31 results about "Lenvatinib" patented technology

The application discloses a method for determining unbound concentration of lenvatinib, which comprises the following steps: sending standard curve working solution and quality control working solution into a liquid chromatography tandem mass spectrometry detection system to obtain a standard curve; adding a plasma sample into an ultrafiltration tube, centrifuging under the condition of a centrifugal force of 3000g for 15 min, and collecting an ultrafiltrate of the plasma sample; adding the ultrafiltrate of the plasma sample into blank plasma ultrafiltrate, mixing uniformly, taking supernatant into a collection plate, sending the collection plate into the liquid chromatography tandem mass spectrometry detection system to obtain a ratio of a peak area of lenvatinib to a peak area of an internal standard, and then bringing the area ratio into the standard curve to obtain the unbound concentration of lenvatinib in the plasma sample. The method for determining the unbound concentration of lenvatinib can accurately determine the unbound concentration of lenvatinib in plasma and overcome the prejudice of the prior art.

The invention relates to the field of biological medicines, and discloses application of serum EPSTI1 in preparation of a product for diagnosing liver cancer and evaluating whether a liver cancer patient is resistant to a revatinib or not. The invention provides a detection means which is convenient and rapid in sampling, small in risk and relatively low in cost, the content of EPSTI1 in serum is detected through an enzyme-linked immunosorbent assay, a liver cancer patient and a non-liver cancer patient can be effectively distinguished, and a lovatinib drug-resistant liver cancer patient and a non-drug-resistant liver cancer patient can be effectively distinguished. Prognosis analysis shows that the serum EPSTI1 can be used as a marker for evaluating the prognosis state of the liver cancer patient taking the lenvatinib, and has important significance in improving the survival rate of the liver cancer patient.

Provided herein are a humanized anti-alpha-2-delta-1 monoclonal antibody and an application thereof. Specifically provided is a humanized antibody, or a biologically active fragment derived from the antibody, that binds to a voltage-gated calcium channel alpha-2-delta-1 subunit (subtype 5). The antibody or the biologically active fragment derived from the antibody, either alone or in combination with lenvatinib, is capable of significantly inhibiting the self-renewal capacity of liver cancer cells and the growth of transplanted tumors in animals. The antibody, either alone or in combination with lenvatinib, can be used for a combination of liver cancer drugs targeting liver cancer stem cells, and can also be used for the in vivo diagnosis of alpha-2-delta-1+ tumors.

The invention is directed to a pharmaceutical composition comprising a therapeutically effective dose of Lenvatinib salt and potassium carbonates, in particular potassium hydrogen carbonate, wherein the weight ratio of Lenvatinib salt to potassium carbonates is selected within a range from 1 : 0.3 to 1 : 3.0.

A system for treating cancer is disclosed. According to an embodiment of the present invention, the system comprises: an electric field applying device for applying an electric field for tumor treatment; the delivery system is used for delivering a drug, and the drug comprises at least one of an immune checkpoint inhibitor and a chemical drug; the immune checkpoint inhibitor is selected from one of a duvaleriumab, a palbolizumab, an atelizumab, a Nasuliumab and a tereprenil monoclonal antibody; the chemical drug is selected from at least one of gemcitabine, cis-platinum, GEMOX and lenvatinib. According to the system, proliferation of the biliary tract cancer cells can be inhibited, migration of the biliary tract cancer cells can be inhibited, mitosis of the biliary tract cancer cells can be interfered, and immunogenic death of the biliary tract cancer cells can be promoted.

The invention discloses application of combination of carboxamidotriazole and revatinib in preparation of liver cancer drugs, a pharmaceutical composition and a preparation of the carboxamidotriazole and the revatinib, the drug combination of carboxamidotriazole and revatinib is used for the first time, the carboxamidotriazole and the revatinib show a remarkable synergistic effect, and in clinical medication, for patients with low sensitivity of using revatinib, the drug combination of carboxamidotriazole and revatinib has a remarkable curative effect on liver cancer. Through combination with carboxamidotriazole, the sensitivity of a patient to the medicine can be improved, and a synergistic effect is achieved. Meanwhile, as a non-cytotoxic drug, the carboxamide triazole can regulate the tumor inflammatory microenvironment, so that the tumor growth environment is changed, and the possibility of later development and metastasis of tumors is reduced. Meanwhile, the combination of carboxamidotriazole and lenvatinib has high safety, and provides more medication options for first-line patients.

