51 results about "Brexpiprazole" patented technology

The invention belongs to the field of pharmaceutical preparations, and relates to a brexpiprazole long-acting microsphere and a preparation method thereof, and the preparation 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 through a microfluidic technology to obtain an oil-in-water emulsion; and (3) under a stirring condition, carrying out curing, washing and freeze drying on the oil-in-water type emulsion to obtain the brexpiprazole long-acting microspheres. By adjusting the volatilization stirring time when the O / W primary emulsion is formed, the final in-vitro release rate of the microspheres is adjusted, and the microspheres which are free of burst release and hysteresis period and are slowly released can be screened out. The brexpiprazole long-acting microsphere provided by the invention is simple in preparation process, easy to industrially amplify, high in encapsulation efficiency, large in drug loading capacity, uniform in microsphere particle size distribution, round in shape, good in flowability and good in needle passing property, is easier to inject, has an obvious slow release effect, and can be used for reducing the fluctuation of blood concentration and effectively improving the compliance of psychiatric patients.

The invention provides a brexpiprazole oral soluble film and a preparation method thereof, the brexpiprazole oral soluble film comprises brexpiprazole, a film forming material and a plasticizer, the film forming material is a combination of polyvinyl alcohol and polyethylene glycol, and the plasticizer is glycerol. The brexpiprazole oral soluble film is not easy to curl in the preparation process, and the finished product is also not easy to curl; and after being placed under a high-temperature condition, oxidation impurities and total impurity growth are effectively inhibited, and the stability is excellent.

Provided are methods and compositions for enhancing radiotherapy in various cancers by administering dopamine receptor (DRD2)‐binding phenylpiperazine derivatives such as brexpiprazole, cariprazine, pipamperone, and perospirone. In vitro studies show that combining these agents with ionizing radiation (e.g., 5 Gy) significantly reduces cancer cell survival, suppresses metastatic and stemness markers (e.g., CD44, MMP‑2, Snail, Nanog), and promotes apoptosis. Fractionated or single‐fraction radiation regimens can be paired with DRD2 antagonists to lower treatment‐resistant phenotypes, decrease the likelihood of recurrence, and potentially reduce necessary radiation dosages. The approach applies to breast, prostate, lung, pancreatic, and brain cancers, among others. Depending on tumor characteristics, additional chemotherapeutic or immunotherapeutic agents may further improve outcomes.

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 relates to the technical field of crystal form drug molecules, and particularly provides a novel brexpiprazole-benzoic acid-dihydrate salt form as well as a preparation method and application thereof. The brexpiprazole-benzoic acid-dihydrate disclosed by the invention is radiated by Cu-K alpha, and an X-ray diffraction pattern expressed by 2 theta has characteristic peaks at least at the positions of 8.2 + / -0.2 degrees, 8.4 + / -0.2 degrees, 8.9 + / -0.2 degrees, 13.7 + / -0.2 degrees, 14.8 + / -0.2 degrees and 16.4 + / -0.2 degrees. The purity of the prepared brexpiprazole-benzoic acid-crystal form is higher than 99.85%, and the brexpiprazole-benzoic acid-crystal form is high in solubility and good in stability. The method is simple in preparation process and has a relatively good industrial application prospect.

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 relates to the technical field of crystal form medicine molecules, and particularly discloses a brexpiprazole-p-toluenesulfonic acid crystal form as well as a preparation method and application thereof. The brexpiprazole-p-toluenesulfonic acid-crystal form disclosed by the invention is radiated by Cu-K alpha, and an X-ray diffraction pattern represented by 2 theta has characteristic peaks at least at 3.2 + / -0.2 degrees, 6.3 + / -0.2 degrees, 9.4 + / -0.2 degrees, 18.6 + / -0.2 degrees and 28.0 + / -0.2 degrees. The purity of the prepared brexpiprazole-p-toluenesulfonic acid-crystal form is higher than 99.9%, and the brexpiprazole-p-toluenesulfonic acid-crystal form has high solubility and good stability. The method is simple in preparation process and has a relatively good industrial application prospect.

