- Large-steric-hindrance N-heterocyclic carbene palladium complex, preparation method and application thereof, and synthesis method of sonidegib based on large-steric-hindrance N-heterocyclic carbene palladium complex
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The invention belongs to the technical field of organic synthesis and chemical catalysis, and discloses a large-steric-hindrance N-heterocyclic carbene palladium complex, a preparation method thereof,an application of the complex in efficient catalysis of a C-N coupling reaction under a room-temperature air condition, and a synthesis method of sonidegib based on the complex. According to the large-steric-hindrance N-heterocyclic carbene palladium complex, diphenyl imidazole serves as a main ligand framework, functionalized allyl serves as an auxiliary ligand, the functionalized allyl is introduced beside a metal center of a catalyst to serve as an auxiliary ligand, the catalytic activity and stability are remarkably improved, the large-steric-hindrance N-heterocyclic carbene palladium complex can be applied to efficient catalysis of a CN coupling reaction, particularly, the CN coupling reaction can be efficiently catalyzed under the room temperature condition, and the yield can reachup to 99%. The invention also provides a method for synthesizing sonidegib by taking aryl/aliphatic amine and aryl chloride as reactants and a three-step method at room temperature under the catalysisof a palladium catalytic system, the synthetic method has few steps, and the total yield can reach 74.5%.
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Paragraph 0195; 0208-0210
(2021/01/24)
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- Preparation method of brexpiprazole intermediate 7-hydroxy-1H-quinoline-2-ketone
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The invention belongs to the field of chemical engineering, and particularly relates to a preparation method of a brexpiprazole intermediate 7-hydroxy-1H-quinoline-2-ketone. According to the novel method for preparing the 7-hydroxy-1H-quinoline-2-ketone, DDQ is replaced with palladium on carbon, the obtained product is high in yield, few in impurity and easy to operate, the catalyst can be recycled, a target compound is synthesized through direct catalytic dehydrogenation, and the method has green atom economy and is suitable for industrial production.
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Paragraph 0028; 0070-0073
(2021/05/05)
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- Method for preparing
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The invention relates to a preparation method of brexpiprazole and an intermediate thereof; the method includes the steps of carrying out a reaction of a compound represented by the formula II with 1-bromo-4-chlorobutane in a reaction solvent to obtain a compound represented by the formula III, in the presence of 2,3-dicyano-5,6-dichlorobenzoquinone, oxidizing the compound represented by the formula III into a compound represented by the formula IV, carrying out a reaction of the compound represented by the formula IV with a compound represented by the formula V to obtain brexpiprazole, then carrying out hydrochloride formation and refining, adding an alkali, and allowing brexpiprazole to drift away. The purity of brexpiprazole obtained by the method is more than 99.5%, the total yield is more than 80%, the process is simple and the cost is low.
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Paragraph 0033-0036
(2021/05/12)
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- Novel method for preparing new antipsychotic drug brexpiprazole
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The invention discloses a new electrochemical preparation method of a new antipsychotic drug brexpiprazole. The preparation method specifically comprises the following steps of: preparing a key intermediate, namely -1-(benzo [b] thiophene-4-yl)-4-(4-(-3nitrophenoxy) butyl) piperazine, and carrying out electric reduction on the key intermediate to prepare 3-[4-[4-(benzo [b] thiophene-4-yl) piperazine-1y-l] butoxy] aniline; and carrying out acylation reaction with cinnamyl chloride and intramolecular Friedel-Crafts acylation reaction to prepare brexpiprazole.
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- Industry-Oriented Route Evaluation and Process Optimization for the Preparation of Brexpiprazole
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Efforts toward route evaluation and process optimization for the preparation of brexpiprazole (1) are described. Starting from commercially available dihydroquinolinone 11, a three-step synthesis route composed of O-alkylation, oxidation, and N-alkylation was selected for industry-oriented process development aiming to reduce side reactions and achieve better impurity profiles. The reaction conditions of the three steps were investigated, and the control strategy for the process-related impurities was established. The optimized process was validated on the kilogram scale and now is viable for commercialization, with the results of not less than 99.90% purity of 1 (by HPLC) and not more than 0.05% of persistent impurities 15 and 16.
