40 results about "Temozolomid" patented technology

The invention discloses temozolomide derivatives or pharmaceutically acceptable salts, crystal forms and solvates, wherein the structure of the temozolomide derivatives is shown as a formula I in the specification. According to the temozolomide derivative disclosed by the invention, damage caused by repairing temozolomide by cells is prevented by inhibiting PARP1 protein, so that the purpose of improving the overall anti-glioblastoma effect is achieved. The invention further discloses application of the temozolomide derivative or the pharmaceutically acceptable salt, the crystal form and the solvate to preparation of a PARP1 inhibitor. The invention also discloses application of the temozolomide derivative or the pharmaceutically acceptable salt, the crystal form and the solvate in preparation of medicines for preventing and / or treating tumors. The invention also discloses a pharmaceutical composition, and the pharmaceutical composition takes a safe and effective amount of temozolomide derivative or pharmaceutically acceptable salt, crystal form and solvate as effective components or main effective components, and is prepared into a pharmaceutically acceptable dosage form together with a pharmaceutically acceptable carrier.

Disclosed are methods of treating a subject having a biopsy-only glioblastoma tumor comprising applying an alternating electric field to a target site of the subject for a period of time, wherein the target site comprises one or more glioblastoma cells; administering a therapeutically effective amount of temozolomide (TMZ); and administering a therapeutically effective amount of a checkpoint inhibitor to the subject. Disclosed are methods of increasing survival of a subject having a biopsy-only glioblastoma tumor comprising applying an alternating electric field to a target site of the subject for a period of time, wherein the target site comprises one or more glioblastoma cells; administering a therapeutically effective amount of temozolomide (TMZ); and administering a therapeutically effective amount of a checkpoint inhibitor to the subject.

The application belongs to the field of pharmaceutical preparations and relates to a novel temozolomide preparation and use thereof, and the novel temozolomide preparation is a temozolomide sustained-release granule.The temozolomide sustained-release granule provided by the application contains the following components: 10-50 parts by weight of temozolomide, 5-20 parts by weight of sustained-release material I, 30-60 parts by weight of cyclodextrin, 20-50 parts by weight of sustained-release material II, 5-15 parts by weight of a pore-forming agent, 0.5-2 parts by weight of an anti-sticking agent, 80-150 parts by weight of a filler, 5-20 parts by weight of a disintegrant, 5-15 parts by weight of a binder, and 5-30 parts by weight of a flavoring agent.The temozolomide sustained-release granule prepared by the application has obvious sustained-release effect, can effectively maintain stable blood drug concentration, reduces the frequency of use and the amount of medication, and improves the compliance of patients.

Bioadhesive and biodegradable polymeric nanoparticles can be administered intrathecally, for example, via the cisterna magna, into the spinal column to allow widespread distribution for the treatment of tumors such as leptomeningeal metastases. The nanoparticles rapidly spread to all cerebrospinal fluid (CSF) compartments, including the brain parenchyma and spinal column. The bioadhesive nanoparticles penetrate and are retained for long periods of time, during which time they can continue to release drugs. These nanoparticles can be loaded with different therapeutic, preventive, or diagnostic agents, most preferably DNA repair inhibitors, to enhance the killing of leptomeningeal tumors, such as leptomeningeal metastases, and disseminated tumors, such as medulloblastoma. In a preferred embodiment, patients are treated with a combination of a PARP inhibitor and temozolomide.

The invention relates to a copper / temozolomide / metformin nano prodrug as well as a preparation method and application thereof. The nano prodrug is formed by coordination self-assembly of temozolomide, copper ions and metformin, the mass fraction of temozolomide is 20%-60%, the mass fraction of copper ions is 20%-40%, and the mass fraction of metformin is 1%-60%. The invention provides a preparation method of a nano prodrug, which comprises the following steps: on the basis of a copper / temozolomide prodrug, introducing a metformin aqueous solution, and stirring and reacting in a water phase at normal temperature to obtain a three-component nano prodrug with glutathione response release characteristic. The prodrug is clear in structure and stable in particle size, copper ions and temozolomide can be released in a tumor microenvironment to induce copper death, and efficient treatment of drug-resistant glioblastoma is achieved in cooperation with metabolic intervention of metformin. Compared with the prior art, the preparation method disclosed by the invention is simple and convenient, an additional carrier is not needed, and the prodrug has good targeting property, biodegradability and treatment effect and has a good application prospect.

