40 results about "Nintedanib" patented technology

The present invention relates to a combination therapy of pexidartinib and nintedanib for use in the prevention or treatment of pulmonary fibrosis, in particular to a combination therapy of pexidartinib and nintedanib for use in the prevention or treatment of pulmonary fibrosis.

The invention discloses a medicine for relieving side effects of gastrointestinal tracts caused by nintedanib, a medicine for preventing or treating pulmonary fibrosis and application of stachyose, and belongs to the technical field of medicines. The medicine taking the stachyose as the active ingredient can effectively relieve gastrointestinal tract side effects caused by the nintedanib, for example, intestinal mucosa lesions caused by the nintedanib can be obviously relieved, for example, intestinal mucosa tissue structure abnormity, intestinal cell proliferation activity reduction, intestinal cell apoptosis increase, intestinal tissue inflammatory factor gene expression level up-regulation and the like.

The invention discloses a method for measuring the delivery rate and the total delivery amount of nintedanib lipidosome, and relates to the technical field of detection of pharmaceutical preparations, and the method comprises the following steps: placing filter paper into a filter paper device, connecting an atomizer by using an adapter, and setting a respiration simulator as an adult mode; pouring the to-be-detected Nintedanib liquid medicine into an atomizer, starting the respiration simulator, working for 60 seconds, synchronously starting and stopping the compressor during the period, taking out the filter paper to obtain a first piece, replacing the filter paper with new filter paper, continuously atomizing until no smoke, and taking down to obtain a second piece; a test solution is obtained through treatment, the test solution and the reference solution are injected into a chromatograph, the result of the first test solution is the delivery rate, and the result of the second test solution is the total amount; according to the method for determining the delivery rate and the total delivery amount of the nintedanib liposome, atomized medicine can be accurately and effectively extracted, the recovery rate is high, the detection method is simple in mobile phase, convenient to operate and good in accuracy, the problem of accurate detection of main components in the delivery of the nintedanib liposome medicine is solved, and the accuracy of a detection result is improved.

The invention discloses a pharmaceutical composition for inhibiting tumor drug resistance and application thereof. The pharmaceutical composition comprises an exosome inhibitor, nintedanib and gemcitabine, the exosome inhibitor, the nintedanib and the gemcitabine are used in a combined manner, so that the cell viability of the CTS can be remarkably reduced, and the proportion of apoptotic cells in the CTS can be remarkably increased; the pharmaceutical composition interferes with the mutual transformation process between normal fibroblasts and CAFs, and inhibits secretion and release of EVs and reduces formation of new CAFs while restoring the CAFs existing in TME to normal fibroblasts, thereby successfully reversing the drug resistance of tumors.

The present invention relates to a pharmaceutical formulation containing nintedanib or a pharmaceutically acceptable salt thereof and a methacrylic acid copolymer, wherein the formulation provides an excellent dissolution rate of 90% or more after 180 minutes under the conditions of the Korean Pharmacopoeia dissolution method II (paddle method) at 50 rpm in a test solution of pH 4.5.

The application discloses a compound inhalation powder aerosol and a preparation method thereof. The compound inhalation powder aerosol comprises apremilast or a pharmaceutically acceptable salt thereof and an efficacy enhancing substance, wherein the efficacy enhancing substance is nintedanib or a pharmaceutically acceptable salt thereof; and the amount of the efficacy enhancing substance is 0.1-10 times the amount of the apremilast or the pharmaceutically acceptable salt thereof. In the compound inhalation powder aerosol, the drug exposure of apremilast is greatly improved under the action of nintedanib, and a significant enhancement effect is exhibited. Meanwhile, nintedanib further improves efficacy. The powder aerosol is used for pulmonary inhalation administration, and apremilast or the pharmaceutically acceptable salt thereof and nintedanib or the pharmaceutically acceptable salt thereof are used for treating lung diseases, so that the drugs can be directly delivered to effective sites, the administration dose can be further effectively reduced or the drug utilization rate can be improved, the deposition rate can be improved, and the treatment effect can be greatly improved.

This invention provides a method for treating ocular indications involving abnormal neovascularization. [Solution] The present invention provides a method comprising the step of administering an effective amount of nintedanib or a pharmaceutically acceptable salt thereof in the form of a topical eye drop or implant to the eye of a subject.

The present invention concerns the compounds of formula (I)wherein R1, R2, R3, X, and Y are as described in the description, and their use as antagonists of the LPA1 receptor, in combination with one or more therapeutically active ingredients acting as anti-fibrotic agent(s); such as especially pirfenidone and / or nintedanib, in the prevention and / or treatment of fibrotic diseases. The invention further relates to pharmaceutical compositions comprising the compounds of formula (I) in combination with one or more therapeutically active ingredients acting as anti-fibrotic agent(s) such as pirfenidone or nintedanib.

