20 results about "Nilotinib" patented technology

Amorphous solid dispersions of nilotinib fumarate or nilotinib tartrate are provided, as well as pharmaceutical compositions thereof, wherein the compositions exhibit enhanced bioavailability in the fasted state. Preferably, the compositions may be orally administered to a patient in either the fed or fasted state, with a decrease or elimination of the food effect. Preferably, following oral administration of the pharmaceutical compositions, there is no substantial difference in the pharmacokinetic parameters (e.g., Cmax, AUC0-t and / or AUC0-infinity) of nilotinib, regardless of whether the pharmaceutical compositions are administered to a subject in the fed or fasted state.

The present application belongs to the technical field of pharmaceutical analysis, and particularly relates to a kind of analytical method for determining genetic toxic impurities in nilotinib composition.The present application has good specificity, simple operation, high sensitivity, low cost, and is suitable for frequent detection in mass production, etc., for determining impurity A in compositions such as nilotinib oral suspension, nilotinib dry suspension or nilotinib capsules.The method can effectively separate the nilotinib impurity A peak from its adjacent impurity peak, and solve the problem of easy damage of the chromatographic column during the determination of nilotinib impurity A.

The application relates to the technical field of biological medicine, and discloses application of Nilotinib in preparation of a drug for inhibiting p53-AKT interaction. Relying on a double-fluorescence reporting system NanoBRET system, high-throughput screening is completed at a live cell level, and it is determined that a tyrosine kinase inhibitor Nilotinib can inhibit p53-AKT interaction. Function verification shows that Nilotinib can dose-dependently destroy a p53-AKT complex in HEK293T tool cells and U87MG, T98G and other glioma cells, release the inhibition of p53 function, and induce cell apoptosis. The above results illustrate a new path of precise intervention with the "p53-AKT interface" as a target, and provide experimental basis for redirecting Nilotinib to overcome p53-related drug resistance.

This invention provides a nilotinib capsule with reduced food-related effects and its preparation method, addressing the shortcomings of existing products. It solves the problem that existing products require avoiding the influence of food. This invention innovatively improves the dissolution and release of the drug in media with different pH values ​​by adding a specific combination of acidic pH adjusters and solubilizers to the formulation. This innovative formulation adjustment solves the problem of food affecting the release and absorption of this product, and improves the time-limited nature of administration. Therefore, this invention has great application value and promising prospects for promotion.

The invention discloses a preparation method of nilotinib, which is characterized in that easily available industrial raw materials and common intermediates are adopted, and the nilotinib is prepared through optimized carbon-nitrogen coupling reaction. The preparation method has the advantages of easily available raw materials, simple process, mild conditions and few side reactions, can better control the generation and transmission of drug impurities, and improves the drug quality and safety. Compared with the prior art, the process can effectively reduce the production cost and reduce the environmental pollution, has industrial production prospects, and can promote the economic and technical development of the raw material medicine.

Amorphous solid dispersions of nilotinib fumarate or nilotinib tartrate are provided, as well as pharmaceutical compositions thereof, wherein the compositions exhibit enhanced bioavailability in the fasted state. Preferably, the compositions may be orally administered to a patient in either the fed or fasted state, with a decrease or elimination of the food effect. Preferably, following oral administration of the pharmaceutical compositions, there is no substantial difference in the pharmacokinetic parameters (e.g., Cmax, AUC0-t and / or AUC0-infinity) of nilotinib, regardless of whether the pharmaceutical compositions are administered to a subject in the fed or fasted state.

Disclosed herein is a composition comprising: an amorphous solid dispersion (ASD) comprising nilotinib and at least one polymeric stabilizing and matrix-forming component; and at least one solid organic acid in admixture with the ASD, and uses thereof in the treatment of proliferative disorder.