The invention relates to amorphous solid forms and pharmaceutical compositions comprising amorphous lenvatinib besylate (benzene sulfonate), and the processes for their preparation.

The invention relates to amorphous solid forms and pharmaceutical compositions comprising amorphous lenvatinib besylate (benzene sulfonate), and the processes for their preparation.

This invention belongs to the field of biomedical technology and provides the application of 16'-DEC in the preparation of anti-hepatocellular carcinoma drugs. This bisindole alkaloid compound can inhibit the proliferation and migration of hepatocellular carcinoma cells and can produce a synergistic anti-tumor effect with lenvatinib, solving the problems of limited efficacy and insufficient patient survival benefit of existing targeted drugs in hepatocellular carcinoma treatment. Experiments have confirmed that 16'-DEC exerts its anti-tumor effect by directly inhibiting mTOR kinase activity. This compound can specifically bind to mTOR protein, significantly upregulate the expression of autophagy-related genes by blocking the mTOR signaling pathway, and induce autophagic cell death in tumor cells. In vitro and in vivo experiments have demonstrated that inhibiting autophagy can reverse the anti-cancer effect of 16'-DEC, indicating that its pharmacodynamic mechanism mainly depends on the activation of the autophagy pathway. This invention is applicable to the development of novel targeted therapies for hepatocellular carcinoma, especially specific inhibitors of the mTOR signaling pathway.

The application discloses a kind of drug for treating heart toxicity caused by VEGFR inhibitor with CXCL12 gene or protein as target point, belongs to medical technology field.The drug reverses heart toxicity caused by VEGFR inhibitor by down-regulating the expression of CXCL12 gene or the accumulation of CXCL12 protein in heart.Specifically, the application provides shRNA, neutralizing antibody or small molecule drug targeting CXCL12 as drug for reversing heart toxicity caused by VEGFR inhibitor.The application provides new intervention target and effective strategy for intervention of heart dysfunction caused by VEGFR inhibitor such as lefratinib, and provides feasible medication scheme for clinic.

The invention discloses a liver cancer clinical new auxiliary curative effect prediction system and medium, and the prediction system comprises an input unit which is used for inputting the value of a diagnostic serological detection index of a patient; the prediction unit is used for generating a prediction result of whether the new adjuvant therapy is invalid to the patient or not based on the prediction model and the diagnostic serological detection indexes; and the output unit is used for outputting the prediction result. According to the present invention, the diagnosis serological detection index of the patient can be conveniently and rapidly obtained based on the detection results of the blood biochemical detection, the specific protein detection and the like during the liver cancer treatment process so as to predict whether the new adjuvant therapy of the tiranibizumab combined with the lenvatinib is invalid to the patient based on the diagnosis serological detection index; therefore, the delay of the operation process of a part of patients with invalid new adjuvant therapy is avoided, and the method has wide application value clinically.

The invention belongs to the technical field of medical treatment, and particularly relates to a pharmaceutical composition and application thereof in preparation of antitumor drugs. The pharmaceutical composition provided by the invention comprises the lenvatinib and the cirametin. It is found for the first time that combination of cirametin and lenvatinib has a synergistic effect on inhibition of liver cancer cell proliferation and migration and induction of apoptosis, and also can synergistically enhance liver cancer cell lysosomal membrane permeability, so that the treatment effect of the pharmaceutical composition on liver cancer is effectively improved. Animal experiments prove that in-vivo combined use of the cirametin and the lenvatinib can more effectively inhibit proliferation of xenotransplantation tumors in nude mice compared with single use of cirametin or lenvatinib. In addition, the pharmaceutical composition can generate an ideal effect in an oral administration mode, and toxic and side effects are controllable. Therefore, the pharmaceutical composition has a good application prospect in the aspect of targeted prevention and treatment of hepatocellular carcinoma, and a new scheme with transformation potential is provided for clinically coping with the drug resistance of the lenvatinib.