The invention provides application of combination of an ROR1 intervention agent and temozolomide in treatment of brain glioma. Experiments prove that the intervention of glioma stem cells ROR1 can block the interaction between glioma stem cells and macrophages, inhibit the generation of endothelial-like stem cells and induce the normalization of glioma blood vessels. The ROR1 intervention agent is combined with temozolomide, so that the delivery efficiency of temozolomide can be improved, the killing effect of temozolomide is enhanced, and the treatment effect is finally improved.

The invention discloses a construction method of mitochondrial nano vesicles Pep-1 (at) TMZm (at) MitoNVs capable of enhancing penetration of blood brain barriers, belongs to the field of preparation of nano drug delivery systems of targeted glioblastoma, and relates to a construction method of nano particles modified and linked with modified temozolomide and Pep-1. According to the mitochondrial nano-vesicle of the Pep-1 (at) TMZm (at) MitoNVs, provided by the invention, the mitochondrial nano-vesicle which can carry temozolomide and has relatively high bioavailability, relatively good histocompatibility, considerable drug loading ratio and encapsulation efficiency and relatively light toxic and side effects is developed; the mitochondrial nano-vesicle based on TMZ modification and Pep-1 is an effective carrier capable of improving the blood brain barrier penetrating capability of a clinical first-line chemotherapeutic drug TMZ and the tumor targeting property and enhancing the anti-tumor activity of the clinical first-line chemotherapeutic drug TMZ.

Provided are methods of treating a subject for a CNS tumor, such as glioma. Such methods include administering to the subject olutasidenib in combination with temozolomide as maintenance therapy to treat the tumor. Additionally, the treatment schedule can have multiple time periods where different amounts of olutasidenib and temozolomide are administered to the subject. Such methods of treatment can cause a reduction or complete disappearance of the tumor. The methods can be used for different types of subjects, such as those with certain IDH1 mutations and for those with glioma, such as high-grade glioma (HGG).

The invention discloses a temozolomide spherocrystal based on nano confinement crystallization regulation and a method and application thereof. The preparation method of the temozolomide spherocrystal based on nano confinement crystallization regulation and control comprises the following steps: dissolving glycyrrhizic acid and temozolomide in pure water under an ultrasonic condition, adjusting the pH value to 3-4, heating until the solution is clear, and cooling to 0-5 DEG C under a stirring condition to obtain the temozolomide spherocrystal based on nano confinement crystallization regulation and control. Compared with the temozolomide raw material I crystal form, the temozolomide spherocrystal disclosed by the invention shows excellent nasal administration characteristics, including uniform particle size, high sphericity and excellent fluidity. Cell experiments show high cytotoxicity (IC50 = 51.9 [mu] g mL <-1 >) to glioblastoma, and in vivo experiments prove efficient brain targeting ability of the polypeptide. The preparation method has the characteristics of mild preparation conditions, easiness in process control, good reproducibility, high brain targeting property and the like, and is suitable for treating cancers delivered into the brain through the nose.

The invention discloses a combined application of a PARP7 inhibitor or a pharmaceutically acceptable salt thereof and temozolomide, which is characterized in that the PARP7 inhibitor is used for recovering an I-type interferon signal channel and promoting T cell-mediated immune response and polarization of TAMs to M1 type, so that the side effect of temozolomide is reduced, the sensitivity of temozolomide is enhanced, and an excellent synergistic anti-tumor effect is achieved; the traditional Chinese medicine composition especially has a remarkable curative effect on brain glioma with high malignant degree, and is safe and effective.

This disclosure provides a pharmaceutical composition for treating glioma and its application, belonging to the pharmaceutical field. The pharmaceutical composition comprises temozolomide and pueraria lobata extract, with a mass ratio of temozolomide to pueraria lobata extract of (4:1)–(1:1). The combined use of temozolomide and pueraria lobata extract exhibits a significant synergistic inhibitory effect on glioma. This pharmaceutical composition can be used in the preparation of drugs for treating glioma and has broad application prospects.

