40 results about "Temozolomida" patented technology

The present invention relates to a polypeptide-drug conjugate that binds to IL4Ra and a use thereof, and provides: a polypeptide comprising a ligand that specifically binds to IL4Ra and a temperature-responsive disordered domain; and a polypeptide-drug conjugate in which a cytotoxic drug is bound to the polypeptide. More specifically, the polypeptide, in which an IL4RA-binding ligand and a temperature-responsive disordered domain are repetitively linked, exhibits high selectivity in binding to IL4Ra, and the polypeptide-drug conjugate, in which a cytotoxic drug is bound to the polypeptide, demonstrates significantly enhanced cancer cell-killing efficacy and anti-tumor activity compared to unbound drugs or conventional anticancer agents, and has been confirmed to suppress drug resistance in cancer cells that are resistant to the anticancer agent temozolomide. Accordingly, the polypeptide-drug conjugate can be provided as an effective anticancer therapeutic agent for the treatment of tumors overexpressing IL4Ra and as a pharmaceutical composition for inhibiting drug resistance in cancer cells exhibiting resistance to anticancer drugs.

Through extensive and deep research, a new path Parkin / Park / Mul1 / Mfn2 for regulating and controlling the drug resistance of a tumor chemotherapy temozolomide (TMZ) drug by the TRPC5 is found, and the new path has a close relationship with the generation of the drug resistance of the tumor chemotherapy temozolomide (TMZ) drug. Compared with primary cells U87 and U251, the expression level of the TRPC5 in temozolomide tolerant cells U87R and U251R is remarkably improved, and a mitochondrial autophagy pathway is activated. By reducing the expression of the TRPC5 gene, the sensitivity of a cell strain to a temozolomide drug can be enhanced, and the proliferation capacity of tumor cells can be inhibited. According to the invention, not only is new data provided for a malignant glioma drug resistance mechanism, but also a new target spot is provided for the design of anti-tumor drug resistance drugs.

The present disclosure is directed to a method of treating glioblastoma in a subject in need thereof comprising administering to said subject an efficient amount of a radiopharmaceutical compound. The present disclosure is also directed to methods of treating glioblastoma in a subject in need thereof comprising administering to said subject an efficient amount of a radiopharmaceutical compound in combination with a step of irradiating the subject with an efficient dose of ionizing radiations, and optionally, with a therapeutically efficient amount of an alkylating agent, preferably temozolomide.

The invention discloses application of baclofen in preparation of a medicine for treating glioma, and belongs to the technical field of biological medicine. Through systematic in-vitro and in-vivo experiments, it is proved for the first time that baclofen (especially R-configuration) has a remarkable anti-tumor effect on glioma including temozolomide (TMZ) drug resistance. The invention not only provides a brand-new clinical strategy for treating TMZ drug-resistant glioma, but also shows important value in the field of scientific research: baclofen can be used as a valuable tool compound and is used for exploring a new function of a GABAB receptor signal channel in glioma progress and drug resistance; meanwhile, a key tool is provided for constructing a stable TMZ drug-resistant model, the high-throughput drug screening and evaluation efficiency can be remarkably improved, and the TMZ drug-resistant monoclonal antibody can serve as a positive control drug to accelerate the conversion process from basic research of glioma to clinical application and has wide scientific research application prospects and conversion potential.

A single-cell transcriptome-guided multimodal synergistic injectable magnetically responsive biomimetic hydrogel system, its preparation method, and its application are described. This hydrogel platform is a three-level composite system of "matrix-microsphere-nanoparticle": the primary structure is a photocrosslinked methacryloyl hyaluronic acid three-dimensional network matrix; the secondary structure is GelMA microspheres loaded with MTPT nanoparticles prepared by microfluidic control; and the tertiary structure consists of bevacizumab and magnetite nanoparticles dispersed in the HAMA matrix. The MTPT nanoparticles have a mesoporous silica core, which is sequentially coated with temozolomide, a polydopamine coating, and a T7 targeting peptide. Under the activation of an alternating magnetic field, Fe3O4 generates a magnetothermal effect, which not only achieves local hyperthermia but also accelerates the time-sequential release of bevacizumab and MTPT, synergistically exerting the effects of chemotherapy, anti-angiogenic therapy, and hyperthermia.

