74 results about "Lenvatinib" patented technology

The invention discloses application of a composition containing isovaleric acid and lenvatinib in preparation of anti-cancer drugs, and belongs to the technical field of biological medicines. It is found for the first time that after the isovaleric acid and the lenvatinib are combined for use, the isovaleric acid and the lenvatinib have a synergistic effect, the anti-cancer activity of the composition containing the isovaleric acid and the lenvatinib can be remarkably improved, and especially the composition has better inhibitory activity on in-vitro liver cancer cells. Animal experiments further verify that the combination of isovaleric acid and lenvatinib can synergistically inhibit the growth of liver cancer cells in mice. Therefore, the composition containing the isovaleric acid and the lenvatinib has a relatively good application prospect in the prevention and / or treatment of the hepatocellular carcinoma.

The invention relates to the technical field of bioengineering, and discloses a marker for predicting liver cancer treatment sensitivity and application thereof.The marker for predicting liver cancer treatment sensitivity comprises HECTD2, the nucleotide sequence of the HECTD2 is shown as SEQ ID NO: 1, oxidative stress of the HECTD2 is limited through KEAP1 / NRF2 so as to promote drug resistance of the revatinib, the marker comprises H3K181a, H3K182a, H3K182a, H3K182a, H3K182a, H3K182a, H3K182a, H3K182a, H3K182a, H3K182a, H3K182a, H3K182a, H3K182a, H3K182a, H3K182a, H3K182a, H3K182a The nucleotide sequence of the H3K18la is as shown in SEQ ID NO: 2, and the H3K18la induces up-regulation of HECTD2 in HCC cells, so that the drug resistance of the lenvatinib is promoted. According to the present invention, the HECTD2 is adopted as the E3 ubiquitin ligase, and the K48-connected multi-ubiquitin chain is added on the K551 residue of the KEAP1 so as to alleviate the oxidative stress stimulated by the treatment of the lenvatinib; the transcription of the HECTD2 is enhanced by the H3K18la; the expression level of the HECTD2 is an independent prediction index of prognosis of the HCC patient; a new visual angle is provided for understanding the drug resistance of the HCC to the lenvatinib, and a promising diagnosis and treatment strategy is possibly provided for clinical treatment of the HCC.

The invention discloses a method for determining the concentration of letemovir in plasma by using liquid chromatography-tandem mass spectrometry, which comprises the following steps: S1, preparing a calibrator working solution and a quality control working solution of letemovir, respectively adding the calibrator working solution and the quality control working solution into a plasma matrix to obtain a plasma calibrator and a plasma quality control, preparing an internal standard working solution taking the lenvatinib-d5 as an internal standard substance; s2, respectively adding a plasma calibration material and a plasma quality control material into the internal standard working solution obtained in the step S1, carrying out protein precipitation treatment, collecting supernate, carrying out liquid chromatography-tandem mass spectrometry analysis on the supernate, and drawing a liquid chromatography-tandem mass spectrometry standard curve; and S3, obtaining the concentration of letemovir in the plasma of a sample to be detected according to the liquid chromatography-tandem mass spectrometry in the step S2. According to the method, the sample pretreatment step is simplified, the operation difficulty and time consumption are reduced, a rapid, accurate and high-sensitivity analysis result is ensured, and the method is suitable for the requirements of rapid clinical and research fields.

The invention discloses a kit for simultaneously determining five liver cancer multi-kinase targeted drugs and active metabolites thereof based on LC-MS / MS. The kit comprises an internal standard solution, a standard substance solution, a protein precipitant and a solution used as a mobile phase, the internal standard solution is a gefitinib solution; the standard substance solution is a solution of sorafenib, sorafenib nitric oxide, lenvatinib, lenvatinib nitric oxide, dorafenib, dorafenib nitric oxide, regorafenib, regorafenib nitric oxide, cabozatinib and cabozatinib nitric oxide; the protein precipitant is an ice acetonitrile solution; the mobile phase comprises a mobile phase A and a mobile phase B, the mobile phase A is an aqueous solution containing formic acid, and the mobile phase B is an acetonitrile solution containing formic acid. The invention also discloses a method for determining the liver cancer multi-kinase targeted drug and the active metabolite thereof. The method can be used for monitoring drug concentration and preparing a drug time monitoring curve, and can simultaneously improve the sensitivity and selectivity of the method and shorten the analysis time so as to improve the analysis flux.

