47 results about "Mesylate" patented technology

The invention relates to the technical field of pharmaceutical preparations, in particular to a solid dispersion-based sustained-release drug composite carrier as well as a preparation method and application thereof. The preparation method comprises the following steps: carrying out synergistic spray drying on double polymers (hydroxypropyl methylcellulose acetate succinate and polyvinylpyrrolidone-vinyl acetate copolymer) to form a solid dispersion; compounding with mesoporous silica and calcium silicate for localization, and spraying ethanol to activate pores; calcium stearate and magnesium stearate are sequentially added for lubrication; prefabricating a sustained-release skeleton master batch; and finally, mixing, rolling and forming. According to the method, through hierarchical structural design, the drug stability, the powder fluidity and the release controllability are remarkably improved, the method is suitable for industrial production of the dihydroergoline mesylate sustained release preparation, and a release curve is smooth and reliable.

The invention provides a bromocriptine mesylate enteric-coated tablet and a preparation method thereof. Specifically, the bromocriptine mesylate enteric-coated tablet comprises a tablet core and an enteric coating layer wrapping the tablet core. The enteric-coated tablet disclosed by the invention is simple in process, good in stability and small in gastrointestinal side effect, the bioavailability of the enteric-coated tablet is more than two times that of a common tablet sold in the market, the dosage is expected to be reduced, the side effect is further reduced, and the enteric-coated tablet has excellent clinical value.

Mesylates of heterocyclic cytokinins of general formula I:wherein R is selected from the group comprising C3-C15 cycloalkyl, furfuryl, allyl, 4-hydroxy-3-methylbut-2-en-1-yl, 3-methylbut-2-en-1-yl, 4-hydroxy-3-methylbutyl, 4-hydroxy-1,3-dimethylbut-2-en-1-yl, 4-hydroxy-1,3-dimethylbutyl, benzyl, wherein the cycloalkyl, allyl, benzyl and furfuryl may be unsubstituted or optionally substituted with 1 to 3 substituents selected from the group containing hydroxy, halogen, methyl, hydroxymethyl and methoxy, and salts, solvates and addition salts thereof. These compounds are particularly suitable for agricultural and biotechnological use, and their great advantage is increased water solubility as compared to the corresponding free bases of heterocyclic cytokinins.

The invention discloses a mesoporous polydopamine (MPDA) nanoparticle which is loaded with a CeO2 nano enzyme and mitoxantrone mesylate (MitoQ) and is released by an intestinal tract, a preparation method of the mesoporous polydopamine (MPDA) nanoparticle, and an application of the mesoporous polydopamine (MPDA) nanoparticle, the preparation method of the mesoporous polydopamine (MPDA) nanoparticle, the preparation method of the mesoporous polydopamine (MPDA) nanoparticle and the preparation method of the mesoporous polydopamine (MPDA) nanoparticle, the preparation method of the mesoporous polydopamine (MPDA) nanoparticle, and the preparation method of the mesoporous polydopamine (MPDA) nanoparticle. The mesoporous polydopamine nanoparticle loaded with the CeO2 nano enzyme and the mitoxantrone mesylate and released by the intestinal tract comprises mesoporous polydopamine loaded with the CeO2 nano enzyme and MitoQ, and an enteric coating of chitosan and sodium alginate. The preparation method comprises the following steps: synthesizing mesoporous polydopamine by adopting a triblock copolymer as a template, then loading a small molecular drug MitoQ into MPDA through ultrasonic waves, and loading CeO2 nano-enzyme on the surface of MPDA through metal coordination to form MPDA (at) CeO2-MitoQ. And finally, coating chitosan and sodium alginate on the surfaces of the nanoparticles through electrostatic adsorption to obtain the final MPDA (at) CeO2-MitoQ (at) SA / CS. The drug-loaded nano-particles prepared by the preparation method disclosed by the invention have a good treatment effect on ulcerative colitis.

The present invention relates to a process for the preparation of belumosudil mesylate and its crystalline form. Further, the present invention relates to a 10 pharmaceutical composition comprising a therapeutically effective amount of the crystalline form of belumosudil mesylate obtained by the process of the present invention.

