29 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.

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.

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 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 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.

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.

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.

This invention relates to the field of biomedical technology, specifically to a targeted inhibition ELK3 Gene expression products and their applications. The product is shRNA, and the target sequence of the shRNA is shown in SEQ ID NO. 5. The shRNA provided by this invention inhibits... ELK3 Gene expression was reversed, temozolomide resistance in glioma cells was enhanced, TMZ-induced apoptosis and DNA damage were increased, tumor growth was inhibited, and the survival of nude mice bearing drug-resistant gliomas was prolonged.

The application discloses a kind of hydrophilic drug supramolecular nanoscale drug delivery systems and its assembly method, belong to medical technical field, hydrophilic drug, such as tirapazamine (Tirapazamine, TPZ), temozolomide (Temozolomide, TMZ), gemcitabine hydrochloride (Gemcitabine hydrochloride, GEM) or 5-azacytidine (5-azacytidine, 5AC) as model drug, with dihydrophenanthrene (Ce6) is directly co-assembled under ultrasonic condition, forms nanoscale drug delivery system;The method does not need chemical synthesis and greatly simplifies the preparation of nanoscale drug delivery system. It is proved by experiment, the supramolecular hydrophilic drug (CTNPs) assembled in the application can effectively improve the intratumoral accumulation of drug in tumor-bearing mice, and can significantly inhibit the growth and metastasis of tumor through synergistic antitumor effect. Therefore, the supramolecular assembly method in the application provides a new mode for developing easy-to-manufacture and multifunctional hydrophilic nanomedicine delivery system.

The invention provides methods and compositions for treatment of a subject with a glioma that has failed treatment with temozolomide (TMZ) comprising administration of a composition comprising a Coenzyme Q10 compound to the subject. The invention also provides a method of treating a cancer that exhibits increased Complex II activity in a subject comprising administration of a composition comprising a Coenzyme Q10 compound to the subject.

The present application relates to a kind of RRM1T52 phosphorylation antibody and its application in brain glioma, belong to biological medicine technical field.The present application first proposes that RRM1T52 can be used as new index for predicting diagnosis glioblastoma, provides new judging basis for the progress of current clinical glioblastoma patient after using temozolomide treatment, perfects the early diagnosis of present stage to glioblastoma.The present application finds biomarker for glioblastoma drug resistance based on the mechanism of glioblastoma drug resistance, and early diagnosis of glioblastoma can be realized by detecting biomarker expression level, changes the limitation and credibility of previous detection means and index.

The application discloses a lncATRIG inhibitor and application thereof in preparation of a drug for treating glioma. The lncATRIG inhibitor comprises one or more of sequences LNA-1, LNA-2 and LNA-3 shown in the following formula; wherein the sequence of the LNA-1 is shown in Seq ID No. 2; the sequence of the LNA-2 is shown in Seq ID No. 3; the sequence of the LNA-3 is shown in Seq ID No. 4; and the cDNA sequence of the lncATRIG is shown in Seq ID No. 1. The lncATRIG inhibitor provided by the application can inhibit the proliferation of brain glioma cells and promote temozolomide sensitization.

This invention relates to the field of biomedical technology, and more particularly to the use of a combination of RVX208 and temozolomide for the treatment of glioblastoma. It also relates to the use of RVX208 to resensitize temozolomide-resistant cancers to temozolomide treatment. The use of at least one of RVX208, a pharmaceutically acceptable salt of RVX208, a solvate of RVX208, a hydrate of RVX208, a polymorph of RVX208, an isomer of RVX208, a prodrug form of RVX208, and temozolomide in the preparation of a glioblastoma therapeutic agent. RVX208 inhibits the transcriptional activity of various genes related to cell cycle progression and proliferation maintenance by inhibiting BET family proteins or other target molecules, leading to cell cycle arrest, inhibition of cell proliferation, and induction of programmed cell death. RVX208 also interferes with the transcriptional expression of genes related to mitochondrial homeostasis regulation, resulting in a decrease in mitochondrial membrane potential and reduced ATP production, thus enabling RVX208 to disrupt mitochondrial function in GBM cells and produce a synergistic antitumor effect with temozolomide.

The invention discloses application of an METTL1 inhibitor in preparation of a product for improving sensitivity of glioma to temozolomide, and belongs to the field of biological medicine. The si-METTL1-1 of which the nucleotide sequence is shown as SEQ ID NO.1 and the si-METTL1-3 of which the nucleotide sequence is shown as SEQ ID NO.2 are used as the METTL1 inhibitors to carry out glioma drug sensitivity research, and experimental results show that proliferation, migration and invasion capabilities of glioma cells can be effectively reduced and the sensitivity of temozolomide in glioblastoma can be remarkably improved by interfering expression of METTL1 by using the METTL1 inhibitors. Therefore, the METTL1 inhibitor not only can be used for diagnosing and treating glioma, but also can improve the sensitivity of glioma cells to temozolomide. The invention provides a novel auxiliary product for improving the curative effect of a targeted drug, and has a wide application prospect.

The present disclosure provides a composition comprising temozolomide or lenalidomide, a medium chain triglyceride (e.g., miglyol), silica, and a surfactant wherein the composition optionally comprises an antioxidant and / or a flavouring agent, and wherein the temozolomide composition is a non-aqueous, preservative-free suspension. Also provided are methods for treating cancer in a subject (e.g., a child or a subject with and / or with dysphagia).

The present invention provides a therapeutic combination comprising (a) an isoindole-piperidine compound of formula (I) as described in the specification and (b) an alkylating agent temozolomide wherein the active ingredient is present in each case in free form or in the form of a pharmaceutically acceptable salt or any hydrate thereof; and the use of the therapeutic combination in the treatment of glioma.