46 results about "Baricitinib" patented technology

The invention discloses an application of baricitinib in treatment of cerebral arterial thrombosis, and the baricitinib is used as a neuroprotective agent and is applied to treatment of cerebral arterial thrombosis after large vascular occlusion. The application of the invention reduces neuroinflammatory response, reduces nerve injury, protects nerves, improves stroke prognosis, and improves treatment effect.

The invention belongs to the technical field of crystal form medicine molecules, and particularly provides a baricitinib-salicylic acid eutectic crystal and baricitinib-5-sulfosalicylate, and the stability and solubility of the baricitinib-salicylic acid eutectic crystal and the baricitinib-5-sulfosalicylate are investigated. It is found that the stability or solubility of the compound is improved to a certain extent. And the two crystal forms are simple in preparation process. Good industrialization prospects are realized.

The invention belongs to the technical field of crystal form drug molecules, and particularly relates to a baricitinib-trimesic acid eutectic crystal and a preparation method thereof. The baricitinib-trimesic acid eutectic crystal provided by the invention is good in stability and high in solubility, and has improved pharmacokinetics, so that subsequent development requirements of drugs are met; the preparation method is simple to operate, easy to control the crystallization process, good in reproducibility and suitable for industrial production.

The application discloses a preparation method of baricitinib, and belongs to the technical field of drug synthesis. The method comprises the following steps: firstly, 2-[1-(ethylsulfonyl)-3-azetidinyl]acetonitrile and 4-pyrazole boron pinacol ester are subjected to a Michael addition reaction to obtain 1-(ethylsulfonyl)-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]-3-azetidine acetonitrile as an intermediate I; secondly, a protection group is introduced on the amino group of 4-chloropyrrolopyrimidine to obtain an intermediate II; finally, the intermediate I and the intermediate II are subjected to a Suzuki coupling process by adopting a method of combining a nickel pre-catalyst with a supporting ligand to obtain the baricitinib. The preparation method creatively realizes cross coupling of the baricitinib by adopting the cheap metal nickel as a catalyst, avoids the use of a heavy metal palladium catalyst, and has the advantages of low cost, low toxicity, small pollution, green environmental protection and the like.

The invention belongs to the technical field of crystal form drug molecules, and particularly relates to a preparation method and application of a baricitinib and glutaric acid eutectic acetonitrile solvate. The eutectic compound disclosed by the invention is good in solubility, and the bioavailability of the baricitinib is remarkably improved. The preparation process is simple. Good medical industrial application prospects are realized.

The invention belongs to the technical field of crystal form medicine molecules, and particularly relates to a preparation method and application of a baricitinib-saccharin eutectic crystal. Compared with eutectic crystals disclosed in the prior art, the baricitinib-saccharin eutectic crystal disclosed by the invention is high in stability, good in solubility and simple in preparation process. The bioavailability of the baricitinib can be obviously improved, and the baricitinib has a relatively good medical industrial application prospect.

The invention relates to the field of medicine and pharmacology, in particular to a deuterated balosavir precursor compound as well as a preparation method, a pharmaceutical composition and application of the deuterated balosavir precursor compound. The deuterated balosavir precursor compound is a compound as shown in a formula I, or a tautomer, a stereoisomer, a crystal form, a pharmaceutically acceptable salt, a hydrate or a solvate thereof, in the formula, R is the following groups: in the formula, R1, R2, R3, R4 and R5 are respectively and independently hydrogen or deuterium and at least contain one deuterium atom or are all deuterium. The compound and the composition have good cap-dependent endonuclease activity and better pharmacokinetic properties, have better safety to normal cells and better in-vitro antiviral effect, and can be used for preparing medicines for treating and / or preventing symptoms caused by influenza virus infection.

The application belongs to the technical field of tumor treatment and prevention, and particularly relates to application of Baloxavir (molecular formula: C 24 H 19 F2N3O4S, molecular weight: 483.487, CAS number: 1985605-59-1) in preparation of esophageal cancer, gastric cancer and other tumor drugs. The application first discovers that Baloxavir has toxic effects on esophageal cancer and gastric cancer cells and can inhibit the proliferation ability of the esophageal cancer and gastric cancer cells. The general design idea of the application is that esophageal cancer and gastric cancer cell drug treatment is carried out in vivo and in vitro, and the application of Baloxavir in esophageal cancer, gastric cancer and other tumors is determined by affecting the growth of esophageal cancer and gastric cancer cells. The results show that appropriate concentration of Baloxavir has toxic effects on esophageal cancer and gastric cancer cells and can inhibit the proliferation ability of the esophageal cancer and gastric cancer cells, thereby providing a new therapeutic drug for treatment and prevention of esophageal cancer, gastric cancer and other tumors.

