16 results about "Vonoprazan" patented technology

This invention relates to the crystal form of vonorazine pyroglutamate and its preparation method. The vonorazine pyroglutamate crystal form obtained by this invention not only has good solubility but also excellent storage stability; in vitro activity experiments show that crystal form I of this invention is effective against H+. + K + The inhibitory effect of ATPase is comparable to that of TAK-438; animal experiments show that the crystal form of the present invention, when administered intravenously, can significantly inhibit histamine-induced gastric acid secretion in rats, and can exert its pharmacological effect faster than that of TAK-438 administered duodenally.

The invention belongs to the technical field of medicines, and particularly relates to a bifunctional compound with anti-helicobacter pylori and acid inhibition activity, a preparation method of the bifunctional compound and application of the bifunctional compound in preparation of medicines for treating peptic ulcer and helicobacter pylori infection. According to the compound, a potassium ion competitive acid blocker vonoprazan is used as an acid inhibition unit, and rifobetine is used as an anti-helicobacter pylori unit; the two compounds are respectively subjected to covalent modification through linking groups Linker 1 and Linker 2, and then are connected by virtue of a triazole ring to form a series of bifunctional compounds shown as a general formula (I). The compound can simultaneously and synergistically act on two key targets of gastric acid secretion and helicobacter pylori, so that not only is the treatment effect remarkably enhanced, but also better safety is shown due to the fact that the same curative effect can be achieved at a lower dosage.

The invention discloses vonoprazan fumarate, intragastric retention tablets of the vonoprazan fumarate and application of the vonoprazan fumarate to gastrointestinal tracts, and relates to the technical field of medicines.The vonoprazan fumarate is prepared through a synthesis method comprising the following steps that in the presence of an organic solvent and alkali, 5-(2-fluorophenyl) pyrrole-3-formaldehyde and pyridine-3-sulfonyl chloride are subjected to a reaction, and the vonoprazan fumarate is obtained. Hydroxypropyl-beta-cyclodextrin is added into a reaction system, and a compound WNLZ-1 is generated; reacting the compound WNLZ-1 with methylamine, and then reducing to obtain a compound WNLZ-3; the compound WNLZ-3 and fumaric acid are subjected to a salt forming reaction, and vonoprazan fumarate is obtained. According to the preparation method, hydroxypropyl-beta-cyclodextrin is introduced as a reaction accelerant in the synthesis step, the yield and purity of an intermediate are improved, meanwhile, hydroxypropyl-beta-cyclodextrin and xanthan gum are jointly used in the preparation, and the whole process optimization from raw material medicine synthesis to preparation performance is achieved.

The application provides a preparation method of low-impurity vonerogefumate. The application provides a method for removing impurities A-E in the preparation of vonerogefumate, wherein vonerogefumate is reacted with hydrobromic acid to obtain vonerogefumate hydrobromide, and the method specifically comprises the following steps: (1) dissolving vonerogefumate and hydrobromic acid in a solvent; (2) cooling or directly precipitating a solid; and (3) separating to obtain vonerogefumate hydrobromide. The method can remove impurities A-E which are difficult to remove by a recrystallization refining method, and the method has good selectivity for impurities A-E. The application provides an impurity D, a preparation method thereof and application of the impurity D as an impurity control sample of vonerogefumate.

The present invention discloses a method for preparing a series of vonoprazan intermediates using an isonitrile and a Michael acceptor. In the method of the present invention, α-(p-toluenesulfonyl)-2-fluorobenzylisonitrile is used as the starting material, which attacks a series of Michael acceptors under basic conditions and undergoes cyclization to form a series of 3-substituted 5-(2-fluorophenyl)-1H-pyrroles. These 3-substituted pyrrole intermediates can be further chemically transformed to prepare vonoprazan. Compared with the prior art, the technical means of the present invention are characterized by a short synthetic route, high overall yield, simple post-treatment, and low cost.

Providing granules or solid formulations with reduced dissolution delay of Vonoprazan Fumarate after storage SOLUTION: The disclosed granules or solid formulations comprise Vonoprazan Fumarate, carbonate and aspartic acid.SELECTED DRAWING: Figure 2

The application belongs to the technical field of preparation of pharmaceutical compounds, and particularly relates to a preparation method of an intermediate for preparing vonomacarbazone fumarate, wherein compound S1 and compound S2 are used as raw materials to synthesize compound S3, and then the intermediate S4 is synthesized from the compound S3, wherein the structural formulae of the compounds S1 and S2 are as follows: S1: S2: S3: The above technical scheme of the application fundamentally changes the construction strategy of the key pyrrole ring skeleton of vonomacarbazone fumarate, and two open-chain molecules S1 and S2 with simple structures, which are commercially available or easy to prepare, are used to efficiently and selectively construct the target pyrrole ring structure (S4) on site through a simple addition-electrophilic cyclization reaction. The method not only greatly reduces the cost of raw materials, but also avoids the dependence on unstable intermediates, and simplifies the synthesis path from the source.

