72 results about "Molecular targeted drug" patented technology

The invention provides a synthetic process method for a novel antineoplastic molecular targeted drug of crizotinib, and relates to the resolution process optimization of chiral isomers of a crizotinib precursor and the recycling of by-products. The method adopts a catalyzing resolution method that Boc-L-proline, namely, N-(tert-butoxycarbonyl)-L-proline) is combined with a catalyst of p-toluenesulfonic acid and a condensating agent of 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride to split 1-(2,6-dichloro-3-fluorophenyl)ethanol racemate into S-type alcohol and R-type alcohol, and a resolution by-product mixture is subjected to hydrolysis and configuration transition to obtain the (S)-1-(2,6-dichloro-3-fluorophenyl)ethanol; the total yield is improved to 76% from 30%, the time is shortened, pollution is reduced, and application to industrialized production is easy.

The invention relates to a gel injection combining a molecular targeted drug and a cytotoxic drug. The gel injection comprises a small molecular targeted drug, a traditional cytotoxic drug, a temperature-sensitive material, a solvent and pharmaceutical excipients, wherein the temperature-sensitive material is selected from poloxamer, polylacticacid-polyethylene glycol-polylactic acid or polyglycolide lactide-polyethylene glycol-polyglycolide lactide and the like; the solvent is selected from water, brine salt or 5% glucose aqueous solution and the like, the prepared gel injection can be injected intratumorally or peritumorally, the anti-tumor effect is obvious, and the side effects are fewer.

The invention relates to a test method of KRAS gene mutation for screening and assessing therapeutic effects of molecular targeted agents, which is characterized by the following specific steps: acquiring serum or tumor tissue samples of testees, extracting genomic DNA, testing a No.2 exon of the KRAS gene, designing corresponding site-specific primers and adopting experimental schemes, reagents and report generation systems for sequence determination and assessing the effectiveness of EGFR tyrosine kinase inhibitors used for treating cancer individuals by simultaneously testing and analyzingwhether mutation exists on the No.2 exon of the individual KRAS gene. The method has the advantage of being used for application of the EGFR tyrosine kinase inhibitors used for treating cancer individuals.

The invention belongs to the field of biological medicines, and relates to a molecular targeting drug-entrapped liposome and application of the liposome in preparation of a drug for treating tumors. The molecular targeting drug-entrapped liposome is composed of a molecular targeting drug, and lipidosome components such as phospholipid, cholesterol, mPEG-DSPE and / or targeting molecule modified PEG-DSPE. The liposome is prepared by loading a molecular targeting drug into a water phase or phospholipid bilayer in a liposome in an active or passive drug loading manner so that tumor targeting drug delivery can be realized, and the anti-tumor effect, especially the anti-brain tumor effect, of the molecular targeting drug is remarkably enhanced. Furthermore, the combination of the molecular targeting drug-entrapped liposome and pharmaceutically acceptable medicinal components and / or diluents can be prepared into various dosage forms for targeting treatment of tumors and has potential clinicalapplication value.

The invention provides novel application of artesunate. The artesunate is used for reversing erlotinib drug resistance of lung adenocarcinoma, or the artesunate is used together with erlotinib. The problem that clinical application of a conventional molecular targeted drug is limited as drug resistance can be resulted ultimately can be solved. The invention belongs to the field of lung cancer treatment.

The invention discloses application of lncRNA combination to preparation of a product for predicting renal clear cell carcinoma prognosis and molecular targeted medicine treatment sensitivity. The lncRNA or the lncRNA combination serving as a detection target point is applied to preparation of the product for predicting renal clear cell carcinoma prognosis and molecular targeted medicine treatmentsensitivity, and the lncRNA or the lncRNA combination is selected from any one or more of SEQ ID NO.1 to SEQ ID NO.4. A new clinical method is provided for evaluating prognosis of patients sufferingfrom renal clear cell carcinoma, new reference advice is provided for auxiliary treatment after operation of the renal clear cell carcinoma, and important clinical significance and popularization andapplication prospect in the aspects of timely taking effective clinical measures, formulating an individualized diagnosis and treatment scheme and finally increasing the survival rate of the patientssuffering from the renal clear cell carcinoma are achieved.

The invention provides a tumor-targeting near-infrared fluorescent probe and a preparation method thereof, and is characterized in that the fluorescent probe comprises a cyanine fluorescent dye part and a targeting carrier part; the cyanine fluorescent dye part and the targeting carrier part are coupled by covalent bonds, wherein, the cyanine fluorescent dye part comprises IDCC and ITCC, and the targeting carrier part comprises EBP molecules. After entering a body, the tumor-targeting near-infrared fluorescent probe reaches tumor tissue and is bonded with EGFR of cells, and exhibits a strong effect of targeted fluorescent labeling, thereby not only improving the specificity and the sensitivity of tumor fluorescence imaging significantly, but also providing important information for the evaluation of molecular typing and molecular targeted drug efficacy of tumors, and having strong practicality for guiding and monitoring the application of molecular targeted drugs.