The invention discloses an application of a substance for detecting a marker group. The application comprises one or more of the following applications: A1) an application in preparation of a product for predicting sensitivity of bicitinib combined with narrow-spectrum medium-wave ultraviolet rays in treatment of leucoderma, and A2) an application in preparation of a product for predicting sensitivity of bicitinib combined with narrow-spectrum medium-wave ultraviolet rays in treatment of leucoderma; a2) is applied to preparation of a product for screening sensitivity of bicitinib combined with narrow-spectrum medium-wave ultraviolet rays in treatment of leucoderma; a3) in preparation of a product for evaluating sensitivity of bicitinib combined with narrow-spectrum medium-wave ultraviolet rays in treatment of leucoderma; the marker group is composed of CCL5, FGL1, EZR and GAPDH (glyceraldehyde-phosphate dehydrogenase). The invention screens and verifies the plasma and urine biomarker group capable of predicting the sensitivity of treating leucoderma by combining baricitinib with narrow-spectrum medium-wave ultraviolet rays of a subject through ELISA (Enzyme-Linked Immunosorbent Assay), and the plasma and urine biomarker group provided by the invention has higher prediction accuracy, sensitivity and specificity; the individualized treatment of vitiligo can be improved, and good clinical application and popularization prospects are achieved.

This invention belongs to the technical field of pharmaceutical preparation, specifically relating to baloxavir derivatives, their preparation methods, and applications. The baloxavir derivatives are compounds I, II, or III, with the following general structural formulas: Formula I: where R1 and R2 are H, OCH3, or Br; Formula II: where R1 and R2 are H or F, R3 is H, F, OCH3, or a benzene ring, and A is C or O; Formula III: where A is S or O, B is C or N, and X is CH3, Cl, or a benzene ring. This invention provides a baloxavir derivative for use as a nuclease inhibitor, and also provides a method for its preparation.

This disclosure relates to methods of treating, preventing, or reversing inflammation-associated central nervous system (CNS) disorders or conditions comprising administering an effective amount of a Janus kinases (JAK) inhibitor such as baricitinib to a patient in need thereof. In certain embodiments, the CNS associated inflammatory disorder is depression, treatment resistant depression, fatigue, or cognitive dysfunction.

The invention belongs to the technical field of crystal form drug molecules, and particularly relates to baricitinib-maleic acid-gallate. After the three components form the salt, the solubility of baricitinib can be remarkably enhanced, the oral bioavailability is improved, and the salt has a very high patent medicine value and a relatively good application prospect in the medical industry.

The invention relates to the technical field of pharmaceutical preparations, and particularly discloses a tablet composition for treating alopecia areata and a preparation method thereof.The tablet composition is a composition comprising two main drugs including finasteride and baricitinib and is prepared by mixing and pressing finasteride particles and baricitinib particles which are prepared through specific auxiliary materials and a process, the finasteride granules and the baricitinib granules have good Karl index and Hausner ratio after being mixed, the pressed tablet composition has good performance in a plurality of test items such as acceleration for 6 months, long-term 6 months and high-humidity test, and the auxiliary material formula and the process can simultaneously meet the quality requirements of finasteride and baricitinib. Meanwhile, the degradation condition of the main medicine is relieved, the increase of related impurities of finasteride and baricitinib is reduced, the quality stability of the medicine under different storage conditions is improved, and the safety and effectiveness of the medicine within the period of validity and the integrity of the appearance of the tablet are ensured.

This invention belongs to the field of pharmaceutical formulation technology and discloses a baloxavir derivative tablet, its preparation method, and its application. The tablet comprises a surface-acidified passivated magnesium aluminum silicate carrier, baloxavir ester, poloxamer 188, microcrystalline cellulose, and magnesium stearate. During preparation, anhydrous citric acid is used to neutralize the basic active sites of pure magnesium aluminum silicate to construct micro-acidic channels. Subsequently, the carrier, baloxavir ester, and poloxamer 188 are mixed and heated, causing the polymer to melt, encapsulate the drug, and penetrate into the mesopores of the carrier. Finally, forced quenching treatment is performed to confine the drug in an amorphous or nanocrystalline state within the channels. This invention blocks the alkaline-catalyzed degradation pathway of baloxavir ester, maintains the high free energy state of the drug through physical spatial confinement, improves the in vitro dissolution rate, and enhances the flowability of the compressed powder.

