102 results about "Nintedanib" patented technology

The invention discloses an anti-adhesion membrane loaded with nintedanib and a preparation method of the anti-adhesion membrane loaded with the nintedanib. The anti-adhesion membrane loaded with the nintedanib is prepared from a drug-loading substrate material and the nintedanib through electrostatic spinning, the material of the drug-loading substrate is one or more of polylactic acid, poly (p-dioxanone), a polylactic acid-glycolic acid copolymer, polycaprolactone and polyethylene glycol; a solvent adopted in the electrostatic spinning is hexafluoroisopropanol, and the voltage adopted in the electrostatic spinning is 10-14 kV. The nintedanib-loaded anti-adhesion membrane has the advantages that the tensile strength and the elongation at break are obviously improved, the mechanical property is obviously improved, the fiber distribution is uniform, the obvious anti-adhesion effect is realized, the nintedanib-loaded anti-adhesion membrane is suitable for common laparotomy, and the application prospect is wide.

The invention belongs to the technical field of medicines, and provides application of Nintedanib and a plant-derived cyclic peptide and radix pseudostellariae cyclic peptide B combined medicine in preparation of a medicine for treating pulmonary fibrosis, the Nintedanib and the plant-derived cyclic peptide and radix pseudostellariae cyclic peptide B combined medicine can play a synergistic effect, and the inhibition effect on the pulmonary fibrosis process is remarkably improved. The toxic and side effects of diarrhea and intestinal mucosa injury caused by nintedanib are reduced, and a good choice is provided for clinical treatment of pulmonary fibrosis.

The invention belongs to the technical field of bionic nano-drugs, and particularly relates to a bionic vesicle preparation as well as a preparation method and application thereof. The bionic vesicle preparation disclosed by the invention is prepared from the following raw materials: mesenchymal stem cell outer vesicles, nintedanib and DSPE-PEG-HA (hyaluronic acid modified pegylated phospholipid); the nintedanib is loaded in the mesenchymal stem cell outer vesicle, and the DSPE-PEG-HA is coupled to the surface of the mesenchymal stem cell outer vesicle. The bionic vesicle preparation disclosed by the invention can be used for directly delivering a drug to a pulmonary fibrosis injury part through inhalation type drug delivery, and acting on a focus part at a higher local concentration, meanwhile, the exposure of the drug in whole-body circulation is remarkably reduced, the occurrence of side effects is reduced, and the specific targeting intervention and regulation on fibroblasts are realized.

The present invention discloses the application of a 1,7-dihydro-6H-purin-6-one compound in the preparation of an anti-pulmonary fibrosis drug, which relates to the technical field of biomedicine. The application of the 1,7-dihydro-6H-purin-6-one compound of the present invention in the preparation of an anti-pulmonary fibrosis drug detects the anti-pulmonary fibrosis pharmacological activity of the 1,7-dihydro-6H-purin-6-one compound after structural modification and transformation, tests the pharmacological activity of this type of compound in a variety of animal disease models, and provides data on the activity of preventing and treating different types of pulmonary fibrosis, confirming that they all have good activity, and the effect is significantly better than the clinically commonly used positive drug nintedanib, and the effect is also better than hypoxanthine analogs A, B, and C. The application of the 1,7-dihydro-6H-purin-6-one compound of the present invention in the preparation of an anti-pulmonary fibrosis drug can provide a new skeleton for the screening of new compounds for the preparation of anti-pulmonary fibrosis drugs, and lay a theoretical foundation for the development of new lead compounds.

The invention includes dry powder nintedanib formulation for dispersion and inhalation administration including salts thereof, indolinone derivative or salts thereof and in fixed dose combinations with carrier agents and other active ingredients. The aerosol delivery combination formulation may be administered as an inhaled aerosol over a few actuations or by two or more actuations. Each dose may be administered one or more times daily on a regular or interval daily dosing regimen. The special formulation parameters of the invention include the selection of the salt for complexation with the form of nintedanib used for an isolated dry powder along with particle size distributions and combination with a force control agent for improved aerosol delivery. Methods of the invention include therapeutically effective doses of the described invention used to treat interstitial lung disease.

