97 results about "Pemetrexed" patented technology

The invention relates to a pemetrexed disodium lyophilized powder injection, which consists of pemetrexed disodium, mannitol and sodium sulfite in the following weight portions: 50 portions of the pemetrexed disodium, 10 to 50 portions of mannitol, and 0.1 to 1 portions of sodium sulfite; and the pH value of the pemetrexed disodium lyophilized powder injection is between 7.0 and 8.0. The process for preparing the pemetrexed disodium lyophilized powder injection comprises the following steps: placing the mannitol in a sterile chamber; adding 80 percent of water for injection into the sterile chamber to dissolve the mannitol; adding the sodium sulfite to the mixture after the water for injection is cooled to a temperature of between 15 and 25 DEG C, and evenly stirring the solution for dissolving the sodium sulfite; then, adding the pemetrexed disodium into the solution, and stirring the solution to completely dissolve the pemetrexed disodium and evenly mixing the pemetrexed disodium, and adjusting the pH value of the solution to between 7.0 and 8.0; decarbidizing; after an intermediate compound passes examination, carrying out volume fixing, filtering, filling, partially stopping, traying, lyophilizing, nitrogen aerating, stopping and unboxing, sealing by a plastic-aluminum combined cap, and packaging after passes quality inspection to obtain the pemetrexed disodium lyophilized powder injection. The invention has the advantages of simple preparation process, convenience and practicality, good repeatability and low production cost, and can realize industrial large-scale production easily.

The present invention provides one kind of medicine composition, which contains Pemetrexed, at least one kind of antioxidant selected from L-arginine, L-glutathione, L-methionine and L-tryptophan, and pharmaceutically acceptable excipient. The medicine composition has high stability and acceptable storing period, and is suitable for liquid administration through no gastrointestinal tract.

Long term storage stable pemetrexed-containing liquid pharmaceutical compositions are disclosed. The compositions can include pemetrexed or pharmaceutically acceptable salts thereof; an antioxidant selected from lipoic acid, dihydrolipoic acid, methionine and mixtures thereof; a chelating agent selected from lactobionic acid, sodium citrate, tribasic and mixtures thereof; and a pharmaceutically acceptable fluid. The pH of the compositions is in a range of about 8 to about 9.5. The pemetrexed-containing compositions have less than about 5% total impurities, on a normalized peak area response (“PAR”) basis as determined by high performance liquid chromatography (“HPLC”) at a wavelength of 227 nm, after at least about 18 months of storage at a temperature of from about 5° C. to about 25° C. Methods of preparing the formulation as well as methods of treatment of pemetrexed-susceptible diseases using the same are also disclosed.

The invention discloses a drug composition with Peimeiqusai and stabilizer at 5: 2-7, wherein the weight rate of Peimeiqusai and shaping agent is 0.5-1: 1. The invention is stable for light and heat, which can be reserved at normal temperature.

The invention relates to a nitro compound and process of its preparation, as well as the use in the preparation of pemetrexed, a kind of anti-tumor medicament, which has the advantages of simplified post-reaction treatment, high product purity, and facilitation of industrialized production.

The invention provides a method of treating a subject with cancer, particularly leukemia, lymphoma, solid cancer such as colorectal cancer, gastric cancer, bladder cancer, non-small cell lung cancer, and breast cancer, comprising administering to the subject a compound of formulae (I) 40 or (Ia) in combination with an antimetabolite such as methotrexate, pemetrexed, cytarabine or nelarabine, or 5-fluorouracil, or capecitabine or their derivatives.

The invention discloses a pemetrexed salt and a preparation method and use thereof, the pemetrexed salt can be dipotassium salt, arginine salt, heme-L-lysinate salt and tromethamine salt of the pemetrexed, and the pemetrexed salt can be used for treatment of various cancers such as mesothelioma, lung cancer and the like.

The invention discloses a preparation method of a pemetrexed intermediate. The pemetrexed intermediate is 4-[2-(2-amino-4,7-dihydro-4-oxy-1H-pyrrolo[2,3-d]pyrimidyl-5-yl)ethyl]benzoic acid (I). The preparation method comprises the following steps: carrying out Friedel-Crafts alkylation reaction on benzene and 4-halogen-1-butanol by using aluminum trichloride as a catalyst to generate 4-phenyl-1-butanol (II); carrying out Friedel-Crafts acylation reaction on the compound (II) to obtain 4-(4-carbalkoxyphenyl)-1-butanol (III), and carrying out oxidation reaction on the compound (III) to generate 4-(4-carbalkoxyphenyl)-1-butanal (IV); and carrying out substitution reaction on the compound (IV) and bromine, carrying out condensation and cyclization reaction with 2,4-diamido-6-hydroxypyrimidine (VI) to obtain a compound (VII), and finally, carrying out hydrolysis reaction to obtain the pemetrexed intermediate. The preparation method is simple, convenient, classic and stable, and has the advantage of low cost.