The present application relates to the technical field of medicine, and particularly relates to an anti-pulmonary fibrosis prodrug compound and a preparation method and application thereof. The prodrug compound is a novel prodrug, and the structure comprises: a) an active drug unit selected from pirfenidone and nintedanib; b) a lung targeting unit selected from diphenyl chloroiodonium salt and a mimic thereof 521; and c) a linker unit which is a responsive linkage sensitive to a biomarker specifically overexpressed in a pulmonary fibrosis microenvironment. The prodrug is stable in the systemic circulation and has no activity or low activity, and can be actively targeted to a pulmonary fibrosis lesion; under the specific stimulation of the PFM, the linker is broken, and the original drug molecule is accurately released, so that the concentration of the drug in the lesion site is significantly increased, the toxic side effects caused by systemic exposure are reduced, and the anti-pulmonary fibrosis effect is enhanced.

The invention discloses application of nintedanib in preparation of a medicine for treating plant migration and plant mineralization, and belongs to the technical field of biological medicine. The research shows that the nintedanib has the effects of reducing deposition of extracellular matrix of an allogeneic kidney transplantation model mouse, improving renal tubular atrophy, relieving mouse CD206 + macrophage infiltration and reducing rejection injury degree and immune infiltration degree of kidney grafts after being administered under the administration dosage without generating liver and kidney toxicity and intestinal side effects; the lesion process of mouse chronic transplanted kidney rejection is obviously slowed down, and the damage of excessively activated inflammatory cells to the transplanted kidney is reduced. The results show that nintedanib can delay the progress of chronic transplantation renal fibrosis.

The invention relates to a crystal form of a novel nintedanib derivative as shown in a formula (I), a preparation method of the crystal form, and medical application of a medicinal preparation containing the crystal form. The invention further provides application of the compound shown in the formula (I) in preparation of drugs for treating systemic sclerosis related pulmonary interstitial diseases, idiopathic pulmonary fibrosis and non-small cell lung cancer. The compound has the advantages of being remarkable in stability and long-acting.

The invention relates to the use of a tyrosine kinase inhibitor, specifically nintedanib or one of the pharmaceutically acceptable salts thereof, for the treatment of Castleman disease or the prevention or treatment of one of its complications.

The invention provides a pharmaceutical composition of a nintedanib solution for inhalation. The pharmaceutical composition comprises a first container and a second container, the first container is filled with a first solution, and the first solution contains nintedanib or pharmaceutically acceptable salt thereof and does not contain a nonionic osmotic pressure regulator; the second container is filled with a second solution, and the second solution contains an ionic osmotic pressure regulator and a nonionic osmotic pressure regulator. The medicinal composition disclosed by the invention is simple in component, stable in preparation, capable of avoiding generation of genotoxic impurities, high in safety, lower in irritation to respiratory mucosa and capable of improving the compliance of a patient.

The invention relates to the technical field of medicine, in particular to an ethanesulfonic acid nintedanib sublingual tablet and a preparation method thereof.The ethanesulfonic acid nintedanib sublingual tablet contains ethanesulfonic acid nintedanib, a carrier material, a filling agent, a disintegrating agent, a flavoring agent and a lubricating agent, and the ethanesulfonic acid nintedanib sublingual tablet is prepared by setting the specific proportion of the raw materials and the auxiliary materials. Compared with an original research medicine, namely a nintedanib ethanesulfonate soft capsule, the problem that the bioavailability is low due to the liver first-pass effect is effectively solved, the medicine provided by the invention is good in taste, excellent in stability, rapid in disintegration and rapid in dissolution rate, and each detection item meets the quality standard. And meanwhile, the clinical use compliance of a patient is also improved.

The present invention relates to the technical field of biomedicine and discloses use of a hypoxanthine derivative in the preparation of a drug for treating renal fibrosis and / or kidney disease. By assaying pharmacological activities of structurally modified and altered hypoxanthine derivatives for treating renal fibrosis and / or kidney disease, the pharmacological activities of such compounds were tested in animal disease models, and data on activities for preventing and treating renal fibrosis and / or kidney disease were provided. It is proven that the hypoxanthine derivatives have good activities, and the effects are significantly superior to those of clinically commonly used positive drugs nintedanib and losartan, and the effects are also significantly superior to those of hypoxanthine derivatives A, B, and C and other hypoxanthine derivatives in the prior art. The hypoxanthine derivative of the present invention can provide a novel skeleton for the screening of novel compounds for the preparation of a drug for treating renal fibrosis and / or kidney disease.

