39 results about "Carfilzomib" patented technology

The invention belongs to the field of pharmaceutical preparations, and particularly relates to a zomib nano-micelle preparation and a preparation method thereof. The carfilzomib nano-micelle preparation comprises carfilzomib, a micelle carrier material and a stabilizer, wherein the mass ratio of the carfilzomib to the micelle carrier material to the stabilizer is 1: (15-30): (15-30); and the carrier material is PEG (Polyethylene Glycol)-DSPE (Distearoyl PEG-DSPE is used as a drug carrier to prepare the carfilzomib micelle preparation, the particle size is 8-20 nm, the encapsulation efficiency is high, and the carfilzomib micelle preparation has a very strong cell penetration effect and cannot be quickly cleared. Meanwhile, the preparation operation is simple, and freeze-drying operation is avoided. Compared with the existing carfilzomib preparation, the toxicity is reduced under the same dosage.

The invention relates to application of SMARCC1 in preparation of a medicine for treating carfilzomib-resistant multiple myeloma, and belongs to the technical field of biological medicine. According to the invention, direct association between SMARCC1 and the drug resistance of multiple myeloma to carfilzomib is determined for the first time, and the sensitivity of drug-resistant cells to carfilzomib can be significantly enhanced by down-regulating the expression of the gene. Specifically, through systematic analysis on clinical data, SMARCC1 is found to be remarkably and highly expressed in relapse / refractory MM patients and is closely related to poor survival. The SMARCC1 knock-down obviously inhibits the multiplication capacity of multiple myeloma drug-resistant cells, so that the SMARCC1 not only promotes the multiplication capacity of the drug-resistant cells, but also is closely related to the drug resistance of the multiple myeloma cells to carfilzomib, which prompts that the SMARCC1 can be used as a potential therapeutic target and is used for reversing the carfilzomib drug resistance of multiple myeloma.

The present invention provides a method for determining isomers in carfilzomib and its preparations by reverse phase liquid chromatography, and belongs to the technical field of drug analysis. The present invention adopts high performance liquid chromatography to determine isomers in carfilzomib and its preparations, and the chromatographic conditions are as follows: chromatographic column: octylsilane bonded silica gel as filler; mobile phase: sulfobutyl-β-cyclodextrin sodium aqueous solution-acetonitrile as mobile phase. The chromatographic column used in the present invention is a conventional chromatographic column, which is inexpensive and has a longer life; the chiral separation agent added to the mobile phase has a lower cost than special chiral reagents. Through systematic methodological verification, the results show that the method of the present invention has good specificity, sensitivity, accuracy, repeatability, durability, etc., and is suitable for the detection of chiral isomers in carfilzomib and its preparations.

Disclosed herein are methods and compositions for alleviating resistance to chemotherapy in a subject using one or more therapeutic agents that perturb the interaction between integrin β4 (ITGB4) and paxillin (PXN), e.g., by inhibiting the expression of ITGB4, PXN, or both. Also disclosed is a combinational therapy for treating cancer with a chemotherapeutic agent such as cisplatin or carboplatin and an inhibitor of ITGB4, PXN or both, such as carfilzomib.

The present invention provides room temperature stable, i.e., dilution injectable formulations comprising carfilzomib or a pharmaceutically acceptable derivative thereof. The invention also provides a method of treating a patient suffering from multiple myeloma by administering a room temperature stable, i.e., dilution injectable formulation comprising carfilzomib or a pharmaceutically acceptable derivative thereof.

The invention discloses application of carfilzomib in preparation of a medicine for preventing and treating Nipah virus, and belongs to the technical field of medicine. The method mainly aims at ubiquitination modification of nipah virus M protein, the carfilzomib is used for inhibiting a host proteasome path, free ubiquitination factors in cells are depleted to achieve the effect of inhibiting ubiquitination of the M protein, then nucleoplasm shuttle of the M protein is inhibited, replication of the nipah virus is inhibited, and the effect is good. At present, most of research and development of virus medicines and vaccines are designed or modified aiming at viruses, a new thought is provided for research and development of medicines and vaccines in the future, and a new application is also provided for Carfilzomib.