To provide pharmaceutical compositions for treating solid tumor, in particular, glioblastoma multiforme (GBM).SOLUTION: Provided herein is a pharmaceutical composition for use in a method for retarding progression of brain tumor, where the composition comprises a therapeutical effective dose of F16, that is, isoindole (1, 3-dioxy-2, 3-dihydro-1H-isoindol-4-yl)-amide and a therapeutically effective dose of a chemotherapeutic agent in a pharmaceutical carrier, where the brain tumor is glioblastoma multiforme, and the chemotherapeutic agent is temozolomide (TMZ) or bevacizumab (BVZ) or similar agent.SELECTED DRAWING: Figure 1

The invention relates to a solid pharmaceutical composition containing temozolomide. The solid pharmaceutical composition comprises temozolomide, a suspending aid, colloidal silicon dioxide and a pH regulator.

Methods of treating glioma using a WEE1 inhibitor are disclosed.

The invention belongs to the technical field of medicines, and particularly relates to application of temozolomide bromide as a sound-sensitive agent, and the temozolomide bromide has a structure shown in a formula (I). The invention provides a novel preparation and purification scheme of the sound-sensitive agent temozolomide bromide, and compared with traditional temozolomide, the product has a better killing effect on tumor cells, and has an extremely remarkable killing effect on the tumor cells and cell cycle arrest under the ultrasonic synergistic effect. The temozolomide derivative has a low toxicity effect similar to that of temozolomide on normal neuronal cells at low concentration, and animal experiments prove that the temozolomide derivative can penetrate through a blood-brain barrier. In addition, the invention has immeasurable clinical application value in the treatment of tumors, especially glioma and / or melanoma.

The invention provides new pharmacological approaches to the treatment of benign and malignant primary brain tumors, and specifically glioblastomas (GBM) and astrocytomas in which treatment is complicated by resistance to conventional chemotherapies. To which end the invention provides compositions and methods using modulators of intracellular nitrosative / oxidative stress and modulators DNA replication and apoptosis, with examples of specific inhibitors of neuronal and inducible NO synthetases (nNOS and iNOS) that were found to be effective either when administered alone or more effective when administered in combination temozolomide (TMZ), even in tumors displaying TMZ resistance.

The invention belongs to the technical field of liposome pharmaceutical preparations, and particularly relates to a liposome and application thereof, a liposome preparation and a preparation method and application thereof. The invention provides a liposome. A glutathione group and an indole residue are modified on a liposome membrane. The lipidosome provided by the invention has excellent transmembrane transport capacity, can efficiently penetrate through a blood-brain barrier and can be taken by glioma cells, and also shows excellent endosome escape characteristic, so that the technical problem of low blood-brain barrier transmittance in the glioma treatment process of temozolomide is effectively solved. Meanwhile, the invention provides a liposome preparation, the delivery efficiency and the anti-tumor curative effect are improved, the liposome preparation has an inhibiting effect on human / mouse glioma cells, the wide clinical application potential is shown, and an efficient and low-toxicity novel treatment scheme is provided for glioma patients.