This invention relates to a combination therapy of dacomitinib and nintedanib for the prevention or treatment of pulmonary fibrosis.

Formulations and intravitreal implants containing nintedanib can be used in methods for the treatment of back-of-the-eye diseases.

This invention relates to a combination therapy of pexidartinib and nintedanib for the prevention or treatment of pulmonary fibrosis.

The invention relates to the field of cell therapy, in particular to application of NK cells in preparation of drugs for treating fibrosis diseases. The invention discloses application of NK (natural killer) cells in preparation of medicines for treating fibrosis diseases, and compared with nintedanib or pirfenidone, the NK cells have equivalent or even better effects in treatment of pulmonary fibrosis diseases, are higher in safety and do not cause side effects such as hepatotoxicity or renal toxicity. Also disclosed is a method of treating a subject suffering from a fibrotic disease by administering one or more NK cells to the subject.

The invention relates to the technical field of biological medicines, and discloses an application of an inoxanthine derivative in preparation of a medicine for treating peritoneal diseases, the pharmacological activity of the compound is tested in various animal disease models by detecting the pharmacological activity of the inoxanthine derivative subjected to structure modification and transformation in treatment of peritoneal diseases, and the application of the inoxanthine derivative in preparation of the medicine for treating peritoneal diseases is provided. The invention also provides data of activity of preventing and treating different types of peritoneal diseases, which proves that the compound has good activity, the effect is obviously superior to that of a clinically common drug nintedanib, and the effect is also obviously superior to that of hypoxanthine derivatives A, B and C and other hypoxanthine derivatives in the prior art. The hypoxanthine derivative provided by the invention can provide a novel skeleton for screening a novel compound for preparing a medicine for treating peritoneal diseases, and lays a theoretical foundation for developing a novel lead compound.

The invention discloses a light-operated biological hybrid micro-robot drug-loaded delivery carrier and preparation and application thereof, and the light-operated biological hybrid micro-robot drug-loaded delivery carrier is composed of polymer nanoparticles carrying anti-fibrosis drugs and flexible living microorganisms, wherein 0.1-1 mg of the anti-fibrosis drug can be loaded on each flexible living microorganism with the order of magnitude of 1 * 10 < 5 >-1 * 10 < 6 >; the anti-fibrosis drug in the polymer nanoparticles loaded with the anti-fibrosis drug is nintedanib, the polymer is a polylactic acid-glycolic acid copolymer, and the mass ratio of the polylactic acid-glycolic acid copolymer to the nintedanib is (10: 1)-(20: 1). The ratio of lactide to glycolide in the polylactic acid-glycolic acid copolymer is 30: 70-50: 50, and the molecular weight of the polylactic acid-glycolic acid copolymer is 38000-54000. According to the photo-biological hybrid micro-robot, flexible living microalgae and a micro-robot drug delivery system are combined to achieve light-operated accurate regulation and control, light-operated permeation enhancement is achieved, drug retention time is prolonged, and good biocompatibility and safety are achieved.

The invention belongs to the field of pharmaceutical preparations, and provides an auxiliary material system for pulmonary administration of insoluble drugs and a preparation method of the auxiliary material system. According to the invention, a collaborative design of lipid-coated indissolvable drug nanocrystal core-shell particles and a ternary lipid dispersion intermediate is adopted, and an anti-solvent precipitation in-situ coating and high-pressure microjet refining technology is adopted; the preparation method comprises the following steps: coating the outer surface of a nintedanib nanocrystal with a lipid shell layer composed of dipalmitoyl-sn-glycerol-3-phosphorylcholine, cholesterol and propylene glycol caprylate to form core-shell particles with the mass median particle size D50 value of 150-250 nm and the volume distribution D90 value of less than or equal to 400 nm. According to the invention, high drug loading capacity, low viscosity and atomizable property are realized, lung deposition distribution and long-term particle size stability are optimized, the contradiction between high solid content and rheological property, low irritation and colloid stability, and atomization efficiency and core-shell structure integrity in lung administration of insoluble drugs is effectively relieved, and the preparation method has wide clinical application value.

To provide a method for treating ocular indications involving abnormal neovascularization.SOLUTION: There is provided a method comprising administering to an eye of a subject an effective amount of nintedanib or a pharmaceutically acceptable salt thereof in a form of topical eye drop or an implant.SELECTED DRAWING: None

The present application provides a halogenated indolinone compound and a preparation method therefor and a use thereof, a halogenated indolinone derivative and a use thereof, and a pharmaceutical composition and a use thereof, relating to the technical field of biomedicine. The halogenated indolinone compound provided in the present application, through kinase profiling analysis, shows that in addition to having inhibitory activities against VEGFR, FGFR, and PDGFR kinases, it also has very strong inhibitory activity against AXL kinase, with an IC50 value reaching a low nanomolar level, which is 45 times that of nintedanib in inhibiting AXL kinase activity. The halogenated indolinone compound provided in the present application exhibits better antitumor activity than nintedanib at both the cellular level and in vivo in animals, has a better effect than nintedanib in inhibiting tumor invasion and metastasis, and can effectively treat malignant tumors and the invasion and metastasis thereof.