The application discloses application of an HTRA1 inhibitor in preparation of a drug for treating pancreatitis-cancer transformation, and belongs to the technical field of medicines.The HTRA1 inhibitor is screened through a drug database, the HTRA1 inhibitor is used to treat a pancreatic cancer cell line and a mouse pancreatitis-cancer transformation in-vivo model, it is proved that the HTRA1 inhibitor Carfilzomib can inhibit the malignant phenotype of Panc1 cells in vitro, and can inhibit the transformation of a KC mouse stimulated by cerulean into a pancreatic ductal adenocarcinoma in vivo, and the application provides a basis for using the HTRA1 inhibitor as the drug for treating pancreatitis-cancer transformation.

The invention discloses a preparation method of a carfilzomib intermediate, which comprises the following steps: adding ASC007-I into a reaction container, adding a solvent at room temperature, starting stirring, reducing the temperature to 5-10 DEG C, dropwise adding an alkali metal hydroxide solution into a reaction bottle, slowly heating to maintain the temperature at 20-25 DEG C after dropwise adding, reacting, adjusting the pH value to 3-4 with glacial acetic acid after the reaction is completed, separating out a large amount of white solid, and filtering to obtain the carfilzomib intermediate. Washing the filter cake with purified water until the filtrate is neutral; and recrystallizing to obtain the product ASC007-II. Alkali metal hydroxide and ASC007-I react, no catalyst or hydrogen is needed, the reaction yield finally reaches 90% through improvement of a feeding mode and adjustment of a reaction solvent, and compared with a hydrogenation method, the method has the advantages that the requirement for equipment is low, the reaction condition is milder, the process controllability is higher, and the method is more suitable for industrial production.

The present disclosure provides methods for treating multiple myeloma. In certain embodiments, the present methods comprise administering to a subject in need thereof a BCMA inhibitor in combination with a proteasome inhibitor. In certain embodiments, the subject has been previously treated with one or more anti-cancer therapies. In certain embodiments, the proteasome inhibitor is carfilzomib.

The present invention provides stable pharmaceutical compositions of pegylated carfilzomib compounds, methods for preparing the compositions, and uses of the compositions for treating cancer, including hematologic malignancies such as multiple myeloma. The compositions can be stored in frozen form or lyophilized to dry solid form.

This disclosure provides a stable cyclodextrin free carfilzomib formulation in aqueous solution which is suitable for injection, a kit comprising said cyclodextrin free carfilzomib formulation, and methods for preparation of said cyclodextrin free carfilzomib. Such formulation, kit and methods substantially increase the solubility and stability of the carfilzomib in aqueous solution and facilitate both their manufacture and administration.

Disclosed herein are compositions and kits which comprise anti-CD38 antibodies and carfilzomib compounds. Also disclosed are methods for treating cancers, such as multiple myeloma, in subjects with the compositions and kits.

The invention discloses a production process for a carfilzomib freeze-drying preparation for injection, which comprises the following steps: compounding a biodegradable high polymer material and natural polysaccharide to form a nano-scale coating material, and preparing a nano-particle suspension; carfilzomib is placed in the nano-particle suspension, after ultrasonic dispersion, phase separation freeze-drying treatment is carried out, and a carfilzomib freeze-drying agent is obtained; the invention relates to the technical field of freeze-drying preparation preparation. According to the production process for the carfilzomib freeze-drying preparation for injection, carfilzomib is coated through compounding of the biodegradable high polymer material and the natural polysaccharide, oxygen and moisture are effectively isolated, degradation of carfilzomib is reduced, the redissolving efficiency is high, the carfilzomib freeze-drying preparation has the advantage of slow release, blood concentration fluctuation is effectively reduced, the injection frequency of carfilzomib is reduced, and the carfilzomib freeze-drying preparation is suitable for clinical application. According to the method, carfilzomib can be efficiently utilized, auxiliary material residues are further reduced in a phase separation freeze-drying oriented deposition mode, the occurrence probability of irritant anaphylactic reaction risks can be reduced, and the method has a wide application prospect.