- Chen, Weiming,Suo, Jin,Liu, Yongjian,Xie, Yuanchao,Wu, Mingjun,Zhu, Fuqiang,Nian, Yifeng,Aisa, Haji A.,Shen, Jingshan
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p. 852 - 857
(2019/04/01)
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- Brexpiprazole derivative and preparation method thereof
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The invention provides a brexpiprazole derivative, and a preparation method thereof. According to the chemical structure of the brexpiprazole derivative, the brexpiprazole derivative is prepared through following steps: brexpiprazole, and (HCHO) are reacted in the presence of a first alkaline catalyst to prepare N-hydroxymethyl brexpiprazole; and then N-hydroxymethyl brexpiprazole and an alkylformyl chloride compound are reacted in the presence of a second alkaline catalyst to obtain the brexpiprazole derivative. The brexpiprazole derivative is long in half life, and is capable of reducingmedicine administration frequency; and the brexpiprazole derivative prepared using the preparation method is low in impurity content and cost.
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Paragraph 0076; 0083; 0084; 0090; 0097; 0098; 0104; 0111
(2019/08/12)
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- Process for preparing Brexpiprazole
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The invention relates to a method for preparing Brexpiprazole with a one-pot process. 7-hydroxyl-2-quinolone reacts with added 1-bromine-4-chlorobutane in the presence of alcohol and alkali, 1-(benzo[B]thiophen-4-yl) piperazine hydrochloride and water are added for a further reaction, finally, filtration, separation and drying are performed, and Brexpiprazole is obtained. Compared with the prior art, the method has the benefits as follows: 1, the problems of insufficient reaction and difficulty in purification in the prior art are solved; 2, the operation process is simplified, and the production efficiency is greatly improved; 3, used solvents are safe, and less environment pollution is caused.
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Paragraph 0010; 0044-0047
(2019/01/22)
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- Preparation method and application of substituted quinoline-2(1H)-one compound
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The invention belongs to the field of pharmaceutical chemistry and chemical synthesis, and concretely relates to a preparation method of a substituted quinoline-2(1H)-one compound. The invention provides a preparation method of the substituted quinoline-2(1H)-one compound. The preparation method performs an oxidation reaction on a compound represented by a formula I and an oxidant in a solvent toobtain a compound represented by a formula II. The preparation method has the advantages of simple method, high yield and low cost and is suitable for industrial production. The substituted quinoline-2(1H)-one represented by the formula II is an important intermediate of a variety of pharmaceutical active ingredients.
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Paragraph 0085-0088
(2019/11/29)
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- PROCESS FOR THE PREPARATION OF BREXPIPRAZOLE AND ITS INTERMEDIATES
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The present invention discloses to a process for the preparation of brexpiprazole and its pharmaceutically acceptable salt. The present invention further discloses novel intermediates and process for the preparation of the novel intermediates of brexpiprazole. The invention also discloses a process for purification of brexpiprazole to reduce or eliminate impurities.
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Page/Page column 27; 28
(2019/05/02)
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- Oxidative Aromatization of 3,4-Dihydroquinolin-2(1 H)-ones to Quinolin-2(1 H)-ones Using Transition-Metal-Activated Persulfate Salts
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Inorganic persulfate salts were identified as efficient reagents for the oxidative aromatization of 3,4-dihydroquinolin-2(1H)-ones through the activation of readily available transition metals, such as iron and copper. The feasible protocol conforming to the requirement of green chemistry was utilized in the preparation of the key intermediate (7-(4-chlorobutoxy)quinolin-2(1H)-one 2) of brexpiprazole in 80% isolated yield on a 100 g scale, and different quinolin-2(1H)-one derivatives with various functional groups were demonstrated in 52-89% yields.
- Chen, Weiming,Sun, Changliang,Zhang, Yan,Hu, Tianwen,Zhu, Fuqiang,Jiang, Xiangrui,Abame, Melkamu Alemu,Yang, Feipu,Suo, Jin,Shi, Jing,Shen, Jingshan,Aisa, Haji A.
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p. 8702 - 8709
(2019/07/03)
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- An innovative approach for the synthesis of 7-hydroxyquinolin-2(1H)-one: A key intermediate of brexpiprazole
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2,3-Dichloro-5,6-dicyano-p-benzoquinone (DDQ) mediated oxidation of 7-hydroxy-1,2,3,4-tetrahydro-2-quinolinone has been prepared from 3-hydroxy aniline to obtain 7-hydroxyquinolin-2(1H)-one in aqueous media. Stoichiometric quantities of DDQ and THF provides a high out put of 7-hydroxyquinolin-2(1H)-one and reduces the consumption of organic solvents and discourages by-products. Overall advantage with this approach was reduce the time cycle and cost of the brexpiprazole intermediate.