The invention discloses a medicinal composition for improving the sensitivity of an anti-tumour medicament and the application thereof in preparation of the anti-tumour medicament. The composition comprises effective dose of sulfasalazine and nano-zinc oxide and a pharmaceutically acceptable carrier, and can be used for preparing a tumour medicament sensitizer. The combined use of the sulfasalazine and the nano-zinc oxide can achieve a synergistic effect and improve the tumour cancer cell killing effect of a traditional chemotherapy medicament, a molecular targeted medicament and immunotherapymedicaments. According to the medicinal composition for improving the sensitivity of the anti-tumour medicament and the application thereof in the preparation of the anti-tumour medicament, the sulfasalazine and the nano-zinc oxide are combined for use for the first time; the sensitivity of the anti-tumour medicament is improved by the synergistic effect of the sulfasalazine and the nano-zinc oxide; moreover, the composition is safe and non-toxic to normal cells, provides a new strategy for the treatment of a clinical tumour patient, and has a good clinical application prospect.

The invention discloses a method for measuring the concentration of molecular targeted drugs in plasma by using ultra-high performance liquid chromatography tandem mass spectrometry. The method comprises the following steps of respectively dissolving anlotinib, ceritinib and ibrutinib by adopting acetonitrile in order to prepare a standard curve working solution, and dissolving diazepam by adopting methanol in order to prepare an internal standard substance working solution; respectively adding 0-5 microliters of standard curve working solution into blank plasma to make up to 50 microliters, carrying out vortex to prepare a standard curve plasma sample, adding the internal standard substance working solution, carrying out vortex and centrifugation, taking supernate, carrying out UPLC-MS / MSquantitative analysis, and drawing a standard curve; and precisely sucking to-be-detected plasma with the concentration of 50 microliters, adopting the same sample pretreatment method, and measuringthe concentration of the anlotinib, the ceritinib and the ibrutinib according to a standard curve of the batch. According to the method, the blood concentration of various anti-tumor molecular targeted drugs can be measured simultaneously, the method is high in sensitivity, strong in specificity, rapid and good in reproducibility and is suitable for clinical high-throughput simultaneous detectionand monitoring of various anti-tumor molecular targeted drugs.

The invention discloses a molecularly targeted aza aromatic ring axially substituted phthalocyanine complex and a preparation method thereof. The molecular target drug N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-morpholine-4-propoxy)quinazoline-4-amine with an alkoxy long chain is introduced to the axial direction of a phthalocyanine large ring so as to increase its amphipathy, biocompatibility and photosensitizer targeting. The compound has the advantages of single structure, definite composition, no isomer, and easy product purification, also the complex is not easy to gather, thus being conducive to increasing the cell uptake rate. The synthesis method of the complex provided by the invention is simple, and has the characteristics of few side reaction, easily available raw materials, and low cost, and is in favor of industrial production.

The invention discloses a self-assembled nano-drug of a single drug of molecular targeted drugs, a co-assembled nano-drug of molecular targeted drugs and other hydrophobic drugs, a preparation methodand an application thereof. Meanwhile, all drugs used have been approved by the US FDA for market use and have good application prospects. The nanoparticle is formed by single-drug self-assembly of molecular targeted drugs, multi-drug co-assembly of molecular targeted drugs and hydrophobic drugs, does not need an additional carrier, has a passive targeting effect, and is easy to stay at a tumor site through an EPR effect, so that the toxic and side effects of the drugs on normal tissues are greatly reduced.

The invention belongs to the technical field of medical and chemical engineering, and particularly relates to acid-responsive polycation and a synthesis method thereof, and a preparation method of acid-responsive polycation micelle nanoparticles with acid sensitivity prepared from the acid-responsive polycation. The invention also relates to application of the multi-layered cationic micelle nanoparticles with double acid sensitivity to synchronous co-delivery of nucleic acid and molecular targeted drugs which are mainly used for gene therapy and immunotherapy of cancers. The acid-responsive polycation has the structure shown in formula 1 in specification.

