection. The brexpiprazole sustained-release injection is prepared from brexpiprazole, N-methyl pyrrolidone and a polylactic acid-glycolic acid copolymer according to the weight ratio of (0.1 to 0.2): (3 to 3.8): 1, wherein the intrinsic viscosity of the polylactic acid-glycolic acid copolymer is (0.1 to 0.3) dL / g. The preparation process of the brexpiprazole sustained-release injection is relatively simple and convenient, and the brexpiprazole sustained-release injection is a homogeneous solution before injection, so that the injection tolerance of a patient is effectively improved; the inherent problems that brexpiprazole is extremely high in hydrophobicity, rapid in-vivo elimination and free of remarkable central activity of metabolites are solved, stable slow release of blood concentration for several weeks is achieved, the drug release kinetics is highly predictable and good in reproducibility, and the purposes of reducing the drug administration frequency and improving the patient compliance are achieved.

The invention belongs to the technical field of pharmaceutical preparations, and particularly discloses an anti-schizophrenia lyotropic liquid crystal long-acting injection and a preparation method and application thereof, and the anti-schizophrenia lyotropic liquid crystal long-acting injection is composed of an anti-schizophrenia drug, an amphiphilic compound and an organic solvent; the anti-schizophrenia medicine is selected from any one of brexpiprazole, cariprazine and aripiprazole; the amphiphilic compound is selected from any one or more of soybean phosphatidylcholine, egg yolk phosphatidylcholine, glyceryl monooleate, glyceryl monopalmitate, glyceryl dioleate, glyceryl trioleate, vitamin E acetate and phytantriol; the organic solvent is selected from one or more of ethanol, N-methyl pyrrolidone, dimethyl sulfoxide and 1, 2-propylene glycol. The anti-schizophrenia lyotropic liquid crystal in-situ gel long-acting injection forms a stable semi-solid drug reservoir through solvent exchange after administration so as to play a therapeutic effect in long-acting treatment of positive schizophrenia and negative schizophrenia and prevention of schizophrenia relapse.

The invention belongs to the technical field of medicines, and particularly relates to a pharmaceutical composition containing brexpiprazole and a pharmaceutical preparation, a preparation method and application thereof. The pharmaceutical composition disclosed by the invention mainly comprises brexpiprazole (or pharmaceutically acceptable salt or solvate thereof) and a lipid material. The brexpiprazole in the composition exists in the form of lipid particles, is uniform in particle size distribution and has excellent stability; besides, the brexpiprazole exists in the form of insoluble particles, and a sustained-release drug reservoir can be formed in vivo after administration, so that the treatment effect, medication compliance and medication safety of a patient are improved.

The present invention relates to a tablet composition comprises brexpiprazole or a salt thereof and at least one binder and at least one glidant, wherein glidant is colloidal silicon dioxide. Further, the present invention also relates to a simple, rapid, cost effective, time-saving and industrially convenient process.

The application belongs to the field of pharmaceutical preparations and relates to a brexpiprazole long-acting microsphere and a preparation method thereof, which comprises the following steps: (1) dissolving brexpiprazole and a degradable polymer in an organic solvent to obtain a drug-containing polymer solution as an oil phase; (2) mixing the drug-containing polymer solution and a polyvinyl alcohol solution by microfluidic technology to obtain an oil-in-water emulsion; and (3) solidifying, washing and freeze-drying the oil-in-water emulsion under stirring to obtain the brexpiprazole long-acting microsphere. The application adjusts the volatile stirring time when the O / W primary emulsion is formed, thereby adjusting the in-vitro release rate of the final microsphere, and the microsphere without burst release, no lag period and slow release can be screened. The application has the advantages that the preparation process of the brexpiprazole long-acting microsphere is simple, easy to be industrialized, has high encapsulation efficiency, large drug loading, uniform microsphere particle size distribution, good flowability, good needle passability, is easier to be injected, has obvious slow-release effect, can be used for reducing the fluctuation of blood drug concentration and effectively improving the compliance of patients with mental illness.

