115 results about "Mesylate" patented technology

The invention relates to the technical field of medicines, in particular to a sustained-release coating as well as a preparation method and application thereof. The coating adopts a three-layer gradient structure design and comprises an inner layer coating, a middle layer coating and an outer layer coating, and the layers are compounded and matched through ethyl cellulose and hydroxypropyl methylcellulose with different molecular weights and are combined with talcum powder filling amount with gradient decreasing and a triethyl citrate plasticizer, so that accurate regulation and control of drug release are realized. Through hierarchical swelling-diffusion dynamic balance, burst release is inhibited, the inner layer has high talcum powder content to resist initial swelling stress, the outer layer has low filling amount to maintain hydrophobic continuity, interface defects are reduced in combination with high-temperature curing, and the release stability and long-term storage performance of drugs such as dihydroergoline mesylate are remarkably improved; the problems of sudden release, damp-heat sensitivity, impurity generation and the like of a traditional single-layer coating are solved.

The present invention discloses a method for preparing a linker-drug conjugate and its intermediates. Specifically, a method for preparing compound LE14 is provided, which comprises subjecting an intermediate compound of formula II to an amide condensation reaction with a compound of formula III or its mesylate in the presence of a condensing agent, a base, and a solvent to obtain a compound of formula I. This method can produce a high-purity intermediate II, which is directly condensed with isotecan mesylate to obtain compound I, and then subjected to subsequent reactions to obtain the final product LE14. The preparation method of the present invention has one or more of the following advantages: using intermediate II as the starting material for the production process reduces process steps, facilitates product quality control, significantly reduces impurities in the final product, and improves purity. Furthermore, using the more economical isotecan for the condensation reaction significantly reduces production costs, making it more suitable for industrial production.

A drug combination of purinostat mesylate and an analog thereof for preventing and treating multiple myeloma, and the use thereof. Specifically, provided is a three-drug or four-drug combination of purinostat mesylate and an analog thereof, dexamethasone and other drug, which drug combination has significantly enhanced synergistic anti-tumor activity in vitro and in vivo, synergistically inhibits the expression of the key survival protein in multiple myeloma, is superior to existing clinical combination regimens, and has no significant toxic side effects. In addition, the drug combination significantly down-regulates the expression of CDK6, and overcomes the drug resistance to an immunomodulator. In particular, the three-drug combination of puisostat mesylate, a glucocorticoid and an immunomodulator has an excellent prevention and treatment effect on multiple myeloma, especially relapsed / refractory multiple myeloma.

Purinostat mesylate (PM) for preventing and treating diffuse large B-cell lymphoma (DLBCL), an analogue thereof, a drug for combined use, and the use. PM exhibits excellent in-vivo and in-vitro anti-tumor therapeutic effects on DLBCL (DEL and DHL) subtypes with poor prognosis, DLBCL subtypes having TP53 deletion and mutation combined with a plurality of poor prognosis gene mutations, and DLBCL having TP53 mutation with double expressors, which are superior to that of most existing DLBCL clinical therapy plans. A doublet or triplet therapy of PM with rituximab, R-CHOP, venetoclax and R-CHP also exhibits excellent in-vivo therapeutic effects against DLBCL and a plurality of subtypes. Thus, PM and the drug for combined use have an important clinical significance for the DLBCL and a plurality of subtypes.

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

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 preparation method of a key intermediate (3aR, 5S, 6aS)-5-(methylamino) hexahydrocyclopenta [c] pyrrol-2 (1H)-tert-butyl formate mesylate of a JAK kinase inhibitor, and belongs to the field of medical intermediates. The preparation method comprises the following steps: taking cis-5-oxohexahydrocyclopenta [C] pyrrol-2 (1H)-carboxylic acid tert-butyl ester as a raw material to react with methylamine equivalent to obtain an intermediate A; then carrying out reduction reaction in metal sodium and isopropanol to obtain a crude product, adding L-DBTA to form salt, removing isomers, and carrying out re-dissociation and salt formation with methanesulfonic acid to obtain a pure product. The method greatly shortens the reaction steps, reduces the raw material cost, is simple and reliable in process, and is easy for industrial production.

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.

The invention discloses treatment of EGFR mutation positive non-small cell lung cancer brain metastasis by administering an effective dose of an EGFR inhibitor. The EGFR inhibitor is N-(2-((2-(dimethylamine) ethyl) (methyl) amine)-4-methoxy-5-((4-(1-deuterated methyl-1H-indol-3-yl) pyrimidine-N '-2-yl) amine) phenyl) acrylamide mesylate.

