68 results about "Muzolimine" 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.

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.

This invention provides a combination for use in treating cancers that express prostate-specific membrane antigen (PSMA). [Solution] A combination comprising a PD-1 inhibitor, a CTLA-4 inhibitor, and a radiolabeled compound of formula Ia for use in treating PSMA-expressing cancer in the subject. JPEG2026049728000042.jpg45132 The aforementioned combination comprises one or more further anticancer agents, wherein the further anticancer agents are selected from octreotide, lanreotide, vapreotide, pasireotide, satreotide, everolimus, temozolomide, telotristat, sunitinib, sulfatinib, ribociclib, entinostat, and pazopanib.

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.

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 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.

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 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 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 application discloses application of a swertianol derivative in preparation of a glioma treatment drug and belongs to the technical field of medicines. The application finds that the compound has significant inhibitory activity on SF126, T98G, A172, U-87 MG, U251 and various glioma cell lines, and the activity is better than that of temozolomide, a commonly used clinical anti-glioma drug, and the compound has lower toxicity to normal brain cells. The application further provides a preparation method of the compound and a pharmaceutical composition containing the compound, and the pharmaceutical composition can be prepared into injection, tablets and various dosage forms. The application provides a new effective drug selection for the treatment of glioma, has a mature preparation process, various drug dosage forms and a wide clinical 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 invention discloses application of carabrone derivatives in preparation of glioma drugs, and belongs to the technical field of medicines. It is found for the first time that the compound has remarkable inhibitory activity on multiple glioma cell lines such as SF126, T98G, A172, U-87 MG and U251, the activity of the compound is superior to that of temozolomide which is a clinically common anti-glioma drug, and meanwhile the compound is low in toxicity to normal brain cells. The invention also provides a preparation method of the compound and a pharmaceutical composition containing the compound. The pharmaceutical composition can be prepared into various dosage forms such as injections, tablets and the like. The invention provides a new effective drug choice for the treatment of glioma, and has the advantages of mature preparation process, various dosage forms and wide clinical application prospect.

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 invention relates to a method for modifying Mg-Al layered double hydroxide drug-loaded particles by a one-step method, which comprises the following steps: preparing wet Mg-Al layered double hydroxide by hydrothermal reaction, preparing a sulfydryl modifier, and adding a modification solution into the wet Mg-Al layered double hydroxide for modification to obtain the modified Mg-Al layered double hydroxide. And then adding temozolomide to obtain the Mg-Al layered double hydroxide medicine carrying material. The Mg-Al layered double hydroxide is modified by adopting a trimercaptopropylmethoxysilane one-step method, the operation is simple, the experimental environment is not complicated, the controllability in the reaction process is good, and the modified Mg-Al layered double hydroxide has relatively high drug loading capacity.

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 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 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.

Disclosed is a method for treating a condition, which includes the steps of: selecting a patient for treatment who has the condition; administering to the patient at least one active pharmaceutical ingredient (API); and administering to the patient at least one metal complex represented by formula (I):including hydrates, solvates, pharmaceutically acceptable salts and prodrugs thereof. Also disclosed is a composition for conducting the method, which includes: at least one API selected from the group consisting of Cisplatin, Temozolomide, Vandetanib, Withaferin A, Vemurafenib, Amiodarone, Vinblastine, Metformin, Gemcitabine and Acyclovir; and at least one metal complex effective to potentiate an efficacy of the API to treat the condition, wherein the at least one metal complex is represented by formula (I), including hydrates, solvates, pharmaceutically acceptable salts and prodrugs thereof.

The invention discloses an application of a 3-fluoroalkyl quinoxalinone derivative in preparation of anti-glioma drugs, and belongs to the technical field of medicines. The 3-fluoroalkyl quinoxalinone derivative has excellent anti-glioma activity, especially has a remarkable inhibition effect on glioma Glioma 261 cells, the inhibition effect of the 3-fluoroalkyl quinoxalinone derivative is remarkably superior to that of temozolomide which is widely applied at present, and the 3-fluoroalkyl quinoxalinone derivative has good development value and wide application prospects.

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 discloses a temozolomide and Boc-1-methyl-D-tryptophan axial asymmetric disubstituted silicon phthalocyanine conjugate as well as a preparation method and application of the temozolomide and Boc-1-methyl-D-tryptophan axial asymmetric disubstituted silicon phthalocyanine conjugate. 1, 3-diimino isoindoline is used as an original raw material, dichlorosilicon phthalocyanine is generated through a ring formation reaction, silicon phthalocyanine with double chains being tetraethylene glycol is obtained through a nucleophilic reaction, and finally, a target product DTPC is generated through an esterification reaction. The target product DTPC can enhance targeting and killing effects on cancer cells, can resist angiogenesis and effectively and synergistically promote anti-tumor immunity, and provides a new thought for improving photodynamic therapy.