The subject of the present invention is a hydrogel carrier, a pharmaceutical composition, use thereof and process for their preparation. The biopolymeric photocrosslinked delivery system for temozolomide obtained according to the invention should be particularly suitable for local therapy of brain glioblastoma.

The present invention discloses a combined pharmaceutical composition for treating glioblastoma. The pharmaceutical composition comprises temozolomide, MK-803, and / or MK-2206. Among them, the combination of temozolomide and MK-803 has a synergistic effect on the treatment of glioblastoma, which is significantly superior to the use of TMZ or MK-803 alone. The combination of temozolomide, MK-803, and / or MK-2206 can significantly inhibit the growth of glioblastoma cells and prolong the survival period of patients. The present invention provides a new strategy and idea for the treatment of glioblastoma.

The present invention relates to a polypeptide drug conjugate binding to IL13Ra2 and use thereof, and provides: a polypeptide comprising ligands specifically binding to IL13Ra2 and temperature-sensitive atypical domains; and a polypeptide-drug conjugate in which an apoptotic drug is bound to the polypeptide. More specifically, a polypeptide, in which IL13Ra2 binding ligands and temperature-sensitive atypical domains are repeatedly linked, binds to IL13Ra2 very selectively, and a polypeptide-drug conjugate, in which an apoptotic drug is bound to the polypeptide, exhibits greatly enhanced anticancer and anti-tumor activities compared with unbound drugs or existing anticancer agents, and was identified to have an effect of inhibiting anticancer agent resistance of cancer cells retaining resistance to the anticancer agent temozolomide. Therefore, the polypeptide-drug conjugate can be provided as an effective anticancer therapeutic agent for the treatment of tumors overexpressing IL13Ra2 and as a pharmaceutical composition for inhibiting drug resistance of cancer cells showing drug resistance to anticancer agents.

The application discloses an anti-glioma pharmaceutical composition and application thereof, and the pharmaceutical composition comprises a STING agonist or a pharmaceutically acceptable salt thereof, and temozolomide or a pharmaceutically acceptable salt thereof, and / or echinomycin. The application proves through experiments that the pharmaceutical composition containing two or three active ingredients can significantly inhibit the growth of glioma cells and promote the apoptosis of glioma, and provides a brand-new strategy and thought for the treatment of glioma.

The application discloses a temozolomide dexchlorpheniramine derivative and application thereof in preparation of an antitumor drug, and is based on new cognition of a TMZ drug resistance mechanism, designs and synthesizes two temozolomide derivatives. The target compounds retain the alkylating activity of TMZ, and metabolites do not produce 5-amino-imidazole-4 amide (AICA), but produce dexchlorpheniramine derivatives of AICA. Thus, the TMZ chemotherapy sensitivity is enhanced, and the TMZ drug resistance of glioma is delayed or reversed. The application first reconstructs the TMZ molecule from the metabolic product level, breaks through the action mode of the inherent drug resistance, and provides a brand-new drug design idea for overcoming the TMZ drug resistance. A new generation of TMZ derivative drugs can be developed, a single drug or a combined treatment scheme with higher efficacy and lower drug resistance is realized, and more breakthrough treatment options are provided for GBM patients.

The present invention relates generally to a method of treating a glioblastoma comprising administering a therapeutically effective amount of 4-L-[131I]iodo-phenylalanine in combination with external beam radiotherapy and optionally Temozolamide chemotherapy, to a patient in need thereof. Also provided is a composition of 4-L-[131I]iodo-phenylalanine suitable for intravenous administration.

The invention belongs to the technical field of biological medicines, and particularly relates to application of PD-1-IN-22 in preparation of a medicine for treating tumors. According to the application, research finds that myosin heavy chain 9 is combined with heterogeneous ribonucleoprotein K to promote lactylation of a K163 site and induce mitochondrial division of glioma cells, so that the sensitivity of temozolomide is reduced. Through molecular drug screening, it is found that the compound shown in the formula I can block combination of MYH9 and hnRNPK, then glioma proliferation and glioma stem cell formation are inhibited, and the sensitivity of related glioma cells and organoids to temozolomide can be improved.

The invention discloses application of FR054 in reversing temozolomide drug resistance of glioblastoma, FR054 is used as a sensitizer of temozolomide, and the sensitivity of temozolomide to tumor cells and the killing effect of temozolomide to GBM cells are enhanced by targeted inhibition of a key metabolic enzyme PGM3 in an HBP pathway.