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.

Provided are: a therapeutic drug for hepatocellular carcinoma, a therapeutic method, etc., which can exert a strong and lasting anti-tumor effect compared with existing multi-kinase inhibitors. The present invention is characterized in that it is a combination drug for treating hepatocellular carcinoma, which comprises: lenvatinib or its prodrug, or a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof; and an antibody against human DLK-1 having anti-tumor activity in vivo or an antibody fragment derived from the antibody.

A pharmaceutical composition for prevention or treatment of a disease or disorder characterized by chronic inflammation, associated with angiogenesis and fibrosis. The pharmaceutical composition includes a multi-target inhibitor, multi-phase modulator, or multi-kinase inhibitor, such as axitinib, nintedanib, pirfenidone, riociguat, sorafenib, sunitinib, lenvatinib, regorafenib, ponatinib, or pazopanib.

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.

The invention discloses application of long-chain non-coding RNA LINC01532 in preparation of a medicine for prognosis evaluation and treatment of hepatocellular carcinoma, the gene sequence of the long-chain non-coding RNA LINC01532 is as shown in SEQ ID NO.1, and the LINC01532 is highly expressed in hepatocellular carcinoma, is related to poor prognosis of a hepatocellular carcinoma patient and can be used as a marker for preparation of a reagent for prognosis evaluation of hepatocellular carcinoma; besides, the compound can be used as a target spot for preparing a tyrosine kinase inhibitor treatment effect evaluation reagent, the sensitivity of a drug-resistant patient to treatment of the lenvatinib is improved by interfering or inhibiting expression of LINC01532, and a new strategy is provided for diagnosis and treatment of hepatocellular carcinoma.

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.

This disclosure provides methods for treating a hepatocellular carcinoma (e.g., unresectable HCC) with lenvatinib or a pharmaceutically acceptable salt thereof. Also encompassed by the disclosure are dosage regimens described herein of lenvatinib or a pharmaceutically acceptable salt thereof for use in treating hepatocellular carcinoma (e.g., unresectable hepatocellular carcinoma) according to any of the methods described herein. Particularly useful dosages and dose modifications upon the occurrence of an adverse event or events are also disclosed.

The present invention discloses the application of a protein kinase CK2 inhibitor in enhancing the therapeutic efficacy of liver cancer treatment, which relates to the field of biomedicine. The present invention proves that the combined use of CX-4945 and lenvatinib has a synergistic effect on the proliferation inhibition of liver cancer cells resistant to lenvatinib, and has a good tumor inhibitory effect in the liver cancer xenograft mouse experiment, significantly inhibiting the growth of liver cancer both in vitro and in vivo. At the same time, it provides a potential combined drug target for the treatment of liver cancer patients resistant to lenvatinib. Moreover, CX-4945 plays a role in reversing lenvatinib resistance with a small dosage, and has very little toxic and side effects, showing broad application prospects in the treatment of liver cancer resistant to lenvatinib.

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 present invention relates to pharmaceutical compositions comprising a therapeutically effective dose of a salt of lenvatinib and a potassium carbonate, in particular potassium bicarbonate, wherein the weight ratio of the salt of lenvatinib to the potassium carbonate is selected from the range of 1:0.3 to 1:3.0.

The invention discloses application of lenvatinib (E7080) in treatment of alveolar echinococcosis, and belongs to the field of biomedicine. The technical problem to be solved by the invention is how to treat and / or prevent alveolar echinococcosis. It is found that lenvatinib (E7080) can cause falling of a head hook of an original head section of echinococcus multilocularis, shrinkage of a body section, damage to structures such as a suction cup and microvillus, and the in-vivo pathogenicity is remarkably reduced; the structure of the vesicles in the middle polyester period can be destroyed, so that the hair growth layers of the vesicles shrink and are separated from the cuticle. It is shown that lenvatinib (E7080) has a good killing effect on echinococcus multilocularis and can be used for preparing the medicine for treating the alveolar echinococcosis.

The invention provides an application of a compound WAY-226570 in preparation of an anti-liver cancer drug. The invention firstly finds that WAY-226570 (the molecular formula is C14H10F3N3) can inhibit the proliferation effect and migration and invasion activity of liver cancer cells, and further, the lenvatinib and WAY-226570 are combined to generate a synergistic inhibition effect on the proliferation of the liver cancer cells, so that the lenvatinib can be used as a combined medicine composition to be applied to the preparation of the medicine for preventing and / or treating the liver cancer, and has a clinical application prospect.