The present application relates to the field of biological medicine, and particularly relates to a drug composition for reversing lenvatinib drug resistance and application thereof. One object of the present application is to provide a drug composition containing cubenix and lenvatinib. Through the synergistic effect of cubenix and lenvatinib, the inhibitory effect on liver cancer lenvatinib drug-resistant cells is significantly improved, at the same time, the lenvatinib drug-resistant cell colony formation can be significantly inhibited, the lenvatinib drug-resistant cell apoptosis is promoted, and a better tumor inhibition effect is achieved in the liver cancer tumor-bearing mouse experiment.

The invention provides a method for establishing a multi-group biomarker system based on lenvatinib, and relates to the technical field of biomedicine. The method comprises the following steps: collecting a sample and treating the sample to obtain a blood concentration threshold value of lenvatinib; processing the sample to obtain a to-be-detected sample, and processing the to-be-detected sample to obtain original mass spectrum data; carrying out preprocessing and multivariate statistical analysis on the original mass spectrum data, and screening differential metabolites; extracting an exosome in the sample; paraffin sections of tumor tissues, para-carcinoma tissues and normal components are obtained, and immune cell subpopulation differences between different tissues and different lenvatinib concentration groups are compared; and a plurality of groups of biomarker systems of lenvatinib in liver cancer cell cancer quality are established. According to the present invention, the plasma concentration, the plasma metabolite, the exosome miRNA and the tumor immune microenvironment of the lenvatinib are subjected to integrated analysis to construct the multi-dimensional treatment effect evaluation system, and the limitation of the single biomarker is exceeded;

The invention relates to amorphous solid forms and pharmaceutical compositions comprising amorphous lenvatinib besylate (benzene sulfonate), and the processes for their preparation.

Provided are a liver cell cancer therapeutic agent, a therapeutic method, etc., which can exhibit more potent and sustained antitumor effects than a conventional multi-kinase inhibitor. The present invention is characterized by including, as a combination medicament for treating liver cell cancer: a lenvatinib or a prodrug thereof, or a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof; and an antibody against human DLK-1 having an in-vivo anti-tumor activity or antibody fragments derived from said antibody.

The application discloses application of a composition containing isovaleric acid and lenvatinib in preparation of anticancer drugs and belongs to the technical field of biological medicines.It is found for the first time that isovaleric acid and lenvatinib have a synergistic effect after being combined, and the anticancer activity of the composition containing isovaleric acid and lenvatinib can be significantly improved, especially the inhibitory activity on liver cancer cells in vitro is better.Then, through animal experiments, it is further verified that the combination of isovaleric acid and lenvatinib can synergistically inhibit the growth of liver cancer cells in mice.Therefore, the composition containing isovaleric acid and lenvatinib has a good application prospect in the prevention and treatment of hepatocellular carcinoma.

The invention relates to the technical field of biology, in particular to a pharmaceutical composition capable of overcoming drug resistance of lenvatinib and application of the pharmaceutical composition. The pharmaceutical composition comprises an active ingredient targeting a KDM4A-AS1 / ZDHHC3 / WNK1 regulation axis; the active component is at least one of a KDM4A-AS1 targeting inhibitor, a ZDHHC3 targeting inhibitor or a palmitoylation inhibitor of WNK1 at a Cys411 site, and a pharmaceutically acceptable carrier of the active component. The KDM4A-AS1 / ZDHHC3 / WNK1 axis is used for driving the drug resistance of hepatocellular carcinoma (HCC) to lenvatinib by inhibiting pyroptosis. Therefore, each constituent part of the shaft represents a promising treatment target, and a feasible strategy can be provided for restoring the sensitivity of a patient with advanced hepatocellular carcinoma to lenvatinib by inhibiting each treatment target; the compound has a wide prospect in preparation of drugs for treating hepatocellular carcinoma or overcoming drug resistance of hepatocellular carcinoma to lenvatinib.

