45 results about "Vonoprazan" patented technology

The invention discloses a compound preparation capsule and a preparation method thereof, wherein the compound preparation capsule is composed of Vonoprasone or a pharmaceutical salt microtablet thereof, an amoxicillin microtablet and a rifampicin or rifampetine microtablet. The Vonoprazan is a novel potassium ion competitive acid blocker, and the compound preparation capsule is used for treating gastric ulcer, duodenal ulcer, gastric MALT lymphoma, idiopathic thrombocytopenic purpura, and helicobacter pylori infection and helicobacter pylori infection gastritis in the stomach after early gastric cancer endoscopic therapy. According to the compound preparation capsule, the cure rate of helicobacter pylori can be increased, the drug resistance can be reduced, and a better treatment choice is provided for clinical patients.

The present invention relates to a method for preparing nitrosamine impurities in vonoprazan fumarate, belonging to the technical field of chemical synthesis. By mixing vonoprazan with an organic solvent and reacting the mixture with a nitrosating agent at room temperature, the nitrosamine impurities prepared by this method have a purity exceeding 85%. This method solves the problem of preparing nitrosamine impurities and also provides a reference substance for the study of impurities in vonoprazan fumarate.

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 present invention belongs to the technical field of pharmaceutical chemistry, and specifically provides a method for preparing vonoprazan and vonoprazan fumarate with efficient reaction and short route. The method uses a novel intermediate compound (5-(2-fluorophenyl)-1-(pyridine-3-sulfonyl)-1H-pyrrole-3-yl)-pyridine-3-sulfonic acid methyl ester to obtain vonoprazan by amination; vonoprazan fumarate can be obtained by salt-forming reaction, which can avoid dangerous redox operation and the introduction of toxic impurities, thereby improving the yield and product quality, thereby overcoming the problem of complicated operation process of existing process, and being suitable for industrial production.

Disclosed are: a pharmaceutical composition capable of inhibiting the generation of a nitrosamine impurity of a vonoprazan drug product by means of an antioxidant; and a preparation method therefor.

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 invention relates to a compound medicine composition and application thereof in resisting helicobacter pylori infection, in particular to the compound medicine composition, a medicine preparation, a preparation method and application, and the composition comprises at least two selected from the following components: (I) Vonoprazan or pharmaceutically acceptable salt thereof, (II) Vonoprazan or pharmaceutically acceptable salt thereof, (III) Vonoprazan or pharmaceutically acceptable salt thereof, (III) Vonoprazan or pharmaceutically acceptable salt thereof, (III) Vonoprazan or pharmaceutically acceptable salt thereof and (III) Vonoprazan or pharmaceutically acceptable salt thereof; (II) amoxicillin or a pharmaceutically acceptable salt thereof; (III) clarithromycin; according to the composition prepared by compounding different anti-infection active ingredients, the problems of patient compliance and medication convenience can be effectively solved, for example, the tablet dosage is reduced, wrong taking, missing taking, excessive taking and the like of a patient are avoided, the stability and safety of the preparation can be accidentally improved, and the content of harmful impurities is particularly reduced.

The preparation method comprises the following steps: mixing 5-(2-fluorophenyl)-1-[(pyridine-3-yl) sulfonyl]-1H-pyrrole-3-formaldehyde with an organic solvent, adding a methanol solution of dimethylamine, carrying out an amination reaction, adding a reducing agent, and carrying out a reduction reaction to obtain a compound B in a free state; and after the reaction is finished, adjusting the pH value of the reaction solution to 2-3 by using hydrochloric acid, cooling and crystallizing to obtain a compound B. The purity of the compound B prepared by the method reaches 99% or above, the yield reaches 85% or above, and the method is suitable for industrial production. The method has mild and simple reaction conditions, and is convenient for reaction reproduction and enlarged production.

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.