The present invention relates to the field of medical intermediates, and provides a preparation method for a key intermediate tert-butyl (3aR,5S,6aS)-5-(methylamino)hexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate mesylate of a JAK kinase inhibitor. The method comprises: reacting tert-butyl cis-5-oxohexahydrocyclopenta[C]pyrrole-2(1H)-carboxylate as a raw material with a methylamine equivalent to obtain intermediate A; and then carrying out a reduction reaction in metallic sodium and isopropanol to obtain a crude product, adding L-DBTA to form a salt, removing isomers, and then carrying out re-liberation and salt formation with methanesulfonic acid to obtain a purified product. The method significantly reduces reaction steps, reduces raw material costs, has a simple and reliable process, and is easy for industrial production.

The invention discloses a synthesis method of 3-amino-2-(tert-butyldimethylsilyl) phenyl trifluoromethanesulfonate, which is characterized in that a compound 2-bromo-3-nitrophenol is used as a raw material, and the target compound 3-amino-2-(tert-butyldimethylsilyl) phenyl trifluoromethanesulfonate is obtained through four-step reaction. According to the synthesis method disclosed by the invention, tert-butyllithium which is commonly used in the prior art is not used in key steps, and bis (trimethylsilyl) amino lithium (LiHMDS) is adopted to convert a compound 3, namely, 2-bromo-3-((tert-butyldimethylsilyl) oxy) aniline into a compound 4, namely, 3-amino-2-(tert-butyldimethylsilyl) phenol; the reaction risk is greatly reduced, meanwhile, the reaction effect is remarkably improved, no by-product is generated, post-treatment and purification are simple, and the yield is ideal.

Provided herein are salts and solid forms of 1-((S)-4-((R)-7-(6-amino-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-6-chloro-8-fluoro-2-(((S)-1-methylpyrrolidin-2-yl)methoxy)quinazolin-4-yl)-3-methylpiperazin-1-yl)prop-2-en-1-one, including adipate, fumarate, ethylenesulphonate, besylate, and mesylate salts thereof.

The invention relates to the technical field of medicines, in particular to a dihydroergoline mesylate sustained-release tablet containing an antioxidant synergistic system and a preparation method of the dihydroergoline mesylate sustained-release tablet. The preparation method comprises the following steps: firstly, preparing double-molecular-weight polyethylene glycol composite microspheres as a pore-foaming agent; preparing antioxidant regulation particles, forming a buffer microenvironment by tartaric acid, citric acid monohydrate, sodium citrate and the like, and adding a water-soluble antioxidant; then preparing a fat-phase antioxidant skeleton mixture, and loading a fat-soluble antioxidant; preparing drug-containing core particles from dihydroergoline mesylate and a part of the skeleton mixture; and after mixing and tabletting, sequentially carrying out bottom layer hydrophilic film coating, middle powder layer coating and outer layer functional film coating. The sustained release tablet is stable in release within 24 hours and good in batch-to-batch consistency, oxidation impurities in acceleration and long-term stability tests are remarkably reduced, and the medication safety and the long-term effect are effectively guaranteed.

This invention relates to the field of pharmaceutical technology, specifically to a sustained-release tablet of dihydroergot mesylate with composite network regulation and its preparation method. The sustained-release tablet comprises a composite structure consisting of a drug-resin composite core, an inner interface regulation structure, and an outer composite network. The key to its preparation lies in: forming a wet complex of dihydroergot mesylate with a strongly acidic cation exchange resin; sequentially introducing low-viscosity hydroxypropyl methylcellulose and a first portion of ethyl cellulose to construct the inner interface regulation layer; and after semi-drying, adding high-viscosity hydroxypropyl methylcellulose and a second portion of ethyl cellulose to form the outer composite network framework. This structure can significantly inhibit the burst release of the drug in gastric juice and achieve a stable and sustained release in intestinal juice, with stable tablet quality and good industrialization prospects.

The compound can be used for preparing an intermediate and related compounds of iprotecan mesylate. Further provided are methods for preparing these compounds. Also provided are improved, scalable synthesis of iprotecan mesylate using the provided intermediates. The synthesis of iprotecan mesylate utilizes a convergent pathway, includes fewer steps and utilizes fewer reagents and improves efficiency.