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 belongs to the technical field of medicine synthesis, and particularly relates to an efficient synthesis method of brexpiprazole. The invention provides a novel preparation method of bupreprazole, which comprises the following steps: by taking 1-(benzo [b] thiophene-4-yl)-4-(4-bromobutyl) piperazine as a starting material, carrying out substitution reaction on the 1-(benzo [b] thiophene-4-yl)-4-(4-bromobutyl) piperazine and 7-hydroxy-2H-benzopyran-2-ketone to prepare an intermediate 7-(4-(4-(benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy)-2H-benzopyran-2-ketone; according to the present invention, with the process, the use of the noble metal catalyst and the generation of the related dimer and the heterotopic substitution impurity can be effectively avoided, and the product obtained through the process has characteristics of high yield and high purity, and is suitable for industrial production.

The invention discloses a suspension liquid. The suspension comprises brexpiprazole or a salt thereof, a suspending aid and a surfactant, wherein the surfactant is selected from the group consisting of Tween 20; and at least one of span, poloxamer, lauryl sodium sulfate and sodium deoxycholate. By adopting the surfactant, the suspension can be prevented from generating precipitates after being placed for a long time, and the particle size of the brexpiprazole or the salt of the brexpiprazole can be ensured to be within 10 microns after the brexpiprazole or the salt of the brexpiprazole is placed for one month; the suspension can be rapidly released after being injected into an animal body, achieves an effective treatment level, is continuously and slowly released to maintain the effective treatment level for 30 days or more, has good pharmacokinetic properties, and can solve the problem of patient compliance to the greatest extent. The suspension provided by the invention has the advantages of lasting drug effect, accurate particle size control, high stability, good pharmacokinetic property and the like.

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 relates to a long-acting sustained-release pharmaceutical preparation and a preparation method thereof, the long-acting sustained-release pharmaceutical preparation is a microsphere preparation, the microsphere comprises brexpiprazole and PLGA, the content of the brexpiprazole is 45%-75% of the total weight of the microsphere, and the content of the PLGA is 55%-25% of the total weight of the microsphere; the viscosity of the PLGA is 0.15 to 0.25 dl / g, and the molecular weight of the PLGA is 8000 to 32000. The microsphere is high in drug loading capacity, the administration dosage can be effectively reduced, subcutaneous or muscle administration pain of a patient is reduced, the prepared sustained-release microsphere has no burst release phenomenon, and the change of the blood concentration in an effective release period in a rat is stable.

The invention discloses an oral membrane for treating schizophrenia and a preparation method and application thereof, and belongs to the technical field of pharmaceutical preparations. The invention aims to solve the technical problems of low dissolution rate and disintegration speed, difficulty in swallowing, high medicine hiding probability of patients, easiness in variation of medicines, complex composition and preparation process and certain side effects. The technical scheme is as follows: 1) the oral film agent comprises an active drug component lonanserin, a film-forming composition copovidone, polyoxyethylene and sodium hydrogen sulfite and a plasticizer polyethylene glycol, and the oral film agent can be delivered in an amorphous solid dispersion form, so that the oral film agent can maintain a supersaturated state in an intestinal environment, inhibit devitrification and improve the bioavailability of the oral film agent; therefore, more consistent and stable system exposure is obtained; 2) the sodium hydrogen sulfite serving as an antioxidant can reduce impurities in related substances of the blonanserin film agent;

The present application relates to novel compounds that are prodrugs of brexpiprazole. The novel compounds of the present invention, upon administration to a subject, undergo chemical conversion by one or more metabolic processes to release the active agent in vivo. Brexpiprazole sold by Rexulti (registered trademark) is an atypical antipsychotic drug, is suitable for being used as an adjuvant therapy of an antidepressant drug, and is used for treating major depressive disorder (MDD) of adults and schizophrenia of adults and children patients over 13 years old. # imgabs0 #

The invention belongs to the technical field of medicine synthesis, and particularly relates to a preparation method of brexpiprazole. 4-halogenated benzo [b] thiophene is used as a starting material and reacts with piperazine-2-ketone to obtain a product, the product is reduced to obtain 1-(benzo [b] thiophene-4-yl) piperazine hydrochloride, then the 1-(benzo [b] thiophene-4-yl) piperazine hydrochloride reacts with 7-(4-chlorobutoxy)-1H-quinoline-2-ketone to obtain brexpiprazole, the reaction conditions are milder, only sodium borohydride is needed to participate in the lactam reduction step in the process, the yield is high, and the yield is high. No other activators are needed, and the operation is simpler and more convenient.