The invention belongs to the technical field of cerebral apoplexy treatment medicine research, and particularly relates to a nano delivery system and application thereof. The nano delivery system is prepared according to the following steps: modifying cationic starch spheres with mitochondrial targeting peptide, loading PDK4-IN-1, and carrying out self-assembly to obtain an inner core; the preparation method comprises the following steps: modifying aminated anionic starch with homing peptide, and loading carfilzomib to form a starch spiral shell; and mixing the inner core with the starch spiral shell, and self-assembling to form the nano drug delivery system. According to the invention, a three-targeting, double-controlled-release and double-drug nano drug delivery system is constructed and is accurately delivered to a matrix action site in cytoplasm or mitochondria, so that double-channel synergistic enhancement of IS mitochondrial autophagy and toxicity attenuation and synergistic treatment of IS are realized.

Provided herein are methods and compositions for treating multiple myeloma, such as relapsed and / or refractory multiple myeloma and newly-diagnosed multiple myeloma, including transplant-ineligible newly-diagnosed multiple myeloma (TI-NDMM). The methods involve administering to human patients diagnosed with multiple myeloma an anti-BCMA antigen binding protein (e.g., an anti-BCMA antibody or anti-BCMA antibody drug conjugate) in combination with lenalidomide, pomalidomide, bortezomib, carfilzomib and / or dexamethasone.

To provide a novel pharmaceutical composition containing carfilzomib or a pharmaceutically acceptable salt thereof, enabling solubilization and stabilization in water of carfilzomib or the pharmaceutically acceptable salt thereof.SOLUTION: According to the present invention, there is provided a carfilzomib-containing pharmaceutical composition, comprising carfilzomib or a pharmaceutically acceptable salt thereof, a cyclodextrin, and an acid, wherein the acid is one or more selected from the group consisting of lactic acid, ascorbic acid, phosphoric acid, tartaric acid, L-aspartic acid, maleic acid, acetic acid, and succinic acid, or is an acid in an amount of 3.7 molar equivalents or more based on 1 molar equivalent of carfilzomib or the pharmaceutically acceptable salt thereof.SELECTED DRAWING: Figure 1

The invention is directed to room temperature stable injectable formulations of carfilzomib or its pharmaceutically acceptable derivatives thereof in the form of ready to dilute solution and concentrates with no hemolytic potential. Further the invention is directed to a method for treating patients with relapsed or refractory multiple myeloma by administering such composition.

Disclosed herein are compositions and kits which comprise anti-CD38 antibodies and carfilzomib compounds. Also disclosed are methods for treating cancers, such as multiple myeloma, in subjects with the compositions and kits.

There is provided inter alia a storage stable liquid solution composition comprising carfilzomib or a pharmaceutically acceptable salt thereof and a solvent consisting of (a) an organic solvent component comprising propylene glycol optionally together with polyethylene glycol (PEG), present at a total concentration of at least about 65% (v / v based on the total volume of the composition) and (b) water at a concentration of no more than about 15% (v / v based on the total volume of the composition); and a neutral amino acid, wherein the pH of the storage stable liquid solution composition is in the range 2.5 to 4.0.

The invention provides a method for determining isomers in carfilzomib and a preparation thereof through reversed-phase liquid chromatography, and belongs to the technical field of pharmaceutical analysis. According to the method, the isomers in the carfilzomib and the preparation thereof are determined by adopting a high performance liquid chromatography. Chromatographic conditions are as follows: a chromatographic column takes octyl silane bonded silica gel as a filling agent; and a mobile phase: a sulfobutyl-beta-cyclodextrin sodium water solution-acetonitrile is used as the mobile phase. A chromatographic column used in the method is a conventional chromatographic column, and is low in price and longer in service life; compared with a special chiral reagent, the cost of a chiral resolving agent added in the mobile phase is lower. Through systematic methodology verification, the result shows that the method is good in specificity, sensitivity, accuracy, repeatability, durability and the like, and is suitable for detecting the chiral isomers in the carfilzomib and the preparation thereof.