The invention belongs to the technical field of drug analysis and detection, and particularly relates to a method for detecting potential genotoxic impurities in Vonoprasone fumarate and application. The invention discloses a high performance liquid chromatography method for detecting potential genotoxic impurities of Vonoprazan fumarate, which adopts a chromatographic column with octadecylsilane chemically bonded silica as a filler and adopts phosphate buffered solution-acetonitrile as a mobile phase for gradient elution. The potential genotoxic impurities in the Vonoprasone fumarate can be rapidly and effectively separated. The method has the advantages that the separation degree of each chromatographic peak and an adjacent impurity peak is good, the detection limit and the quantitation limit also meet the analysis requirements, the sensitivity and the accuracy are high, the detection of the potential genotoxic impurities of the Vonoprazan fumarate can be met, and the product quality is ensured.

The invention belongs to the technical field of pharmaceutical analysis, particularly relates to a method for detecting methylamine in Vonoprasone fumarate, and provides a convenient, efficient and accurate detection method for solving the problem of detection of methylamine in Vonoprasone fumarate. Derivative products are detected by liquid chromatography, the content of methylamine in the Vonoprazan fumarate can be detected, so that medication safety is effectively guaranteed, quality control of the Vonoprazan fumarate is facilitated, the method is convenient, efficient and accurate, the system applicability, repeatability, specificity and accuracy completely conform to the guidance principle verified by methods in Chinese pharmacopoeia, and the method is suitable for popularization and application. The method can be used for quality control of the Vonoprasone fumarate.

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 a compound pharmaceutical composition and its application in preventing Helicobacter pylori infection, and more specifically, to the compound pharmaceutical composition, pharmaceutical preparation, preparation method and use. The composition comprises at least two selected from the following components: (I) vonoprazan or a pharmaceutically acceptable salt thereof; (II) amoxicillin or a pharmaceutically acceptable salt thereof; (III) clarithromycin; and (IV) a bismuth agent. The composition prepared by compounding different anti-infective active ingredients can not only effectively solve the problems of patient compliance and medication convenience, such as reducing the dosage of tablets and avoiding patients from taking the wrong tablets, missing a dose, or taking more than one dose, but also unexpectedly improve the stability and safety of the preparation, and is particularly conducive to reducing the content of harmful impurities.

The invention discloses a method for preparing a series of vonoprazan intermediates from isonitrile and a Michael receptor. According to the method, alpha-(p-toluenesulfonyl)-2-fluorobenzyl isocyanide is used as a raw material, attacks a series of Michael receptors under an alkaline condition, and forms a series of 3-substituted 5-(2-fluorophenyl)-1H-pyrrole through cyclization. The 3-substituted pyrrole intermediates can be used for preparing vonoprazan through further chemical conversion. Compared with the prior art, the technical scheme provided by the invention has the characteristics of short synthesis route, high comprehensive yield, simple post-treatment and low cost.

The invention discloses a compound medicinal preparation and a preparation method thereof, wherein the compound medicinal preparation consists of Vonoprasan or medicinal salt thereof, amoxicillin and levornidazole or levornidazole phosphate. The Vonoprazan is a novel potassium ion competitive acid blocker, and the compound preparation is used for treating gastric ulcer, duodenal ulcer, gastric MALT lymphoma, idiopathic thrombocytopenic purpura, and helicobacter pylori infection and helicobacter pylori infection gastritis in the stomach after early gastric cancer endoscopic therapy. According to the compound preparation, the cure rate of helicobacter pylori can be increased, the drug resistance can be reduced, and a better treatment choice is provided for clinical patients.

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 invention relates to the technical field of medicines, and particularly discloses a fumaric acid Vonoprazan tablet and a preparation method of the fumaric acid Vonoprazan tablet. The invention relates to a fumaric acid Vonoprazan tablet, which is prepared from the following raw materials in parts by weight: 5 to 8 parts of fumaric acid Vonoprazan, 0.5 to 1.5 parts of lubricating agents, 5 to 10 parts of disintegrating agents, 10 to 20 parts of filling agents and 1 to 3 parts of bonding agents. The fumaric acid vonorbitan tablet is coated with a polymethylacrylic acid composite material; according to the preparation method, the fumaric acid vonorbitan tablet is coated by adopting the polymethylacrylic acid composite material, moisture and illumination are isolated, degradation of active components of the fumaric acid vonorbitan tablet is reduced, and the dissolution rate and stability of the fumaric acid vonorbitan tablet are improved.