The invention discloses a method for determining the concentration of a molecular targeting drug AMG 510 in blood plasma through ultra-high performance liquid chromatography-tandem mass spectrometry.The method comprises the following steps: preparing a standard curve working solution and an internal standard substance working solution; adding 0-5 microliters of standard curve working solution into blank plasma for making up to 20 microliters, performing vortex to prepare a standard curve plasma sample, adding the internal standard substance working solution and methanol, performing vortex andcentrifugation, taking supernatant, performing UPLC-MS / MS quantitative analysis, and drawing a standard curve; precisely sucking 20 microliters of to-be-detected plasma, and determining the concentration of AMG 510 according to the standard curve of the current batch by the same sample pretreatment method. The blood concentration of the non-small cell lung cancer resistant molecular targeted drugAMG 510 is determined for the first time, the sensitivity is high, the specificity is high, the speed is high, the reproducibility is good, the method can be further popularized to clinical high-throughput detection or monitoring of the AMG 510 concentration, and the benefit risk ratio of cancer patients is increased.

The invention discloses a synthetic method of anti-tumor molecular targeted drug crizotinib, belongs to the field of pharmaceuticals, and relates to a synthetic method of a crizotinib intermediate. The method comprises two reduction processes: a bromination reaction process comprises the following reaction steps: a reduction process I: carrying out reduction reaction on a (R)-3-[1-(2,6-dichloro-3-fluorophenyl)ethoxyl]-2-nitropyridine compound and sodium dithionate under a mechanical chemical condition to generate (R)-3-[1-(2,6-dichloro-3-fluorophenyl)ethoxyl]-2-aminopyridine; a reduction process II: dissolving the (R)-3-[1-(2,6-dichloro-3-fluorophenyl)ethoxyl]-2-nitropyridine compound into an organic solvent, carrying out catalytic hydrogenation and reduction treatment to generate (R)-3-[1-(2,6-dichloro-3-fluorophenyl)ethoxyl]-2-aminopyridine; the bromination reaction process comprises a step of carrying out reaction between the compound and potassium hydrogen persulfate as well as bromate to obtain the crizotinib intermediate. The process is low in cost, the raw materials are easy to purchase, the operation is simple, convenient and safe, and the yield is high; moreover, the process is suitable for large-scale production.

The invention discloses a preparation method of a molecular targeted drug liposome preparation. The preparation method comprises the operating steps of blank liposome preparation, liposome preprocessing, drug preprocessing, preparation production and postprocessing, the production processes of the steps are optimized, and finally the problem that the product obtained by adopting a conventional production method is turbid and the drug encapsulation efficiency is low is solved. According to the technical scheme, the encapsulation efficiency can be improved by 95% or above, a solution is clear and transparent, and gefitinib drugs are not easy to degrade in the preparation process. The production method is simple and easy to operate and facilitates production expanding, and the finally obtained product is high in stability.

The present disclosure describes how all-retinoic acid (ATRA) binds and inhibits Pin1 activity and induces degradation of the activated Pin1 monomer selectively in cancer cells. Identification of the binding mechanism of ATRA with Pin1 confirm ATRA binding specificity to Pin1 residues in the PPIase active site, thus demonstrating that drug-induced Pin1 ablation has potent anticancer activity, such as in acute promyelocytic leukemia (APL), by inducing PML-RARa degradation, as well as against other types of cancer and diseases that are associated with Pin1 overexpression, such as aggressive triple negative breast cancer, lupus, asthma, cocaine addiction, among others, due to their unique ability to simultaneously block numerous cancer-driving pathways, with relatively lower toxicity. The present disclosure also provides a rationale for developing sustained released ATRA-containing formulations. ATRA-containing formulations may be used in combinations with other existing therapies including chemotherapy or molecularly targeted drugs and other standard of care.

The invention provides application of a purine metabolism marker in preparation of a reagent for screening and diagnosing acquired drug resistance of a lung cancer molecular targeted drug. The purine metabolism marker is one or more of adenosine monophosphate, guanosine monophosphate, inosine monophosphate, xanthosine monophosphate, adenosine, guanosine, inosine, xanthosine, adenine, guanine, hypoxanthine, xanthine and uric acid. The metabolic marker has good diagnostic potential for acquired drug resistance of the lung cancer molecular targeted drug, can be used for diagnosis and curative effect monitoring of acquired drug resistance of the lung cancer molecular targeted drug, and has good guiding significance for development of subsequent clinical application research.

The invention discloses a traditional Chinese medicine composition for treating rash caused by a molecular targeted drug. Effective ingredients of the traditional Chinese medicine composition include the following bulk pharmaceutical chemicals in parts by weight: 10 to 14 parts of densefruit pittany root-bark, 8 to 10 parts of honeysuckle, 10 to 14 parts of erythrina bark, 10 to 14 parts of siegesbeckia herb and 8 to 10 parts of fragrant solomonseal rhizome. The traditional Chinese medicine composition has a remarkable treatment effect on the rash caused in a process of using the molecular targeted drug by a patient suffering from a non-small cell lung cancer.