The present invention relates to an improved process for the preparation of Belumosudil mesylate compound of formula-1a and its intermediates which is represented by the following structural formula: Formula-1a.

The utility model discloses a nitrogen filling device for nafamostat mesylate for injection, including the cabinet body and setting in the cabinet body downside for the foot stand of mobile, the rear upper side four corners of cabinet body are provided with slide rod respectively, the upper side of slide rod is provided with nitrogen filling tank, the front lower side of nitrogen filling tank is provided with the air pump box, the front lower side of air pump box is provided with nitrogen filling pipe, the downside bottom of nitrogen filling pipe is provided with the sealing plug, the front upper side of cabinet body is provided with the placing tray, the upper side inside of placing tray is provided with a plurality of placing mouth with equidistance annular array, this novel mainly helps chuck, spring, trigger ball's mechanical linkage, and the whole process of " putting in - clamping - loosening - taking out " of the penicillin bottle does not need manual intervention. The chuck area opens automatically when placing, which is convenient for feeding. After rotating, it is automatically clamped to ensure process stability. After processing, it is automatically loosened to facilitate unloading, which greatly improves the production line turnover efficiency.

The present application provides an isolated compound which is a related substance of paritaprevir mesylate. The present application also provides the use of said compound for the preparation of paritaprevir mesylate or a composition comprising paritaprevir mesylate.

A method for synthesizing an aluminium-fluoride complex obtainable by reacting together: a salt made of aluminium(III) and counterions of aluminium(III) other than chloride(I), and a fluoride anion; or a chelate bearing molecule precomplexed with aluminium(III), obtained from treating the chelate bearing molecule with a salt made of aluminium(III) and counterions of aluminium(III) other than chloride(I), and a fluoride anion; the fluoride being [19F]fluoride or radioactive [18F]fluoride; wherein the counterions of aluminium(III) other than chloride are selected from bromide, iodide, nitrate, phosphate, sulfate, sulphonate, hydroxide, any anionic salt of natural and non-natural amino acids, 2,4-pentanedionate, 8-hydroxyquinoline, acetate, acrylate, ascorbate, aspartate, benzenesulfonate, benzoate, besylate, bitartrate, camphorsulfonate, citrate, decanoate, esylate, fumarate, gentisate, gluconate, glutamate, glutarate, glycinate dihydroxide, glycolate, hexanoate, hydroxynaphthoate, isethionate, lactate, lactobionate, malate, maleate, malonate, mandelate, mesylate, methylsulfate, methylsulfonate, mucate, napsylate, octanoate, oleate, oxalate, pamoate, pantothenate, phthalate, polygalacturonate, propionate, salicylate, stearate, succinate, tartrate, teoclate, toluenesulfonate, trifluoroacetate, trifluoromethanesulfonate, and any combination thereof.

The present disclosure provides methods of administering belumosudil mesylate salt to patients with cGVHD.

Provided are an intermediate for synthesizing a camptothecin derivative, a preparation method therefor, and the use thereof. An intermediate A can be obtained from 3-fluoro-4-methylaniline by means of acylation, bromination, and cross-coupling reactions. The intermediate A can be used for preparing an intermediate B to further prepare exatecan mesylate. The intermediate compound B can be obtained from the intermediate A by means of a rearrangement reaction, and exatecan mesylate can be obtained from the intermediate compound B by means of deprotection for acetamido and amino at the a site, a condensation reaction, and a hydrolysis reaction. The reaction starting materials have a low price, the reaction conditions of each step are moderate, the operation is simple, and the yield is high, such that the intermediate is suitable for industrial production.

This invention discloses a method for preparing benzyl 3-methyl-5-oxopiperidin-1-carboxylic acid ester and its intermediates. The method uses ethyl acetoacetate as a starting material, proceeding through trifluoromethanesulfonation to generate an enol trifluoromethanesulfonate intermediate, palladium-catalyzed cyanation, catalytic hydrogenation, reduction-cyclization transformation under a borohydride / transition metal salt system, nitrogen carbonyl protection, and sulfonium ylide-mediated transformation to obtain the intermediate. The intermediate is further rearranged / cyclized to obtain the target compound. Compared with existing routes, this invention avoids the use of malodorous / high-risk thiol reagents and highly corrosive acids, thus enabling the preparation of the target compound.