A pharmaceutical composition of Pemetrexed represented by formula (I), which is a liquid ready to use solution formulation or a lyophilized pharmaceutical composition for parenteral administration comprising a pharmaceutically acceptable organic amine, an inert gas and optionally containing at least one or more pharmaceutically acceptable excipients. Also provided are processes for preparation of the ready to use solution formulation or lyophilized pharmaceutical composition of the present invention.

The invention discloses a pemetrexed thiocarbamide salt and a preparation method thereof, and a medicinal composition containing the pemetrexed thiocarbamide salt. The pemetrexed thiocarbamide salt is generated through the reaction of pemetrexed and thiocarbamide in water and / or an organic solvent. The preparation process is simple, the yield is high and the stability is good.

The invention provides a pemetrexed liposome, which is characterized by being prepared from a pemetrexed and a liposome mixture, wherein the mass ratio of the pemetrexed and the liposome mixture is 1:(0.1-10); through the prepared pemetrexed liposome, the drug resistance can be reduced by more than 60% of non-liposome pemetrexed. Known from stability test, the liposome is favorable in stability. Known from clinical trials, the efficacy of the liposome can be improved by more than 80% compared with the common preparation, the in-vivo retention time can be prolonged by more than 65%, and the targeting effect is obvious.

Three new crystalline forms of pemetrexed diacid, preparation methods and uses thereof are disclosed. These preparation processes are simple and have better practicality.

The slow released anticancer medicine injection containing both amrubicin and its synergist consists of slow released microsphere and solvent. The slow released microsphere includes effective anticancer component and slow releasing supplementary material, and the solvent is special solvent containing suspending agent carboxymethyl cellulose, etc. and with viscosity of 100-3000 cp at 25 deg.c. The effective anticancer component is amrubicin, idarubicin, etc and / or antimetabolite composition selected from carmofur, tegafur, zalcitabine, etc. The slow releasing supplementary material is selected from EVAc, sebacic acid copolymer, lactic acid polymer, etc. The slow released microsphere may be also prepared into slow released implanting agent set around or inside the tumor to strengthen the chemotherapy or radiotherapy effect.

Provided are processes for preparing intermediates of pemetrexed.

The present invention relates to a stabilized pemetrexed formulation, and more particularly to a stabilized pemetrexed formulation comprising acetylcysteine as antioxidant and a citrate salt as buffer.

The present invention relates to an intravenous infusion dosage form of pemetrexed or its pharmaceutically acceptable salt, having long term stability.

The invention relates to a di-glutamate derivative and a preparation method and application in the preparation of pemetrexed thereof. The glutamate derivative is used as a key intermediate for preparing pemetrexed. The method has simple treatment after reaction and high product purity, and facilitates the industrialized production.

The present invention relates to a stabilized pemetrexed formulation, and more particularly to a stabilized pemetrexed formulation comprising acetylcysteine as antioxidant and a citrate salt as buffer.

Methods are provided for identifying whether a lung tumor will be responsive to treatment with the combination of the therapeutic agents cisplatin and pemetrexed. Specified ERCC1, TS, p16, and FRα fragment peptides are precisely detected and quantitated by SRM-mass spectrometry directly in lung tumor cells collected from lung tumor tissue that was obtained from a cancer patient and compared to reference levels in order to determine if the lung cancer patient will positively respond to treatment with the combination of cisplatin and pemetrexed therapeutic agents.

The present invention relates to arginine salt of pemetrexed of formula (1), particularly to a stable solid form thereof, and to pharmaceutical compositions comprising such salt.

The present invention provides methods for treating cancer patients comprising assaying tumor tissue from patients and identifying those patients most likely to respond to treatment with a platinum-based agent, such as cisplatin, in combination with pemetrexed. Methods are provided for identifying those lung cancer patients most likely to respond to treatment with the combination of cisplatin+pemetrexed chemotherapy agents (“CDDP+PEM”) by determining expression patterns of a set of 38 specific proteins directly in tumor cells derived from patient tumor tissue using SRM mass spectrometry. The method further comprising determining if the patient will respond to treatment with combination therapy, and when proteomic analysis of patient tissue indicates that the patient will respond to treatment with combination therapy, the patient is administered a regimen that includes the pemetrexed / platinum agent combination.

The invention discloses a compound XI, which is a key intermediate for synthesizing pemetrexed with chemical name of N-[4-(2-halo-butyraldehyde-4-base)-benzoyl]-L-glutamic acid and structural formula shown in formula XI, wherein * represents L-configuration carbon, and X represent bromine, chlorine or iodine. The invention also discloses a preparation method of the intermediate and a method for preparing pemetrexed with the intermediate. The method for preparing pemetrexed with the compound XI has the advantages of simple reaction process, easy purification of intermediate, short preparation period, high product purify, and applicability to industrial production.

A pharmaceutical composition of Pemetrexed represented by formula (I),which is a liquid ready to use solution formulation or a lyophilized pharmaceutical composition for parenteral administration comprising a pharmaceutically acceptable organic amine, an inert gas and optionally containing at least one or more pharmaceutically acceptable excipients. Also provided are processes for preparation of the ready to use solution formulation or lyophilized pharmaceutical composition of the present invention.