The invention provides a hepatocellular carcinoma drug resistance reversing product of a targeted ABHD6-mediated drug resistance pathway and application, relates to the technical field of biomedicine, and discloses application of the ABHD6-mediated drug resistance pathway as a target spot in preparation of a product for reversing hepatocellular carcinoma (HCC) lenvatinib drug resistance and related biomarkers. The core mechanism of the pathway is that lactic acid induces the K245 site of ABHD6 to be lactylated, so that the mitochondrial translocation is promoted, the mitochondrial translocation is competitively combined with FIS1, the excessive fusion of the mitochondrial is caused, and the apoptosis and ROS generation are inhibited. The product comprises an ABHD6 K245 lactic acid inhibitor, an ABHD6-FIS1 interaction blocking agent, an allosteric inhibitor WWL70, an LDHA inhibitor and a natural substrate 2-AG / C16: 0 MAG. The invention further discloses a preparation method of the product. Cell, xenotransplantation, PDX and orthotopic liver transplantation model verification shows that the product can effectively reverse drug resistance, and the ABHD6 K245 lactylation level can predict drug resistance. The invention fills the blank of the drug resistance mechanism of the lenvatinib, provides various efficient drug resistance reversal products and accurate prediction markers, and provides a new scheme for clinical treatment.

This invention discloses the application of BAY-850 in the preparation of drugs that inhibit hepatocellular carcinoma stemness and reverse lenvatinib resistance. This invention confirms that ATAD2 is highly expressed in hepatocellular carcinoma tissues and is positively correlated with tumor stemness; knockout of ATAD2 significantly inhibits hepatocellular carcinoma stemness; the ATAD2 inhibitor BAY-850 can inhibit the spheroidization ability of hepatocellular carcinoma cells in a concentration-dependent manner, reducing tumor stemness. In lenvatinib-resistant hepatocellular carcinoma cells, BAY-850 can significantly reduce the IC50 of lenvatinib. 50 This invention enhances drug sensitivity, and both drugs exhibit synergistic anti-cancer effects within a specific concentration range. This invention is the first to reveal that BAY-850 can inhibit hepatocellular carcinoma stemness and reverse lenvatinib resistance by targeting ATAD2, providing a new target and combination therapy for the treatment of advanced hepatocellular carcinoma.

Provided are a pharmaceutical combination and a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable form thereof and at least one other anticancer agent, and use thereof in the preparation of a medicine for treating a malignant tumor disease. The other anticancer agent is a CDK inhibitor or a pharmaceutically acceptable salt thereof (such as palbociclib), lenvatinib or a pharmaceutically acceptable salt thereof, sorafenib or a pharmaceutically acceptable salt thereof, or any combination of the above.

The present disclosure describes a combination therapy comprising an antagonist of Programmed Death 1 receptor (PD-1), a lenvatinib or a pharmaceutically acceptable salt thereof, and (6S,9aS)-N- benzyl-8-({6-[3-(4-ethylpiperazin-l-yl)azetidin-l-yl]pyridin-2- yl}methyl)-6-(2-fluoro-4-hydroxybenzyl)-4,7-dioxo-2-(prop-2-en-l- yl)hexahydro-2H-pyrazino[2,l-c][l,2,4]triazine-l(6H)-carboxamide (E7386) or a pharmaceutically acceptable salt thereof, and the use of the combination therapies for the treatment of a cancer.

This invention discloses a compound, composition, and application for increasing the sensitivity of anti-liver cancer drugs. The compound is a biguanide compound with the following structural formula: R1 is a C4 saturated alkyl group, R2 is a para-substituted aromatic cyclic group, and the substituent is trifluoromethoxy. The composition comprises the above-mentioned biguanide compound and lenvatinib. The compound and composition of this application can improve the sensitivity of anti-liver cancer drugs and have a significant anti-liver cancer effect.

The invention particularly discloses application of antibiotics in preparation of a medicine for treating liver cancer in combination with lenvatinib, and relates to the technical field of biological medicine. Under the combined use of antibiotics, the inhibition capability of the lenvatinib on tumor cells is obviously enhanced, and a remarkable treatment effect is achieved.