The present invention provides stable pharmaceutical compositions of a pegylated carfilzomib compound, methods for preparing the compositions, and uses of the compositions for the treatment of cancer, including hematological malignancies such as multiple myeloma. The composition can be stored in frozen form or lyophilized into dry solid form.

The invention relates to a method for analyzing and detecting isomers of a carfilzomib starting material, which adopts a normal-phase chiral chromatographic column, takes a mixed solution containing normal hexane and C2-C3 alcohol as a mobile phase, effectively separates the isomers of the carfilzomib starting material from the carfilzomib starting material and impurities of the carfilzomib starting material, and has a good separation effect.

This disclosure provides a stable cyclodextrin free chlorobutanol carfilzomib formulation in aqueous solution which is suitable for injection, a kit comprising said cyclodextrin free carfilzomib formulation, and methods for preparation of said cyclodextrin free carfilzomib. Such formulation, kit and methods substantially increase the solubility and stability of the carfilzomib in aqueous solution and facilitate both their manufacture and administration.

The present invention provides a stable pharmaceutical composition of a pegylated carfilzomib compound, a method for preparing the composition, and the use of the composition for treating cancer, including hematological malignancies such as multiple myeloma. The composition can be stored in a frozen form or lyophilized into a dry solid form.

The present disclosure provides methods for treating multiple myeloma. In certain embodiments, the present methods comprise administering to a subject in need thereof a BCMA inhibitor in combination with a proteasome inhibitor. In certain embodiments, the subject has been previously treated with one or more anti-cancer therapies. In certain embodiments, the proteasome inhibitor is carfilzomib.

The invention relates to a composition comprising an anti-CD38 antibody and carfilzomib. Compositions and kits comprising an anti-CD38 antibody and a carfilzomib compound are disclosed. Methods and uses for treating cancer, such as multiple myeloma, in a subject using the compositions and kits are also disclosed.

To provide a stable modified carfilzomib formulation. [Solution] The present invention provides a stable pharmaceutical composition of a PEGylated carfilzomib compound, a method for preparing the composition, and the use of the composition for treating cancer, including vascular malignancies such as multiple myeloma. The composition can be stored in a frozen form or lyophilized in a dry solid form.

The invention is directed to room temperature stable injectable formulations of carfilzomib or its pharmaceutically acceptable derivatives thereof in the form of ready to dilute solution and concentrates with no hemolytic potential. Further the invention is directed to a method for treating patients with relapsed or refractory multiple myeloma by administering such composition.

The invention discloses a method for detecting N-methyl pyrrolidone in a carfilzomib intermediate, which comprises the following steps: adopting a high performance liquid chromatography, using a ZORBAX Eclipse C18 ball porous filler chromatographic column to realize reverse phase separation, and using a diode array detector to perform quantitative analysis. Chromatographic conditions are as follows: a mobile phase A is water; a mobile phase B is methanol, and carrying out gradient elution on the phase A and the phase B; the flow velocity is 0.8 to 1.0 ml / min; the column temperature is 25-40 DEG C; the detection wavelength is 205 to 220 nm; the sample size is 10-20 [mu] l; and the diluent is a 50-70% methanol aqueous solution. The N-methyl pyrrolidone disclosed by the invention is relatively high in response, high in detection sensitivity, good in peak pattern and accurate and reliable in detection result; the high performance liquid chromatography is adopted, instruments, solvents and chromatographic columns used for detection are conventional and easy to obtain, samples and reference substances are easy to prepare and operate, and the method can be widely applied to detection of N-methyl pyrrolidone.

Provided herein are improved methods for measuring the concentration of carfilzomib in a sample. The method comprises the steps of diluting the sample with a diluent comprising water and less than 50% by volume of acetonitrile to form an analysis sample; and subjecting the analysis sample to high performance liquid chromatography (HPLC) to determine the carfilzomib concentration in the sample.