The application relates to an application of nilotinib or a pharmaceutically acceptable salt thereof in preparation of a radiotherapy synergistic and attenuated drug for rectal cancer, and belongs to the technical field of medicines.The technical problem to be solved by the application is that the existing radiotherapy combined scheme is difficult to simultaneously realize enhancement of tumor radiosensitivity and reduction of normal intestinal radiation injury.The new application provided by the application is that: as a ZAK alpha inhibitor, the nilotinib weakens radiotherapy resistance, enhances DNA damage accumulation and promotes apoptosis in tumor cells by inhibiting ionizing radiation-induced ZAK alpha-mediated ribosome toxicity stress response, and reduces radiation-induced apoptosis in normal intestinal epithelial cells and protects the intestinal mucosal barrier.In vitro and in vivo experiments prove that the nilotinib can effectively enhance the radiotherapy effect of colorectal cancer and significantly relieve radiation-induced intestinal injury under the same administration scheme, realizes the double functions of radiotherapy "synergism" and "attenuation" of a single drug, and has important clinical transformation value.

Disclosed herein is a composition comprising: an amorphous solid dispersion (ASD) comprising nilotinib and at least one polymeric stabilizing and matrix-forming component; and at least one solid organic acid in admixture with the ASD, and uses thereof in the treatment of proliferative disorder.

This invention discloses the application of ZAK inhibitors in the preparation of drugs for treating EV71 virus infection, relating to the biomedical field. The ZAK inhibitors exert their effects by inhibiting the ZAK-p38 MAPK signaling pathway and by inhibiting the ZAKα-mediated ribosomal toxicity stress response (RSR). The ZAK inhibitor is nilotinib or a pharmaceutically acceptable salt thereof. Cellular and animal experiments of this invention demonstrate that EV71 infection activates the ZAKα-mediated p38 MAPK pathway (RSR), promoting viral replication and leading to multi-organ damage. ZAK inhibitors (such as nilotinib) can inhibit this pathway, reduce the expression of the viral protein VP1, and improve infection-induced renal function damage, metabolic disorders, and muscle damage. Therefore, ZAK inhibitors can be used to prepare anti-EV71 drugs.

The invention discloses a nilotinib sustained release tablet and a preparation method thereof, the nilotinib sustained release tablet comprises a bleaching assisting layer and a drug-containing sustained release layer, the bleaching assisting layer is prepared from a hydrophilic polymer with the viscosity of 2000 mpa.s-6000 mpa.s, a hydrophobic bleaching assisting agent, an adhesive and a lubricant; the drug-containing sustained-release layer is prepared from the following raw materials: an amorphous solid dispersion containing nilotinib or salt thereof, a hydrophilic polymer with the viscosity of 40 mpa.s-2000 mpa.s, a water-soluble filler, a flow aid and a lubricant. The nilotinib sustained-release tablet can effectively prolong the retention time of nilotinib in the stomach, slowly release the medicine in the stomach, improve the solubility and bioavailability of the medicine and reduce the overall dosage, so that the adverse reaction of the medicine is reduced, and meanwhile, on the basis of ensuring that the nilotinib sustained-release tablet is not affected by food effects, the nilotinib sustained-release tablet only needs to be orally taken once every day, and the curative effect of the nilotinib sustained-release tablet is greatly improved. The medicine taking compliance of a patient is improved by reducing the medicine taking times.

Provided are pharmaceutical compositions which include a mixture of a lipophilic active pharmaceutical ingredient such as nilotinib, a hydrophilic polymer, one or more surfactants, and optionally an adsorbent. Also described are methods for preparing and using such pharmaceutical compositions. In one aspect, disclosed herein is an amorphous solid dispersion comprising the active pharmaceutical ingredient.

Provided are pharmaceutical compositions which include a mixture of a lipophilic active pharmaceutical ingredient such as nilotinib, a hydrophilic polymer, one or more surfactants, and optionally an adsorbent. Also described are methods for preparing and using such pharmaceutical compositions. In one aspect, disclosed herein is an amorphous solid dispersion comprising the active pharmaceutical ingredient.