A method for co-administrating hydroxyprogesterone caproate, tyrosine kinase inhibitor, and / or anti-PD-I / PD-LI an-1 tibodies for tumor treatment. The present application also provides a corresponding pharmaceutical use and a pharmaceutical product. Co-administration with hydroxyprogesterone caproate can further improve the therapeutie effect of lenvatinib and anti-PD-I / PD-L1 antibodies against tumors.

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 application belongs to the technical field of biological medicine, and particularly relates to application of lenvatinib combined with ursodeoxycholic acid in liver cancer treatment. Specifically, the application constructs a cell strain Huh7R of human liver cancer cell Huh7 cells resistant to lenvatinib to carry out experiments. The results show that lenvatinib and UDCA can produce a synergistic inhibitory effect on HCC at multiple concentrations. Further, animal experiments also confirm the anti-HCC effect of the drug combination. The application provides a method capable of effectively inhibiting HCC progression, thereby overcoming the drug resistance problem of lenvatinib in clinical treatment, bringing new treatment options for liver cancer patients, and hopefully improving tumor treatment effect and improving the quality of life of patients, and therefore has important clinical significance and social value.

The invention discloses a kit for determining the concentration of letemovir in plasma by using liquid chromatography-tandem mass spectrometry. The kit is used for detecting the concentration of letemovir in plasma. The kit comprises a calibrator working solution of letemovir, a quality control working solution of letemovir, a plasma matrix and an internal standard working solution taking lenvatinib-d5 as an internal standard substance. According to the kit, the sample pretreatment step is simplified, the operation difficulty and time consumption are reduced, the rapid, accurate and high-sensitivity analysis result is ensured, and the kit is suitable for the requirements of rapid clinical and research fields.

A macrophage-loaded drug-loaded nanoparticle, its preparation method, and its application belong to the field of drug-targeted carrier technology. To address the problem that the therapeutic efficacy of drugs such as lenvatinib for HCC after minimally invasive ablation is limited by their nonspecific accumulation and distribution in the body, the LEN-loaded MΦs prepared by the present invention are constructed by engulfing Escherichia coli membrane-coated LEN-loaded nanoparticles by natural M1-type MΦs. The E. coli membrane camouflage enhances the phagocytic efficiency of MΦs, prevents the leakage of LEN within the MΦs, and maintains the M1 type of LEN@MΦs within the immunosuppressive tumor microenvironment. The natural inflammatory gradient induced by ablation is used to guide LEN-loaded macrophages to target tumors, increasing the in vivo delivery efficiency of LEN in postoperative HCC by 10-fold. This method significantly inhibits tumor cell proliferation and angiogenesis, and this enhanced LEN delivery stimulates systemic immune responses and induces long-lasting immune memory.

The invention belongs to the technical field of biological medicine, and particularly relates to application of lenvatinib combined with ursodesoxycholic acid in liver cancer treatment. Specifically, a human hepatoma carcinoma cell Huh7 cell is constructed to carry out an experiment on a lenvatinib drug-resistant cell strain Huh7R cell. The result shows that the lenvatinib and the UDCA can generate a synergistic inhibition effect on the HCC under multiple concentrations. Further, animal experiments also prove the anti-HCC effect of the pharmaceutical composition. The invention provides a method capable of effectively inhibiting the progress of HCC, so that the problem of drug resistance of lenvatinib in clinical treatment is solved, a new treatment choice is brought to a liver cancer patient, the tumor treatment effect is expected to be improved, the life quality of the patient is improved, and therefore, the lenvatinib has important clinical significance and social value.

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 present invention belongs to the field of pharmaceutical chemistry, and particularly relates to a preparation method of a lenvatinib intermediate. The present invention uses tert-butyl cyclopropylcarbamate as the starting material, and reacts with 4-amino-3-chlorophenol under the action of a catalyst to obtain the key intermediate of lenvatinib, 1-(2-chloro-4-hydroxyphenyl)-3-cyclopropylurea. This preparation method effectively avoids the use of reagents with strong toxicity such as chloroformate, making the reaction operation safer and more suitable for industrial scale-up production.