The invention relates to the field of animal models, and discloses a hepatocellular carcinoma in-vivo lentinib acquired drug resistance model construction method. The method comprises the following steps: step 1, inoculating mouse hepatoma carcinoma cells under the skin of a mouse to form a transplanted tumor; step 2, when the transplanted tumor grows to a predetermined size, carrying out Lenvatinib intragastric administration on the mouse; 3, under the condition of lavage administration of the lenvatinib, carrying out continuous passage on the surviving tumor tissues in the bodies of similar mice; and 4, repeating the steps 2 and 3 for multiple times until no statistical difference exists between the tumor volume of the subcultured tumor and the tumor volume of the non-dosed control group under the condition of dosing the lenvatinib. The construction method has the advantages of being easy and convenient to operate, short in construction period, stable in drug resistance and the like, the acquired drug resistance mechanism of the lentinib in the human body can be effectively simulated, and a reliable and repeatable experimental model basis is provided for hepatocellular carcinoma drug screening, drug resistance mechanism research and individualized treatment scheme development.

The present application relates to the field of biopharmaceuticals, in particular to drug-loaded nanoclusters, a preparation method and application thereof. The present application provides drug-loaded nanoclusters, comprising: nanoclusters and an antitumor drug; the mass ratio of the nanoclusters and the antitumor drug is (92.00~92.32):(7.68~8.00). The present application develops a cobalt-based drug-loaded nanocluster for delivering lenvatinib, which utilizes the drug-loading characteristics and immunogenicity of ovalbumin and metal immunity mediated by cobalt ions to improve the immunosuppressive microenvironment of hepatocellular carcinoma, improve the therapeutic effect of lenvatinib and reduce drug resistance, and combines with PD-1 monoclonal antibody to form a new immune activation scheme for systemic drug treatment, and enhances the immunotherapy effect of hepatocellular carcinoma.

To provide appropriate treatment for liver cancer patients, we offer indicators of sensitivity to multi-kinase inhibitors. [Solution] The present invention provides a testing method, testing apparatus, and testing program that use the fat content in liver cancer tissue as an indicator of sensitivity to multi-kinase inhibitors. This makes it possible to predict the therapeutic effect of multi-kinase inhibitors and provide appropriate treatment to individual liver cancer patients. The fat content can be calculated from images of liver cancer tissue or signals for image display. Images include MRI images, CT images, ultrasound images, stained images of tissue biopsies, etc. Signals for image display include MR signals, etc. Examples of multi-kinase inhibitors include lenvatinib and sorafenib.

The invention discloses a pharmaceutical composition of carboxamide triazole and lenvatinib, a solid dispersion and application thereof, the composition of carboxamide triazole and lenvatinib mesylate is a drug for regulating and controlling a tumor microenvironment and is combined with an RTK inhibitor for the first time, and the difficulty that carboxamide triazole is poor in solubility and permeability is broken through. Through continuous preparation improvement, the effect of the prepared composition of carboxamide triazole and lenvatinib mesylate is more remarkable than that of an original drug.

The invention discloses a prognosis model for predicting the curative effect of treating a patient with non-resectable hepatocellular carcinoma by combining transcatheter arterial chemoembolism with truditinib and revatinib. The research finds that four indexes of AFP, ALP, DBIL and NLR are all independent prognosis factors of a uHCC patient which is treated by a TACE (triplex angiotensin converting enzyme) combined Czodimab and lenvatinib triplex therapy. By constructing the AADN scoring model, the prognosis of the patient can be comprehensively evaluated. The AADN score has the advantages that a baseline index before treatment is easy to obtain; the treatment response is directly related; the score is dynamic and can be adjusted according to index changes in the treatment process. According to the AADN scoring model, blood indexes (AFP, ALP, DBIL and NLR) with low cost and high accessibility are adopted, the prognosis of the uHCC patient can be accurately layered, and a practical tool is provided for formulating an individualized scheme for treatment by combining TACE with the Czodimab and the lenvatinib.