The utility model discloses a mixing granulator for preparing temozolomide capsules, which relates to the technical field of mixing equipment and comprises a mixing cylinder, a linkage mechanism is mounted in the mixing cylinder, and the linkage mechanism comprises a connecting rod, a rotating rod and mixing blades; a protruding block is installed at one end of the connecting rod, the end, away from the connecting rod, of the protruding block is meshed with a tooth groove of a first gear installed in the mixing barrel, a second rotating rod is inserted into the first gear, and a first rotating disc and a second rotating disc are inserted into the bottom and the top of the second rotating rod correspondingly; and the second rotating disc is connected with a fixing plate. A second transmission wheel drives a bearing rod through a first rotating rod to enable a rack to rotate, a tooth groove in one side of the rack is meshed with a tooth groove in the surface of a second gear, so that the second gear is driven to enable a second rotating disc to rotate, and meanwhile a plurality of linkage mechanisms installed on the outer wall of the second rotating disc rotate; meanwhile, a lug meshed with a tooth groove of a first gear drives a plurality of linkage mechanisms to rotate around a first turntable, so that the mixing uniformity of temozolomide capsule raw materials is improved.

The present invention belongs to the technical field of liposome pharmaceutical preparations, and specifically relates to a liposome and its application, a liposome preparation and its preparation method and application. The present invention provides a liposome, wherein the liposome membrane is modified with a glutathione group and an indole residue. The liposome provided by the present invention has excellent transmembrane transport ability, efficiently penetrates the blood-brain barrier and can be taken up by glioma cells, while exhibiting excellent endosomal escape properties, thereby effectively solving the technical problem of low blood-brain barrier permeability during the treatment of gliomas with temozolomide. At the same time, the present invention provides a liposome preparation that improves delivery efficiency and anti-tumor efficacy, has an inhibitory effect on both human and mouse glioma cells, shows a wide range of clinical application potential, and provides a new treatment plan for glioma patients with high efficiency and low toxicity.

The application belongs to the field of antitumor drugs, and particularly relates to trifluoromethylated temozolomide and derivatives thereof, a preparation method and application. The trifluoromethylated temozolomide has a better killing effect on tumor cells relative to traditional temozolomide, has a lower toxic effect on normal neuron cells at a low concentration relative to temozolomide, and can penetrate the blood-brain barrier through animal experiments.

The invention relates to the technical field of biomedical engineering and brain drug delivery, in particular to a phase-change controlled-release multi-stage implantable brain drug delivery device and a preparation method thereof. The system is specially designed for postoperative treatment of brain malignant tumors and is composed of a fibroin nanofiber substrate, a drug-loaded phase change material nanoparticle layer, a degradable packaging layer and a wireless heating module. Fatty acid mixtures with different melting points are used as phase change matrixes to wrap chemotherapeutic drugs (such as temozolomide) and anti-aging drugs (such as ABT-263) respectively, and nano-drug carriers with specific thermal response temperatures (such as 39 DEG C and 42 DEG C) are constructed. After the system is implanted into a brain tumor excision lacuna, under the action of an external radio frequency magnetic field, accurate heat is generated through the wireless heating module, the phase change material is triggered to be melted in a graded mode, programmed sequential release of medicine to brain tissue is achieved, collaborative treatment of'chemotherapy-senescent cell removal 'in the brain is achieved, the limitation of a blood brain barrier is effectively broken through, and the treatment effect is good. The brain tumor recurrence problem is solved.

The invention belongs to the technical field of pharmaceutical co-crystals, and relates to a temozolomide-ferulic acid co-crystal hydrate as well as a preparation method and application thereof. And mixing a temozolomide raw material, a ferulic acid raw material and water, adding the grinding balls, grinding, and drying to obtain the temozolomide-ferulic acid eutectic hydrate. One temozolomide-ferulic acid eutectic hydrate molecule contains one temozolomide molecule, one ferulic acid molecule and one water molecule; the molecular formula of the temozolomide-ferulic acid eutectic hydrate is C < 6 > H < 6 > N < 6 > O < 2 >. C < 10 > H < 10 > O < 4 >. H < 2 > O. Compared with a TMZ-FEA.ACN eutectic crystal in the prior art, the temozolomide-ferulic acid eutectic crystal hydrate prepared by the invention has excellent physical and chemical stability, and provides more choices and guarantees for storage and application of medicines.