The present invention includes dry powder nintedanib formulations for dispersive and inhalation administration, including salts thereof, indolone derivatives or salts thereof, and in fixed dose combinations with a carrier agent and other active ingredients. The aerosol delivery combination formulation may be administered as an inhalation aerosol over several actuations or by two or more actuations. Each dose may be administered one or more times per day according to a regular or interval daily dosing regimen. Specific formulation parameters of the present invention include the selection of salts complexed with the nintedanib form for the isolated dry powder, as well as particle size distribution and in combination with force control agents to improve aerosol delivery. The methods of the invention comprise therapeutically effective doses of the described invention for the treatment of interstitial lung disease.

Formulations and intravitreal implants containing nintedanib can be used in methods of treating diseases of the posterior portion of the eye.

The invention belongs to the technical field of development of nintedanib preparations, and particularly relates to a nintedanib suspension preparation, a preparation method thereof and application of the nintedanib suspension preparation in treatment of pulmonary fibrosis. The preparation method comprises the following steps: dissolving a phospholipid material in an organic solvent at 50-70 DEG C, and preserving heat to obtain a solution A; dissolving inorganic salt in water for injection, and preserving heat to obtain a solution B; dissolving the ethanesulfonic acid nintedanib in the water for injection to obtain a solution C; dissolving an osmotic pressure regulator in the water for injection to obtain a solution D; mixing the solution A and the solution B by using microfluidics to obtain a suspension E; filtering through a tangential flow membrane to remove the organic solvent in the suspension E, adding the solution C, keeping the temperature for a period of time, adding the solution D as required, and uniformly mixing; and filtering the suspension with a sterilization filter to obtain the nintedanib suspension preparation. The liposome suspension prepared from the nintedanib prepared by the invention is stable in physical state and excellent in slow release effect, is suitable for low-dose inhalation administration in the lung, and is beneficial to improving the treatment effect and reducing side effects.

The invention relates to a nintedanib dry powder inhalant as well as a preparation method and application thereof. The dry powder inhalant comprises nintedanib and magnesium stearate. According to the nintedanib dry powder inhalant, by controlling the adding proportion of magnesium stearate and the particle size distribution of co-micro powder, the dosage of fine particles can be remarkably increased, the nintedanib dry powder inhalant still has the high dosage of fine particles under the high drug loading capacity, the drug bioavailability is high, and the safety risk of a patient in the medication period can be reduced. Meanwhile, the preparation method of the nintedanib dry powder inhalant is simple and controllable, and the final product is safe, reliable and high in stability.

The invention discloses an anti-VEGF (vascular endothelial growth factor) intraocular sustained-release implant with high drug loading capacity and a preparation method thereof, and belongs to the technical field of medicines. The preparation method comprises the following steps: firstly, uniformly mixing crushed and sieved anti-VEGF active ingredients with a water-insoluble biodegradable sustained-release polymer to obtain premixed powder, setting the temperature of a hot-melt extruder and the rotating speed of a screw, mounting a mold, preheating, completely feeding the premixed powder, timing for 5-30 minutes, and starting extrusion to obtain the anti-VEGF intraocular sustained-release implant. Wherein the anti-VEGF medicine is prepared from ethanesulfonic acid nintedanib, nintedanib and voranib, and the water-insoluble biodegradable slow-release polymer is prepared from polylactic acid, a polylactic acid-glycolic acid copolymer and polycaprolactone. The in-vitro release characteristic of the prepared anti-VEGF intraocular sustained-release implant conforms to a zero-order release model, and the implant has an excellent sustained-release effect.

The invention relates to the technical field of pharmaceutical preparations, in particular to inhalable drug-loaded nanoparticles as well as a preparation method and application thereof. The drug-loaded nanoparticles comprise a polymer nano-carrier and nintedanib loaded on the polymer nano-carrier through a hydrogen bond, the polymer nano-carrier is obtained by self-assembling cationic polysaccharide and an anionic polymer through electrostatic interaction. The cationic polysaccharide and the anionic polymer form a polymer nano-carrier with a stable internal structure through electrostatic interaction, and the entrapment efficiency of the nintedanib can be remarkably improved. The drug-loaded nanoparticles prepared by adopting an ionic cross-linking method are uniform in particle size, have good bioavailability and slow-release treatment effect, and can be used as a powerful choice for treating idiopathic pulmonary fibrosis as a lung inhalation preparation.

Compositions and methods of using nintedanib for treating indications with abnormal neovascularization in the front part of the eye are disclosed.