- Reddy, T Ram,Reddy, Desireddy Neha,Reddy, Bhimireddy Krishna,Kasturaiah, Chapala,Yadagiri, Kurra
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p. 834 - 836
(2018/03/13)
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- Identification, Synthesis, and Control of Process-Related Impurities in the Antipsychotic Drug Substance Brexpiprazole
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This article describes the identification, synthesis, and control of several unknown related substances present in the form of critical impurities that were observed during the process development for the antipsychotic drug substance brexpiprazole (BRX). On the basis of liquid chromatography-mass spectrometry (LC-MS) evidence of impurities and analysis of the employed synthetic route of BRX, the structures of the unknown impurities were proposed. Many critical impurities were synthesized, and their chemical structures were established using different spectroscopy techniques. To the best of our knowledge, this is the first report where several new impurities were recognized, addressed, and controlled effectively during the development of a robust and efficient process for the BRX drug substance.
- Tyagi, Rahul,Singh, Harnam,Singh, Jagat,Arora, Himanshu,Yelmeli, Vijayalaxmi,Jain, Mohit,Girigani, Sathyanarayana,Kumar, Pramod
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p. 1471 - 1480
(2018/11/25)
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- Method for purifying brexpiprazole
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The invention discloses a method for purifying brexpiprazole. The invention provides the method for purifying brexpiprazole. The method comprises the following step: in an organic solvent, purifying abrexpiprazole crude product I, thereby obtaining brexpiprazole I, wherein the organic solvent is a mixed solvent of an aliphatic alcohol solvent, an aliphatic ether solvent and an aliphatic halogenated hydrocarbon solvent; the purity of the brexpiprazole crude product is 90-100%, including 90% but not 100%. The method disclosed by the invention is simple and safe to operate, simple in aftertreatment, high in product purity which can meet raw material medicine standards, low in production cost and applicable to industrial production.
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Paragraph 0035; 0036; 0037
(2018/04/02)
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- PROCESSES FOR THE PREPARATION OF 7-{4-[4-(1-BENZOTHIOPHEN-4-YL)PIPERAZIN-1-YL]BUTOXY}QUINOLIN-2(1H)-ONE
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The Present Invention relates to process for the preparation of 7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}quinolin-2(1H)-one represented by the following structural formula-1.
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Page/Page column 36
(2018/05/27)
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- PROCESS FOR THE PREPARATION OF BREXPIPRAZOLE
-
Processes for preparation of Brexpiprazole, intermediates used during preparation, and polymorphs of Brexpiprazole are provided.
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Page/Page column 59; 60
(2018/10/19)
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- Delineating an alternate convergent synthesis of brexpiprazole: a novel use of commercial 6,7-dihydrobenzo[b]thiophen-4(5H)-one as precursor to an efficacious Buchwald–Hartwig amination step
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Abstract: Brexpiprazole – an anti-psychotic drug approved for the treatment of schizophrenia – has been synthesized via an extremely concise and convergent route, which involves in essence two key C–N bond formation (amination) steps that serve to link the piperazine core between the constituent benzo[b]thiophene and 7-butoxyquinolin-2(1H)-one fragments. The highlight of this synthesis is the first amination step, which was effected quite efficaciously by a novel palladium mediated Buchwald–Hartwig coupling between N-Boc-piperazine and the triflate ester of benzo[b]thiophen-4-ol (conveniently prepared in three steps from commercially available 6,7-dihydrobenzo[b]thiophen-4(5H)-one). Indeed, even without an extensive screening of catalysts, ligands and reaction conditions, this amination step could be performed quite efficiently with merely 1?mol% catalyst loading, which cleanly afforded in 87% overall yield 1-(benzo[b]thiophen-4-yl)piperazine—the starting material for the second C–N bond formation and the final step in the synthesis of Brexpiprazole. Graphical Abstract: Synopsis An alternate convergent synthesis of the anti-psychotic drug Brexpiprazole has been described. In particular, a novel palladium catalyzed Buchwald–Hartwig coupling of N-Boc-piperazine with benzo[b]thiophen-4-yl trifluoromethanesulfonate (prepared from commercially available 6,7-dihydrobenzo[b]thiophen-4(5H)-one) has been shown to furnish 1-(benzo[b]thiophen-4-yl)piperazine (a key intermediate in the synthesis of the API) in excellent yield even with 1?mol% catalyst loading. [Figure not available: see fulltext.].