The invention discloses an amorphous nilotinib oral soluble film preparation and a preparation method thereof. The amorphous nilotinib oral soluble film preparation is prepared from the following raw and auxiliary materials in percentage by mass: 0.1-30% of nilotinib, 1-40% of an enteric polymer material, 30-70% of a film-forming agent and 5-40% of a plasticizer, the enteric polymer material is one or more of hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose phthalate, polyvinyl alcohol phthalate acetate, cellulose trimellitate acetate, cellulose acetate phthalate, acrylic resin EuS100 and acrylic resin EuL100. According to the oral soluble film preparation disclosed by the invention, the saturation solubility of nilotinib in an environment with the pH value being greater than 4.5 is remarkably improved, the dissolution and absorption of a nilotinib medicine in an intestinal environment are increased, the bioavailability is improved, the administration dosage is further reduced, the administration requirements of children are met, the food effect and toxic and side effects are reduced, and the administration safety of patients is improved.

The application relates to application of nilotinib in preparation of anti-neuroblastoma drugs, and discloses a novel signal axis driving neuroblastoma progression: USP39-KLF1-SNARE-Golgi diffusion, and finds a new use of nilotinib in preparation of anti-neuroblastoma drugs. The application finds that nilotinib can effectively destroy the protein interaction between USP39 and KLF1. The destruction leads to the decrease of KLF1 protein stability, the inhibition of the transcription activity of KLF1, the down-regulation of the expression of VAMP3 / VAMP8, the weakening of the SNARE complex function, the reversal of the Golgi diffusion phenotype, and the slowing down of the growth of neuroblastoma. Nilotinib is a marketed drug, and has clear human safety data, so the clinical transformation can be accelerated.

Provided herein are amorphous solid dispersions of nilotinib fumarate or nilotinib tartrate, and pharmaceutical compositions thereof, wherein the compositions exhibit enhanced bioavailability in the fasted state. Preferably, the compositions can be orally administered to a patient in the fed or fasted state with a reduction or elimination of food effect. Preferably, there is no substantial difference in the pharmacokinetic parameters (e.g., C max , AUC 0‑t , and / or AUC 0‑无穷大 ) of nilotinib following oral administration of the pharmaceutical composition, whether the pharmaceutical composition is administered to the subject in the fed or fasted state.

Disclosed herein are compositions that contain a salt of Nilotinib and a polymer, which composition have improved properties in terms of solubility and bioavailability and which are useful for treating disorders of uncontrolled cellular proliferation. Methods of using the compositions are also described

The invention provides a novel anti-cancer drug for improving toxic and side effects of the heart and application thereof, the anti-cancer drug is a compound preparation containing a kinase inhibitor and a calcium ion antagonist, and the anti-cancer drug can effectively reduce ventricular depolarization and repolarization disorder caused by the kinase inhibitor nilotinib and the like. And then the possibility of triggering arrhythmia and / or sudden cardiac death. The invention also provides an application of the calcium channel blocker diltiazem in preparation of a medicine for improving cardiac electrical activity and a corresponding treatment method.

The present application relates to the biomedical technology field, and more particularly to a kind of nano drug preparation and its preparation method and application.The nano drug preparation includes rosmarinic acid and nilotinib, and the mass ratio of rosmarinic acid and nilotinib is 1:0.1-2.The present application provides a kind of composition of rosmarinic acid and nilotinib, which can synergistically activate autophagy, has the effect of neuroprotection and antioxidant stress.The drug loaded with rosmarinic acid and nilotinib provided by the present application can effectively protect dopaminergic neurons in substantia nigra, and then improve the motor symptoms of MPTP-induced PD mice, and provide a prospective scheme for PD targeted therapy.

The invention relates to an application of ensatinib or a pharmaceutically acceptable salt in preparation of a medicine for treating psoriasis. The purpose of treating the psoriasis is achieved by providing the application of the ensatinib or the pharmaceutically acceptable salt in preparation of the medicine for treating the psoriasis, and the research shows that the ensatinib has a remarkable effect in the aspect of treating the psoriasis and has small side effects.