The application discloses a monomer compound DTA and application thereof in preparation of a temozolomide-sensitive glioma inhibiting drug. Through a glioma primary cell model, it is proved that the monomer compound Demethylenedelcoine A (DTA) can produce a better anti-chemotherapy resistant glioma effect than a clinical first-line chemotherapy drug temozolomide and carmustine. Therefore, in clinical treatment of temozolomide chemotherapy resistance and radiotherapy failure recurrent glioma, the monomer compound DTA can have a potential treatment advantage, and therefore has a potential drug development value.

The invention discloses a tumor treatment system based on an ultrasonic fatigue effect, which directly damages a cancer cell membrane structure and destroys the integrity of the cancer cell membrane structure through the continuous action of low-intensity ultrasonic energy, specifically targets a disordered tumor extracellular matrix by utilizing the ultrasonic fatigue effect, and simultaneously causes mechanical damage to tumor blood vessels. The tumor core hypoxia caused by nutrition delivery is blocked, so that cell apoptosis is induced. And the multi-layer mechanical-biological effect jointly inhibits tumor growth. The tumor treatment system is combined with temozolomide for use, can synergistically amplify the anti-tumor effect, and is suitable for hypoxic tumors tolerated by a traditional therapy. According to the treatment system, a non-invasive and controllable tumor treatment mode is achieved through accurate regulation and control of energy, and a new thought is provided for tumor treatment.

The invention relates to temozolomide for use in methods of treating a subject having a glioblastoma tumor, preferably 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 invention also relates to temozolomide for use in 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 invention discloses combined application of temozolomide and metformin to treatment of liver cancer, and belongs to the field of biological medicine. In-vivo and in-vitro experiments prove that combined administration of temozolomide and metformin can remarkably inhibit proliferation and growth of liver cancer cells, animal experiments find that combined use of temozolomide and metformin can remarkably inhibit growth of tumors, obvious liver and kidney toxicity cannot be generated, the liver cancer treatment effect can be improved, and the application of temozolomide and metformin in liver cancer treatment can be promoted. And a new drug combination scheme is provided for liver cancer treatment.

The invention discloses a construction method and application of a refractory pituitary tumor organ. The method comprises the following steps: culturing pituitary tumor tissues by using a pituitary tumor organoid culture medium, the pituitary tumor organoid culture medium comprises a basic culture medium and an additive, and the additive comprises triiodothyronine and / or thyroid stimulating hormone releasing hormone. The organoid constructed by the method can stably express pituitary tumor markers such as SF1 / FSH / synapsin and accurately simulate clinical drug resistance characteristics (such as temozolomide resistance) in vitro, solves the problems that primary tumor cells are low in activity and drug resistance phenotypes are difficult to maintain, fills the blank that no reliable in-vitro model exists in the field, and has good application prospects. And a platform is provided for drug resistance mechanism research and individualized drug screening.

The invention discloses an application of a small molecule inhibitor HY-Q66655 in preparation of a medicine for treating glioma. The compound HY-Q66655 capable of targeting YRDC is obtained by taking YRDC as a target spot and utilizing a virtual screening technology. In-vivo and in-vitro experiments show that the HY-Q66655 can significantly inhibit the proliferation ability of glioma stem cells and temozolomide-resistant glioma cells, and enhance the sensitivity of the cells to a first-line chemotherapeutic drug temozolomide, and is high in safety; the combination of HY-Q66655 and TMZ shows a good synergistic inhibition effect on the proliferation of glioma stem cells and glioma cells with drug resistance to temozolomide. Therefore, the invention provides a small-molecule inhibitor HY-Q66655 capable of targeting YRDC and inhibiting proliferation of glioma stem cells and drug-resistant cells thereof, and a brand new candidate drug and a promising combined treatment strategy are provided for treating glioma and overcoming TMZ drug resistance of glioma.