The application refers to a novel combination treatment / combination medicament for PF-ILD treatment, comprising as a first combination partner a therapeutically effective amount of Nintedanib or a pharmaceutically acceptable salt thereof and as a second combination partner a therapeutically effective amount of a PDE4B-inhibitor of formula Iwherein Ring A is a 6-membered aromatic ring which may optionally comprise one or two nitrogen atoms andwherein R is Cl and wherein R may be located either in the para-, meta- or ortho-position of Ring A,wherein S* is a sulphur atom that represents a chiral center or a pharmaceutically acceptable salt thereof.Hereby the second combination partner is preferably a therapeutically effective amount of the PDE4B-inhibitior of formula IIIor a pharmaceutically acceptable salt thereof.

The invention relates to the field of pharmaceutical compositions, in particular to a nintedanib-containing pharmaceutical composition or pharmaceutical composition for resisting progressive fibrotic interstitial lung disease (PF-ILD), which comprises a therapeutically effective amount of nintedanib or pharmaceutically acceptable salts, stereoisomers, solvates, prodrugs or derivatives of nintedanib, or pharmaceutically acceptable salts, stereoisomers, solvates, prodrugs or derivatives of nintedanib, or pharmaceutically acceptable salts, stereoisomers, solvates, prodrugs or derivatives of nintedanib. Optionally a pharmaceutically acceptable carrier; the composition has a synergistic inhibition effect on lung fibroblast proliferation through combined administration, can be applied to PF-ILD through inhalation combined administration or prepared into a fixed-dose inhalation compound preparation, especially to patients with idiopathic pulmonary fibrosis (IPF), and aims to solve the problems that the treatment effect is insufficient and the treatment effect is poor in the prior art. The safety and the tolerance are poor.

The invention discloses a lipid microbubble loaded with an anti-fibrosis drug Nintedanib as well as a preparation method and application of the lipid microbubble, and belongs to the technical field of biological medicines. The preparation method comprises the following steps: mixing DPPC, DSPE-PEG, DSPG, cholesterol and an anti-fibrosis drug Nintedanib according to a ratio, adding the mixture into a flask, dissolving with chloroform, and carrying out rotary evaporation at 55-60 DEG C to obtain a dry film mixture; adding a hydration solution into the film mixture for hydration, and repeatedly extruding the obtained lipid suspension by a phospholipid extruder to form a homogeneous lipid suspension; and filling the homogenized lipid suspension into a sealed bottle, pumping out upper-layer air, filling SF6 gas, and carrying out mechanical oscillation to form the lipid microbubble Nin-MBs loaded with the anti-fibrosis drug Nintedanib. The anti-fibrosis drug Nintedanib and the ultrasonic microbubble are prepared into the lipid microbubble, the compact ECM structure of the HCC is changed by targeting the CAF, the barrier hindering effect is overcome, the activity of the CAF is reduced, the tumor promoting effect of the CAF is weakened at the same time, the ECM is adjusted, and a new strategy is provided for treatment of the HCC.

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.

A pharmaceutical composition for prevention or treatment of a disease or disorder characterized by chronic inflammation, associated with angiogenesis and fibrosis. The pharmaceutical composition includes a multi-target inhibitor, multi-phase modulator, or multi-kinase inhibitor, such as axitinib, nintedanib, pirfenidone, riociguat, sorafenib, sunitinib, lenvatinib, regorafenib, ponatinib, or pazopanib.

A preparation method of the methacrylated gelatin with the dual functions comprises the following steps: firstly, preparing collagen methylated polymethacrylate, then mixing 5% of collagen methylated polymethacrylate, 0.2% of trimethylbenzoyl phosphonate, 10 mg / ml of a herba houttuyniae extract and 20 micrograms / ml of nifedimab, and carrying out uniform mixing, so as to obtain the methacrylated gelatin with the dual functions, the collagen methylated polymethacrylate and the trimethylbenzoyl phosphonate, the herba houttuyniae extract, the nifedimab and the collagen methylated polymethacrylate, the herba houttuyniae extract and the nifedimab. The methacrylated gelatin is prepared under ultraviolet irradiation, and the loose cross-linked network structure of the methacrylated gelatin can realize continuous release of drugs, so that the demand of continuous and stable drug delivery is met; in addition, the gelatin methacrylamide, the herba houttuyniae extract and the nintedanib are combined to relieve hemorrhagic intestinal adhesion and can regulate inflammation and anti-fibrosis functions.