- Kumar, A Sravanth,Kandanur, Sai Giridhar Sarma,Sen, Saikat,Oruganti, Srinivas
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- PROCESS FOR THE PREPARATION OF BREXPIPRAZOLE AND INTERMEDIATES THEREOF
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The present invention relates to process for preparation of Brexpiprazole of formula-l and intermediates thereof. The present invention is further directed to process for the preparation of anhydrous form of Brexpiprazole, pharmaceutical compositions containing them.
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- THE METHOD FOR MANUFACTURE OF BREXPIPRAZOLE, INTERMEDIATES USED IN THIS METHOD, AND THE METHOD FOR MANUFACTURE THEREOF
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The invention relates to a method for manufacture of brexpiprazole comprising in step (a) reaction of 4-[(2-oxo-1,2-dihydroquinolin-7-yl)oxy]butanal or a solvate thereof with 1-(1- benzothiophen-4-yl)piperazine or a salt thereof in a solvent, optionally in the presence of a catalyst, and in step (b) reduction of the iminium salt formed in step (a) using a reducing agent in a solvent, optionally in the presence of a catalyst. The invention relates also to the intermediates used for the manufacture of brexpiprazole, and the method for manufacture of these intermediates.
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Page/Page column 9-10
(2018/02/22)
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- PROCESS FOR THE PREPARATION OF BREXPIPRAZOLE FROM 7-(4-CHLOROBUTOXY)QUINOLIN-2(1H)-ONE AND 1-(BENZO[B]THIOPHEN-4-YL)PIPERAZINE
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The present invention relates to a process for the preparation of 7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy} quinolin-2(1H)-one (brexpiprazole) from 7-(4-chlorobutoxy)quinolin-2(1H)-one and 1-(benzo[b]thiophen-4-yl)piperazine. The intermediate 7-(4-chlorobutoxy)quinolin-2(1H)-one is prepared from 7-hydroxy-quinolin-2(1H)-one and 1-bromo-4-chloro-butane at a temperature below 45°C. The crude intermediate 7-(4-chlorobutoxy)quinolin-2(1H)-one is then treated with a resin (e.g. AMBER LITE IR 120 h) in an alcohol solvent (e.g. methanol) whereby the dimer impurity D is removed. The brexpiprazole obtained by this process is substantially free from dimer impurity D. Brexpiprazole is a D2 dopamine partial agonist called serotonin-dopamine activity modulator (SDAM) used for the treatment of schizophrenia and as an adjunct for major depressive disorder.
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Page/Page column 15-16
(2018/01/20)
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- PROCESS FOR THE PREPARATION OF BREXPIPRAZOLE AND INTERMEDIATES THEREOF
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The present invention relates to Brexpiprazole having a purity of about 99.5% or more by area percentage of HPLC, having total impurities not more than 0.5% relative to brexpiprazole as measured by area percentage of HPLC, and having less than 0.1% 1-(benzo[b]thiophen-4-yl)piperazine or a salt thereof relative to brexpiprazole by area percentage of HPLC. The present invention also provides a composition comprising brexpiprazole having 1-(benzo[b]thiophen-4-yl)-piperazine or a salt thereof in an amount less than about 0.1% relative to brexpiprazole by area percentage of HPLC and process for the preparation of brexpiprazole.
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Paragraph 0181; 0189; 0190
(2017/11/30)
-
- Preparation method for synthesizing brexpiprazole
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The invention provides a preparation method for synthesizing brexpiprazole. The preparation method comprises the following specific steps of using 4-nitrobenzo[b]thiophene as a raw material to carry out a hydrogenation reaction to synthesize an intermediate compound (II), and using 7-hydroxy-1H-quinolin-2-one as a raw material to carry out a reaction to synthesize and obtain a compound (III) at a first step and to obtain an intermediate compound (IV) at a second step; afterwards, condensing the intermediate compound (II) and the intermediate compound (IV) to make a target compound (I), namely the brexpiprazole. Raw materials of the entire synthetic route of the preparation method are both obtained easily; the operation is simple and convenient; the operation cost is low; the preparation method is green and environment-friendly; further, the yield of each step is high; the preparation method is quite suitable for industrialized production, and has extremely high industrial application value.