The present invention relates to a tablet, injection and compound formulation of vonoprazan pyroglutamate. The tablet comprises a core and a film coating layer, the core comprising a vonoprazan pyroglutamate crystal form I, a filler, a binder, a pH regulator, a disintegrating agent and a lubricant, and the film coating layer comprising an Opadry film coating premix. An oral solution comprises the vonoprazan pyroglutamate crystal form I, a preservative, a sweetening agent, a flavoring agent, a pH regulator and water. The compound formulation is a vonoprazan pyroglutamate-aspirin compound tablet and sequentially comprises, from inside to outside, an aspirin plain core, an enteric coating layer, an isolation coating layer, the vonoprazan pyroglutamate crystal form I loaded layer and a film coating layer.

Described herein is a method for purifying vonoprazan fumarate of formula (I).

Disclosed in the present invention is a method for preparing a series of vonoprazan intermediates from isonitrile and a Michael receptor. The method of the present invention comprises: using α-(tosyl)-2-fluorobenzyl isonitrile as a raw material, attacking a series of Michael receptors under an alkaline condition, and forming by cyclization a series of 3-substituted 5-(2-fluorophenyl)-1H-pyrroles. Moreover, these 3-substituted pyrrole intermediates can be further subjected to chemical conversion for the preparation of vonoprazan. Compared with the prior art, the technical solution of the present invention has the characteristics of short synthetic route, high comprehensive yield, simple post-treatment, and low cost.

The invention discloses a fumaric acid Vonoprazan suspension and a preparation method thereof, the fumaric acid Vonoprazan suspension is prepared from fumaric acid Vonoprazan, a suspending aid, a wetting agent, an acidifying agent, a flavoring agent and essence, the prepared preparation is easier to swallow compared with tablets, proper auxiliary materials are screened and added through a prescription, the bitter taste of the fumaric acid Vonoprazan during oral administration is obviously reduced, and the oral administration effect of the fumaric acid Vonoprazan is improved. The clinical compliance of a patient is improved; and the defects that the tablet is taken after being broken apart, the dosage is not accurate enough, the coating is damaged and the taste masking effect is influenced are overcome. The oral suspension is packaged in unit dose, and is accurate in dose and convenient to administrate.

The present invention provides a vonoprazan fumarate composition and a preparation method thereof, belonging to the field of medical technology. Specifically, a vonoprazan fumarate composition is provided, comprising the following components: vonoprazan fumarate, vitamin C, an oil phase, and sodium bicarbonate or calcium carbonate; a preparation method of the vonoprazan fumarate composition is also provided. The vonoprazan fumarate composition provided by the present invention greatly improves the efficacy of treating gastric diseases, reduces the dosage of vonoprazan fumarate, and effectively solves the problem of large toxic and side effects of existing vonoprazan fumarate agents.

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 invention discloses a compound medicinal preparation and a preparation method thereof, wherein the compound medicinal preparation is prepared from Vonoprasone or medicinal salt thereof, amoxicillin and rifampicin or rifampetine. The Vonoprazan is a novel potassium ion competitive acid blocker, and the compound preparation is used for treating gastric ulcer, duodenal ulcer, gastric MALT lymphoma, idiopathic thrombocytopenic purpura, and helicobacter pylori infection and helicobacter pylori infection gastritis in the stomach after early gastric cancer endoscopic therapy. According to the compound preparation, the cure rate of helicobacter pylori can be increased, the drug resistance can be reduced, and a better treatment choice is provided for clinical patients.

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.