71 results about "Nintedanib" patented technology

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 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.

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 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.

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 provides application of nobiletin and nintedanib combined administration in treatment of pulmonary fibrosis, and belongs to the technical field of combined medication. The invention provides application of nobiletin and nintedanib combined medicine in preparation of medicine for preventing and / or treating pulmonary fibrosis. According to the invention, TGF-beta1 is adopted to induce MRC-5 cells to establish an in-vitro pulmonary fibrosis model, and bleomycin is adopted to induce a C57BL / 6J mouse to establish an in-vivo pulmonary fibrosis model. Researches find that the combination of nobiletin and nintedanib can inhibit MRC-5 cell epithelial-mesenchymal transition and significantly down-regulate the expression of fibrosis marker protein. In-vivo experiments show that nobiletin and nintedanib are combined to obviously improve the pathological state of mouse pulmonary fibrosis. The nobiletin and the nintedanib are combined to play an obvious treatment role in inhibiting the pulmonary fibrosis, so that the nobiletin and the nintedanib can be used as potential medicines for preventing and treating the pulmonary fibrosis, and new clues and ideas are provided for developing medicines for treating the pulmonary fibrosis.

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.

In particular, the present invention relates to methods of (i) treating a disease in a subject, (ii) ameliorating a decrease in forced vital capacity in a subject in need thereof, (iii) modulating an avf36 integrin, an avf31 integrin, or both an avf36 integrin and an avf31 integrin in a subject in need thereof, (iv) increasing expression of one or more genes in a subject in need thereof, (v) reducing the expression of one or more genes in a subject in need thereof, and (vi) modulating the activity of at least one gene that affects fibrosis activity in a subject in need thereof, comprising administering a compound of Formula (A), Formula (I), Formula (II) as described herein or (S)-4-((2-methoxyethyl) (4-(5, 6, 7, 8-tetrahydro-1, 3, 4, 5, 6, 7, 8-tetrahydro-1, 3, 4, 5, 6, 7, 8-tetrahydro-1, 3, 4, 5, 6, 7, 8-tetrahydro-1, 3, 4-tetrahydro-1, 3, 4-tetrahydro-1, 3, 4-tetrahydro-1, 3, 4-tetrahydro-1, 3, 4-tetrahydro-1, 3-tetrahydro-1, 3 The present invention relates to a pharmaceutically acceptable salt of 2-(5, 8-naphthyridine-2-yl) butyl) amino)-2-(quinazoline-4-ylamino) butyric acid or a pharmaceutically acceptable salt thereof; and administering to the subject a second drug selected from at least pirfenidone and nintedanib or a salt thereof.

The present invention discloses a use of a hypoxanthine compound in preparing a drug for treating pulmonary fibrosis and relates to the technical field of biological medicines. In the use of the hypoxanthine compound in preparing the drug for treating the pulmonary fibrosis, through pharmacological activity detection for treatment of pulmonary fibrosis with hypoxanthine compounds subjected to structural modification and transformation, the pharmacological activities of such the compounds in various animal disease models are tested and data about the activities of preventing and treating different types of pulmonary fibrosis are provided, which proves that the hypoxanthine compounds have good activities, with an effect being obviously superior to that of a positive drug Nintedanib commonly used in clinic, and that of hypoxanthine analogues A, B, C and D as well as other hypoxanthine analogues in the prior art. The use of the hypoxanthine compound in preparing the drug for treating the pulmonary fibrosis can provide a novel skeleton for screening novel compounds for preparing drugs for treating pulmonary fibrosis and lay a theoretical foundation of developing a novel lead compound.

The invention relates to the technical field of biological medicines, in particular to application of surface-engineered mitochondria for activating mitochondrial autophagy in preparation of a medicine for treating pulmonary fibrosis. According to the present invention, the antibody is covalently coupled to the PLL modified exogenous mitochondrial surface to construct the Ab-mito with characteristics of positive electricity and targeting function, such that the efficient mitochondrial transplantation to the recipient cell is promoted, the problems of poor selectivity and low efficiency confronted by the existing mitochondrial delivery research are overcome, and the new direction is provided for the pulmonary fibrosis treatment. The treatment effect of the traditional Chinese medicine composition on pulmonary fibrosis is equivalent to that of a clinical medicine nintedanib, and the method is simpler and more effective.