The invention discloses a preparation method of an oxygen-carrying and fluorocarbon chain-modified drug and photosensitizer targeted co-delivery nano-composite and application of the nano-composite to preparation of anti-epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) drug-resistant lung cancer drugs. The preparation method of the nano-composite comprises the steps of performing fluorocarbon chain and EGFR-targeted aptamer (Apt) modification on polyamidoamine (PAMAM) to form a nano-drug delivery carrier APF with oxygen carrying capacity and tumor targeting property, and then co-entrapping photosensitizer hematoporphyrin and molecular targeting drug gefitinib to construct the targeting nano-composite APFHG for enhancing the photodynamic therapy effect. The nano-composite overcomes the defect that photodynamic therapy is limited by a tumor anoxic microenvironment and improves the sensitivity of drug-resistant lung cancer cells to EGFR-TKIs, thereby promoting the combined treatment effect of molecular targeted therapy and photodynamic therapy.

To provide means for treating and preventing a wide variety of cancers and tumors, including cancer in which there is PI3K / Akt pathway activation or p53 deactivation, or tumors for which chemotherapy, radiation therapy, hormone therapy, and other such conventional treatment methods have low effectiveness, different molecularly targeted drugs such as OBP-801 and PI3K inhibitor—preferably LY294002, BKM120, GDC-0941, BEZ235, BYL719, or CH5132799—are used in combination. This makes it possible to simultaneously obtain a plurality of different marked pharmaceutical benefits which are synergistic, not being obtainable through use of a formulation with either of the respective molecularly targeted drugs alone, such as caspase pathway activation, enhanced expression of Bim, increased accumulation of intracellular reactive oxygen species, and suppressed expression of survivin and XIAP protein, and makes it possible to provide new and clinically effective tumor treatment / prevention strategies.

The present invention provides an antitumor agent having high safety, which is a molecular target drug against malignant tumors. An anti-malignant tumor agent characterized by containing, as an active ingredient, a substance targeting ribosomal proteins shows increased expression in malignant tumor cells. The substance of the present inventions targeting the ribosomal protein showing increased expression in the malignant tumor cell may be a substance involved in one of biological defense mechanisms which are considered to be intrinsically provided in a living body and prevent onset of disease even if cancer cells develop. Specifically, the ribosomal protein showing increased expression is RPL29 and / or RPS4X. A substance targeting RPL29 and / or RPS4X is an anti-RPL29 antibody and / or anti-RPS4X antibody, a substance capable of activating or enhancing an endogenous anti-RPL29 antibody and / or anti-RPS4X antibody in a living body, a substance capable of inducing production of the anti-RPL29 antibody and / or anti-RPS4X antibody in a living body, or an antagonist of RPL29 and / or RPS4X. Furthermore, the present invention also extends to an examination method of malignant tumors which uses the anti-RPL29 and / or anti-RPS4X antibody titer as an indicator.

The invention relates to application of Synsepalum dulcificum leaf extract in the preparation of molecular targeting drugs; the Synsepalum dulcificum leaf extract is extracted via the steps of homogenizing and crushing Synsepalum dulcificum leaf into Synsepalum dulcificum leaf powder, ultrasonically extracting with 70-90% (v / v) ethanol solution, and centrifugally collecting supernate; distilling the supernate under reduced pressure, and lyophilizing to obtain Synsepalum dulcificum leaf crude extract; dissolving the Synsepalum dulcificum leaf crude extract in water, treating with macroporous resin, eluting with an eluent, and collecting eluant; distilling the eluant under reduced pressure, and lyophilizing to obtain Synsepalum dulcificum leaf extract powder. Molecular targeting drugs containing the Synsepalum dulcificum leaf extract are small toxic and side effects, have significant effect in resisting tumor angiogenesis and are good in safety and reliability.

The invention discloses a PLK1 inhibitor-loaded polymer vesicle drug and a preparation method and application thereof. The polymer vesicle A3-Ps based on PEG-P (TMC-DTC) has a compact disulfide bond cross-linked membrane, excellent stability and rapid intracellular drug release are brought, short-chain polyaspartic acid in an inner shell of the vesicle membrane can enhance the capacity of the vesicle for loading a molecular targeting drug Volasertib (Vol), and the A3-Ps is high in drug loading capacity and drug loading rate and small in particle size. The Vol-loaded vesicles A3-Ps-Vol have the advantages that the anti-tumor activity of the Vol is improved, the systematic toxicity of the Vol-loaded vesicles A3-Ps-Vol is reduced, the A3-Ps-Vol, the non-targeted Ps-Vol and the free drug Vol have the best activity of inhibiting SKOV-3 cells compared with the A3-Ps-Vol, the non-targeted Ps-Vol and the free drug Vol, the IC50 is 49 nM and is 3.5 times lower than that of the free drug Vol, and the double-targeted nano preparation is a high-efficiency and low-toxicity therapy for treating ovarian cancer.