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- Novel preparation method of brexpiprazole
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The invention discloses a novel preparation method of brexpiprazole, comprising: subjecting 7-hydroxy-1H-quinoline-2-one (2) as starting material and 1-chloro-4-bromobutane to substitution reaction to obtain 7-(4-chlorobutoxy)-1H-quinoline-2-one (3); subjecting the compound (3) and N-Boc piperazine to substitution reaction under the action of potassium hydroxide, and carrying out deprotection to obtain 7-(1-piperazine)-butoxy-1H-quinoline-2-one dihydrochloride (4); subjecting the compound (4) to substitution reaction under the action of isopropylmagnesium chloride to finally obtain brexpiprazole. The preparation method has the advantages of high product conversion rate and good product purity, is simple and easy to perform, high in yield and good in quality and facilitates industrial production.
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Paragraph 0028; 0029; 0030
(2017/08/28)
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- Preparation method of brexpiprazole, and compound used for preparing brexpiprazole
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The invention discloses a preparation method of brexpiprazole, and a compound used for preparing brexpiprazole. A compound IV reacts with a compound VIII to obtain the brexpiprazole. The preparation method has the advantages of cheap and easily available raw materials, simple synthesis technology, greenness and environmental protection, and suitableness for industrial production.
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- PROCESSES FOR PREPARING BREXPIPRAZOLE
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The present disclosure provides processes for preparing brexpiprazole. The present disclosure also provides processes for the purification of brexpiprazole. The processes for preparing and purifying brexpiprazole of the present invention provide substantial improvements over currently known methods. In certain embodiments, the conversion of Formula XI and XII to form XIII provides increased selectivity over previously reported methods. This offers increased yield and purity. The improved process for purifying brexpiprazole disclosed herein provides brexpiprazole with superior purity and is also more suitable for industrial production.
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Paragraph 0128
(2017/05/20)
-
- PROCESS FOR THE PREPARATION OF BREXPIPRAZOLE
-
The present disclosure provides processes for the preparation of brexpiprazole or pharmaceutically acceptable salts thereof. The present disclosure also provides intermediates useful in the preparation of brexpiprazole.
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- Preparing method for brexpiprazole
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The invention belongs to the technical field of chemical drug synthesis and particularly relates to a preparing method for brexpiprazole. According to the preparing method, crystalline brexpiprazole is prepared through five steps. The preparing method has the advantages that the synthetic yield is high, operation is simple, purification is easy, and the end product is stable. In addition, a metal catalyst is effectively avoided, and the number of reaction steps is greatly reduced, so that the reaction difficulty is lowered, post-treatment is simplified, the yield is increased, the reaction cost is greatly reduced, and thus industrialized mass production is facilitated.
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Paragraph 0088-0090
(2017/01/31)
-
- Preparation method of brexpiprazole
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The invention discloses a preparation method of a compound brexpiprazole represented by formula (1). The preparation method adopts 4-aminobenzo[b]thiophene as an initial raw material to synthesize a piperazine ring, avoids a heavy metal palladium catalyzed reaction, reduces the synthesis steps and impurities, and reduces the cost.
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Paragraph 0011; 0024-0026
(2017/03/08)
-
- Preparation method of novel brexpiprazole, aripiprazole and salts thereof
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The invention provides a preparation method of novel Brexpiprazole and salts thereof, aripiprazole and salts thereof, or key intermediates thereof. The method uses a starting material of 7-hydroxycoumarin or 7-hydroxy dehydrocoumarin, which is subjected to a substitution reaction, a dehydrogenation reaction and / or amination reaction. The method has the advantages of sufficient supply of easily available raw materials, low cost, high safety, simple operation, high product yield and good quality, and is suitable for enlarge production.
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- Preparation method and intermediate of brexpiprazole and preparation method of intermediate
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The invention relates to the technical field of medicinal chemical synthesis and in particular relates to a preparation method and an intermediate of brexpiprazole and a preparation method of the intermediate. The preparation method of the brexpiprazole is shown in the following flow chart (described in the specification), wherein X1 and X2 are halogen, X1 is bromine preferably, and X2 is chlorine preferably. The invention provides a preparation method of a new compound 1 by providing new compounds 2 and 3. The preparation method of the new compound 1 mainly comprises two-step reaction, namely substitution and cyclization. Byproducts produced in the preparation method of the new compound 1 are less and are easy to separate, and column chromatography treatment does not need to be carried out. Meanwhile, the invention also provides a preparation method of the compound 2. The preparation method of the compound 2 has the advantages that generation of byproducts is greatly reduced, overall yield of reaction is improved, column chromatography treatment does not need to be carried out and production time is shortened while production cost is reduced, so that the preparation method of the compound 2 is applicable to industrial production.