The invention belongs to the technical field of chemical analysis, and particularly relates to a method for separating and determining a rucotinib mesylate intermediate Z1 and related impurities thereof. The impurities comprise any one or more of an impurity SM2a, an impurity SM1d, an impurity Z1c, an impurity Z1b, an impurity Z1a, triphenylphosphine oxide, an impurity SM2, an impurity SM1 and an impurity Z1d. Octadecylsilane chemically bonded silica is adopted as a chromatographic column filling agent; a monopotassium phosphate buffer solution is used as a mobile phase A, a mixed solution of methanol and acetonitrile is used as a mobile phase B, and main components are separated from impurities through gradient elution; and detecting in a detector to obtain a chromatogram. The method is high in specificity, short in separation time, high in sensitivity and good in durability, and has important significance on quality control of rukotinib mesylate bulk drugs and preparation products.

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 salt form of a coronavirus 3CL protease inhibitor PLC-01 as well as a preparation method and application of the salt form, and belongs to the technical field of medicinal chemistry. Salt types of PLC-01 comprise inorganic acid salt, organic acid salt, sodium salt and a free state. According to the present invention, various organic acids, inorganic acids and solvents are mainly screened so as to obtain the PLC-01 hydrochloride Pattern A, the PLC-01 mesylate Pattern A, the PLC-01 sodium salt Pattern C and the PLC-01 free state Pattern A, wherein the PLC-01 hydrochloride Pattern A, the PLC-01 mesylate Pattern A, the PLC-01 sodium salt Pattern C and the PLC-01 free state Pattern A have characteristics of high purity and good stability; the invention also discloses a pharmaceutical composition of the salt form of the compound shown in the formula I. All salt forms of PLC-01 in the invention have strong inhibition efficacy on 3CL protease, and are expected to become novel active pharmaceutical ingredients for preventing or treating novel coronavirus infection.

The invention belongs to the technical field of biological medicines, and particularly relates to an application of Mitoquinone mesylate in resisting mycobacterium tuberculosis infection. According to the application disclosed by the invention, the biological effect of the Mitoquinone mesylate in resisting mycobacterium tuberculosis infection is found, the MIC of the Mitoquinone mesylate to a mycobacterium tuberculosis standard strain can reach 1.25 mu M, and the MIC of the Mitoquinone mesylate to a drug-resistant mycobacterium tuberculosis clinical isolated strain is more concentrated to be 1.25 mu M. In conclusion, the autophagy regulation effect of the Mitoquinone mesylate is remarkable, and the Mitoquinone mesylate can become a new treatment medicine in the anti-mycobacterium tuberculosis infection process. The clinical guiding significance is realized; moreover, the Mitoquinone mesylate is easy to obtain and low in cost, the prepared medicine takes effect quickly, and the Mitoquinone mesylate has actual production and application prospects. The Mitoquinone mesylate is high in safety, small in side effect and good in patient compliance.

The invention relates to mesylate of a heterocyclic substituted fused gamma-carboline derivative, a crystal form and a preparation method and application thereof. In particular, the present invention relates to a mesylate and a crystal form of a compound (6bR, 10aS)-8-(4-(4-fluorophenyl)-4-oxobutyl)-3, 6b-dimethyl-6b, 7, 8, 9, 10, 10a-hexahydro-1H-pyridine [3 ', 4': 4, 5] pyrrole [1, 2, 3-dequinoxaline-2 (3H)-one, a preparation method and application thereof, and a pharmaceutical composition containing a therapeutically effective amount of the mesylate and the crystal form of the compound, the invention also relates to application of the compound in preparation of medicines for preventing and / or treating neuropsychiatric diseases.

The present disclosure relates to a pharmaceutically acceptable salt and a crystal form of a fused pyridine ring derivative and a preparation method therefor. Specifically, the present disclosure relates to a choline salt, sodium salt, potassium salt, calcium salt, arginine salt, lysine salt, meglumine salt, ethanolamine salt, hydrosulfate, hydrochloride, tartrate, maleate, citrate, malate, p-toluenesulfonate, and mesylate, and a crystalline form of a compound as represented by formula (I).

1. Name of the designed product: packaging box (veterinary fleroxacin mesylate injection); 2. Use of the designed product: veterinary drug packaging; 3. Design points of the design: the pattern of the product; 4. Picture or photo best indicating the design points: front view.

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 invention discloses a preparation method of a key intermediate of darolamide (S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chlorobenzonitrile, and belongs to the technical field of pharmaceutical chemical industry. The invention uses 3-bromopyrazole as a starting material, and replaces it with (S)-2-((tert-butyloxycarbonyl)amino)propyl methanesulfonate to obtain (S)-(1-(3-bromo-1H-pyrazol-1-yl)propyl-2-yl)carbamate tert-butyl ester, and then couples it with 2-chloro-4-cyanophenyl borate to obtain (S)-(1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propyl-2-yl)carbamate tert-butyl ester, and finally hydrolyzes it to obtain (S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chlorobenzonitrile. The method has few synthetic steps, simple operation, high safety, high yield and the like, and is suitable for industrial production.