The invention relates to the technical field of biological medicines, and discloses an application of an inosine derivative in preparation of medicines for treating non-alcoholic fatty liver diseases and hepatic fibrosis, and the pharmacological activity of the inosine derivative subjected to structural modification and transformation in treatment of the non-alcoholic fatty liver diseases and / or hepatic fibrosis is detected. The pharmacological activity of the compound is tested in various animal disease models, and data for preventing and treating different types of non-alcoholic fatty liver diseases and / or hepatic fibrosis activity is provided, so that the compound is proved to have good activity, and the effect is obviously superior to that of a clinically common positive drug nintedanib; the effect is obviously superior to those of hypoxanthine derivatives A, B and C and other hypoxanthine derivatives in the prior art. The hypoxanthine derivative disclosed by the invention can provide a novel skeleton for screening a novel compound for preparing a medicine for treating the non-alcoholic fatty liver disease and / or hepatic fibrosis, and lays a theoretical foundation for developing a novel lead compound.

The invention provides application of nintedanib in prevention and treatment of wound proliferative fibrosis diseases, the nintedanib or pharmaceutically acceptable salt thereof is prepared into a medicament by adding auxiliary materials, acts on wounds of subjects in manners of smearing, spraying, application, oral administration, injection and the like, can inhibit neovascularization, reduce fibroblast growth and reduce inflammation, and can be used for preventing and treating the wound proliferative fibrosis diseases. The wound skin can be recovered as far as possible. According to the invention, nintedanib is adopted to carry out external local treatment during wound stitch removal, so that the growth of new vessels is inhibited in the early stage, the number of fibroblasts is reduced, the wound skin is recovered to be normal as far as possible, a treatment window is advanced to the abnormal stage of the new vessels, and wound fibrosis and scar formation are avoided. The treatment is greatly simplified, the treatment pain of a patient is reduced, and the treatment cost is also greatly reduced.

Use of nintedanib or a medicinal salt thereof for the manufacture of a drug for treating tuberculosis, wherein the nintedanib or a medicinal salt thereof is used in combination with another antituberculous drug to treat tuberculosis or as an adjunct to tuberculosis treatment, the other antituberculous drug being selected from rifampicin, isoniazid, pyrazinamide, ethambutol, fluoroquinolones, streptomycin, kanamycin, amikacin, capreomycin, sodium 4-aminosalicylate, ethionamide, cycloserine, clofazimine, and linezolid.

The present invention relates to novel sublingual compositions comprising an anti-fibrotic agent, as well as methods for their preparation. Wherein the composition comprising an anti- fibrotic agent such as pirfenidone or nintedanib and its analogs or pharmaceutically acceptable salts thereof. These novel sublingual compositions are intended for use in the treatment of fibrotic diseases, disorders, or conditions, such as idiopathic pulmonary fibrosis (IPF), and hypertensive diseases, disorders, or conditions such as pulmonary hypertension.

The invention discloses a lipid nano composition and a preparation method thereof, and belongs to the field of pharmaceutical preparations. The lipid nano composition comprises nintedanib, oleic acid, phospholipid, glycerol and water, the pH value of the lipid nano composition is 7.3-80, and the particle size of the lipid nano composition is smaller than 350 nm. The nintedanib lipid nanoparticles are prepared by taking oleic acid as a dispersing solvent of the nintedanib and taking phospholipid as an emulsifier, so that the oral bioavailability of the nintedanib is improved.

The invention belongs to the technical field of targeted drugs, particularly relates to a membrane-loaded FAP (Fibroblast Amplification Protein) targeted delivery nintedanib salvia miltiorrhiza-derived exosome as well as a preparation method and application thereof, and aims to treat pulmonary fibrosis in an aerosol inhalation way. The method comprises the following steps: firstly, separating and identifying a source exosome from salvia miltiorrhiza, and efficiently loading an anti-fibrosis micromolecule drug nintedanib into the exosome by utilizing FAP targeting. The system has a remarkable targeting property, can efficiently relieve lung tissue fibrosis, has non-invasiveness and a good clinical transformation prospect, and provides a brand new thought for clinical treatment of pulmonary fibrosis.