The application provides a small molecule compound EPIC-1042, and the application designs and synthesizes the small molecule compound EPIC-1042, which can specifically block the combination of PTRF and CAV1, and has a lower IC 50 In vivo experiments prove that EPIC-1042 can effectively reduce the exocytosis of sEVs and the stability of PARP1 and block the progress of the autophagic flow. In in vitro experiments, when combined with the first-line chemotherapy drug temozolomide, EPIC-1042 can effectively reverse temozolomide resistance and prolong the survival period, and has a great clinical conversion prospect.

The present disclosure relates to a method of treating glioblastoma in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a radiopharmaceutical compound having a GRPR antagonist moiety, preferably [177Lu] Lu-NeoB, in combination with radiation therapy and optionally a therapeutically effective amount of an alkylating agent, preferably temozolomide.

This invention belongs to the field of biopharmaceuticals, specifically referring to a photo-environment-targeted antitumor nanoparticle IUR, its preparation method, and its application. In this application, HA and RVG29 peptides are chemically linked to generate HA-RVG29. Then, HA-RVG29 is coated onto nanoparticles self-assembled from UA and the photosensitizer IR820 via electrostatic interactions, forming photosensitive nanoparticle IURs with glioma-targeting activity. This IUR exerts a therapeutic effect on gliomas through combination with temozolomide. Cell and animal experiments demonstrate that the combination of these nanoparticles and TMZ has a good antitumor effect. In vivo experiments, using TUNEL cell apoptosis detection, flow cytometry, inverted fluorescence microscopy, and other methods, show that the combination of IUR and TMZ can promote cell apoptosis, inhibit cell proliferation, and has a good inhibitory effect on gliomas.

Novel compositions and methods are provided for effective clinical management of central nervous system (CNS) cancers in mammalian subjects, including humans. The anti-CNS cancer compositions and methods employ lucanthone, alone or in combination with other anti-CNS cancer drugs or methods (including chemotherapy, such as with temozolomide, and radiation), to prevent or reduce CNS cancer, including gliomas. In certain embodiments, lucanthone compositions and methods effectively treat glioblastomas, including high grade glioblastomas. In other embodiments, lucanthone compositions and methods effectively target and control CNS cancer stem cells, for example to reduce or prevent recurrence of glioblastomas unresolved by conventional treatments.

The invention belongs to the technical field of biological medicine, and particularly relates to pachysandra terminalis alkaloid Pactermine Q as well as a preparation method and application thereof. The invention provides a pachysandra terminalis alkaloid Pactermine Q with anti-tumor biological activity, the compound is a new alkaloid separated from pachysandra terminalis, and the inhibition effect on human brain glioma cells is obviously better than that of temozolomide.

A temozolomide compound according to formula (I)is described, wherein R1, L1, and X are defined herein. The temozolomide compound can be used to prepare polymers comprising temozolomide. Additionally, the polymers comprising temozolomide can be particularly useful in the treatment of certain diseases.

The invention belongs to the field of antitumor drugs, and particularly relates to trifluoromethylated temozolomide as well as a derivative, a preparation method and application thereof. Compared with traditional temozolomide, trifluoromethylated temozolomide has a better killing effect on tumor cells, has a toxic effect lower than that of temozolomide on normal neuronal cells at low concentration, and can penetrate through a blood brain barrier through animal experiments.

The invention provides an AUTAC bionic nano-particle as well as a preparation method and application of the AUTAC bionic nano-particle. The nanoparticle has a core-shell structure, and sequentially comprises a core, a functional peptide layer and a cell membrane shell from inside to outside, the core comprises a PLGA-PEG-Mal copolymer carrier, and entrapped temozolomide and cationic lipid DOTAP (Dioctyl Terephthalate); the functional peptide layer is formed by covalently connecting a multifunctional peptide with a maleimide group through sulfydryl; the cell membrane shell is a microcolloid cell membrane; the nanoparticles can efficiently pass through a blood brain barrier, are enriched at a brain tumor part in a targeted manner, reduce MGMT expression by degrading beta-catenin, reverse TMZ drug resistance and enhance a chemotherapy effect, and are suitable for treating temozolomide drug-resistant glioblastoma.