The invention discloses a composition for treating brain glioma and application thereof, and relates to the technical field of biological medicine. The composition for treating the brain glioma is prepared from temozolomide and tetrathiomolybdate. According to the application disclosed by the invention, by analyzing the inhibition condition of temozolomide and tetrathiomolybdate on glioma cells under the conditions of independent medication and combined medication and quantitatively calculating the combined inhibition effect, a result shows that temozolomide and tetrathiomolybdate have a synergistic treatment effect in a glioma cell line. In a nude mouse subcutaneous tumor implantation model, temozolomide and tetrathiomolybdate are combined for treatment, the tumor weight and the animal survival condition are detected, the combined inhibition effect is quantitatively calculated, the side effect of the medicine is detected, and the result shows that temozolomide and tetrathiomolybdate have the synergistic treatment effect. The evidence shows that the tetrathiomolybdate can remarkably improve the chemosensitivity of glioma to temozolomide, meanwhile, the safety is guaranteed, and the tetrathiomolybdate has high clinical application value.

The invention provides a pharmaceutical composition for treating glioma, and relates to the technical field of medicines. The pharmaceutical composition for treating glioma is characterized by being composed of a small molecule compound and temozolomide. The small molecule compound H027-2175C disclosed by the invention can penetrate through a blood brain barrier, and is specifically combined with and inhibits milk acylation modification of a PDP2 K38 site. By inhibiting PDP2 K38 lactoacylation and H027-2175C, TCA circulation activation mediated by lactic acid is blocked, so that the drug resistance of glioma cells to temozolomide is reversed. The combined use of the small molecule compound H027-2175C and temozolomide can significantly enhance the antitumor activity, specifically, in an in-vitro experiment, the combined medication significantly inhibits the proliferation of glioma cells, and the IC50 value is reduced; in an in-vivo experiment, the lifetime of a glioma model mouse is remarkably prolonged and the tumor volume is reduced by virtue of drug combination. The small molecule compound H027-2175C and temozolomide are combined for use, so that the toxic and side effects of temozolomide can be reduced, and the treatment safety is improved.

This invention discloses a method, system, and apparatus for computer-aided drug screening based on temozolomide and ADAMTS1. This application is the first to discover that ADAMTS1 is significantly enriched in recurrent gliomas following temozolomide exposure; temozolomide strongly induces a stable senescence program, leading to excessive secretion of ADAMTS1. This senescence-induced protease coordinates significant changes in extracellular matrix composition. The remodeled microenvironment acts as a mechanobiochemical signaling agent, recruiting and polarizing host-derived myeloid cells to transform into the immunosuppressive M2 phenotype, thereby conferring chemotherapy resistance to residual glioma cells through paracrine signaling. This application reveals that the "senescence-ADAMTS1-ECM-M2" axis is a key non-cellular autonomous mechanism of temozolomide resistance. Targeting ADAMTS1-mediated matrix reprogramming can eliminate the immunosuppressive niche in gliomas and overcome chemotherapy resistance, showing broad application prospects.

This invention belongs to the field of chemical medicine, specifically relating to a phenylpropanoid compound, its preparation method, and its application. The phenylpropanoid compound specifically refers to the compound, solvate, optically pure isomer, stereoisomer, or pharmaceutically acceptable salt thereof, or mixtures thereof, represented by general formula (Ⅰ), wherein X is selected from O or N; R1, R2, R3, R4, and R5 are the same or different, and are independently selected from hydrogen, hydroxyl, halogen, alkoxy, and alkylthio groups; R 13 Selected from hydrogen or C1-C4 alkyl, or R 13 Connect R5 to form a loop; R 14 The compounds are selected from cycloalkyl groups with 5-6 substituted carbon atoms. The phenylpropanoid compounds synthesized in this invention exhibit significant inhibitory effects on glioma cells, and their inhibitory effect is superior to that of the positive control drugs temozolomide and the original chlorogenic acid. Simultaneously, some of the synthesized phenylpropanoid compounds significantly improve neuronal cell survival rates, and their protective effect is superior to that of the positive control drug edaravone, demonstrating potential for treating stroke.