Provided herein are methods related to the administration of metopimazine, or a pharmaceutically acceptable salt thereof (e.g., metopimazine mesylate), and a GLP-1 agonist.

Disclosed are a salt (mesylate salt) of methanesulfonic acid and a triazolopyrazine derivative of formula (1), pharmaceutical compositions thereof, methods of making the salt, and therapeutic use thereof:

The present disclosure relates to the use of neuroactive steroids, including alfaxalone, alfadolone, alfadolone acetate, pregnanediol, pregnanolone, ent-pregnanolone, pregnanedione, allopregnanediol, allopregnanedione, acebrochol, ganaxolone, hydroxydione, minaxolone, renanolone, (2β,3α,5β)-21-chloro-3-hydroxy-2-morpholin-4-ylpregnan-20-one (Org-20599), 2β-(2,2-dimethyl-4-morpholinyl)-3α-hydroxy-11,20-dioxo-5α-pregnan-21-yl methanesulfonate (Org-21465), 20-(hydroxyimino)pregn-4-en-3-one (EIDD-036), posovolone (Co 134444), zuranolone (SAGE-217), 3α-hydroxy-3β- methyl-21-(pyrazolo[3',4'-c]pyridin-2'-yl)-19-nor-5β-pregnan-20-one (SGE-872), alfaxalone / alfadolone (CT1341), (3β,5β,17β)-3-hydroxyandrostane-17-carbonitrile (3β- OH), (3α,5α)-3-hydroxy-13,24-cyclo-18,21-dinorchol-22-en-24-ol (CDNC24), 3α- dihydroprogesterone (3α-DHP), ent-progesterone, dihydrodeoxycorticosterone (DHDOC), tetrahydrodeoxycorticosterone (THDOC), and betaxalone, for treating or at least partially inhibiting the development or progression of an infection caused by a neurotropic virus in a subject. This disclosure also relates to the use of neuroactive steroids for treating or at least partially inhibiting the development or progression of a condition associated with an infection caused by a neurotropic virus, such as encephalopathy or acute encephalitis.

The application discloses a preparation method of a naphthomostat mesylate impurity standard substance, and specifically comprises the following steps: firstly, reacting m-aminobenzoic acid with a hydrochloric acid solution to obtain an m-aminobenzoic acid hydrochloride solution; then, adding a magnetic solid acid catalyst and a 20-30% mass concentration cyanamide aqueous solution, and stirring and reacting at room temperature under a pulse magnetic field to obtain 3-guanidinobenzoic acid hydrochloride; then, adding 3-guanidinobenzoic acid hydrochloride, 6-amidino-2-naphthol mesylate, N,N'-dicyclohexyl carbodiimide and a supported catalyst into pyridine, stirring and reacting at room temperature to obtain 6-amidino-2-naphthyl-3-guanidinobenzoic acid ester; and finally, salifying to obtain 6-amidino-2-naphthyl-3-guanidinobenzoic acid ester mesylate. The 6-amidino-2-naphthyl-3-guanidinobenzoic acid ester mesylate with high purity and high yield obtained by the application is of great significance for the quality research of naphthomostat mesylate.

The invention discloses a preparation method of an aromatic pyrazole amine compound. According to the method, cesium fluoride is used as alkali, a 2-(trimethylsilyl) phenyl trifluoromethanesulfonate compound and 3-cyclopropyl-5-amino-1H-pyrazole react in acetonitrile at room temperature, and the aromatic pyrazole amine compound can be prepared through extraction, separation and purification. The method is simple to operate and simple in step, does not need additional catalyst or heating, and provides an efficient and practical new method for synthesis of the aromatic pyrazole amine compound with important value.