The invention concerns an oral pharmaceutical composition consisting essentially of • the PDE4B-inhibitor of formula III in the dose of 18 mg or 9 mg and • optionally of one or more pharmaceutically acceptable carriers or excipients for use in the treatment of a patient suffering from one or more progressive fibrosing interstitial lung diseases (PF-ILD), wherein this oral pharmaceutical composition is to be administered to the patient twice daily. The invention further concerns oral pharmaceutical compositions comprising the PDE4B-inhibitor of formula III in the dose of 18 mg or 9 mg and a therapeutically effective dose of a second active ingredient selected from nintedanib or pirfenidone, wherein these oral pharmaceutical compositions are administered to the patient twice daily.

The present application provides a kind of nintedanib solution for inhalation and preparation method and application, the inhalation solution includes active substance, solvent and auxiliary material, the single dose specification of the inhalation solution is 1-5ml, and the active substance in single dose specification is 2.41-12.04mg / ml nintedanib ethanesulfonic acid;The solvent is sterile injection solution water;The auxiliary material includes isotonicity regulator and pH regulator and can also include antioxidant;The addition amount of the isotonicity regulator is to make the inhalation solution have the weight molal osmotic concentration of 240-400mOsmol / kg;The addition of the pH regulator is to make the pH value of the inhalation solution preparation 3.0-4.0.The inhalation nintedanib solution of the present application can provide a kind of nintedanib for inhalation with convenient, safe and effective, and good stability of drug dosage form and drug delivery system in combination with liquid atomization device.

The application belongs to the technical field of nintedanib preparation development, and particularly relates to a nintedanib suspension preparation, a preparation method thereof and application of the nintedanib suspension preparation in treatment of pulmonary fibrosis. A phospholipid material is dissolved in an organic solvent under the condition of 50-70 DEG C to obtain solution A; an inorganic salt is dissolved in water for injection to obtain solution B; nintedanib ethanesulfonic acid is dissolved in water for injection to obtain solution C; an osmotic pressure regulator is dissolved in water for injection to obtain solution D; solution A and solution B are mixed by microfluidic to obtain suspension E; the organic solvent in the suspension E is removed by tangential flow membrane filtration, then solution C is added and kept for a period of time, and solution D is added as needed and mixed; the suspension can be filtered by a sterilization filter to obtain the nintedanib suspension preparation. The nintedanib prepared in the application is in a stable physical state, has excellent slow-release effect, is suitable for low-dose inhalation administration in the lung, and is helpful to improve the treatment effect and reduce side effects.

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.

To provide a stable pharmaceutical composition comprising Nintedanib.SOLUTION: Provided is a pharmaceutical composition comprising Nintedanib or a pharmaceutically acceptable salt thereof and a stabilizer. The stabilizer comprises polyoxylglyceride. Also provided is a method for preventing, ameliorating, or treating fibrotic disease and / or lung cancer. The method comprises administering an effective amount of the pharmaceutical composition to a subject in need thereof.SELECTED DRAWING: None

The invention provides an anti-tumor combined treatment method for improving a radiotherapy curative effect by using nintedanib, and relates to the technical field of tumor treatment. The anti-tumor combined treatment method comprises the following steps: selecting a male mouse or a male nude mouse as an experimental animal, and subcutaneously constructing a tumor-bearing mouse model on the back of the experimental animal; when the tumor volume of the tumor-bearing mice reaches 70-100mm < 3 >, randomly dividing the tumor-bearing mice into four groups, namely a control group, a nintedanib single drug group, a radiotherapy group and a combined group; measuring the subcutaneous tumor volume and weight of the tumor-bearing mouse every three days; drawing a mouse tumor growth curve, a mouse survival curve and a mouse weight change curve according to the measured data; a tumor-bearing mouse is subjected to living body imaging, tumor tissue paraffin embedding, immunohistochemical staining, TUNEL staining and Hamp; and E, carrying out section staining and blood biochemical detection, and carrying out data analysis by utilizing corresponding analysis software, so as to evaluate the anti-tumor effect and safety of the combined treatment. According to the invention, tumor growth can be effectively inhibited.

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.