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- Novel preparation method of brexpiprazole
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The invention provides a novel preparation method of brexpiprazole, belonging to the technical field of medicines and chemical synthesis, and solving the problems of more impurities, low yield and serious pollution of existing brexpiprazole preparation methods. According to the method, 4-hydroxy benzothiophene is taken as a starting material, an intermediate V is obtained by four steps of reactions, an intermediate VII is obtained from 7-hydroxy-2-quinolone by two steps of reactions, and the intermediate V and the intermediate VII are subjected to condensation to obtain the brexpiprazole meeting clinic medicinal requirements. The preparation method is easy for getting raw materials, low in price, simple in operation, and mild in reaction condition, and has good industrialized application values.
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- Elopiprazole preparation method
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The invention provides an elopiprazole preparation method which includes the following steps that 7-(4-chlorobutoxy)-1H-quinoline-2-ketone (6) serves as a starting material, 7-(4-chlorobutoxy)-1H-quinoline-2-ketone (6) and piperazine monohydrochloride have a mono-substituted reaction to generate a midbody 7-(4-butoxy piperazine)-1H-quinoline-2-keto-hydocholoride (13), and 13 and 4-benzo[b]thiophene (14) are prepared into a final product of elopiprazole (1) through catalytic coupling reaction. The elopiprazole preparation method has the advantages that raw materials are easy to obtain, the process is simple, operation is convenient, the total yield is high and reaches 75%, and industrial production is easy. The reaction general formula is shown in the specification.
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Paragraph 0046; 0047; 0048
(2016/10/08)
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- Injectable Formulation
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An object of the present invention is to provide a sustained-release injectable preparation which is in a medication administration form that can provide the effect of 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1H-quinolin-2-one for a prolonged period of time, the preparation releasing a therapeutically effective amount of 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1H-quinolin-2-one for at least one week. The present invention provides an injectable preparation containing 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-3H-quinolin-2-one or a salt thereof as an active ingredient, which releases the active ingredient in such a manner that its blood concentration is maintained for at least one week.
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Paragraph 0166; 0167; 0168; 0169; 0170; 0171; 0172; 0173
(2015/03/31)
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- METHOD FOR PRODUCING BENZO[B]THIOPHENE COMPOUND
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The present invention provides a method for producing a compound of Formula (4): wherein R1 is a hydrogen atom etc. by reacting a compound of Formula (2): wherein X1 is a leaving group, with a compound of Formula (3): wherein R1 is as defined above, in the presence of (a) a palladium compound and a tertiary phosphine or (b) a palladium carbene complex, in an inert solvent or without a solvent. The present invention can produce the compound of Formula (4), with high purity and high yield, and by a simple operation.
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Page/Page column 44; 45
(2013/03/26)
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- DIHYDRATE OF BENZOTHIOPHENE COMPOUND OR OF A SALT THEREOF, AND PROCESS FOR PRODUCING THE SAME
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An object of the present invention is to provide a compound that can be used as a more superior therapeutic agent for central nervous system diseases. The present invention provides a dihydrate of 7-[4-(4-benzo[b]thiophen-4-y1-piperazin-1-y1)butoxy]-1H-quinolin-2-one or of a salt thereof, and a process for producing the same.
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Page/Page column 20; 21
(2013/11/18)
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- INJECTABLE PREPARATION
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An object of the present invention is to provide a storage-stable injectable preparation comprising a composition comprising a poorly soluble drug as an active ingredient and a dispersion medium. Another object of the present invention is to provide a compact, lightweight prefilled syringe by filling a syringe with the injectable preparation. The present invention provides an injectable preparation comprising a composition comprising a poorly soluble drug, a dispersion medium, and a specific suspending agent, the composition having a viscosity of 40 pascal-seconds or more in at least one point in the shear rate range of 0.01 to 0.02 s-1 and having a viscosity of 0.2 pascal-seconds or less in at least one point in the shear rate range of 900 to 1,000 s-1, as measured.
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Page/Page column 78; 79
(2013/11/18)
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- PIPERAZINE-SUBSTITUTED BENZOTHIOPHENES FOR TREATMENT OF MENTAL DISORDERS
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The present invention provides a heterocyclic compound represented by the general formula (1): The compound of the present invention has a wide treatment spectrum for mental disorders including central nervous system disorders, no side effects and high safety.
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Page/Page column 69-70
(2010/11/24)
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