The present invention relates to the use of baloxavir sodium and / or solvates thereof and / or hydrates thereof of Formula I, for the preparation of a medicament for the treatment of a Bunyavirus, in particular Crimean-Congo hemorrhagic fever virus (CCHFV) infection,

The invention belongs to the technical field of crystal form drug molecules, and discloses a baricitinib oxalate crystal form and a preparation method thereof. The invention particularly relates to a crystal form 1 and a crystal form 2 of Baricitinib oxalate and a preparation method of the crystal form 1 and the crystal form 2. And the stability and solubility of the compound are investigated. It is found that the stability or solubility of the compound is improved to a certain extent. And the two crystal forms are simple in preparation process. Good industrialization prospects are realized.

This invention belongs to the field of analytical detection technology and discloses an analytical method for detecting N-nitrosobaricitinib impurities in baricitinib tablets. The method includes solution preparation and detection steps: blank, 0.9 ng / ml reference standard, and test sample solutions are prepared using a 40%–60% acetonitrile aqueous solution as a diluent; an Agilent Poroshell 120 EC-C18 column is used with 0.1% formic acid-methanol gradient elution; mass spectrometry is performed using an AJS ESI ion source in MRM scanning mode; and the content is calculated using the external standard method. This method is simple to operate, rapid in analysis, highly specific, highly sensitive (detection limit 4.30 ppb), and exhibits excellent precision, accuracy, and linearity. It can accurately quantify target impurities, providing reliable technical support for the quality control of baricitinib tablets.

The invention discloses a baricitinib refining method, which comprises: mixing a baricitinib crude product, a mixed solvent of a solvent A and a solvent B, and water, and stirring at a temperature of 70-90 DEG C until the solution is clear; adding activated carbon, stirring, decolorizing and filtering to obtain filtrate; and cooling the filtrate, stirring for crystallization, filtering and drying to obtain a baricitinib finished product. According to the invention, the crude product with low purity can be subjected to one-step refining to obtain the high-purity finished product. The purity of the baricitinib finished product prepared by the method reaches 99.95% or above, the yield reaches 90% or above, and the method is suitable for industrial production. The baricitinib refining method disclosed by the invention is mild and simple in reaction condition, and convenient for reaction reproduction and amplified production.

The invention provides a baricitinib in-situ sustained-release gel preparation. The baricitinib in-situ sustained-release gel preparation comprises an active component, a gel carrier, an organic solvent and other optional pharmaceutically acceptable auxiliary materials. The in-situ sustained-release gel preparation disclosed by the invention can realize long-term stable release, reduce the administration frequency, reduce the treatment risk caused by blood concentration fluctuation, reduce the toxic and side effects and improve the medication compliance of patients; the local concentration of the medicine is improved, and the bioavailability is improved, so that the medicine effect is better played, and the application value is high.

This invention relates to compounds of Formula I or salts thereof. The invention also provides the application of Formula I in the preparation of medicaments for treating JAK-related autoimmune diseases, inflammatory diseases, or cancers, which exhibit significant stability, maintain effective blood concentrations for a certain period, thereby prolonging the drug administration cycle, improving patient compliance, and reducing side effects caused by rapid drug release.

The invention relates to the technical field of medicine synthesis, and particularly discloses a preparation method of a baricitinib key intermediate. According to the method, sodium hydroxide and other cheap strong bases with better stability are adopted to replace flammable and explosive NaH, the use amount of an expensive tetrakis (triphenylphosphine) palladium catalyst is reduced, petroleum ether extraction and other operations are adopted to replace column chromatography purification, N, N-dimethylformamide is selected as a reaction solvent, and the method is suitable for industrial production. The method not only improves the total yield and the product purity of the baricitinib key intermediate, but also reduces the production cost, simplifies the operation process, shortens the production cycle, improves the production safety, is more environment-friendly, solves the limitation of large-scale industrial production of the original research route, and has higher practical value and industrial application potential.

The invention provides a synthesis method of a key intermediate of baricitinib, namely a method for synthesizing 2-[1-(ethylsulfonyl)-3-azacyclobutyl subunit] acetonitrile. By optimizing the preparation process, the reaction time is shortened, the yield and the purity are improved, and batch modular industrial production is facilitated.

The present invention relates to microspheres comprising a baricitinib inclusion compound using a cyclodextrin derivative and a preparation method therefor, wherein barricitinib, which is a poorly soluble drug, or a pharmaceutically acceptable salt thereof is prepared as an inclusion compound using a cyclodextrin derivative to increase solubility, and are prepared together with a biodegradable polymer as microspheres by utilizing such dissolution characteristics, thereby exhibiting a sustained release effect of barricitinib or a pharmaceutically acceptable salt thereof for one month or longer. In addition, baricitinib or a pharmaceutically acceptable salt thereof is prepared as an inclusion compound using a cyclodextrin derivative, and the inclusion compound and a biodegradable polymer are used to prepare a W1 / O / W2 emulsion, which is then solidified to form microspheres, thereby suppressing initial burst release and exhibiting a consistent release pattern of baricitinib or a pharmaceutically acceptable salt thereof for one month or longer.