The application provides a synthesis method of metrafenone, and belongs to the technical field of organic synthesis, and comprises the following steps: firstly, subjecting 5-hydroxy-1-methyl-3-(trifluoromethyl)-1H-pyrazole to a hydroxymethylation reaction to obtain 4-(hydroxymethyl)-5-hydroxy-1-methyl-3-(trifluoromethyl)-1H-pyrazole; then, reacting with difluorobromoacetic acid to obtain 4-(hydroxymethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole; then, subjecting to a mesylation reaction to obtain a mesylate intermediate; simultaneously, preparing 3-acetylthio-5,5-dimethyl-4,5-dihydroisoxazole from 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole; then, subjecting the intermediate to a thioetherization reaction with the mesylate intermediate to obtain a thioether coupling intermediate; finally, performing an oxidation reaction in the presence of a catalyst to obtain metrafenone. By adopting the mesylate activated intermediate and combining a continuous flow fixed bed oxidation process, the method is favorable for improving the purity and total yield of the target product and reducing the tungsten residue in the product.

The invention discloses a 3, 4-dimethyl pyrazole salt as well as a preparation method and application thereof, and the 3, 4-dimethyl pyrazole salt is 3, 4-dimethyl pyrazole mesylate. The preparation method comprises the following steps: firstly, dispersing a 3, 4-dimethylpyrazole solid in an inert solvent, and diluting methanesulfonic acid with the inert solvent for later use; slowly adding the diluted methanesulfonic acid solution into a mixture of 3, 4-dimethyl pyrazole and an inert solvent; and after the reaction is finished, cooling materials after the reaction, separating out crystals, filtering and drying to obtain the 3, 4-dimethyl pyrazole mesylate. The 3, 4-dimethylpyrazole mesylate provided by the invention is low in use loss rate, strong in storage stability and good in nitrification inhibition effect.

Provided are an intermediate for synthesizing a camptothecin derivative, a preparation method therefor, and the use thereof. An intermediate A can be obtained from 3-fluoro-4-methylaniline by means of acylation, bromination, and cross-coupling reactions. The intermediate A can be used for preparing an intermediate B to further prepare exatecan mesylate. The intermediate compound B can be obtained from the intermediate A by means of a rearrangement reaction, and exatecan mesylate can be obtained from the intermediate compound B by means of deprotection for acetamido and amino at the a site, a condensation reaction, and a hydrolysis reaction. The reaction starting materials have a low price, the reaction conditions of each step are moderate, the operation is simple, and the yield is high, such that the intermediate is suitable for industrial production.

The utility model relates to the technical field of dihydroergoline mesylate preparation, in particular to a dihydroergoline mesylate discharging and sterilizing device which comprises a sterilizing cylinder, a stirring assembly used for uniformly sterilizing dihydroergoline mesylate is arranged in the sterilizing cylinder, and the stirring assembly comprises an inner cylinder fixedly connected to the interior of the sterilizing cylinder. According to the utility model, through the structural design of the stirring assembly, the central cylinder in the inner cylinder and the stirring plate, dihydroergoline mesylate can be effectively and uniformly stirred, so that the uniformity of materials is ensured, and the sterilization effect is improved; meanwhile, by arranging a ventilation pipe and forming holes in the outer part of the center cylinder, when the center cylinder drives the stirring plates to stir, air is blown into the center cylinder through the ventilation pipe, so that the air is blown into the inner cylinder through the outer part of the center cylinder, and an auxiliary stirring effect is achieved; the problem that the materials are adhered to the outside of the central cylinder and cannot be fully sterilized is avoided.

The present application provides a sublingual tablet composition of lumeritopine tosylate and a preparation method thereof. The sublingual tablet composition of lumeritopine tosylate comprises the following ingredients by weight percentage: lumeritopine tosylate 2% to 15% (1.4 mg / tablet to 10 mg / tablet), filler 15% to 75%, disintegrant 2% to 10%, surfactant 0.1% to 10%, lubricant 0.5% to 2%, glidant 0.5% to 2%, and flavoring agent 0.5% to 2%. The sublingual tablet composition is prepared by direct compression of powder. The sublingual tablet composition has good taste, does not irritate mucosa, is rapidly absorbed under the tongue, and has significantly higher bioavailability than ordinary oral tablets.