Provided are methods of treating a subject for a CNS tumor, such as glioma. Such methods include administering to the subject olutasidenib in combination with temozolomide as maintenance therapy to treat the tumor. Additionally, the treatment schedule can have multiple time periods where different amounts of olutasidenib and temozolomide are administered to the subject. Such methods of treatment can cause a reduction or complete disappearance of the tumor. The methods can be used for different types of subjects, such as those with certain IDH1 mutations and for those with glioma, such as high-grade glioma (HGG).

The invention relates to the technical field of tumor prognosis prediction, and discloses a temozolomide drug resistance prediction model for a patient with MGMT negative glioblastoma, and the method comprises the following steps: obtaining gene expression profile data of temozolomide sensitive strains and resistant strains of glioblastoma cell lines, and screening differential genes through difference analysis; and sequentially carrying out single-factor Cox regression, Kaplan-Meier survival analysis, Lasso regression and multi-factor Cox regression analysis on the differential genes in an MGMT negative patient queue of a TCGA database, and determining a candidate gene combination consisting of OLR1, ULBP2, KCNK5, BDKRB2 and MUS81. The prediction model is based on five candidate gene signatures, the risk score can be calculated according to the expression level of the five candidate gene signatures, the survival probability is predicted through the column diagram, the prediction accuracy of the drug resistance risk of the MGMT negative patient is improved, and the early recognition of the high-risk patient is facilitated to provide a basis for individualized treatment.

Provided are combinations of an oncolytic virus and temozolomide (TMZ) for the treatment of glioma, and a method of treating TMZ resistant glioma. Wherein the oncolytic virus expresses an interferon encoded by SEQ ID NO: 2, 3 or 4. Also provided are kits for the treatment of glioma comprising an oncolytic adenovirus and TMZ wherein the oncolytic adenovirus expresses a consensus interferon and the oncolytic adenovirus and TMZ are in the same or different containers.

The invention discloses an intelligent regulation and control system for combined treatment of glioblastoma, and relates to the technical field of intelligent equipment. The intelligent regulation and control system for glioblastoma combined treatment comprises a patient screening module used for acquiring tumor image data and cell cycle data of a patient; the drug delivery module comprises a temozolomide drug delivery unit and an IL-6 receptor antibody drug delivery unit; the biomarker monitoring module is used for detecting a DNA damage marker level, a serum cell factor concentration and a neuron damage marker level in tumor cells of the patient; the data analysis and decision-making module is used for receiving the patient tumor image data and the cell cycle data output by the patient screening module and the detection result output by the biomarker monitoring module, automatically judging a treatment node based on a built-in preset threshold value and sending a regulation and control instruction to the drug administration module; the synergistic administration of the temozolomide and the IL-6 receptor antibody is realized. The system can realize precise treatment of glioblastoma.

The invention belongs to the field of biological medicine, and discloses a pharmaceutical composition combining an aquaporin inhibitor and temozolomide for treating brain glioma, and the pharmaceutical composition comprises an AQP4 inhibitor AER270 and TMZ. The invention further discloses a pharmaceutical preparation containing the pharmaceutical composition and application of the pharmaceutical preparation to preparation of drugs for treating brain glioma. The composition provided by the invention provides an effective drug combination strategy for treatment of brain glioma, and it is found for the first time that the combination of AER270 and TMZ has a synergistic effect on treatment of brain glioma.

The present invention describes nitrogen-containing heterocyclic compounds with an oxane ring of the general formula I, where the meanings of individual substituents are given in the claims. The compounds are suitable for the treatment of cancer, especially glioblastoma. The compounds can be used in monotherapy and in combination therapy, for example together with temozolomide.

The invention provides application of prodigiosin in preparation of a medicine for treating brain glioma, and belongs to the technical field of biological medicine. The invention provides application of prodigiosin in treatment of brain glioma, and prodigiosin and temozolomide can synergistically inhibit proliferation capacity of brain glioma cells, induce apoptosis of tumor cells, reduce healing and migration capacity of cell wounds, reduce formation of cell adhesion spots and block autophagy tumors of tumor cells, so that the prodigiosin and temozolomide can be used for treating brain glioma. The treatment effect on brain glioma is remarkably improved, the dosage of temozolomide is reduced, and the pharmaceutical composition has important significance on improvement of the lifetime and the life quality of a patient.