26 results about "Baricitinib" patented technology

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.

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.

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.

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 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 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.

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 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.

The invention belongs to the technical field of crystal form drug molecules, and particularly provides a baricitinib-4-hydroxybenzoic acid eutectic crystal and a preparation method thereof. The baricitinib-4-hydroxybenzoic acid eutectic crystal disclosed by the invention is greatly improved in the aspects of stability and solubility, and the bioavailability of the baricitinib is remarkably improved. And the preparation process of the eutectic is simple. Good industrialization prospects are realized.

The invention belongs to the technical field of crystal form drug molecules, and particularly relates to a new salt crystal form of baricitinib glycolic acid. The obtained baricitinib glycolate crystal form is good in stability and high in solubility. The bioavailability of the baricitinib is remarkably improved, and the baricitinib has a relatively good medical industrial application prospect.

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 isophthalic acid eutectic dichloromethane solvate. The eutectic compound is high in stability, good in solubility and simple in preparation process. And the bioavailability of the baricitinib is obviously improved. Good medical industrial application prospects are realized.

The present disclosure relates to a method of treating or ameliorating symptoms of a motor neurone disease and improving motor neuron survival in a subject, more specifically treating or ameliorating symptoms of amyotrophic lateral sclerosis (ALS) and related neurodegenerative disorders. The treatment method comprises administering a Janus kinase (JAK) inhibitor in combination with one or more compounds selected from a glutamate antagonist and an N-methyl-D-aspartate (NMDA) receptor antagonist, in particular baricitinib in combination with riluzole and / or memantine, and compositions and kits thereof for same.

The invention provides a novel intermediate for synthesizing baloxvir and baloxvir dipivoxil and a preparation method of the novel intermediate. According to the method, a compound 7 is used as a starting material, and a new intermediate compound 8 is prepared in the presence of a lithium salt. According to the preparation method of the compound 8 provided by the invention, the use of a Grignard reagent is avoided, industrial amplification is safer, and treatment is easier. Meanwhile, the invention provides an intermediate compound 8-5, the intermediate compound 9-5 prepared from the intermediate compound 8-5 has a higher dr value and yield, the content of isomer impurities of baloxvir is reduced, the difficulty of later purification of baloxvir is greatly reduced, the yield of later purification of baloxvir is greatly increased, and the production cost is reduced.

The invention discloses a marker group for evaluating sensitivity of bicitinib combined with narrow-spectrum medium-wave ultraviolet rays in treatment of leucoderma, a substance for detecting the marker group, a kit and an evaluation method. The marker group contains a plasma biomarker P selectin (SELP), an apolipoprotein A4 (APOA4), a mannan binding lectin associated serine protease 1 (MASP1), and a urine biomarker immune globulin J chain (IGJ) and an interleukin 18 binding protein (IL-18BP). By detecting the expression change of the group of markers in a sample before and after treatment and combining with a vitiligo area scoring index (VASI), the treatment sensitivity of a patient can be accurately evaluated, an individualized scheme can be made in an assisted manner, the blank of the combination therapy curative effect evaluation marker is filled, and the combination therapy curative effect evaluation marker has a relatively high clinical transformation value.

The application discloses a baloxavir ester crystal form B1 and a preparation method thereof. Using Cu-Kα radiation, the X-ray powder diffraction pattern expressed by a 2θ angle has characteristic peaks at positions of 8.24°±0.2°, 9.80°±0.2°, 11.24°±0.2°, 11.76°±0.2°, 13.50°±0.2°, 14.80°±0.2°, 18.08°±0.2°, 19.44°±0.2°, 20.60°±0.2°, 21.18°±0.2°, 21.46°±0.2°, 22.58°±0.2°, 24.38°±0.2°, 25.28°±0.2°, 27.18°±0.2° and 33.42°±0.2°. The crystal habit is blocky, the filtration resistance is smaller than that of Form I with a fine needle-like crystal habit, the particle sample after grinding has a smaller angle of repose, has better particle flowability, and is more beneficial to subsequent preparation process treatment.

The invention discloses a new crystal form of baricitinib and a preparation method thereof, a pharmaceutical composition containing the crystal form, and application of the crystal form in preparation of a JAK kinase inhibitor and a pharmaceutical preparation for treating rheumatoid arthritis. Compared with the prior art, the novel crystal form of baricitinib provided by the invention has one or more improved characteristics, and has important value for optimization and development of the medicine in the future. (I).