The present invention relates to stabilization of non-peptidic pharmaceutically active agent or salt thereof. The pharmaceutical compositions comprise non-peptidic pharmaceutically active agent preferably vonoprazan or salt thereof along with glycerophosphoric acid (GPA) for the treatment of healing of all grades of erosive esophagitis and relief of heartburn associated with erosive esophagitis in adults.

The present invention relates to stabilization of non-peptidic pharmaceutically active agent or salt thereof. The pharmaceutical compositions comprise non-peptidic pharmaceutically active agent preferably vonoprazan or salt thereof along with glycerophosphoric acid (GPA) for the treatment of healing of all grades of erosive esophagitis and relief of heartburn associated with erosive esophagitis in adults.

This invention belongs to the field of pharmaceutical technology and relates to a method for preparing vonoprazan fumarate. Compound 3 reacts with a methylamine alcohol solution and a reducing agent at low temperature, followed by quenching, and then forms a salt with fumaric acid to generate vonoprazan fumarate. In this method, the amination-reduction step is performed under mild conditions, and the product can be directly obtained by salt formation with fumaric acid after simple post-treatment following quenching, without the need for pre-preparing other intermediate salts. This method is simple to operate, low in cost, and yields a product with few impurities, making it suitable for industrial production.

The present invention provides a method for producing vonoprazan fumarate with a purity of 99.9% or higher in high yield. Specifically, the present invention relates to a method for producing vonoprazan fumarate with a purity of 99.9% or higher in high yield by forming vonoprazan hydrochloride using a specific amount of hydrochloric acid, and then converting it into a fumarate form to form vonoprazan fumarate. Furthermore, the present invention provides a specific crystalline form of vonoprazan hydrochloride that can be usefully used in the above production method.

The present invention relates to pharmaceutical composition comprises vonoprazan or pharmaceutically acceptable salts thereof.

This invention belongs to the field of pharmaceutical content detection, specifically relating to a method for determining the content of vonoprazan fumarate tablets. The vonoprazan fumarate tablets of this invention are prepared using mannitol, fumaric acid, croscarmellose sodium, hydroxypropyl cellulose, microcrystalline cellulose, and magnesium stearate as excipients. The preparation method described in this invention simplifies the preparation process and reduces production costs. This invention also provides the above-mentioned method for determining the content of vonoprazan fumarate tablets. High-performance liquid chromatography (HPLC) is used to accurately determine the content of the active ingredient vonoprazan in the prepared vonoprazan fumarate tablets. This method effectively eliminates the influence of added excipients and impurities on the determination of the active ingredient vonoprazan content, providing important assurance for clinical medication safety and offering a new method for the quality control of vonoprazan fumarate tablets.

The invention discloses a photochemical synthesis method of a vonoprazan intermediate, and belongs to the technical field of drug intermediate synthesis, the synthesis method comprises the following steps: (1) 2-bromo-1-(2-fluorophenyl) ethyl-1-ketone and acetaldehyde are subjected to a white light irradiation reaction under the action of a photosensitizer and alkali to obtain 4-(2-fluorophenyl)-4-oxobutyraldehyde; (2) carrying out a Paal-Knorr condensation reaction on the 4-(2-fluorophenyl)-4-oxobutyraldehyde and ammonium acetate under the action of an acid catalyst and a dehydrating agent, so as to obtain 2-(2-fluorophenyl)-1H-pyrrole; (3) carrying out formylation reaction on the 2-(2-fluorophenyl)-1H-pyrrole and 1, 1-dichloromethoxymethane under the action of a Lewis acid catalyst, so as to obtain a vonoprazan intermediate; the method has the advantages of cheap and easily available raw materials, high product yield, safe and simple process, mild reaction conditions and low cost, and is suitable for industrial production.

The present invention relates to pharmaceutical composition comprises vonoprazan or pharmaceutically acceptable salts thereof.

The invention discloses a method for detecting ammonia in a Vonoprazan fumarate bulk drug by ion chromatography, and belongs to the technical field of separation and analysis by ion chromatography. Comprising the following steps: (1) preparing a test solution; (2) preparing an ammonia stock solution; (3) drawing a standard curve by adopting ion chromatography; and (4) determining the test sample by adopting an ion chromatography. According to the detection method disclosed by the invention, ammonia detection in the Vonorazan fumarate can be carried out under a chromatographic condition, the solvent and the Vonorazan fumarate do not interfere with ammonia detection, the detection limit and the quantitation limit also meet the qualitative and quantitative analysis requirements of drugs, the sensitivity is high, the reproducibility is good, the accuracy is high, the stability is good, and the quality of the Vonorazan fumarate is favorably controlled; meanwhile, the method is simple to operate, short in detection time and suitable for large-scale industrial production.