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 the technical field of crystal form medicine molecules, and particularly discloses a brexpiprazole-maleic acid-methanol crystal form as well as a preparation method and application thereof. According to the brexpiprazole-maleic acid-methanol crystal form disclosed by the invention, Cu-K alpha radiation is used, and an X-ray diffraction pattern represented by 2 theta has characteristic peaks at least at 16.3 + / -0.2 degrees, 21.9 + / -0.2 degrees, 22.2 + / -0.2 degrees, 24.1 + / -0.2 degrees and 27.3 + / -0.2 degrees. The purity of the prepared brexpiprazole-maleic acid-methanol crystal form is higher than 99.9%, and the brexpiprazole-maleic acid-methanol crystal form is high in solubility and good in stability. The method is simple in preparation process and has a relatively good industrial application prospect.

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 belongs to the technical field of pharmaceutical preparations, and particularly relates to a brexpiprazole oral solid preparation as well as a preparation method and application thereof. The preparation raw materials comprise 1 to 20 parts by weight of brexpiprazole, 0.5 to 20 parts by weight of a transition metal salt, 50 to 900 parts by weight of an ethanol aqueous solution, 0.5 to 1.5 parts by weight of an acidic pH regulator and 150 to 550 parts by weight of other auxiliary material components. The dissolution results of the oral solid preparation in different dissolution media are highly similar to those of an original product, and the oral solid preparation has bioequivalence with the original product in vivo, so that the original product can be replaced.

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 present invention relates to a prophylactic and / or therapeutic agent for behavioral and psychological symptoms associated with neurodegenerative disease or impulsive symptoms associated with mental disease, which contains 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1H-quinolin-2-one or a salt thereof as an active ingredient.

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 provides a brexpiprazole dropping pill and a preparation method thereof, and relates to the technical field of medicine, the brexpiprazole dropping pill comprises brexpiprazole and a dropping pill matrix, the weight part ratio of the brexpiprazole to the dropping pill matrix is 10: 138-356; the dripping pill matrix comprises polyethylene glycol, 70% acetic acid and poloxamer, and the 70% acetic acid is used as a solubilizer to promote dissolution of brexpiprazole and poloxamer under a stirring condition; the poloxamer is used as a penetration enhancer, so that the transdermal effect is remarkably improved; the polyethylene glycol, the 70% acetic acid and the poloxamer are used as dropping pill matrixes to be matched with the brexpiprazole to obtain the spherical dropping pill with sufficient hardness and stability and good dissolution rate. The technical problem that in the prior art, a brexpiprazole tablet or orally disintegrating tablet cannot be rapidly dissolved, so that the absorption effect is slow is solved.

The invention belongs to the technical field of pharmaceutical analysis, and provides a detection method of a brexpiprazole oral suspension, which adopts reverse high performance liquid chromatography for detection, can realize effective separation of brexpiprazole and impurities thereof, can also realize effective separation of brexpiprazole and impurities thereof and preservatives, is simple and convenient to operate, has good specificity and high sensitivity, and can be applied to detection of oral suspension of brexpiprazole. The control requirement of the limit of 0.5% is met, and the method can be used for quality control of the brexpiprazole oral suspension.

Sustained-release microspheres containing brexpiprazole as an active pharmaceutical ingredient, according to the present invention, additionally contain a specific drug loading enhancer as a part of microsphere elements, and thus, while containing a large amount of the active pharmaceutical ingredient, can maintain a low initial release amount on the first day and achieve long-term sustained-release.

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.