The invention provides a pemetrexed quality control method, and preparation of a pemetrexed impurity and salt thereof. The pemetrexed impurity is synthesized from the raw material N-tert-butoxycarbonyl-L-glutamic acid-5-benzyl ester. The pemetrexed quality control method mainly uses the pemetrexed impurity prepared by the technique as a standard control substance in detection and analysis. The method provided by the invention solves the problem that the pemetrexed impurity can only be separated and obtained in the preparation process of the pemetrexed and sodium salt thereof in the prior art, and the high-purity pemetrexed impurity can not be obtained. The method is simple to operate, and has the advantages of low facility request, mild reaction conditions, high product purity and high yield.

The invention provides a method for preparing a pemetrexed disodium 2.5 water crystal. The method comprises the following steps of: (1) dissolving a raw material, namely pemetrexed disodium in water; (2) dropwise adding the aqueous solution of the pemetrexed disodium into an organic solvent which can be miscible with the water, and crystallizing; and (3) filtering, collecting a filter cake, and drying to obtain a target product. The preparation method is high in controllability, easy and convenient to operate, high in repeatability, high in production yield, and stable in crystal form and industrial production is easy to implement, and special equipment is not required.

The invention relates to an anti-cancer compound as a slow release injection which contains platinum compound and / or alkyl agent, formed by slow release micro ball and solvent. The slow release micro ball comprises the anti-cancer effective components and slow release findings, selected from platinum compound of kpeitabing, peimeiquse, caplatinum, or jxitabing and / or alkyl agent, the solvent is a common solvent or a special solvent with suspending agent, while the viscosity of suspending agent is 100cp-3000cp (at 20-30Deg. C), selected from carboxymethyl cellulose, the anti-cancer effective component is phosphoinositide 3-kinase restrainer and / or the phosphoinositide 3-kinase restrainer booster selected from self-anti-cancer antibiotics and / or tetrazine drug, the slow release finding is selected from phosphate polyester as p (LAEG-EOP) or p (DAPG-EOP), or the polyester or mixture of phosphate, PLA, polyphenyl, PLGA, poly (erucic acid dimmer-sebacic acid) or poly (fumaric acid-sebacic acid), and the alkyl agent is selected from ranimustine or the like. The anti-cancer compound can be made as slow release plant agent, to inject cancer or around cancer to hold the effective drug density for more than 60 days, while it can significantly reduce the general reaction of drug and selectively strengthen the effect of non-surgery treatments as chemotherapy or the like.

Methods of treating cancer comprising administering a fibroblast growth factor receptor 1 (FGFR1) extracellular domain (ECD) and / or an FGFR1 ECD fusion molecule in combination with at least one additional therapeutic agent selected from docetaxel, paclitaxel, vincristine, carboplatin, cisplatin, oxaliplatin, doxorubicin, 5-fluorouracil (5-FU), leucovorin, pemetrexed, and bevacizumab are provided. Dosage packs comprising an FGFR1 ECD and / or an FGFR1 ECD fusion molecule and / or at least one additional therapeutic agent selected from docetaxel, paclitaxel, vincristine, carboplatin, cisplatin, oxaliplatin, doxorubicin, 5-fluorouracil (5-FU), leucovorin, pemetrexed, and bevacizumab are also provided. In some embodiments, a dosage pack comprises instructions for administering FGFR1 ECD and / or FGFR1 ECD fusion molecule with at least one additional therapeutic agent.

The invention relates to a slow release injection which contains antimetabolite and / or alkyl agent, formed by slow release micro ball and solvent. The slow release micro ball comprises the anti-cancer effective components selected from platinum compound of kpeitabing, peimeiquse, caplatinum, or jxitabing and / or alkyl agent, the solvent is a common solvent or a special solvent with suspending agent, while the viscosity of suspending agent is 100cp-3000cp (at 20-30Deg. C), selected from carboxymethyl cellulose, the slow release finding is selected from phosphate polyester as p (LAEG-EOP) or p (DAPG-EOP), or the polyester or mixture of phosphate, PLA, polyphenyl, PLGA, poly (erucic acid dimmer-sebacic acid) or poly (fumaric acid-sebacic acid), and the alkyl agent is selected from ranimustine or the like. The anti-cancer compound can be made as slow release plant agent, to inject cancer or around cancer to hold the effective drug density for more than 50 days, while it can significantly reduce the general reaction of drug and selectively strengthen the effect of non-surgery treatments as chemotherapy or the like.

The present invention relates to a long term storage stable multi-dose ready-to use or ready-to dilute pharmaceutical liquid formulation comprising pemetrexed or a pharmaceutically acceptable salt thereof, an antioxidant, a preservative, a buffering agent, and a pharmaceutically acceptable fluid. The invention also relates to a process of preparing the formulation, a kit and a method of treatment of patients having lung cancer by administering the pharmaceutical formulation to a subject in need thereof.