The invention discloses a method for detecting type II diabetes related gene KCNIP1 copy number variation (CNV), and application thereof. The position of CNV on a chromosome is Chr5q35.1:170062275-170064128. According to the detection method, blood genome DNA of patients suffering from type II diabetes and normal individuals serve as templates, primer pairs P1(F1,R1) and P2(F2,R2) serve as primers, a KCNIP1 gene CNV area and a reference gene RNase P are amplified separately through real-time fluorescent quantitative PCR, the CNV is divided into an inserting type, a deletion type and a normal type according to Log2<2-delta delta Ct>, and the distribution difference of the KCNIP1 gene CNV in the patients suffering from type II diabetes and the normal individuals can be identified. The method can serve as a molecular diagnostic mark of the type II diabetes and provides important scientific basis for research and development of molecular targeted medicines.

The invention relates to an lncRNA molecule and application thereof. A new transcript full-length sequence of lncRNA (TCONS-00013523) is identified in paclitaxel-resistant ovarian cancer cells and is named as PRALR-alpha, cell lines for knocking out and overexpressing the PRALR-alpha are further constructed, and the fact that the sensitivity of the ovarian cancer cells to paclitaxel (PTX) can be increased and reduced by knocking out and overexpressing the PRALR-alpha is found, and it proves that PRALR-alpha is closely related to the paclitaxel drug resistance of the ovarian cancer cells. Through the research, a new thought and method can be provided for the treatment of ovarian cancer paclitaxel chemotherapy, and a molecular targeting drug aiming at a PRALR-alpha specific target spot is synthesized; a candidate drug for treating the paclitaxel drug-resistant ovarian cancer can be screened by using a PRALR-alpha overexpression vector or a cell line; and meanwhile, the molecular mechanism generated by ovarian cancer drug resistance can be deeply researched.

The invention relates to application of EFTUD2 and an Epro-LUC-HepG2 modeling method. The EFTUD2 protein can adjust the generation of key signal molecules RIG-1 and MDA5 mRNA in an innate immune signal path through a splicing effect, so that the generation of interferon stimulating genes (ISGs) is influenced to inhibit HBV replication. According to the application, a stable compound screening cellmodel is established by taking EFTUD2 as a target spot so that a new molecular targeted drug can be researched and explored. On the basis of the model, compounds capable of up-regulating EFTUD2 geneexpression are screened, and more treatment options are provided for HBV chronic infection patients, especially patients with poor clinical IFN-alpha treatment response.

An object of the present invention is to provide a labeling agent which exhibits excellent binding to a target molecule in a bioassay or histological staining method that relates to a compound containing a nitrogen-containing aromatic ring.The labeling agent according to the present invention is a labeling agent having a structure in which a molecular target drug, which is a compound containing a nitrogen atom-containing aromatic ring, is bound with a label via a divalent linking group, wherein one end of the divalent linking group is bound to a carbon atom of the nitrogen atom-containing aromatic ring. The label is preferably a fluorescent substance-integrated nanoparticle, and the nitrogen atom-containing aromatic ring is preferably a pyridine ring.

The present invention provides an antitumor agent having high safety, which is a molecular target drug against malignant tumors. An anti-malignant tumor agent characterized by containing, as an active ingredient, a substance targeting ribosomal proteins shows increased expression in malignant tumor cells. The substance of the present inventions targeting the ribosomal protein showing increased expression in the malignant tumor cell may be a substance involved in one of biological defense mechanisms which are considered to be intrinsically provided in a living body and prevent onset of disease even if cancer cells develop. Specifically, the ribosomal protein showing increased expression is RPL29 and / or RPS4X. A substance targeting RPL29 and / or RPS4X is an anti-RPL29 antibody and / or anti-RPS4X antibody, a substance capable of activating or enhancing an endogenous anti-RPL29 antibody and / or anti-RPS4X antibody in a living body, a substance capable of inducing production of the anti-RPL29 antibody and / or anti-RPS4X antibody in a living body, or an antagonist of RPL29 and / or RPS4X. Furthermore, the present invention also extends to an examination method of malignant tumors which uses the anti-RPL29 and / or anti-RPS4X antibody titer as an indicator.