The present invention belongs to the technical field of pharmaceutical synthesis, and specifically relates to a method for synthesizing baricitinib-related substances. The baricitinib-related substances include at least one of related substances A and related substances B. The synthesis steps of related substance A are: (1) reacting a compound of formula III to obtain a compound of formula II, wherein the compound of formula III is 4,6-dichloro-5-pyrimidinecarboxylic acid, (2) reacting the compound of formula II with a compound of formula I to obtain related substance A; the synthesis steps of related substance B are: (1) reacting a compound of formula IV to obtain a compound of formula V, wherein the compound of formula IV is 4-hydroxypyrimidine, (2) reacting the compound of formula V to obtain a compound of formula VI, (3) reacting the compound of formula VI with a compound of formula I to obtain a compound of formula VII, and (4) reacting the compound of formula VII to obtain related substance B. The present invention can rapidly, simply and efficiently synthesize baricitinib-related substances A and B, and the reaction conditions are mild and controllable, the accuracy is good, and the product purity is high.

The invention provides a baricitinib nano-cream and a preparation method thereof, and belongs to the technical field of pharmaceutical preparations. The baricitinib nano-cream provided by the invention comprises a cream matrix and a nano-structure lipid carrier dispersed in the cream matrix, the nano-structure lipid carrier comprises a solid lipid, a liquid lipid and a non-ionic emulsifier, and the types of the solid lipid and the liquid lipid are specifically limited, so that the content of the solid lipid and the liquid lipid in the nano-structure lipid carrier is increased, and the content of the non-ionic emulsifier in the nano-structure lipid carrier is increased. According to the present invention, the solid lipid provides the structure stability, the liquid lipid introduces the lattice defect, such that the solubility and the encapsulation efficiency of the baricitinib or the pharmaceutically acceptable salt thereof are improved so as to improve the release rate and the stability of the baricitinib nano-cream. The nanostructured lipid carrier is dispersed in the cream matrix, so that the permeability and adhesiveness of the baricitinib nanocream can be improved.

The invention belongs to the technical field of drug synthesis, and particularly relates to a method for preparing baricitinib, the baricitinib can be prepared with high yield and high purity through pyrazole ring synthesis, the reaction condition is mild, the post-treatment is simple, and the method is suitable for industrial production.

Among the various aspects of the present disclosure is the provision of conditioning agents for use in allogeneic hematopoietic stem cell transplantation. An aspect of the present disclosure provides for a method of treating a subject or inhibiting alloreactivity in the host-versus-graft direction comprising administering a combination of conditioning agents comprising an anti-body-drug conjugate (ADC) and a JAK1 / JAK2 inhibitor for use in allogeneic hematopoietic stem cell transplantation in an amount sufficient to permit engraftment of allogeneic bone marrow. In some embodiments, the ADC is selected from CD45-SAP, cKit-SAP, CD117-Amanitin, and CD45-PBD. In some embodiments, the JAK1 / JAK2 inhibitor is selected from baricitinib and ruxolitinib. In some embodiments, the method further comprises administering a cancer therapeutic.

The invention provides a preparation method of a JAK inhibitor intermediate, and particularly relates to a preparation method of a baricitinib or ruxolitinib intermediate. The method does not use precious metal reagents, the reagents are cheap and easy to obtain, post-treatment is simple, and the method is suitable for large-scale industrial production.

This invention provides a method for synthesizing a key intermediate of baricitinib, namely, a method for synthesizing 2-[1-(ethylsulfonyl)-3-azacyclobutylene]acetonitrile; this invention optimizes the preparation process, shortens the reaction time, improves the yield and purity, and is conducive to batch-by-batch modular industrial production.

The application relates to the technical field of medicines, and particularly discloses a baricitinib tablet and a preparation method thereof. The baricitinib tablet comprises a tablet core and a coating film, the tablet core is obtained by tabletting core materials, the coating film is formed by solidifying a coating liquid, and the components of the coating liquid comprise hydroxypropyl methyl cellulose, medical-grade polyacrylic acid resin, egg white protein and water. Compared with a single-component hydroxypropyl methyl cellulose coating film, the coating film can make a greater contribution to the hardness of the baricitinib tablet, and is helpful to overcome the adverse effect of microcrystalline cellulose on the hardness of the baricitinib tablet. By adopting the technical scheme, a tablet product with relatively high hardness can be produced by using relatively poor microcrystalline cellulose, the requirement of a tablet production process on raw materials is reduced, and full use of the microcrystalline cellulose is facilitated.