The invention relates to the field of medicines, in particular to a brexpiprazole sustained-release microsphere and a preparation method thereof. The brexpiprazole sustained-release microsphere is prepared by adopting an emulsion solvent evaporation method, and the pH value of an external water phase is adjusted to be alkaline. The brexpiprazole sustained-release microsphere disclosed by the invention can realize high drug loading capacity and good balling property.

The invention relates to the technical field of drug analysis and detection, and particularly discloses a method for detecting genotoxic impurities in brexpiprazole. According to the method, high performance liquid chromatography is adopted for detection, and chromatographic conditions are as follows: a chromatographic column is a pentafluorophenyl chromatographic column; the detection wavelength is 258-262 nm, a mobile phase A is a phosphate buffer solution with the pH value of 2.0-2.4, a mobile phase B is methanol, and gradient elution is carried out. According to the method, effective separation of brexpiprazole from DDQ and DHQ is achieved, effective control over the quality of the brexpiprazole raw material is facilitated, therefore, the quality of brexpiprazole and the quality of a preparation of the brexpiprazole are guaranteed, monitoring of the synthesis process of the brexpiprazole is facilitated, and the method has very important significance on improvement of medication safety and has high practical value.

The invention provides a preparation method of brexpiprazole, which comprises the following steps: by taking 7-hydroxy-2 (1H)-quinolinone as a starting material, carrying out nucleophilic substitution type etherification reaction on the 7-hydroxy-2 (1H)-quinolinone and 4-chloro-1-butanol in an alkaline medium to generate a 7-(4-hydroxybutoxy)-2 (1H)-quinolinone intermediate; then, a ruthenium catalyst is used as a catalytic system, the intermediate and 4-(1-piperazinyl) benzothiophene hydrochloride are subjected to an N-alkylation reaction, and synthesis of the target compound brexpiprazole is completed. The synthesis route of the brexpiprazole has the advantages of being short in technological process, high in atom utilization rate, high in yield, low in cost, environmentally friendly and the like.

The application belongs to the technical field of medicine synthesis, and particularly relates to a preparation method of brexpiprazole. The application takes compound 4-amino benz[b] thiophene and 2-chloroethyl methyl sulfonate as starting materials, first carries out a double-substitution reaction to obtain an intermediate N,N-bis(2-chloroethyl) benz[b] thiophene-4-amine, then carries out a substitution reaction on the intermediate and 7-(4-aminobutoxy) quinoline-2(1H)-ketone to construct a piperazine ring to obtain the target product brexpiprazole. The product obtained through the process has high yield and purity, and is suitable for industrial production.

The present invention belongs to the field of pharmaceutical preparations, and relates to a long-acting brexpiprazole microsphere and a preparation method therefor. The method comprises the following steps: (1) dissolving brexpiprazole and a degradable polymer in an organic solvent to obtain a drug-containing polymer solution as an oil phase; (2) mixing the drug-containing polymer solution with a polyvinyl alcohol solution by means of a microfluidic technique to obtain an oil-in-water emulsion; and (3) under stirring, solidifying, washing and freeze-drying the oil-in-water emulsion to obtain the long-acting brexpiprazole microsphere. In the present invention, the in-vitro release rate of the final microsphere is adjusted by means of adjusting the volatilization and stirring time during the formation of the O / W primary emulsion, thereby screening microspheres with no burst release or lag period, and exhibiting sustained release. The long-acting brexpiprazole microsphere provided in the present invention has a simple preparation process, is readily scalable for industrial production, exhibits high encapsulation efficiency, high drug loading capacity, uniform microsphere particle size distribution, spherical morphology, good flowability, good syringeability and injectability, has a significant sustained-release effect, and can be used to reduce fluctuations in blood drug level and effectively improve the compliance of patients with psychiatric diseases.