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.

The invention belongs to the technical field of medicinal chemistry, and relates to a novel crystal form of Lanziatinib mesylate and a preparation method thereof, in particular to a crystal form Q1, a crystal form Q3 and a crystal form Q6 of Lanziatinib mesylate.

The invention belongs to the technical field of environmental protection, and provides a composite particle for treating water floating algae and a preparation method and application thereof, the preparation method comprises the following steps: a, preparing intranuclear active Gemini type biquaternary ammonium cationic polymer mesylate; b, preparing a coating material; c, preparing composite particles: mixing the coating material in the step b with castor oil and sodium bicarbonate, heating and stirring to obtain a coating solution, and adding the Gemini type biquaternary ammonium cationic polymer mesylate prepared in the step a to obtain the composite particles; and d, evaluating the performance of the composite particles. According to the invention, a biodegradable and non-toxic natural polymer material is used as an outer coating, so that slow release and targeted release of quaternary ammonium salt are realized. Quaternary ammonium salt is coated in a compound formed by PVA and chitosan, the release rate of the quaternary ammonium salt is controlled, floating or suspension is realized through density adjustment, and targeted treatment of blue-green algae on the water surface is realized.

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 a method for determining three methanesulfonate genotoxic impurities in a prasefovir mesylate tablet by gas chromatography-mass spectrometry, and belongs to the technical field of pharmaceutical analysis. The invention relates to a method for determining three methanesulfonate genotoxic impurities in prasefovir mesylate tablets by gas chromatography-mass spectrometry. The method comprises the following steps: (1) preparing three single-standard stock solutions, a mixed standard solution and a mixed standard series solution; (2) preparing a test solution; (3) rapid qualitative screening; and (4) quantitative determination. The gas chromatography-mass spectrometry method (GC-MS method) has remarkable advantages in the aspects of operation simplicity, specificity, sensitivity, accuracy and the like, the method is simple in operation process, sample pretreatment is easy to implement, the detection time is greatly shortened, and the detection efficiency is improved.

The invention discloses a crystal form of carboxamide triazole salt, a preparation method, a pharmaceutical composition and application thereof. The carboxamide triazole salt is at least one of 1-naphthalene sulfonate, benzene sulfonate or mesylate. An X-ray powder diffraction pattern of the crystal form I of the carboxamide triazole 1-naphthalenesulfonate, which is expressed by a 2 theta angle, has the following characteristic peaks: 3.8 degrees + / -0.2 degrees, 13.1 degrees + / -0.2 degrees, 16.2 degrees + / -0.2 degrees, 17.7 degrees + / -0.2 degrees, 18.7 degrees + / -0.2 degrees and 25.8 degrees + / -0.2 degrees. An X-ray powder diffraction pattern of the crystal form I of the carboxamide triazole benzene sulfonate expressed by a 2 theta angle has the following characteristic peaks: 6.1 degrees + / -0.2 degrees, 13.7 degrees + / -0.2 degrees, 19.2 degrees + / -0.2 degrees, 19.8 degrees + / -0.2 degrees, 23.5 degrees + / -0.2 degrees and 27.5 degrees + / -0.2 degrees. An X-ray powder diffraction pattern of the crystal form II of carboxamide triazole mesylate expressed by a 2 theta angle has the following characteristic peaks: 15.9 degrees + / -0.2 degrees, 18.0 degrees + / -0.2 degrees, 19.9 degrees + / -0.2 degrees, 20.7 degrees + / -0.2 degrees, 23.4 degrees + / -0.2 degrees and 29.3 degrees + / -0.2 degrees.

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.

The invention discloses a method for preparing a methanesulfonate product. The method comprises the following steps: in a dichloromethane system, the reaction temperature is controlled to be no higher than 40°C and the reaction rate is controlled, a mixed solution of methanesulfonyl chloride and methanesulfonic anhydride reacts with sodium alkoxide, after the reaction is completed, the reaction solution is cooled to room temperature, filtered, dried, and subjected to rotary evaporation to remove the solvent, and distilled to obtain the methanesulfonate product. The method has a simple synthesis route, does not use an acid binding agent, a phase transfer catalyst or an esterification catalyst, does not require heating, has a short reaction time, and greatly reduces the total production cost in terms of raw materials, production cycle, environmental protection, and the like. The yield and purity of the product prepared by the method are very high, with the yield reaching above 98.2% and the purity reaching above 99.9%. The moisture content of the obtained product is also very low, and the quality of the product obtained by the method far exceeds the product standard for use as an electrolyte.